by Stemedix | Jan 29, 2024 | Parkinson's Disease, Lyme's Disease, Osteoarthritis, PRP, Regenerative Medicine, Stem Cell Therapy, Stroke
Orthopedic rehab is a type of rehabilitation designed to help people who have been injured, had surgery, or have degenerative conditions. Its goal is to aid patients in regaining mobility, balance, and function in their musculoskeletal system. Orthopedic rehab also focuses on finding ways to alleviate pain.
If you have suffered an injury or gone through surgery, or if you have a degenerative condition that affects your mobility, orthopedic rehab could be the right option for you. But what can it help with, and what can you expect from the process?
What Conditions Can Orthopedic Rehab Help With?
Orthopedic rehab is a conservative treatment that can benefit patients of all ages who are suffering from issues that affect their range of motion, joint flexibility, muscle strength, and body function.
It can help with conditions like:
- Joint pain
- Arthritis
- Parkinson’s disease
- Lyme disease
- Scoliosis
- Stroke
- Spinal stenosis
- Knee instability
- Carpal tunnel
- Osteoporosis
- Sciatica
This type of rehab is usually essential for those recovering from joint replacement surgeries and similar procedures. It can also help with pelvic floor issues.
Orthopedic physical therapy is important after certain surgical procedures, including those like:
- Knee replacement
- Rotator cuff replacement
- Knee arthroscopy
- Hip replacement
- Cancer surgery
- Heart surgery
This type of rehab can help to normalize your gait, improve your range of motion, and even prevent excessive scar tissue buildup.
It’s also helpful for people who’ve suffered a chronic injury. A chronic injury is damage that occurs over time, generally because of small movement patterns that lead to repetitive injuries to your bones, joints, or tendons. Tennis elbow or carpal tunnel are examples. With rehabilitation, you can learn how to move without injuring yourself.
Benefits of Orthopedic Therapy
Orthopedic therapy helps increase your mobility. Mobility can be limited after an operation, while recovering from an injury, or when dealing with degenerative diseases. This type of therapy utilizes stretching and exercise strategies to slowly increase your range of motion.
Orthopedic therapy also helps with pain management so that you don’t have to rely as much on pain medications. Therapists can massage the treatment area, increasing circulation and decreasing inflammation. Some orthopedic therapy options use ice packs for dealing with inflammation and heat packs for loosening tension.
Better blood circulation, which orthopedic therapy helps with, also brings oxygen and nutrients to the treatment area. This makes it easier for injuries to heal.
You can also help avoid re-injuring yourself. Therapy assists by teaching you to move safely while also showing you how to gain strength in the area.
Types of Treatments Offered in Orthopedic Therapy
When you turn to orthopedic therapy, you can benefit from a few different types of treatments.
Hot and Cold Therapy
Orthopedic therapy often relies on thermotherapy (heat therapy) and cryotherapy (cold therapy) to treat musculoskeletal swelling and pain.
E-Stim
Electrical stimulation can help diminish pain. With E-stim, your therapist attaches a device to the treatment area. The two main types of devices they may use include TENS, which uses low-voltage electrical currents to offer pain relief, and NMES, which sends electrical impulses to the nerves.
Exercise Therapy
You will get an exercise plan that helps you increase mobility, strength, and balance. You will get a chance to practice them with the therapist so that you can then repeat them at home.
Soft Tissue Manipulation
Soft tissue manipulation is a kind of manual physical therapy in which your physical therapist massages your ligaments, fascia, and muscles. It helps optimize muscle function while also decreasing tension. It may also be effective at improving blood circulation.
Laser or Light Therapy
Low-level lasers and light therapies can help with muscle performance. They have the potential to reduce muscle fatigue and help tissues repair after an injury.
Platelet-Rich Plasma Therapy
Platelet-rich plasma (PRP) therapy uses the growth factors in your blood to encourage healing at the treatment area. It’s an option that often complements other orthopedic therapies.
What an Orthopedic Rehab Plan Can Look Like
The orthopedic plan your healthcare provider recommends will consider your injury, overall health, abilities, and goals. You will have a personalized and unique program that your team can adjust as you progress through it.
