Categories : HospitalsTags :

A New Easy-to-Apply Antimicrobial Coating

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Researchers have developed an inexpensive, non-toxic coating for almost any fabric that decreases the infectivity of SARS-CoV-2 by up to 90%. It could even be developed to be applied to fabric by almost anyone.

“When you’re walking into a hospital, you want to know that pillow you’re putting your head onto is clean,” said lead author Taylor Wright, a doctoral student at the University of British Columbia. “This coating could take a little bit of the worry off frontline workers to have Personal Protection Equipment with antimicrobial properties.”

Researchers soaked fabric in a solution of an antimicrobial polymer which contains a molecule that releases reactive oxygen species when light shines on it. They then used UV light to turn this solution to a solid, fixing the coating to the fabric. “This coating has both passive and active antimicrobial properties, killing microbes immediately upon contact, which is then amped up when sunlight hits the cloth,” said senior author Professor Michael Wolf.

Both components are safe for human use, and the entire process takes about one hour at room temperature, said Wright. It also makes the fabric hydrophobic, without sacrificing fabric strength. The researchers detailed their study in American Chemical Society Applied Materials & Interfaces.

The coating can also be used on almost any fabric, with applications in hospital fabrics, masks, and activewear. While other such technologies can involve chemical waste, high energy use, or expensive equipment, the UBC method is relatively easy and inexpensive, said Wright. “All we need is a beaker and a light bulb. I’m fairly certain I could do the whole process on a stove.”

To test the coating’s antimicrobial properties, the researchers bathed treated fabric in bacterial soups of Escherichia coli and Methicillin-resistant Staphylococcus aureus (MRSA). They found that 85% of viable E. coli bacteria remained after 30 minutes, which fell to three per cent when the treated cloth was exposed to green light for the same amount of time. Similarly, 95% of viable MRSA bacteria remained, dropping to 35% under green light. No bacteria remained after four hours.

While sunlight or fluorescent lights have a lesser percentage of green in their spectrums, the team expects similar but less intense results for fabric exposed to those light sources, said Wright. “Particularly in the Pacific Northwest, it’s not always a sunny day. So, at all times you’re going to have that layer of passive protection and when you need that extra layer of protection, you can step into a lit room, or place the fabric in a room with a green light bulb – which can be found for about $35 online.”

The researchers also looked into whether the coating reduced the infectivity of SARS-CoV-2 by bathing treated fabric in a solution of the virus particles and then adding that solution to living cells to see if they could infect them. They found the passive properties were ineffective against the virus, but when treated fabric was exposed to green light for two hours, there was up to a 90% drop in the virus’ infectivity. “In other words, only one tenth of the amount of virus signal was detected on cells infected with the UV-fabric and light treated virus”, says co-author Professor François Jean.

The team found they needed an 18cm2 piece of fabric to kill microbes with material containing 7% of the active ingredient by weight, but that increasing this to 23% increased the effectiveness of the fabric at four times less material, said Wright.

Researchers also found that keeping the fabric under green light for more than 24 hours failed to produce the sterilising forms of oxygen, highlighting an area for further study. This is a similar effect to the colour fading on clothing after being exposed to sunlight for too long.

“Biomanufacturing face masks based on this new UBC technology would represent an important addition to our arsenal in the fight against COVID, in particular for highly transmissible SARS-CoV-2 variants of concern such as Omicron”, said Prof Jean. The coating can also be used for activewear, with an ‘anti-stink’ coating applied to areas where people tend to sweat, killing off the bacteria that makes us smell. Indeed, hospital fabric and activewear companies are already interested in applying the technology, and the university has applied for a patent in the United States, said Prof Wolf.

Source: University of British Columbia

Categories : CancerTags :

‘A-Maize-ing’ Nanoparticles Target Cancer Cells Directly

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Computer=generated depiction of nanoparticles

Researchers have recently developed novel nanoparticles derived from maize that can target cancer cells directly, via an immune mechanism. The results of this study, published in Scientific Reports, are encouraging, and the technique has demonstrated efficacy in treating tumour-bearing laboratory mice with no adverse effects.

