Year: 2021

Categories : Cardiovascular Disease COVIDTags :

Study Shows That COVID Causes Heart Damage

On By ModernMedia

Heart problems in COVID are caused by the virus invading heart cells and causing damage, according to a new study.

Heart problems such as arrhythmia and lack of pumping ability were associated with COVID even at the start of the pandemic. However, it was not clear whether these effects were caused by the virus, or whether it was due to the body’s inflammatory response in mounting a defence against the virus. 

“Early on in the pandemic, we had evidence that this coronavirus can cause heart failure or cardiac injury in generally healthy people, which was alarming to the cardiology community,” said senior author Kory J Lavine, MD, PhD, an associate professor of medicine. “Even some college athletes who had been cleared to go back to competitive athletics after COVID-19 infection later showed scarring in the heart. There has been debate over whether this is due to direct infection of the heart or due to a systemic inflammatory response that occurs because of the lung infection.”

Dr Lavine, along with other researchers from the Washington University School of Medicine, engineered stem-cell derived tissue as a model for how human heart tissue contracts. Studying these heart tissue models, they came to the conclusion that the viral infection kills muscle cells as well as the muscle fibre units involved in heart muscle contraction. This cell death and muscle fibre destruction happened even without inflammation.

“Our study is unique because it definitively shows that, in patients with COVID-19 who developed heart failure, the virus infects the heart, specifically heart muscle cells,”  Dr Lavine said. “Inflammation can be a second hit on top of the damage caused by the virus, but the inflammation itself is not the initial cause of the heart injury.”

While other viral infections have been linked to heart damage, SARS-CoV-2 is unique in that monocytes and dendritic cells dominate the immune response, while other viruses that damage the heart attract T and B cells.

“COVID-19 is causing a different immune response in the heart compared with other viruses, and we don’t know what that means yet,” Dr Lavine said. “In general, the immune cells seen responding to other viruses tend to be associated with a relatively short disease that resolves with supportive care. But the immune cells we see in COVID-19 heart patients tend to be associated with a chronic condition that can have long-term consequences. These are associations, so we will need more research to understand what is happening.”

Source: News-Medical.Net

Journal information: Bailey, A. L., et al. (2021) SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis. JACC: Basic to Translational Science. doi.org/10.1016/j.jacbts.2021.01.002.

Categories : Mental Health NeurologyTags :

Repurposed Drug Exploits Ion Channel in The Brain To Treat Depression

On By ModernMedia

Researchers from the Icahn School of Medicine at Mount Sinai Hospital have repurposed a drug to treat depression by using an ion channel that is a completely different mechanism than regular antidepressants.

A study demonstrated that a drug called ezogabine, which opens KCNQ2/3 type of potassium channels in the brain, is linked to significant improvements in depressive symptoms and anhedonia (a lack of ability to feel pleasure) in patients with depression. Anhedonia is a complex, core symptom of depression and is associated with poor outcomes such as increased risk of suicide and reduced responsiveness to antidepressants.
Ezogabine is an anticonvulsant for epilepsy treatment; this novel application in treating depression opens up the investigation of the KCNQ2/3 channel as a potential drug target.

“Our study is the first randomized, placebo-controlled trial to show that a drug affecting this type of ion channel in the brain can improve depression and anhedonia in patients. Targeting this channel represents a completely different mechanism of action than any currently available antidepressant treatment,” said Professor James Murrough, MD, PhD, at the Icahn School of Medicine at Mount Sinai, and senior author of the paper.

The KCNQ2/3 channel belongs to the KCNQ (or Kv7) family of ion channels which are important controllers of brain cell excitability and function in the central nervous system, affecting brain cell function by controlling electrical charge flow across the cell membrane in the form of potassium (K+) ions. Previous research in mice also showed involvement of KCNQ2/3 in depression. Mice that were more resilient to stress had increased KCNQ2/3 channels in their brains.

“We viewed enhanced functioning of the KCNQ channel as a potential molecular mechanism of resilience to stress and depression,” said Ming-Hu-Han, PhD, who also discovered that by increasing the activity of this channel, such as by administering ezogabine, to depressed mice, the drug acted as an antidepressant.

