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Bioengineered soluble ACE2 for brain protection against SARS-CoV-2 infection

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In a recent study posted to the bioRxiv* preprint server, researchers compared the efficiency of bioengineered soluble angiotensin converting enzyme-2 (ACE-2) concerning brain protection during coronavirus disease 2019 (COVID-19).

Study: Superiority of intranasal over systemic administration of bioengineered soluble ACE2 for survival and brain protection against SARS-CoV-2 infection. Image Credit: Kateryna Kon/Shutterstock

Background

Studies have noted the potential of ACE2 proteins in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralization using human organoids. The cellular model proposed in the present study expressed human ACE2, an important receptor of SARS-CoV-2 entry in human cells, and transmembrane serine protease 2 (TMPRSS2), which is a protease important for SARS-CoV-2-ACE2 complex internalization.

The k18-hACE2 model has proven deadly when infected with wild-type (WT) SARS-CoV-2 and mimics severe lung disease observed in humans. While there is sufficient evidence of significant brain injury reported by the model, the reason for the universal lethality is yet unknown.

About the study

In the present study, researchers examined the impact of an ACE2 618-DDC-ABD, a bioengineered soluble ACE2 protein with a sufficient duration of action and strong SARS-CoV-2 binding affinity.

In the k18-human ACE2 (hACE2) mouse, the team compared the impact of intraperitoneal (IP) versus intranasal (IN) delivery of the soluble ACE2 protein called ACE2 618-DDC-ABD. As per the study protocol, animals that exhibited a weight loss of over 20% of their body weight or displayed a clinical score of three or more were euthanized.

Four of the nine healthy mice from the IN-pre group were euthanized on day 5 to harvest organs for comparison with the IP-pre group, while the other five mice belonging to the IN-pre group lived until day 14, which was the final day of the study. In contrast, the surviving mice in the IP-pre-group had to be euthanized by the seventh day due to deteriorating clinical ratings and weight loss.

The team utilized k18-hACE2 mice, which expressed human ACE2 in its entirety and are sensitive to SARS-CoV-2 infection. Five to nine days after infection, animals with this viral load always succumb to the disease. The researchers examined the effects of pre-and post-treatment with the ACE2 618-DDC-ABD protein and compared intranasal (IN) and intraperitoneal (IP) delivery effects using distinct methodologies. In the pre-treatment cohorts, ACE2 618-DDC-ABD was delivered IV or IP to k18-hACE2 mice one hour before SARS-CoV-2 infection and then subsequently 24 and 48 hours for three doses. Control animals were administered bovine serum albumin (BSA) in phosphate-buffered saline (PBS), both IP and IN, at dosages and intervals similar to the ACE2 618-DDC-ABD post-treated mice.

Results

All infected untreated control mice had to be euthanized on the fifth day, had serious body weight loss, and received a high clinical score. In the subject mice administered ACE2 618-DDC-ABD before and after viral inoculation, the day 5 survival rate was 90% across the IN-pre group and 40% across the IP-pre group. The survival rate was 0% among untreated infected controls on day 5. In addition, the IN-pre-group had minimal weight loss and superior clinical scores. In contrast, the IP-pre-group reported weight loss and poor clinical ratings.

In mice administered ACE2 618-DDC-ABD after viral inoculation, the survival rate was 30% on day 5 and 20% on day 14 in the IN+IP-post group. Furthermore, in the IN-post cohort, the survival rate on day 5 was 20% and on day 14 was 10%. The IP-post group had a 20% survival rate on day 5 but a 0% survival rate on day 14.

On day five, 0% of untreated and infected mice survived. Most mice that were administered ACE2 618-DDC-ABD post-viral inoculation experienced significant weight loss and deteriorating clinical score, while a few recovered and survived up to day 14.

In the IN-pre group, there were no detectable brain antibodies. On the other hand, brain titers were elevated in five out of eight mice in the IP-pre cohort, which was considerably greater than that in the IN-pre group. The brain virus titers of post-treated mice were slightly and not significantly lower than those of infected untreated animals. Brain titers, however, were undetectable on the fourteenth day within the few survivors of the post-treatment groups. The lung SARS-CoV-2 titers of animals treated with ACE2 618-DDC-ABC.

Conclusion

Overall, the study findings showed that ACE2 618-DDC-ABD provided significantly superior survival and organ protection when administered IN than IP or after viral inoculation and that reducing brain titers is a crucial predictor of survival and organ protection.

*Important notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

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What’s the greatest holiday gift: lips, hair, skin? Give the gift of great skin this holiday season

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Give the gift of great skin this holiday season

Skinstitut Holiday Gift Kits take the stress out of gifting

Toronto, October 31, 2024 – Beauty gifts are at the top of holiday wish lists this year, and Laser Clinics Canada, a leader in advanced beauty treatments and skincare, is taking the pressure out of seasonal shopping. Today, Laser Clincs Canada announces the arrival of its 2024 Holiday Gift Kits, courtesy of Skinstitut, the exclusive skincare line of Laser Clinics Group.