The first step is to determine whether you can benefit more from an inpatient or outpatient orthopedic rehab program. In more complex situations, inpatient care is usually the right choice, while outpatient options are better suited for minor injuries.
Most patients start each rehab session with physical therapy. These sessions can last between 30 and 60 minutes. Those with more serious issues can begin lying on an exam table while the therapist performs some passive exercises. You may then have to perform the same exercises on your own.
Your therapist may then continue to show you more stretches and exercises to incorporate into your home routine. Some of the exercises may even rely on weights or bands.
Orthopedic rehab also focuses on helping patients perform everyday tasks. If you have trouble walking, the session can involve relearning how to do this correctly to avoid falls and further injuries. If you have had a joint replacement, you may relearn to walk with the support of the therapist before moving on to walkers and other devices.
Patients who need to improve grip strength will likely spend a significant amount of time in the session practicing grabbing things of increasing weight.
For patients who have degenerative diseases, balance exercises are particularly useful. They can help the patient better understand where their body is in space. Some of these exercises can include standing on one foot and raising or lowering a foot or knee.
Getting the Care You Need
Orthopedic rehab offers the chance to regain your strength, balance, range of motion, and more after suffering an injury or going through surgery. It is also useful in the process of managing degenerative diseases like Parkinson’s.
By combining various types of therapies, including PRP therapy, you have the chance to get relief from pain while also preventing future injuries.
by admin | Jan 17, 2024 | Exosomes, Glaucoma, Regenerative Medicine, Stem Cell Research, Stem Cell Therapy
According to the World Health Organization, at least 2.2 billion people worldwide have near or distant vision impairment. In at least 1 billion of these cases, vision impairment could have been prevented or has yet to be addressed. Glaucoma, corneal disease, and retinal disorders are among the leading contributors to these vision impairments.
Since the pathogenesis of these eye diseases is not fully understood, fully effective treatments have yet to be developed. Considering this, Li et al. reviewed recent research to examine the effectiveness of exosomes in various diseases in vivo, which provides the potential for a new option for the treatment of eye diseases.
Exosomes are extracellular small vesicles that are formed by the regulation of endocytosis, fusion, and efflux and contain a variety of biologically active substances, including proteins, miRNAs, IncRNAs, and lipids.
Exosomes are found in all biological fluids and have roles that vary depending on their origin. These roles include cell-to-cell communication, waste transfer, and regulation of the immune system in vivo. Additionally, when serving as a carrier, exosomes are involved in many pathological processes such as nerve repair, vascular regeneration, immune response, and fibrosis formation.
Examining the various roles exosomes play within the body, the authors of this review consider their role in the treatment of serious ocular diseases, including glaucoma, diabetic retinopathy, and keratitis. Li et al. point to studies demonstrating exosomes’ ability to promote the repair of injured nerves, inhibit fibrosis, modulate immune function, and promote angiogenesis as evidence of the important role they have in treating ocular disease.
Specifically, exosomes contain a large number of immunosuppressive molecules that inhibit lymphocyte proliferation and effectively increase ocular immune tolerance to prevent ocular autoimmune disease.
Exosomes can also transfer protein and RNA to receptor cells and can accelerate wound healing of corneal epithelial cells, providing a new approach for treating large corneal lesions.
Studies have also demonstrated a link between exosomes and age-related macular degeneration (AMD) with specific exosomes considered to have neuroprotective effects that are closely related to the pathological progression of AMD.
The authors conclude that exosomes are able to be used as therapeutic carriers to participate in processes such as immune response, angiogenesis, and nerve repair in ocular-related diseases. While research into this is still emerging, the presence and accessibility of exosomes will become a potential way to diagnose and treat ocular diseases.
Source: “Progress in exosomes and their potential use in ocular diseases.” 18 Sep. 2020, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7459212/.
by Stemedix | Jan 15, 2024 | Health Awareness, Back Pain, Pain Management, Regenerative Medicine, Stem Cell Research, Stem Cell Therapy
For the treatment of a variety of health conditions, one option more people are relying on is regenerative medicine. This field focuses on helping your body’s natural healing process function at its best, making it possible for tissues to regenerate so that you can obtain pain relief and improve mobility. There are various types of regenerative medicine. Learn more about them to know the choices you have.