A trial with adult human patients showed that, compared to placebo, those treated with ezogabine showed a large reduction in a number of key measures of depression severity, anhedonia, and overall illness severity.
“The fundamental insight by Dr Han’s group that a drug that essentially mimicked a mechanism of stress resilience in the brain could represent a whole new approach to the treatment of depression was very exciting to us,” said Dr Murrough.

In collaboration with Dr Han, Dr Murrough carried out a series of human studies, with an initial open-label (no placebo) study in patients with depression providing initial evidence that ezogabine could improve symptoms of depression and anhedonia.

“I think it’s fair to say that most of us on the study team were quite surprised at the large size of the beneficial effect of ezogabine on clinical symptoms across multiple measures related to depression. We are greatly encouraged by these findings and the hope they offer for the prospect of developing novel, effective treatments for depression and related disorders. New treatments are urgently needed given that more than one-third of people suffering from depression are inadequately treated with currently approved therapeutics.”

Source: Eureka Alert

Categories : Environmental Effects Neurodegenerative DiseasesTags :

With Climate Change, Heat May Worsen Multiple Sclerosis Symptoms

On By ModernMedia

As average global temperatures increase due to climate change, multiple sclerosis (MS) patients can experience worsening symptoms resulting in an increase in hospital visits.

Some 60% to 80% of MS patients experience heat sensitivity. Increased body temperature slows or stops nerve signals in damaged nerves, which has a number of impacts such as blurred vision and other neurological effects. Heat sensitivity is also correlated with fatigue. Together with fatigue, divided attention from heat sensitivity can contribute to falls.

“We know that heat sensitivity is common in multiple sclerosis, and climate scientists expect that periods of anomalously warm weather will become more frequent with climate change,” said study author Holly Elser, PhD. of Stanford University School of Medicine. “Our study suggests that warming trends could have serious health implications over the long term for people living with MS.”

The study defined anomalously warm weather as a month in which local average temperatures were higher than the long-term average temperature for that month by at least 1.5C.

The researchers drew data on insurance claims for 106 225 people with MS living in the US, and then calculated the estimated effect of anomalously warm weather on MS-related emergency department, inpatient and outpatient visits. Then, the number of medical visits for each person during anomalously warm weather periods was compared to those for periods of normal weather periods.

During anomalously warm weather periods, there was a 4% increased chance of an emergency department visit compared to periods of normal weather. Participants had a 3% increased chance of having an inpatient visit and a 1% increased chance of having an outpatient visit during anomalously warm periods compared to periods of normal weather.

Researchers estimate that during the follow-up period, anomalously warm weather periods were linked to an estimated excess of at least 592 emergency department visits, 1260 inpatient visits and 1960 outpatient visits related to MS.

“While the relative increase in risk of visits is small, the associated absolute effect on people with MS and the health care system is meaningful,” concluded Dr Elser.

Source: Medical Xpress

Categories : Diseases, Syndromes and Conditions Immune SystemTags :

New Bacteria-based Atopic Dermatitis Treatment Proves Effective

On By ModernMedia

A skin bacteria-based treatment for atopic dermatitis (AD) was successful in clinical trials, with no serious adverse effects and indications that it reduces eczema symptoms as well.

Atopic dermatitis (AD) is a common, chronic skin disorder which can have great impacts on the lives of sufferers. The disorder seems to result from the complex interplay between the skin, environmental effects and the immune system. Treatment involves a multifaceted approach that involves education, optimal skin care practices, anti-inflammatory treatment with topical corticosteroids and/or topical calcineurin inhibitors, the management of pruritus, and the treatment of skin infections. Severe flare-ups or more difficult-to-control disease may be treated with systemic immunosuppressive agents. Topical corticosteroids are the first-line treatment of choice, and seem to be prophylactic against flareups.

AD is associated with S. aureus colonisation, which induces a proteolytic breakdown of the epidermal barrier and dermal immune dysregulation. Inflammation results in further dysregulation of the skin microbial system. Commensal, coagulase-negative staphylococci (CoNS) were observed to produce bacteriocins which inhibit bacteria such as S. aureus, and these were not seen in the skin of most patients with AD. They hypothesised that reintroduction of CoNS would improve AD in patients.