In time for the busy shopping season, the limited-edition Holiday Gifts Kits are available in Laser Clinics locations in the GTA and Ottawa. Clinics are conveniently located in popular shopping centers, including Hillcrest Mall, Square One, CF Sherway Gardens, Scarborough Town Centre, Rideau Centre, Union Station and CF Markville. These limited-edition Kits are available on a first come, first served basis.

“These kits combine our best-selling products, bundled to address the most relevant skin concerns we’re seeing among our clients,” says Christina Ho, Senior Brand & LAM Manager at Laser Clinics Canada. “With several price points available, the kits offer excellent value and suit a variety of gift-giving needs, from those new to cosmeceuticals to those looking to level up their skincare routine. What’s more, these kits are priced with a savings of up to 33 per cent so gift givers can save during the holiday season.

There are two kits to select from, each designed to address key skin concerns and each with a unique theme — Brightening Basics and Hydration Heroes.

Brightening Basics is a mix of everyday essentials for glowing skin for all skin types. The bundle comes in a sleek pink, reusable case and includes three full-sized products: 200ml gentle cleanser, 50ml Moisture Defence (normal skin) and 30ml1% Hyaluronic Complex Serum. The Brightening Basics kit is available at $129, a saving of 33 per cent.

Hydration Heroes is a mix of hydration essentials and active heroes that cater to a wide variety of clients. A perfect stocking stuffer, this bundle includes four deluxe products: Moisture 15 15 ml Defence for normal skin, 10 ml 1% Hyaluronic Complex Serum, 10 ml Retinol Serum and 50 ml Expert Squalane Cleansing Oil. The kit retails at $59.

In addition to the 2024 Holiday Gifts Kits, gift givers can easily add a Laser Clinic Canada gift card to the mix. Offering flexibility, recipients can choose from a wide range of treatments offered by Laser Clinics Canada, or they can expand their collection of exclusive Skinstitut products.

 

Brightening Basics 2024 Holiday Gift Kit by Skinstitut, available exclusively at Laser Clincs Canada clinics and online at skinstitut.ca.

Hydration Heroes 2024 Holiday Gift Kit by Skinstitut – available exclusively at Laser Clincs Canada clinics and online at skinstitut.ca.

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Here is how to prepare your online accounts for when you die

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LONDON (AP) — Most people have accumulated a pile of data — selfies, emails, videos and more — on their social media and digital accounts over their lifetimes. What happens to it when we die?

It’s wise to draft a will spelling out who inherits your physical assets after you’re gone, but don’t forget to take care of your digital estate too. Friends and family might treasure files and posts you’ve left behind, but they could get lost in digital purgatory after you pass away unless you take some simple steps.

Here’s how you can prepare your digital life for your survivors:

Apple

The iPhone maker lets you nominate a “ legacy contact ” who can access your Apple account’s data after you die. The company says it’s a secure way to give trusted people access to photos, files and messages. To set it up you’ll need an Apple device with a fairly recent operating system — iPhones and iPads need iOS or iPadOS 15.2 and MacBooks needs macOS Monterey 12.1.

For iPhones, go to settings, tap Sign-in & Security and then Legacy Contact. You can name one or more people, and they don’t need an Apple ID or device.

You’ll have to share an access key with your contact. It can be a digital version sent electronically, or you can print a copy or save it as a screenshot or PDF.

Take note that there are some types of files you won’t be able to pass on — including digital rights-protected music, movies and passwords stored in Apple’s password manager. Legacy contacts can only access a deceased user’s account for three years before Apple deletes the account.

Google

Google takes a different approach with its Inactive Account Manager, which allows you to share your data with someone if it notices that you’ve stopped using your account.

When setting it up, you need to decide how long Google should wait — from three to 18 months — before considering your account inactive. Once that time is up, Google can notify up to 10 people.

You can write a message informing them you’ve stopped using the account, and, optionally, include a link to download your data. You can choose what types of data they can access — including emails, photos, calendar entries and YouTube videos.

There’s also an option to automatically delete your account after three months of inactivity, so your contacts will have to download any data before that deadline.

Facebook and Instagram

Some social media platforms can preserve accounts for people who have died so that friends and family can honor their memories.

When users of Facebook or Instagram die, parent company Meta says it can memorialize the account if it gets a “valid request” from a friend or family member. Requests can be submitted through an online form.

The social media company strongly recommends Facebook users add a legacy contact to look after their memorial accounts. Legacy contacts can do things like respond to new friend requests and update pinned posts, but they can’t read private messages or remove or alter previous posts. You can only choose one person, who also has to have a Facebook account.

