Year: 2021

Categories : COVIDTags :

SARS-CoV-2 Mutation Evolved in Immunocompromised Patient

On By ModernMedia

The discovery of SARS-CoV-2 mutations evolving in an immunocompromised patient treated with convalescent plasma has been revealed by Ravindra Gupta, MD, PhD, of University of Cambridge in England, and team.

“We have documented a repeated evolutionary response by SARS-CoV-2 in the presence of antibody therapy during the course of a persistent infection in an immunocompromised host,” the authors wrote.

Previous research has shown that immunosuppressed patients could serve as reservoirs for norovirus variants.

Although they did not claim the UK variant was created by that particular case, Gupta’s group speculated that the plasma therapy could have unleashed the resistant variants, and could do so in other immunosuppressed patients too.

They wrote that, in such patients, “the antibodies administered [in plasma] have little support from cytotoxic T cells, thereby reducing chances of clearance and theoretically raising the potential for escape mutations.” 

They cautioned that convalescent plasma use should be limited, and only with appropriate infection control in monitoring in immunosuppressed patients.

A man in his 70s, who had received immunotoxic chemotherapy to treat lymphoma eight years previously, was initially hospitalised in May with neutropenic sepsis, and, about a week later, tested positive for SARS-CoV-2. He was discharged later in May, but in late June was readmitted with cough and breathlessness.

His condition worsened and he received dexamethasone and two 10-day courses of remdesivir 5 days apart. On two days around July 20, convalescent plasma was administered; more remdesivir and convalescent plasma was administered about 4 weeks later. He died shortly afterward.

Gupta and team took viral samples from this patient on 23 occasions, and over the first 57 days, they observed little change in viral population upon treatment with remdesivir, but after the July round of convalescent plasma, a shift in viral genotype occurred.

Initially the patient’s viral serotype showed a mutation first reported in China. However, in late July, a variant was observed with two alterations in the spike protein, including the deletion seen in the B.1.1.7 variant. Testing showed a twofold reduced susceptibility to the antibodies in the convalescent plasma.

The team wrote that this sort of evolution is unlikely to emerge in immunocompetent patients. They cautioned against using convalescent plasma in severe COVID patients, and especially those who were immunosuppressed.

The study’s limitations included being only a single case, and samples were taken from the upper respiratory tract and not the lower respiratory tract. 
Given South Africa’s large HIV positive population, if viral evolution is driven by convalescent plasma in immunosuppressed patients, this raises questions for the country’s COVID strategy.

Source: MedPage Today

Journal information: Kemp SA, et al “SARS-CoV-2 evolution during treatment of chronic infection” Nature 2021; DOI: 10.1038/s41586-021-03291-y.

Categories : COVIDTags :

As COVID Variants Dominate, Better Mask Use is Needed

On By ModernMedia

Evidence is accumulating that COVID is commonly transmitted through small aerosolised droplets emitted during regular speaking and breathing—a problem compounded by the enhanced contagiousness of variants such as 501Y.V2, the strain which dominates in South Africa.

Masks have become ubiquitous in the pandemic-struck world, and even fashionable, with many different types available. However, their effectiveness varies considerably from top-of-the-range N95 masks to a pulled-up shirt which offers very little protection.
“How well a mask works depends on two things: filtration and fit,” said Professor Linsey Marr, who studies airborne disease transmission at Virginia Tech .

“Good filtration removes as many particles as possible, and a good fit means that there are no leaks around the sides of your mask, where air—and viruses—can leak through,” she said, noting that even a small gap could result in a 50% reduction in effectiveness.

We do not recommend wearing more than two masks. Adding more layers proves diminishing returns and can compromise breathability. It must remain easy to breathe through the layers; otherwise, air is more likely to leak in around the sides of the mask.

Wearing a cloth mask over a surgical mask, or ‘double masking’ does improve effectiveness as it serves to tighten the surgical mask’s fit. Air escapes around the corners and edges of the mask, as anyone who has worn glasses and had them fog up in the cold can attest to.

While N95 masks are the best available, there are also equivalents such as KN95 or FFP2.

“They all provide a similar level of filtration, meaning protection of particles going in and out,” said Ranu Dhillon, a global health physician at Brigham and Women’s Hospital and Harvard Medical School. Dhillon is frustrated at the lack of transparency and education for the public about masks.

Health care workers, for example, get their masks tested for fit, something which could be also done by members of the public.