Patients treated with MSB-0221, which incorporated the naturally occurring skin bacteria S. hominis (ShA9), had fewer AD-related adverse events (AEs) as compared with patients treated with a topical placebo, reported Richard L Gallo, MD, PhD, of the University of California San Diego and co-founder of the company developing MSB-0221.

“Besides its effect on decreasing the redness and itch in a subset of patients, and dramatically and rapidly decreasing the colonisation by Staph aureus, one of the unique aspects of this is that it’s specific for this organism,” said Dr Gallo. “It was not detrimental to other members of the microbiome that could help restore balance.”

Applying MSB-0221 to 54 adults, they found a reduction in S. Areus, which was associated with a significant decrease in AD symptoms compared to placebo.

The next step would be a larger, 150 patient clinical trial over 12 weeks.

“We don’t fully understand all of the ramifications, but there seems to be at least a subset of patients with atopic dermatitis whose disease is influenced and exacerbated by certain bacteria, such as Staph aureus,” said Bruce Brod, MD, of the University of Pennsylvania. “There is still sort of a chicken-and-egg aspect to the relationship. Did the skin inflammation come first or the Staph aureus?“

“This is a proof-of-concept study that provides some evidence that shifting the balance of another bacteria that’s not pathogenic might have some therapeutic benefit in some patients with atopic dermatitis,” he added. “It provides support for larger studies looking at safe bacteria to shift the flora to a more favourable environment. At this point, it’s just another piece of a puzzle that could one day lead to different therapies. It’s probably not the whole picture, but in some patients, it may play a significant role.”

Source: MedPage Today

Journal information: Nakatsuji T, et al “Development of a human skin commensal microbe for bacteriotherapy of atopic dermatitis and use in a phase I randomized clinical trial” Nature Med 2021; DOI: 10.1038/s41591-021-01256-2.

Categories : Gender NeurologyTags :

LGBTQ Concerns Put Brain Imaging Study on Hold

On By ModernMedia
Person holding rainbow-themed cake slice. Photo by Sharon McCutcheon on Unsplash.

A study investigating brain functions of gender dysphoria at UCLA’s Semel Institute for Neuroscience & Human Behavior, has been put on hold after concerns from LGBTQ groups.

According to the Diagnostic and Statistical Manual of Mental disorders, gender dysphoria is a “marked incongruence between their experienced or expressed gender and the one they were assigned at birth.” Gender Justice LA and the California LGBTQ Health and Human Services Network released a joint statement, citing major ethical concerns.

Study leader Jamie Feusner, MD, a psychiatrist, told MedPage Today that he has asked UCLA’s Institutional Review Board to “re-review our entire protocol to ensure that it meets all ethics and safety standards.”

He added that his team is “actively engaged with members of the LGBTQ community” to help inform potential adjustments to study protocols. It wasn’t clear whether the entire study is on hold or just enrollment of new participants.

Ezak Perez, executive director of Gender Justice LA, wrote that the “research design unapologetically aims to cause mental health distress to trigger ‘dysphoria’ to an already marginalised and vulnerable community.”

The advocacy groups said that researchers from the Semel Institute reached out to the transgender, gender non-conforming, and intersex community in the region to take part in a meeting to help the study design. When they expressed concerns during this meeting and realised the study was already underway with approval from the IRB, leaders from Gender Justice LA and the California LGBTQ Health and Human Services Network wrote a letter to UCLA’s Office of the Human Research Protection Program.

“The researchers are falsely advertising this study without clarity about the expectations of participants and without consideration of the need for direct access to mental health after care,” wrote Perez and Dannie Cesena, program manager of LGBTQ Health and Human Services Network.

The call for participants was for looking for transgender, nonbinary, and cisgender adults to complete an assessment and one or more MRI scans. Participants would also be “photographed from the neck down while wearing a unitard,” a point of contention cited by Perez in his statement. The enrollment announcement also noted that participants who experience discomfort during this process could withdraw from the study at any point. Requirements included not being psychiatric medications, and that trans and nonbinary participants could not already be on hormone therapy or have had gender-affirming surgery. Participants would be paid a small amount and have expenses reimbursed.