Nanoparticles, or particles whose size varies between 1 and 100nm, have shown tremendous potential in many areas of science and technology, including therapeutics. However, conventional, synthetic nanoparticles are complicated and expensive to produce and alternatives such as extracellular vesicles (EVs) have mass production challenges.
Another recently emerging option is that of plant-derived nanoparticles (NPs), which can be easily produced in high levels at relatively lower costs. Like EVs, these nanoparticle-based systems also contain bioactive molecules, including polyphenols (which are known antioxidants) and microRNA, and they can serve as vehicles for targeted drug delivery.

Recently, researchers from the Tokyo University of Science (TUS) developed anti-cancer bionanoparticles, using corn (maize) as the raw material.
Lead researcher Professor Makiya Nishikawa explained: “By controlling the physicochemical properties of nanoparticles, we can control their pharmacokinetics in the body; so, we wanted to explore the nanoparticulation of edible plants. Maize, or corn, is produced in large quantities worldwide in its native form as well as in its genetically modified forms. That is why we selected it for our study.” 

The team centrifuged a super-sweet corn juice and then filtered it through a syringe filter with a 0.45μm pore size, then ultracentrifuged to obtain NPs derived from corn. The corn-derived NPs (cNPs) were approximately 80nm in diameter with a tiny net negative charge of -17mV.

The research team then set up experiments to see whether these cNPs were being taken up by various types of cells. In a series of promising results, the cNPs were taken up by multiple types of cells, including the clinically relevant colon26 tumor cells (cancer cells derived from mice), RAW264.7 macrophage-like cells, and normal NIH3T3 cells. RAW264.7 cells are commonly used as in vitro screens for immunomodulators.

The results were astounding: of the three types of cells, cNPs only significantly inhibited the growth of colon26 cells, indicating their selectivity for carcinogenic cell lines. Moreover, cNPs were able to successfully induce the release of tumour necrosis factor-α (TNF-α) from RAW264.7 cells. TNFα is primarily secreted by macrophages, natural killer cells, and lymphocytes, which help mount an anticancer response. “The strong TNFα response was encouraging and indicated the role of cNPs in treating various types of cancer,” explains Dr. Daisuke Sasaki, first author of the study and an instructor and researcher at TUS.

A luciferase-based assay revealed that the potent combination of cNPs and RAW264.7 cells significantly suppressed the proliferation of colon26 cells. Finally, the research team studied the effect of cNPs on laboratory mice bearing subcutaneous tumours. Once again, the results were astonishing: daily injections of cNPs into colon26 tumours significantly suppressed tumour growth, without causing serious side effects, or weight loss.

“By optimising nanoparticle properties and by combining them with anticancer drugs, we hope to devise safe and efficacious drugs for various cancers,” observed an optimistic Prof Nishikawa.

Source: Tokyo University of Science

Categories : Neurology Obstetrics & GynaecologyTags :

Reduced Antiepileptic Drug Effectiveness in Pregnancy Uncovered

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Blood levels of many commonly used antiepileptic drugs drop dramatically with the onset of pregnancy, which can result in ‘breakthrough seizures’ according to a study published in JAMA Neurology.

The findings, collected as part of the multicentre study Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD), explain why many people with epilepsy start experiencing breakthrough seizures after conception, underscoring the need to increase antiseizure medication doses and closely monitor blood levels over the course of pregnancy.

A fine-tuned medication regime is critical in epilepsy. “Some people mistakenly believe that changes in the drugs’ blood concentration won’t occur until after 20 weeks of pregnancy, but our study shows how important it is to start monitoring and adjusting patients’ medication dosages early on,” said lead author Dr Page Pennelll. “Nearly half of all pregnancies in the United States are unplanned, so it is important to ensure that doctors have a clear picture of each patient’s baseline drug level even if they are not trying to conceive.”

A life-altering neurological condition, two-thirds of epilepsy cases do not have a known cause. In people with epilepsy, nerve cells in the brain are hyper-reactive, causing them to change the pattern of their electrical activity and become spontaneously active. That synchronous activation is manifested in seizures.