Regenerative Medicine: What It Is and What It’s Used For
Regenerative medicine is a group of treatments focused on healing tissues throughout the body while also restoring the function you may have lost because of aging, medical conditions, and more.
When you’re young, your body is able to heal more efficiently, but the older you get, the longer the healing process can take. In some instances, this longer length of time even leads to the development of chronic pain issues that can be tough to deal with.
With regenerative medicine, you get the chance to try minimally invasive treatments that can offer results. Most of the best regenerative medicine options focus on stem cells, but some also rely on your blood’s components to provide lasting results.
Regenerative medicine can offer help for many types of issues, including:
The kind of condition you have may dictate the type of regenerative treatment that has the potential to be most effective.
The Different Kinds of Regenerative Medicine Therapies
There are many regenerative medicine therapies to choose from, but some of the most trusted include stem cell therapy, platelet-rich plasma, and prolotherapy.
What Is Stem Cell Therapy?
Stem cell therapy is a treatment option that utilizes stem cells to promote healing. Stem cells are undifferentiated cells that can create specialized ones. They have the ability to self-renew and create functional tissues, working as the body’s repair system.
During stem cell therapy, your healthcare provider injects stem cells into the treatment area. There are different types of stem cells, including adult stem cells and embryonic stem cells.
Adult stem cells are undifferentiated cells found in various tissues throughout the body, including fat and bone marrow. They have a more limited ability to differentiate than embryonic stem cells, but they are much more readily available because they come from your body.
Mesenchymal stem cells are found in fat and bone marrow, among other tissues, and they can help the body respond to inflammation and promote healing.
What Is Platelet-Rich Plasma?
Your blood is made up of a few components, including:
- White blood cells
- Red blood cells
- Plasma
- Platelets
Plasma is the liquid portion of blood. Platelets are not actually cells but cell fragments that help with the clotting process and contain growth factors that can stimulate cellular reproduction as well as healing at the treatment site. Platelet-rich plasma refers to plasma that has more platelets than usual.
To create a PRP injection, your doctor takes a sample of your blood and runs it through a centrifuge. The centrifuge spins the sample very rapidly, dividing the blood components so that your doctor can extract the platelets and add them to the plasma. This is then injected at the treatment area.
PRP therapy can be a good option for the treatment of ligament injuries, osteoarthritis, post-surgical healing, and even hair loss.
These injections work to reduce inflammation at the treatment site, which allows better circulation. More blood flow means the area receives more nutrients and oxygen, helping with the healing process. Less inflammation also means less pain.
What Is Prolotherapy?
Prolotherapy is another type of regenerative medicine that can be used to relieve pain. It involves injecting a small amount of an irritant, like sugar, into the treatment area. This irritant trigger an immune response and jumpstarts your body’s natural ability.
It shows promise in the treatment of musculoskeletal conditions, including issues with your bones, ligaments, soft tissues, and more.
Your body responds to the sugar or other irritant as a threat, triggering your immune and healing responses to rush to the area to remove the irritant and also begin the healing process.
Benefits of Regenerative Medicine
Regenerative medicine offers the chance to get relief from pain and inflammation without having to go through invasive procedures. Most regenerative medicine options require only a minimally invasive procedure, like providing a sample of blood or undergoing a mini liposuction procedure to obtain fat.
Because regenerative medicine procedures don’t require an elaborate process, you don’t have to worry about a long preparation or recovery period. You can usually get back to your normal life right after receiving treatment.
Regenerative medicine works to help manage the underlying cause of the pain you’re experiencing. It doesn’t just mask symptoms as pain medication and anti-inflammatories do. By offering the potential of healing injuries, it may be able to provide lasting relief.
Regenerative medicine is also more affordable than an invasive procedure like surgery. The surgery itself is costly, and the recovery can mean relying on physical therapies that add to the budget. That is not an issue you have to worry about with regenerative medicine options like stem cell therapy, PRP therapy, or prolotherapy.