The study in question would use the ‘body morph’ test, designed in 2015 by Feusner and colleagues. During the test, participants are photographed from various angles in a nude-colored, full-body unitard, with faces, hand and feet cropped out.. Participant images are then morphed with pictures of different bodies.

Writing to MedPage Today, Feusner and co-researcher Ivanka Savic-Berglund, MD, PhD, wrote that at the time that Feusner created the ‘body morph’ test, “experiences of body-self incongruence were not easily understood. The test uses images to estimate the degree of alignment between individuals’ body perception and their gender-specific self-identity.”

Perez and Cesena strongly objected to the idea that capturing the neurological response of gender dysphoria through brian imaging could provide any scientific data that could ‘help’ trans people.

“It is suggestive of a search for medical ‘cure,’ which can open the door for more gatekeeping and restrictive policies and practices in relation to access to gender-affirming care,” the letter stated.

Feusner and Savic-Berglund, however, explained that “by demonstrating that body-self incongruence was linked to brain structure and function, we aimed to help provide a biological basis and increase empathy for the life stories of transgender individuals. From the beginning, the aim was to help increase acceptance of transgender individuals.”

Source: MedPage Today

Categories : COVID General Interest VaccinesTags :

After Receiving Vaccine, Queen Elizabeth Encourages Others

On By ModernMedia

After receiving her COVID vaccine, Queen Elizabeth encouraged those who were wary to think of others and do the same.

She and Prince Philip received their vaccine in the initial wave of vaccinations for the elderly in the UK. Prince Philip, 99,  is currently in hospital for a non-COVID related illness. There are concerns about the health of her husband Prince Philip, but the palace says that he is responding to treatment, but likely to remain in hospital for a few more days.

“Once you’ve had a vaccine you have a feeling of you know, you’re protected which I think is very important and as far as I could make out it was quite harmless,” the 94-year old monarch queen said in a video call with health officials supervising inoculations across the UK.

“It was very quick, and I’ve had lots of letters from people who have been very surprised by how easy it was to get the vaccine. And the jab – it didn’t hurt at all,” she added, likening the virus to a plague.

Earlier this week, the UK’s vaccine minister said that 11% to 15% of people were hesitant about receiving a vaccine, especially among minority groups.

“It is obviously difficult for people if they’ve never had a vaccine because they ought to think about other people other than themselves,” said the queen.

She praised the “remarkable” Britain’s rollout of the vaccination, one of the world’s fastest. Other members of the royal family including Prince Charles and his son Prince William, have been visiting vaccination centres over the last two weeks to convey their thanks to staff and volunteers for their work.

Data from Public Health England suggest that the vaccines are 80% effective in preventing serious COVID in the elderly.

Source: Reuters

Categories : Paediatrics Skeletal SystemTags :

20% of Healthy Children May Have Benign Bone Tumours

On By ModernMedia

Around 20% of healthy children may possess benign tumours, according to a review of radiographs taken nearly a century ago.

Although it sounds alarming, non-ossifying fibromas and other common benign bone tumours in symptom-free children are not dangerous. Such bone tumours are often discovered on x-rays taken for other causes, such as a fracture. 

“Understandably, these tumours cause a lot of anxiety for patients and families as they await confirmation that the tumour is benign,” said Christopher Collier, MD, Indiana University School of Medicine, Indiana University. “They need reassurance and often ask how common these tumours are, when did they first appear, and whether they will resolve over time? We don’t have much evidence to date to address these questions.”

To address these questions, the researchers analysed annual x-rays taken of children’s bones as they grew, however such studies today are not feasible today due to ethical concerns over sensitivity of children to ionising radiation. Therefore, they drew on a unique collection of radiographs from the Brush Inquiry, a study in which a series of healthy, ‘normal’ children in Ohio, underwent annual radiographs from 1926 to 1942.

Dr Collier’s team analysed a total of 25 555 digitised radiographs of 262 children, followed from infancy to adolescence, finding a high prevalence of bone tumours. A total of 35 benign bone tumors were found in 33 children – an overall rate of 18.9 percent when considering that only the left side of the children was radiographed.