Epilepsy has a fraught history of diagnosis and management; people with epilepsy go undiagnosed or under-treated. First-generation drugs to control it had many dangerous side effects and were contraindicated for people who are trying to conceive.

Since then, safer medications have entered the U.S. market and become widely available, but clinicians started noticing a new problem – patients whose epilepsy was successfully managed with medications started having seizures soon after becoming pregnant.

“Identifying which antiseizure medications may have changes in concentrations and at what point in pregnancy those changes occur is important for determining which patients may need to be monitored more closely during pregnancy and after delivery,” said senior author Professor Angela Birnbaum at the University of Minnesota.

To solve the mystery, the researchers embarked on a study to analyse blood concentrations of 10 commonly used antiseizure drugs and compare them across different stages of pregnancy and after childbirth.

The study found that blood levels of seven out of 10 of the medications they examined dropped dramatically — from 29.7% for lacosamide, a commonly prescribed anticonvulsant, and up to 56.4% for lamotrigine.

In addition, the researchers noted that the drop in drug levels occurred mere days after conception.

Source: University of Pittsburgh

Categories : COVID PaediatricsTags :

High COVID Mortality Rate Found in African Children and Adolescents

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African children and adolescents hospitalised with COVID experience much higher mortality rates than Europeans or North Americans of the same age, according to a recent six-country study which included South Africa.

The study, published in JAMA Pediatrics. was conducted by researchers from the Institute of Human Virology (IHV) at the University of Maryland School of Medicine (UMSOM) and the Institute of Human Virology Nigeria (IHVN). Both organisations are members of the Global Virus Network (GVN).

“This study provides important information about COVID among African children, which was not previously available at this scale. We now have evidence from multiple countries to show that African children also experience severe COVID; they experience multisystem inflammatory syndrome; some require intensive care; some also die, and at much higher rates than outside Africa,” said co-first author Nadia Sam-Agudu, MD, Associate Professor of Pediatrics at the UMSOM’s Institute of Human Virology.

The AFREhealth study collected data from 25 health facilities across Nigeria, Ghana, Democratic Republic of the Congo, Kenya, South Africa, and Uganda. The study included 469 African children and adolescents aged three months to 19 years hospitalised with COVID between March and December 2020. The team reported a high overall mortality rate of 8.3%, compared with 1% or less totaled from Europe and North America. Furthermore, African children less than a year old and with pre-existing, non-communicable diseases were more likely to have poorer outcomes.

Eighteen participants had suspected or confirmed multisystem inflammatory syndrome (also known as MIS-C), and four of these children died.

Dr Sam-Agudu, who led the West Africa team for the study, urged health authorities and policymakers in Nigeria and other African countries to act upon the study findings “to protect children by expanding vaccine approvals and procurements for children specifically, as the variants emerging since our study’s completion have either caused more severe disease and/or more cases overall. We cannot leave children behind in the pandemic response.”

Source: University of Maryland

Categories : Mental Health Substance UseTags :

Illicit Use of Amphetamines Magnifies Psychosis Risk

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The illicit use of amphetamines (aka ‘speed’) is linked to a 5-fold heightened risk of psychosis, according to the results of a decade-long study published in the journal Evidence-Based Mental Health.

This increased risk was seen across all age groups, but was especially noticeable among women and those who had been arrested several times for possession of the drug, the findings show.

The estimated global prevalence of amphetamine use is less than 1%, but around 1 in 10 users become addicted.

The drug affects neurotransmitter signalling in the brain and often causes psychosis, the symptoms of which mimic those of schizophrenia, with paranoia, voices, and hallucinations. Though these psychotic episodes usually subside after a few days, in up to 15% of users they may last for years.

While the link between amphetamine misuse and psychosis has been known for many decades, it’s not clear exactly what the magnitude is of this risk or how effective rehab is at successfully weaning users off the drug.

To try and find out, the researchers drew on information supplied to the Taiwan Illicit Drug Issue Database (TIDID) and the National Health Insurance Research Database (NHIRD) between 2007 and 2016.