Donald Milton, a professor of environmental health at the University of Maryland, said that the key to understanding the COVID airborne transmission threat is to treat it like cigarette smoke. Ventilation helps, but if you have someone between you and an exhaust vent, then masks will definitely help.

Before the pandemic, Milton and Dhillon courted controversy by demonstrating that most viral transmission was in the form of small droplets emitted when speaking or breathing, and the contribution to transmission by coughing and sneezing was smaller than previously thought. The two researchers are hopeful that their findings will find their way into official COVID policy, and future research may even see masks becoming a common sight during peak flu seasons.

Source: Japan Times

Categories : Medical Research & TechnologyTags :

New Type of Sensor ‘Bandage’ Alerts Clinicians to Pressure Sores

On By ModernMedia

A new type of wearable sensor ‘bandage’ that can monitor blood oxygenation is being developed.

Driven partly by the growing interest in telemedicine as a result of COVID researchers at Missouri S&T are working on a printable, flexible, disposable sensor that can interact with a smartphone. This new kind of inexpensive sensor could alert health care workers early on to developing conditions such as pressure ulcers. Pressure ulcers normally develop from ischaemia caused by pressure and shear, and often occur in hospitalised patients or bedridden patients at home.

“Our current work focuses on designing and optimising a tissue oxygen sensor by using inexpensive inkjet printing techniques,” said Dr Chang-Soo Kim, professor of electrical and computer engineering at Missouri S&T. “Concurrently, we are developing a smartphone app that can interpret sensor images. This prototype will be evaluated using phantom tissue that mimics a pressure ulcer site.”

Dr Kim is working with other researchers to create a cheap, easy-to-use sensor to help prevent pressure sores which are on the rise due to obesity and diabetes. This might speed recovery, reducing the length of hospital stays and saving millions of dollars. 

Current pressure ulcer monitoring involves manual examination, but with this wearable sensor, drops in oxygen levels are sensed at the at-risk site before they have a chance to turn into a sore. The change could even be detected at home, in say a foot ulcer, alerting a clinician via smartphone who could then provide a diagnosis. 

“Our optical sensor bandage functions by detecting a low skin oxygen level caused by compromised circulation,” said Kim. “This low oxygen produces a color change called luminescence intensity. The smartphone can then take a photograph of the dressing and transmit it to enable remote monitoring or encourage timely intervention before major skin decomposition occurs.”

Source: Medical Xpress

Categories : General InterestTags :

Chinese Actress’ Ordeal Reveals Dangers of Unqualified Cosmetic Clinics

On By ModernMedia

Following a suggestion from her friend, actress and singer Gao Liu went to have cosmetic surgery, but the results proved disastrous. 

The young star had enjoyed a rising career but after being silent for a number of months decided to show what had happened to her as a warning about the dangers of unregulated cosmetic surgery.

Ms Gao had been out of the public eye recently, but returned to Weibo, the leading Chinese social media platform, to explain her absence due to a “cosmetic surgical incident”, where the tip of her nose had turned necrotic. She posted pictures of her ordeal, to which internet users in China have reacted with horror.

She had decided to “get a slight trim” based on suggestions, in order to improve her career. “The entire procedure lasted four hours. I thought that in these four hours, I would be made more beautiful,” she related to her followers.

“I didn’t expect these four hours to be the beginning of a nightmare.”
She said that after the procedure, her nose felt “irritated and tingly” and then became repeatedly infected.

“The skin on the tip of my nose… became darker and darker, and my nose became necrotic,” she said, also experiencing thoughts of suicide. She was hospitalised for two months, and lost out on work. Because of the extent of the necrotic damage, she said reconstructive surgery would not be possible for at least a year.

There is an enormous demand for cosmetic surgery in China, especially from young people, including high school graduates who hope that it will boost their careers or romantic opportunities. In 2019, 20 million people in China went for cosmetic surgery, of whom two-thirds were under 30 years of age.

As a result of this huge demand, there are some 60 000 unqualified cosmetic surgery clinics, compared to about 10 000 qualified ones.

Source: BBC News

Categories : PaediatricsTags :

Foetal Repair of Spina Bifida Improves Outcomes in Children

On By ModernMedia

A follow-up study found further evidence that foetal surgery for spina bifida extends benefits even further into childhood.

Adding to a growing body of research affirming the benefits of fetal surgery for spina bifida, new findings show prenatal repair of the spinal column confers physical gains that extend into childhood.