You can also ask Facebook or Instagram to delete a deceased user’s account if you’re a close family member or an executor. You’ll need to send in documents like a death certificate.

TikTok

The video-sharing platform says that if a user has died, people can submit a request to memorialize the account through the settings menu. Go to the Report a Problem section, then Account and profile, then Manage account, where you can report a deceased user.

Once an account has been memorialized, it will be labeled “Remembering.” No one will be able to log into the account, which prevents anyone from editing the profile or using the account to post new content or send messages.

X

It’s not possible to nominate a legacy contact on Elon Musk’s social media site. But family members or an authorized person can submit a request to deactivate a deceased user’s account.

Passwords

Besides the major online services, you’ll probably have dozens if not hundreds of other digital accounts that your survivors might need to access. You could just write all your login credentials down in a notebook and put it somewhere safe. But making a physical copy presents its own vulnerabilities. What if you lose track of it? What if someone finds it?

Instead, consider a password manager that has an emergency access feature. Password managers are digital vaults that you can use to store all your credentials. Some, like Keeper,Bitwarden and NordPass, allow users to nominate one or more trusted contacts who can access their keys in case of an emergency such as a death.

But there are a few catches: Those contacts also need to use the same password manager and you might have to pay for the service.

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Is there a tech challenge you need help figuring out? Write to us at onetechtip@ap.org with your questions.

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Pediatric group says doctors should regularly screen kids for reading difficulties

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The Canadian Paediatric Society says doctors should regularly screen children for reading difficulties and dyslexia, calling low literacy a “serious public health concern” that can increase the risk of other problems including anxiety, low self-esteem and behavioural issues, with lifelong consequences.

New guidance issued Wednesday says family doctors, nurses, pediatricians and other medical professionals who care for school-aged kids are in a unique position to help struggling readers access educational and specialty supports, noting that identifying problems early couldhelp kids sooner — when it’s more effective — as well as reveal other possible learning or developmental issues.

The 10 recommendations include regular screening for kids aged four to seven, especially if they belong to groups at higher risk of low literacy, including newcomers to Canada, racialized Canadians and Indigenous Peoples. The society says this can be done in a two-to-three-minute office-based assessment.

Other tips encourage doctors to look for conditions often seen among poor readers such as attention-deficit hyperactivity disorder; to advocate for early literacy training for pediatric and family medicine residents; to liaise with schools on behalf of families seeking help; and to push provincial and territorial education ministries to integrate evidence-based phonics instruction into curriculums, starting in kindergarten.

Dr. Scott McLeod, one of the authors and chair of the society’s mental health and developmental disabilities committee, said a key goal is to catch kids who may be falling through the cracks and to better connect families to resources, including quicker targeted help from schools.

“Collaboration in this area is so key because we need to move away from the silos of: everything educational must exist within the educational portfolio,” McLeod said in an interview from Calgary, where he is a developmental pediatrician at Alberta Children’s Hospital.

“Reading, yes, it’s education, but it’s also health because we know that literacy impacts health. So I think that a statement like this opens the window to say: Yes, parents can come to their health-care provider to get advice, get recommendations, hopefully start a collaboration with school teachers.”

McLeod noted that pediatricians already look for signs of low literacy in young children by way of a commonly used tool known as the Rourke Baby Record, which offers a checklist of key topics, such as nutrition and developmental benchmarks, to cover in a well-child appointment.

But he said questions about reading could be “a standing item” in checkups and he hoped the society’s statement to medical professionals who care for children “enhances their confidence in being a strong advocate for the child” while spurring partnerships with others involved in a child’s life such as teachers and psychologists.

The guidance said pediatricians also play a key role in detecting and monitoring conditions that often coexist with difficulty reading such as attention-deficit hyperactivity disorder, but McLeod noted that getting such specific diagnoses typically involves a referral to a specialist, during which time a child continues to struggle.

He also acknowledged that some schools can be slow to act without a specific diagnosis from a specialist, and even then a child may end up on a wait list for school interventions.

“Evidence-based reading instruction shouldn’t have to wait for some of that access to specialized assessments to occur,” he said.

“My hope is that (by) having an existing statement or document written by the Canadian Paediatric Society … we’re able to skip a few steps or have some of the early interventions present,” he said.

McLeod added that obtaining specific assessments from medical specialists is “definitely beneficial and advantageous” to know where a child is at, “but having that sort of clear, thorough assessment shouldn’t be a barrier to intervention starting.”

McLeod said the society was partly spurred to act by 2022’s “Right to Read Inquiry Report” from the Ontario Human Rights Commission, which made 157 recommendations to address inequities related to reading instruction in that province.

He called the new guidelines “a big reminder” to pediatric providers, family doctors, school teachers and psychologists of the importance of literacy.

“Early identification of reading difficulty can truly change the trajectory of a child’s life.”

This report by The Canadian Press was first published Oct. 23, 2024.

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