Managing Pain and Inflammation with Regenerative Medicine
Regenerative medicine holds significant promise for the treatment of conditions that cause pain and inflammation. By relying on your natural healing process, regenerative medicine only improves what your body does.
If you’re considering regenerative medicine to help with any conditions you face, ask your healthcare provider about it to see if it’s a good choice for you.
by Stemedix | Jan 1, 2024 | Stem Cell Therapy, Back Pain, Regenerative Medicine, Stem Cell Research
According to the World Health Organization, lower back pain affects 619 million people around the world. Lower back pain is an issue that people of all ages suffer from, and it can be debilitating. Many conditions, injuries, and damage can lead to this kind of back pain.
If you’re struggling, understanding the causes of the problem can help when deciding on the right treatment. Let’s take a closer look at the causes of lower back pain.
Muscle Strain or Sprain
Perhaps the most common reasons people experience lower back pain are muscle strains and sprains. These issues can occur gradually from overuse, or they can occur suddenly after an injury.
A low back strain occurs if you stretch the muscles that hold your spinal column in place. Tiny tears can form, leading to weaker muscles that have a harder time holding the bones of your spinal column correctly. That leads to the spine being less stable, which causes lower back pain.
A sprain occurs when the ligaments, which are the bands of tissue that hold bones together, tear away from their attachments. This, too, can happen from overuse or from an injury. The most common symptoms of muscle strains or sprains are muscle spasms, stiffness, and pain.
Degenerative Disc Disease
Degenerative disc disease is a condition in which the cushioning in your spine wears away. Your spinal discs are cushions between the bones (vertebrae) in your spinal column. They help you move and act as shock absorbers.
However, as you age, these discs begin to wear away, leading the bones to start rubbing together. Injuries and diseases can also wear away the discs.
Some of the symptoms of degenerative disc disease are:
- Pain that worsens when bending, lifting, or sitting
- Numbness and tingling in your legs or arms
- Pain that radiates down to your lower back and buttocks
The symptoms can come and go, and they can last for weeks or months at a time. The pain can range from mild to severe.
Herniated Discs
Herniated discs are injuries to the spine. Between the vertebrae in your spine are cushions called discs. The discs function as buffers, letting you move around with ease. If one of these discs tears or leaks, you have a herniated disc.
It’s a condition that affects men more than women, and it’s more likely to occur in people who sit for long periods, lift heavy objects, perform repetitive twisting or bending motions, or smoke.
Discs have gel-like centers and a firm outer layer, which can crack over time. When the inner gel-like substance pushes through the crack, you have a herniated disc. That leaked material can press on spinal nerves.
Sciatica
Sciatica is nerve pain that occurs because of an injury or irritation to the sciatic nerve. You have two sciatic nerves, one on each side of the body, that run down your legs until they reach below your knee, where they then split into other nerves. Pain that occurs anywhere along that nerve is considered sciatica pain.
Herniated discs can cause sciatica as can arthritis, degenerative disc disease, and injuries. You are more at risk if you are obese, don’t have a strong core, or have a job that requires lots of lifting.
Osteoarthritis
This is the most common type of arthritis, and it occurs when the cartilage that covers your joints wears down over time, allowing your bones to rub together. Cartilage functions like a shock absorber as well as a lubricant, letting the bones that make up your joints move smoothly. With arthritis, this movement is more difficult and painful.
One of the most commonly affected areas is the lower back. Although it’s not entirely clear what causes osteoarthritis, scientists believe it occurs as a result of aging, health conditions that affect your joints, falls, and other accidents.
Spinal Stenosis
Spinal stenosis is a condition in which the space around your spinal cord becomes too narrow, leading to irritation of the cord or the nerves that branch off from it. You can think of your spinal canal as a tunnel that runs through each of the vertebrae that make up your spine. Your spinal cord is contained within this tunnel.