The TDID contains anonymised data on date of birth, sex, arrest records and deferred prosecution for rehabilitation treatment for illicit drug users, while the NHIRD contains anonymised data on mental and physical health issues for the population of Taiwan.

The researchers identified 74 601 illicit amphetamine users and 298 404 age- and sex-matched comparisons. Their average age was 33 and most (84%) were men.

Compared with those who weren’t using, illicit amphetamine users had poorer health: depression (2% vs 0.4%); anxiety (0.9% vs 0.3%); ischaemic heart disease (1.3% vs 0.8%); cardiovascular disease (0.8% vs 0.45%); and stroke (1.3% vs 0.7%).

By the end of the 10 year monitoring period, amphetamine users were more than 5 times as likely to experience psychosis than those who weren’t using after accounting for age, sex, and coexisting health issues. The annual cumulative incidence rates for psychosis among the comparison group and amphetamine users were 77 and 468 per 100 000 people, respectively.

The number of new cases of psychosis was similar across all age brackets, but was more common in the amphetamine users among those aged 45 and above.

While psychosis risk increased with comorbidities, overall, it was higher among illicit amphetamine users without coexisting conditions, suggesting a direct impact of amphetamine on inducing psychotic symptoms, the researchers said. Psychosis risk rose in tandem with the number of arrests, and fell when patients received psychotherapy for their addiction (rehab).

Those who had been arrested 5 or more times were more than 6 times as likely to experience psychosis, while users who went to rehab during deferred prosecution were 26% less likely to experience psychosis than those who didn’t. This suggests that rehab may help to stave off the risk of subsequent psychosis, say the researchers.

In common with previous research, illicit amphetamine use was linked to greater levels of anxiety and depressive symptoms as well as cardiovascular complications.

“Because persistent psychotic symptoms could represent a risk for cognitive decline in amphetamine users, identifying [those] with psychosis and providing treatment early might prevent subsequent damage of cognitive functions,” write the researchers. But rehab is voluntary, and only offered to around 1 in 10 users, they point out.

By way of an explanation for the gender discrepancy observed, the researchers suggest that the detrimental impact of amphetamines on behaviour might be enhanced by the presence of oestrogen.

“Another possibility is that women arrested for illicit amphetamine use were particularly disadvantaged in comparison with men, with higher levels of trauma, lack of psychosocial support and stigma,” they noted.

As an observational study, it cannot establish cause, and addiction could not be quantified. Illicit amphetamine use could also precipitate and aggravate schizophrenic symptoms, so it’s possible that amphetamine induces rather than causes the psychotic symptoms seen in amphetamine users.

The researchers concluded: “The relation of an induced paranoid psychosis with amphetamine abuse has been known for many decades. None the less, our findings are from a detailed and comparative analysis using a comprehensive and large population dataset.

“Furthermore, it would be worthwhile to investigate the health benefits and cost effectiveness of deferred prosecution for drug crime offenders by providing appropriate therapy for drug addiction.”

Source: The BMJ

Categories : Ageing COVIDTags :

Higher Oestrogen Levels Protect Older Women Against Severe COVID

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An older woman’s oestrogen levels may be linked to her chances of dying from COVID, with higher levels of the hormone seemingly protective against severe infection, according to a study published in BMJ Open.

Supplemental hormone treatment to curb the severity of COVID infection in post-menopausal women could be investigated, the researchers suggested.

Even after accounting for other factors, women seem to have a lower risk of severe COVID infection than men. This holds true for other serious recent viral infections, such as MERS (Middle East Respiratory Syndrome).

Oestrogen may have a role in this gender discrepancy, so to invesitgate the researchers compared the potential effects of boosting and reducing oestrogen levels on COVID infection severity.

They drew on Swedish national data, and the study sample included 14 685 women in total: 227 (2%) had been previously diagnosed with breast cancer and were on oestrogen blocker drugs (adjuvant therapy) to curb the risk of cancer recurrence; and 2535 (17%) were taking hormone replacement therapy (HRT) to boost their oestrogen levels in a bid to relieve menopausal symptoms.