Spina bifida is a birth defect where the vertebral column is open (bifid), often involving the spinal cord. Myelomeningocele (MMC; open spina bifida) is the clinically most significant, where the spinal neural tube fails to close during development of the embryo. The exposed neural tissue degenerates in utero, causing a neurological deficit that varies with the amount of lesion. This occurs in 1 in 1000 births worldwide.

“This study shows that the benefits of fetal surgery for spina bifida extend beyond early childhood and well into a child’s first decade of life,” said co-author of the study N Scott Adzick, MD, Surgeon-in-Chief at Children’s Hospital of Philadelphia (CHOP), Director of CHOP’s Center for Fetal Diagnosis and Treatment. “This is especially important because of previously raised concerns that the advantages from fetal surgery may decrease over time. Contrary to those concerns, there appears to be a long-term benefit from neural protection in utero.”

The present study is a follow-on of the Management of Myelomeningocele Study (MOMS), which was co-led by investigators at CHOP, Vanderbilt University Medical Center, and the University of California, San Francisco, along with the data coordinating centre at the George Washington University Biostatistics Center. MOMS compared the outcomes of prenatal and traditional postnatal repair of myelomeningocele at 12 and 30 months, showing that there are considerable benefits from prenatal repair. Babies with spina bifida who received foetal surgery were less likely to need a shunt for the buildup of spinal fluid in the brain. Two and a half years after surgery, they walked better and had better overall motor function.

In MOMS2, the children from MOMS were comprehensively examined at ages from five to ten. They were assessed on a range of indicators, including fine motor skills and ability to do tasks unaided. The researchers found continuing benefits, including the foetal repair group being six times more likely to go to the toilet unaided than the postnatal repair group, and were 70% more likely to walk unaided, and twice as likely to walk without braces. They also had greater likelihood of engaging in self-care skills such as brushing teeth and using a fork.

“These data are important for demonstrating that fetal surgery for spina bifida improves mobility well into school age, but the implications of these results are even more profound,” said first author Amy J Houtrow, MD, PhD, MPH, Pediatric Rehabilitation Medicine Division Chief at UPMC Children’s Hospital of Pittsburgh. She said that when children are able to move around by themselves, it has significant positive impacts on their quality of life.

“When we began performing fetal surgery more than two decades ago, we did so with the hope that the procedure would improve lives for children and their families,” explained Dr Adzick. “As we continue to improve the technique, shortening surgery times and increasing the gestational age at birth, we are heartened by these results, which show the lasting benefits of fetal surgery.”

Source: Medical Xpress

Categories : Gastrointestinal Immune SystemTags :

Jump-starting Macrophages to Help with IBD Tissue Repair

On By ModernMedia

A novel method which prompts immune cells to aid the repair of damaged intestinal tissues has been developed by researchers at KU Leuven and Seoul National University.

This new approach promises new treatments for inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease. Normally, the immune system defends against pathogens that enter the body. In conditions like IBD, the immune system instead attacks tissues that line the gut, creating ulcers. Some 3.9 million women and 3.0 million women suffer from IBD worldwide.

The origin of IBD is not known, so treatments typically dampen immune response, but at the same time this also obstructs the normal repair of damaged intestinal tissue by other parts of the immune system. Macrophages, for example, consume foreign bodies, clean out debris and direct other steps in inflammatory or repair response through released substances. 

Lead author Professor Gianluca Matteoli, an immunologist at the Translational Research Center for Gastrointestinal Disorders (TARGID) KU Leuven, explained the motivation behind the research. “Our idea is that the migration of macrophages to the damaged tissue in IBD is essential to stimulate its recovery.”

Examining macrophages in the intestines of a handful of people with IBD, the researchers found that a sub-group of cells responding to prostaglandin E2 (PGE2). Prostaglandins are messenger molecules involved in homeostatic functions and mediate pathogenic mechanisms, such as the inflammatory response, and are also involved in tissue repair.

“If the patients had acute disease, they had a lower amount of these beneficial cells, and if they went into remission, then amounts of macrophages went up. This suggests that they are part of the reparative process,” said Professor Gianluca Matteoli, immunologist, Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven

In mice with ulcerative colitis (one the main forms of IBD), there were fewer macrophages responsive to prostaglandin than in healthy mice. However, when PGE2 levels were increased, those macrophages still responsive released a substance that stimulated tissue repair. When the researchers knocked out the PGE2 receptors on the macrophages, the level of tissue repair dropped.