Over half of the tumours were non-ossifying fibromas, which are connective tissue masses that have not hardened into bone. Generally, these fibromas appeared around age five, and again around the time of skeletal maturation, possibly linked to growth spurts. Of 19 non-ossifying fibromas detected, seven disappeared over time. Others may have resolved some time after the annual radiographs stopped.

Rarer benign bone tumoors included enostoses, sometimes called ‘bone islands’; and osteochondromas or enchondromas (tumours in cartilage). In patients with these tumours, they persisted to the last available radiograph.

The findings are similar to the rates of benign bone tumours in healthy adults. Dr Collier noted: “Despite the inherent limitations of our historical study, it may provide the best available evidence regarding the natural history of asymptomatic benign childhood bone tumors.”

Source: News-Medical.Net

Categories : Urogenital VaccinesTags :

New Vaccine for UTIs Developed With a Localised Approach

On By ModernMedia

Urinary tract infections (UTIs) are a common complaint, affecting women more than men, with a lifetime prevalence of 50% in women, but so far an effective vaccine has proved elusive. Now, researchers from Duke University have come up with an approach that could result in an workable vaccine.

UTIs are caused by a wide range of Gram-negative and positive bacteria, such as Escherichia coli, and antibiotic resistance coupled with common recurrence makes it a growing health burden. It is thought that the immune response to bladder infections sends more repair cells to deal with the bacterial infection than cells to kill the invading bacteria. Because of this, there are often surviving bacteria that reproduce to cause a subsequent infection.

“Although several vaccines against UTIs have been investigated in clinical trials, they have so far had limited success,” said senior author Professor Soman Abraham at Duke University.

“There are currently no effective UTI vaccines available for use in the U.S. in spite of the high prevalence of bladder infections,” Prof Abraham said. “Our study describes the potential for a highly effective bladder vaccine that can not only eradicate residual bladder bacteria, but also prevent future infections.”

According to lead author Jianxuan Wu, PhD, “the new vaccine strategy attempts to ‘teach’ the bladder to more effectively fight off the attacking bacteria. By administering the vaccine directly into the bladder where the residual bacteria harbour, the highly effective vaccine antigen, in combination with an adjuvant known to boost the recruitment of bacterial clearing cells, performed better than traditional intramuscular vaccination.”

The study found that mice immunised in this way effectively fought off infecting E. coli, eliminating all residual bladder bacteria. This suggests that the site of administration could be important for determining vaccine effectiveness.

“We are encouraged by these findings, and since the individual components of the vaccine have previously been shown to be safe for human use, undertaking clinical studies to validate these findings could be done relatively quickly,” Prof Abraham said.

Source: Medical Xpress

Journal information: Jianxuan Wu el al., “Local induction of bladder Th1 responses to combat urinary tract infections,” PNAS (2021). www.pnas.org/cgi/doi/10.1073/pnas.2026461118

Categories : Medical Research & Technology New Compounds and TreatmentsTags :

Combination Nanoparticle Therapy Shows Promise as Antiviral

On By ModernMedia

Researchers have developed a new nanoparticle combination as a broad-spectrum anti-RNA virus treatment. 

The results of their study have been published on the bioRxiv preprint server. Note that as a preprint, this paper has not yet been peer reviewed.
Non-specific antivirals offer a number of attractive advantages. Their broad spectrum activity suppresses mutations, and would they also readily be at hand for future outbreaks. Nanoparticles are one possibility, with reduced toxicity.

Silver nanoparticles (AgNPs) are well-established as antibacterial and antiviral agents, and are the subject of many exotic biomedical applications. The mechanism of AgNPs is thought to be through physiochemical destruction of the microbial surface, with internal disruption from free Ag+ ions and reactive oxide species. Graphene oxide (GO) also has anti microbial properties. With its high surface area, GO also acts as a drug carrier.

The researchers produced seven different material combinations using three different methods: reduction with silver salt, direct addition of Ag nanospheres, and direct addition of Ag nanospheres to thiolised graphene.
To test the materials against seasonal-type infections as well as the kind of virus that could be expected from a future pandemic, the researchers tested the nanoparticles with influenza A virus (IAV) and human coronavirus (HCoV) OC43. IAV is an enveloped virus of the orthomyxovirus family with a segmented single-stranded RNA genome; it causes flu pandemics. HCoV-OC43 is an enveloped betacoronavirus with a single-stranded RNA genome associated with the common cold in humans.