Some 11,923 (81%) women acted as the comparison group as they weren’t on any type of treatment, either to enhance or reduce their systemic oestrogen levels.

Analysis of all the data showed that compared with no oestrogen treatment, the crude odds of dying from COVID were twice as high among women on oestrogen blockers but 54% lower among women on HRT.

After accounting for potentially influential factors, COVID mortality risk remained significantly lower (53%) for women on HRT.

Unsurprisingly, age was significantly associated with COVID mortality risk, with each extra year associated with 15% greater odds, while every additional coexisting condition increased the odds of death by 13%.

And those with the lowest household incomes were nearly 3 times as likely to die as those with the highest.

As an observational study, it cannot establish cause. There were no data on the precise doses of HRT or oestrogen blocker drugs, or their duration, nor on weight or smoking, while the number of women on adjuvant therapy was relatively small.

These factors may have been influential. But the researchers conclude: “This study shows an association between oestrogen levels and COVID death. Consequently, drugs increasing oestrogen levels may have a role in therapeutic efforts to alleviate COVID severity in postmenopausal women and could be studied in randomised control trials.”

Source: EurekAlert!

Categories : Cardiovascular DiseaseTags :

Taking Healthcare to SASSA Queues: Pensioners Screened for Hypertension

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Hundreds of pensioners queuing for their old age grants are being screened and tested for hypertension at paypoints in Mpumalanga. In this way, care is provided where and to whom it’s needed most.

In total, more than 4.2 million people in South Africa aged 60 and older currently receive the Older Persons Grant. For many of them, particularly in rural areas, grant collection days often involve standing in queues for hours.

In a pilot project in Bushbuckridge, Mpumalanga, the South African Medical Research Council (SAMRC) and SAMRC/WITS’s Rural Public Health and Health Transitions Research Unit. are using these queues as an opportunity to take screening for hypertension to some of the most vulnerable and often neglected people in the country.

The study is being conducted in collaboration with local communities, the South African Social Security Agency (SASSA), the South African Post Office (SAPO) in Ximhungwe and Boxer Superstores in Thulamahashe.

The project called “Know Your Numbers” was launched in April 2021 with 20 fieldworkers from local communities at six sites where hundreds of pensioners gather each month to collect their grants. The teams take people’s blood pressure using mobile Omron machines.

“Screening about 100 people per queue, we are picking up high blood pressure in about 60% of the participants. These people are all referred to their closest local clinic for further assessment, treatment and care as required. About 30% of the participants are male and about 70% female and that’s because there are sadly less men alive to collect social grants,” said Jane Simmonds, Know Your Numbers project manager at SAMRC/WITS’s Rural Public Health and Health Transitions Research Unit.

Silent killer
Hypertension is known as the ‘silent killer’ because there are no exclusive symptoms that point directly to the disease. A 2021 study by the SAMRC found that the prevalence of hypertension rose between 1998 and 2016, from 27% to 45% in men and 31% to 48% in women. This has a significant impact on the health of older persons. “Older adults contribute critical support to local households, fostering orphans, enabling schooling and countering food insecurity. We can ill afford a rising toll of deaths from stroke and heart failure, or greater vulnerability to Covid-19,” said Steve Tollman, Unit Director.

“Many people don’t have money to travel to the doctor or clinic before they’re already very sick,” said Simmonds. Measuring blood pressure in people standing in the queue could help them manage and improve their health and save them the costs and time involved in visiting a clinic for a simple monthly health check.

“People will not go to town or clinics for treatment or vaccines if they have to choose between spending their R1800 grant on food or for transport,” said Simmonds, who lobbied for what became a successful project to offer the Covid vaccine directly to pensioners while they were queuing.

She explained how transport costs and problems accessing the Electronic Vaccination Data System (EVDS) had become barriers to vaccination for older people when the vaccine was first rolled out.

“When the Covid vaccines became available to people 60 and older in July last year, I thought that if we could meet people in queues for hypertension screening, then why not reach them for vaccines? I spent a lot of time talking to the Minister Of Health, Deputy-Director General or anyone that would listen to me about this concept. Eventually the Solidarity Fund came on board to fund vaccine outreach sites through the national health department. These sites have done over 500 000 vaccines since July 2021,” she said.