Getting the macrophages to absorb a liposome containing a substance to trigger the repair stimulation agent restored the macrophages’ repairing effect. Liposomes are bubbles made of two layers of lipids enclosing an aqueous cavity, often used to hold substances for drug delivery.

“We already knew that prostaglandins were important for inducing proliferation of tissue cells, but this study shows that they are also important for controlling the inflammatory effect, so moving the body from the acute stage where inflammation dominates to the reparative stage,” Professor Matteoli said.

New treatments could involve liposomes being used to prompt macrophages into boosting tissue repair, a well-established experimental tool but which would require considerable work for this new application.

“This is one of the first times it has been used to produce a beneficial, therapeutic effect,” said Professor Seok. 

The next step is to closely examine human macrophages at different stages of IBD. “We want to identify other factors that trip the switch that turns macrophages from inflammatory cells to non-inflammatory cells,” said Professor Matteoli. “Then, using the liposome technology that Professor Seok has developed, these could be used to target the macrophages and so produce very precise drugs.”

Source: News-Medical.Net

Categories : Ageing Cardiovascular DiseaseTags :

Cannabis can Lower Hypertension in Older Adults

On By ModernMedia

Adding to a growing body of evidence as to its health benefits, medical cannabis may lower blood pressure in older adults, according to research from Ben-Gurion University of the Negev (BGU) and its affiliated Soroka University Medical Center.

This is the first such study to investigate cannabis’  effect on blood pressure, heart rate and metabolic parameters in hypertensive adults 60 and older.

“Older adults are the fastest growing group of medical cannabis users, yet evidence on cardiovascular safety for this population is scarce. This study is part of our ongoing effort to provide clinical research on the actual physiological effects of cannabis over time,” said Dr Ran Abuhasira, BGU Faculty of Health Sciences and BGU-Soroka Cannabis Clinical Research Institute

Before and three months after beginning medical cannabis therapy, patients in the study were evaluated using 24-hour ambulatory blood pressure monitoring, ECG, blood tests, and body measurements. Patients ingested cannabis either orally in the form of oil extracts or by smoking.

The findings included a significant drop in 24-hour systolic and diastolic blood pressure values, with the lowest point occurring three hours after ingesting cannabis. Both daytime and nighttime reductions in blood pressure were observed, with more greater changes at night. Higher nighttime than daytime blood pressure may also raise the risk of Alzheimer’s disease, so lowering it at night may offer that benefit.

The pain relief from taking cannabis, often a reason for prescriptions, may also have resulted in a reduction of blood pressure, the BGU researchers postulated.

“Cannabis research is in its early stages and BGU is at the forefront of evaluating clinical use based on scientific studies,” said Doug Seserman, chief executive officer of American Associates, BGU. “This new study is one of several that has been published recently by BGU on the medicinal benefits of cannabis.”

Source: News-Medical.Net

Journal information: Abuhasira, R., et al. (2021) Cannabis is associated with blood pressure reduction in older adults – A 24-hours ambulatory blood pressure monitoring study. European Journal of Internal Medicine.doi.org/10.1016/j.ejim.2021.01.005.

Categories : GeneticsTags :

New Study Finds Critical Flaw in Blood-brain Model

On By ModernMedia

The wrong kind of cells have been used to make in vitro models of the blood-brain barrier, which now throws a decade’s worth of research into question.

The present in vitro human blood-brain barrier model was developed in 2012. By inducing differentiated adult cells, such as skin cells, into developing into stem cells, the pluripotent stem cells obtained from the process are then transformed into nearly any type of mature cell. This includes the type of endothelial cell that lines brain and spinal cord blood vessels, and making a unique barrier that acts as a gatekeeper, restricting potentially dangerous substances, antibodies, and immune cells from entering the brain from the bloodstream.

“The blood-brain barrier is difficult to study in humans and there are many differences between the human and animal blood-brain barrier. So it’s very helpful to have a model of the human blood-brain barrier in a dish,” said co-study leader Dritan Agalliu, PhD, associate professor at Columbia University Vagelos College of Physicians and Surgeons.

Agalliu had noticed that these endothelial cells produced in this manner, did not behave like normal endothelial cells in the human brain. “This raised my suspicion that the protocol for making the barrier’s endothelial cells may have generated cells of the wrong identity,” said Agalliu.
“At the same time the Weill Cornell Medicine team had similar suspicions, so we teamed up to reproduce the protocol and perform bulk and single-cell RNA sequencing of these cells.”

Upon analysis, the researchers discovered that the supposed human brain endothelial cells were missing several key proteins found in natural endothelial cells and had more in common with epithelial cells, which is not usually found in the brain.