Two of the GO-AgNP materials showed rapid, potent antiviral activity in solution against the viruses. The remaining five materials possessed a range of modest to no antiviral effects against IAV, the researchers reported. They observed a synergistic effect between the AgNPs and GO, with mechanism of action possibly being rapid disruption of the viral envelope. With high levels of antiviral agents, the combination of AgNPs with GO was found to show greater antiviral performance and lower toxicity.

“Our finding that graphene oxide/silver nanoparticle ink can rapidly prevent in vitro infection with two different viruses is exciting, and suggests that the ink has the potential to be used in a variety of applications to help reduce the spread of viruses in the environment,” said co-author Dr Meredith J Crane.

Source: News-Medical.Net

Journal information: Graphene oxide/silver nanoparticle ink formulations rapidly inhibit influenza A virus and OC43 coronavirus infection in vitro, Meredith J. Crane, Stephen Devine, Amanda M. Jamieson, bioRxiv 2021.02.25.43

Categories : AllergiesTags :

Rollout of Peanut Allergy Treatment Stalled by Pandemic

On By ModernMedia

Approved in late January 2020, the only FDA-approved peanut immunotherapy was due to be released onto the US market, but the arrival of the pandemic effectively shut it down.

The peanut-powder Palforzia allergen treatment is designed to desensitise peanut allergies in children and adolescents, and circumvent potentially life-threatening reactions.

It is unclear to what extent peanut allergy immunotherapy (IT) and other forms of IT will be embraced by the US public. While subcutaneous IT has been practised for a long time, oral IT such as sublingual IT tablets are relatively new, with only a few products currently having regulatory approval in the US and Europe.

However, there are questions as to whether the US will ever widely accept IT, given factors such as the high treatment burden. Speaking to MedPage Today, Edwin Kim, MD, director of the University of North Carolina Food Allergy Initiative in Chapel Hill, said that it may not be clear for a while to what extent the treatment is accepted.

“COVID-19 shined a spotlight on the downsides of a treatment that requires so many physician visits,” he said. “If it was an easy treatment we might have seen more uptake, but it’s not an easy treatment.”

Thomas Casale, MD, of the University of South Florida in Tampa, acknowledged to MedPage Today that Palforzia’s uptake in the past year has been slow as “A treatment like this requires a lot of contact with the patient.”

The dosing schedule involves around a dozen physician visits, of 30-90 minutes duration each.  A single-day initial dose escalation phase is needed, with up-dosing every two weeks with physician observation to attain 11 increasing dose levels. After this, there is a daily home-dosing maintenance phase.

The 300-mg peanut protein maintenance dose is equivalent to eating a single peanut. “If you are able to tolerate 300 mg of peanut you can effectively prevent about 95% of adverse reactions,” Casale said. “So 300 mg is an important indicator of some degree of safety.”
In pooled trial data on Palforzia presented by Dr Casale, only 1.2% of long-term patients had a treatment-related severe systemic allergic reaction, all of which were treated with epinephrine.

“I think that after COVID is gone, which hopefully will be sooner than later, the uptake of this type of therapy will be a lot greater than it is today,” Dr Casale said.

Viaskin Peanut, an extracutaneous peanut IT, is undergoing investigational trials, with the FDA rejecting application for its approval. The agency cited concerns about the impact of patch-site adhesion on efficacy, and demanded modifications and additional trials.

Christina Ciaccio, MD, chief of allergy/immunology and pediatric pulmonology and sleep medicine at the University of Chicago, said that there were many challenges remaining.

“We have numerous forms of immunotherapy that are currently under investigation,” she said. “The fact that only one allergen-specific IT treatment for food allergy has been approved by the FDA highlights the remaining challenges.”

“For those that do have peanut allergies, this treatment [IT] is not universally effective and it is not universally available,” Ciaccio said. “The side effects are too frequent, and as it stands right now, this is a life-long therapy. These are all things we would like to work on.”

Source: MedPage Today