SASSA’s Dianne Dunkerley told GroundUp that SASSA had agreed to a pilot project with strict conditions to protect the security of beneficiaries and to avoid prolonging their already lengthy wait in line.

Dunkerley said the project is being welcomed by older people. “Older people who didn’t realise they had hypertension were identified, and could then go to local clinics for treatment and further monitoring,” she said.

“In cases where people did not want to make decisions immediately, they were sent home with information to discuss with family and friends which is great.”

Fieldworkers from the community speaking to pensioners about the health screening outside the SA Post Office where they collect their social grant.

Dunkerly said SASSA “would not be averse to expanding this project to other provinces” and discussions were underway.

“We really have started seeing the benefits and the reduction of costs, both of transport and of time, for older people. We think that because they’re old, they don’t have anything else to do. Well, many pensioners look after entire families and do all kinds of things. Where we can minimise the time they spend looking for services, it really is a good thing,” she said.

Professor Andre Kengne, Director of the Non-Communicable Diseases Research Unit at SAMRC, told GroundUp, “Early lessons from the ‘Know Your Number’ project are strongly suggesting that the reach of prevention and control services for common health conditions including chronic diseases such as hypertension, can be substantially improved by taking some of the essential services such as health screening and health promotion to the most vulnerable people in the community.”

He said older persons are the most affected by chronic non-communicable diseases and that improving the detection, linkage to care and control of those conditions through appropriate community-based approaches, significantly reduces the related harmful health effects.

The researchers hope that lessons from the ongoing and thorough pilot evaluation can be used to lobby the government to include screening and tests for diabetes, HIV, TB, cancers and other health issues which affect older persons.

By Barbara October

Source: GroundUp

Categories : PaediatricsTags :

Lower RBC Transfusion Volume in Neonate ECMO Reduces Mortality

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A new study indicates that for newborns in respiratory failure supported by ECMO, the greater volume of the red blood cell (RBC) transfusions that the babies receive, the higher their mortality rate.

“In order for the baby to survive on ECMO, they need red blood cells, they need platelets, they need plasma,” said Dr Brian Stansfield, neonatologist at the Medical College of Georgia and Children’s Hospital of Georgia (CHOG) “You have to have sufficient blood volume to make the whole system work. But there is also increasing evidence that if you can get by with less, that is probably more.”

“We think this supports the overall trend of being more restrictive in transfusion practices and being even more mindful about when you give transfusions and when you don’t while a child is on ECMO,” said Dr Jessica Gancar, neonatology fellow at MCG and CHOG.

The clinicians are the most confident this holds true for ECMO with babies in respiratory failure, while the relationship is more tentative for other causes. Respiratory failure makes up the largest population of newborns needing ECMO. The findings are another good reason for ECMO centres to reexamine when they transfuse babies, the clinicians point out.
Haematocrit levels (red blood cells to volume ratio) are a key measure typically used to determine whether to transfuse.

“Our transfusion practice is when the haematocrit hits 35% we will transfuse,” said Dr Stansfield. “Most ECMO centres still have a threshold of 40%, which means they are transfusing more. Others transfuse at 30%. So in our program we also have to ask the question if we are accepting some unnecessary risks. Could we get by with less?”                                                                    
They looked at 248 newborns treated from 2002-19 at CHOG with an overall survival rate of 93%.

They analysed their medical records for any relationship between blood product transfusion and death and complication rates in these babies.  

“We identified a clear linear relationship between mortality and red blood cell transfusion volume. Specifically, for every transfusion of red cells while on ECMO, a baby’s chances of survival decreased by 14%,” said Dr Gancar.

Plasma or platelet transfusions did not correlate with increased mortality. The findings are being presented during the Southern Society for Pediatric Research meeting.

“While blood product transfusions are necessary for critically ill newborns on ECMO, transfusions are given in response to ‘understudied, arbitrary thresholds and may be associated with significant morbidity and mortality,’” they write in their abstract.