The team also identified three genes that, when activated within induced pluripotent cells, lead to the creation of cells that behave more like actual endothelial cells. More work is still needed, Agalliu says, to create endothelial cells that produce a reliable model of the human blood-brain barrier. His team is working to address this problem.

“The misidentification of human brain endothelial cells may be an issue for other types of cells made from induced pluripotent cells such as astrocytes or pericytes that form the neurovascular unit,” said Agalliu. The protocols to produce these cells were drawn up prior to the advent of single-cell technologies that are better at identifying cells.

“Cell misidentification remains a major problem that needs to be addressed in the scientific community in order to develop cells that mirror those found in the human brain. This will allow us to use these cells to study the role of genetic risk factors for neurological disorders and develop drug therapies that target the correct cells that contribute to the blood-brain barrier.”

Source: Medical Xpress

Categories : COVIDTags :

Reckless to Discard AstraZeneca Vaccines, Says Prof Madhi

On By ModernMedia

Professor Shabir Madhi of Wits University says that it would be reckless to simply abandon South Africa’s stock of AstraZeneca vaccine doses, even after a small trial showed it to have minimal effect against the local variant.

One million doses of AstraZeneca vaccine had been scheduled for rollout, but that plan has been put on hold after preliminary results showed that it conferred minimal effectiveness against mild-to-moderate infections by the dominant 501Y.V2 strain in South Africa. 

Madhi said that scientists needed more time to go through the data, said Madhi.

“I think it would be highly reckless for us to discard the vaccine. We paid a high price for it and so the vaccines do have a role in protecting from severe disease. I think an important feature in all the vaccines is that generally, vaccines work much better in preventing severe disease.”

There is already a closing window of opportunity, since it was recently discovered that the first batch of one million doses received from the Serum Institute of India would be expiring in April.

Madhi said that there were other options to put the vaccine to good use.
“If we’re strategic in terms of the rollout, we might still be able to get the vaccine used, not two doses per individual but at least a single dose and we could possibly follow it up then with another vaccine and a few vaccines that might come online in the next two or three months.”

In an interview with the BBC, he said that the disappointing results of the trial had not been able to show the effectiveness against severe COVID, as the sample size was too small and too young, with an average age of 31, but that it might still have a protective effect in different age groups. “There’s still some hope that the AstraZeneca vaccine might well perform as well as the Johnson & Johnson vaccine in a different age group demographic that I address of severe disease,” he said.

Source: Eyewitness News

Categories : Genetics New Compounds and TreatmentsTags :

Embracing Ethnic Genetic Diversity in Drug Design

On By ModernMedia

Although human beings have a great deal of genetic similarity, small genetic differences can nonetheless lead to very different results in drug effects.

Pharmacologist Namandje Bumpus, PhD—who recently became the first African American woman to head a Johns Hopkins University School of Medicine department, and is the only African American woman leading a pharmacology department in the country—explains why certain drugs can have different effects between distinct populations. Warfarin, for example, is known to be less effective in people of African descent.  

As new vaccines and treatments are developed to fight the COVID pandemic, which have disproportionately affected certain ethnic groups. According to APM Research Lab, in the US as of 2 Feb, Pacific Islanders are 2.7 times as likely to die from COVID as whites (adjusted for age), compared to 0.9 times for Asian Americans.

In light of these differences, Bumpus laid out a four-part plan to improve the equity of drug development.

Merely increasing the representation of races in drug trials is insufficient. Her plan includes: laboratory research to study genetic variability; diversifying the scientific workforce; diversity requirements for funding agencies; and diversity reporting requirements on clinical trial demographics in published articles.

Bumpus said that with genetic technology, animals can be engineered to “bolster predictability of drug outcomes and provide a mechanistic foundation for understanding disparities.”

Genetic variations linked to drug response are often associated with a family of enzymes, cytochromes P450. In humans this enzyme family processes about 75% of clinically available drugs. Subtle genetic differences can however lead to altered enzymes in humans, and these are more common in certain ethnic groups. 

This framework, Bumpus said, could compel the drug development field to move toward a future where “treatments are most likely to work for all people” and “existing health disparities are not further exacerbated.”

Source: Medical Xpress

Journal information: Namandjé N. Bumpus, “For better drugs, diversify clinical trials,” Science  05 Feb 2021: Vol. 371, Issue 6529, pp. 570-571. DOI: 10.1126/science.abe2565