Tag: 2/3/21

New Bacteria-based Atopic Dermatitis Treatment Proves Effective

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.

LGBTQ Concerns Put Brain Imaging Study on Hold

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

After Receiving Vaccine, Queen Elizabeth Encourages Others

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

20% of Healthy Children May Have Benign Bone Tumours

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

New Vaccine for UTIs Developed With a Localised Approach

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

Combination Nanoparticle Therapy Shows Promise as Antiviral

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