“I think we are getting to the point, with neonatal ECMO in particular, where we are transitioning from how do we prevent death by intervening with ECMO – for a long time that was the question – to asking questions like once you are on ECMO, how do we make outcomes better,” said Dr Stansfield. “We already know that going on ECMO is a risk, that all the blood and other products we are giving at the start of ECMO is a risk, but could we limit some of the additional risk?”

ECMO requires essentially doubling the baby’s blood volume, said Dr Gancar. Just priming the pump typically requires two packs of red blood cells along with other select additives like albumin and heparin. Typically two more packs of platelets as well as fresh frozen plasma are given once the baby is on ECMO. Other blood product transfusions may follow over their course on ECMO, which averages three to seven days at CHOG.

At CHOG, the neonatal specialists work hard to give as few transfusions as possible and some babies, typically those on ECMO five days or less, may not require any exposures beyond the pump priming; others, typically the sickest babies, may be given five to 10 transfusions over their treatment course. They note that their study adjusted for sickness severity so that could not explain the increased mortality they found associated with more red blood cell transfusions.

Blood transfusion is known to increase mortality risk in essentially any disease process, Dr Gancar said, as they can prompt problems like increased inflammation, despite modern typing procedures to help ensure a good match between donor and recipient.

In these babies that risk seems linked to red blood cells, which have to be separated from factors they normally circulate with, be exposed to preservatives and may have a protracted storage time before they are transfused.  

Decades of success with ECMO has the CHOG team confident about its value in helping babies overcome potentially deadly but also potentially reversible problems like meconium aspiration, but they still have a “healthy respect” for the technique, Dr Stansfield said.

They rule out traditional therapies first like using a ventilator to support breathing and nitric oxide to dilate the lungs and blood vessels. Dr Stansfield notes that the number of babies needing ECMO has fallen over the years as neonatal teams like theirs have improved.

But sometimes: “We run out of options unfortunately and that is when we bring in ECMO,” said Stansfield. While the team has one of the longest and best track records in the nation with ECMO, the facts remain that it requires surgery on the baby’s neck to place a small cannula in their internal jugular vein and sometimes a second one placed in the carotid artery to return the warmed and oxygenated blood back to the baby. Both those blood vessels no longer function afterward.

Approaches like ventilators are more straightforward and less invasive, Dr Stansfield said. “But the realisation is that we know there is a small percentage of kids that need more intensive therapy,” he said.  

Source: EurekAlert!

Categories : Diseases, Syndromes and ConditionsTags :

New Insights Into Atopic Dermatitis Yield Possible Therapy

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Source: CC0

Atopic dermatitis (AD) is often thought of as an inflammatory disease that arises from a breakdown in the barrier function of the skin. Now a new study pinpoints a cascade of inflammatory signalling that precedes the appearance of skin ulcers, shedding light on the early stages of the condition and possible new drug targets.

The work, published in the journal Science Translational Medicine, was the result of a cross-school and cross-institutional collaboration among researchers.

“You have researchers in the dental school noticing a skin condition, broadening their work to the medical school and experts on computational systems biology,” said Professor Dana Graves, a co-corresponding author on the paper. “Without this interdisciplinary collaboration, that initial finding would not have gone anywhere.”

John Seykora, a co-corresponding author and professor of dermatology, agreed. “This shows one of the benefits of being part of a university with experts across fields,” he says. “Our dental school colleagues developed a mouse that manifested a particular skin phenotype, and the question was, What was this and did it resemble any disease we might know? And in the end it did, and it’s providing some novel insights into a very common skin condition in humans.”

The work began with an exploration of the role of inflammatory signalling in bone fracture healing in diabetes. A focus was on nuclear factor kappa-B (NF-kB), a master regulator of inflammatory responses. As part of that work, researchers developed a mouse model lacking an activator of NF-kB signalling, IKKB. The researchers noticed that these animals developed skin lesions as they became young adults.

“That was interesting to us because these ulcerations looked like an inflammatory event, but we had effectively turned off the activity of NF-kB, which should reduce inflammation,” said Prof Graves. “So this was a paradox.”

To better understand what was driving this response, they sought expertise in skin diseases from Prof Seykora. When they examined the mice, they noted several features quite similar to AD, “albeit the mouse version” said Prof Graves.

In particular, they noted skin thickening and an infiltration of certain types of white blood cells that are also seen in human AD. Delving deeper into how the loss of IKKB was driving these effects, the team performed single-celled RNA analysis combined with a new analysis method. The team learned that fibroblasts were the culprit, a major component of the skin’s dermis layer and typically thought to support the structural integrity of skin.

Though NF-kB typically promotes inflammation, here, decreased NF-kB activity was paradoxically leading to recruitment of immune cells and associated inflammation. Data from the team’s single-cell RNA analysis pointed to high activities of a protein transcription factor called CEBPB, as well as a signalling molecule, CCL11, “We worked out the mechanism in the mouse,” Prof Sekora said, “then showed that much of it applied in human tissue as well.”

When the researchers compared what they had seen in the mouse cells to skin samples from people with AD, they found similar patterns; CCL11 and CEBPB were both found at higher levels in the affected skin than in unaffected skin.

Testing a monoclonal antibody against CCL11 in mice tamped down the inflammatory response they had initially seen in animals lacking IKKB, suggesting that this could be a target to reduce AD-associated inflammation.

The researchers say the work also highlights a developing appreciation that fibroblasts play important roles in immune processes in the skin, indicating that they are important regulators of white blood cells.

AD  typically emerges in childhood, often manifesting along with asthma. Indeed, in the mice, too, the signalling abnormalities the researchers observed occurred in a period corresponding to the animals “childhood.” The group’s findings suggest that fibroblasts may be involved during this period in helping to establish appropriate immune signalling in the skin.

“We have viewed NF-kB as a factor that stimulates inflammation, but it could be that, during development, its activation might be important for maintaining homeostasis,” said Prof Graves.

The team’s next steps are to further explore NF-kB signalling in fibroblasts.

Source: University of Pennsylvania

Categories : VaccinesTags :

Exercise After Vaccination Boosts Antibodies

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Researchers have found that a 90 minute bout of mild- to moderate-intensity exercise directly after a receiving a flu or COVID vaccine may provide an extra immune boost.

In the paper, published in Brain, Behavior, and Immunity, participants who cycled on a stationary bike or took a brisk walk for an hour-and-a-half after receiving a vaccine injection produced more antibodies in the following four weeks compared to participants who sat or continued with their daily routine post-immunisation. When the researchers ran the experiment with mice and treadmills, similar results were observed.

“Our preliminary results are the first to demonstrate a specific amount of time can enhance the body’s antibody response to the Pfizer-BioNtech COVID vaccine and two vaccines for influenza,” said Kinesiology Professor Marian Kohut, lead author of the study.

The vaccine recipients would be able to benefit people who could not cope with such exercise. Nearly half of the participants in the experiment had a BMI in the overweight or obese category. During 90 minutes of exercise, they focused on maintaining a pace that kept their heart rate around 120–140 beats per minute rather than distance.

However, the exercise duration appeared to be important: the researchers also ran the experiment with just 45-minutes of exercising. The shorter workout did not increase the participants’ antibody levels. Prof Kohut said a follow-up study might test whether 60 minutes is sufficient.

As to why prolonged, mild- to moderate-intensity exercise could improve the body’s immune response, Prof Kohut said there may be multiple reasons. Exercise increases blood and lymph flow, which helps circulate immune cells. As these cells move around the body, they’re more likely to detect antigens. The mouse experiment data also suggested that interferon alpha produced during exercise helps generate virus-specific antibodies and T- cells.

“A lot more research is needed to answer the why and how,” said Prof Kohut. “There are so many changes that take place when we exercise – metabolic, biochemical, neuroendocrine, circulatory. So, there’s probably a combination of factors that contribute to the antibody response we found in our study.”

The researchers are continuing to track the antibody response in the participants six months post-immunisation and have launched another study that focuses on exercise’s effects on people who receive booster shots.

Source: Iowa State University