If the space narrows, your nerves can become compressed or pinched, causing back pain. Symptoms can depend on the type of spinal stenosis you have and can include:
- Heavy feeling in your legs
- Tingling or numbness in the foot, leg, or buttocks
- Pain that gets worse when you stand or walk for a long time
- Pain in your lower back
You can have acquired spinal stenosis, meaning it develops over time, or congenital spinal stenosis, which you have from birth. Herniated discs, osteoarthritis, spinal injuries, and many other conditions can cause it.
Spondylolisthesis
Spondylolisthesis is a condition that causes lower back pain, and it occurs when one of the bones in your spine slips out of place and onto the bone below it. This can put pressure on a nerve, resulting in back or leg pain.
Common symptoms of spondylolisthesis include:
- Difficulty walking or standing for long periods
- Back stiffness
- Hamstring muscle spasms
- Pain when bending
- Foot tingling, weakness, or numbness
Young athletes, especially gymnasts and football players, are at risk. Some people are born with spondylolisthesis.
Fractures
If you have a fracture in a bone in the lower back, this can also cause lower back pain. Fractures can occur from traumatic injuries like falls or conditions like osteoporosis.
Regenerative Medicine for Lower Back Pain
No matter what is causing your lower back pain, you can get relief from symptoms. Most people turn to pain medications and anti-inflammatories to treat back pain, but all that those drugs do is hide the symptoms. They don’t get to the underlying cause of the problem. Regenerative medicine offers something different.
Regenerative medicine, also known as stem cell therapy, stimulates the natural healing process that you need to start feeling better. Turn to your healthcare provider to see if it’s the right choice for you.
by Stemedix | Dec 25, 2023 | Health Awareness, Mesenchymal Stem Cells, Regenerative Medicine, Stem Cell Research, Stem Cell Therapy, Stroke, Studies
According to the Centers for Disease Control and Prevention, more than 795,000 people have strokes every year in the United States, and about 610,000 of these are first or new strokes. Recovering from a stroke can be a complex process that involves many types of therapies, and one option that shows promise is stem cell therapy.
Stem cell therapy promotes growth factors and offers relief from inflammation, providing the possibility of healing the damage the stroke caused. Learn more about stem cell therapy when used for the recovery period after a stroke.
How Strokes Affect the Brain
A stroke is like a heart attack, except it takes place in your brain. It occurs when something blocks the blood supply to the brain, not allowing the organ to get the oxygen and nutrients it needs. If your brain doesn’t receive blood, its cells begin to die off or suffer damage, making it impossible for the organ to do its job.
Your brain controls everything your body does, including how you move and how you think, feel, and communicate. The results of a stroke are immediate.
The two main types of strokes are ischemic strokes and hemorrhagic strokes. Ischemic strokes are the most common type and are caused by blockages. They can occur when:
- A blood clot forms in the main brain artery.
- A blockage forms in the small blood vessels deep within the brain.
- A blood clot from the heart or another type of blockage travels via the bloodstream to an artery supplying the brain.
Hemorrhagic strokes occur when there’s bleeding in or around the brain. They can be the result of a blood vessel bursting in the brain, or a blood vessel on the surface of the brain may burst and leak blood in the area between the skull and the brain.
When you have a stroke, the areas of the brain it affects determine the kind of issues you can struggle with.
Some people experience weakness and paralysis in certain parts of their body, while others struggle with language and the processes of speaking or understanding what other people say. A stroke can even affect what your voice sounds like.
Other issues you may experience include:
- Balance problems
- Incontinence
- Trouble swallowing
- Visual problems
- Extreme fatigue
- Feeling pain
You may also struggle with mental processes like memory, concentration, understanding, and perception. Strokes can even affect your emotions.
Understanding Stem Cell Therapy: What Are Stem Cells?
Stem cells are the body’s building blocks. They are responsible for creating organs, tissues, and even your immune system. They are undifferentiated cells that can become and create specialized cell types. In other words, they can become any cell within the body, depending on where they’re placed.
Stem cells can also divide indefinitely, either creating other stem cells or specialized cells. When used to help the recovery period after a stroke, stem cells can differentiate into brain cells.
When they’re used in the brain, they don’t integrate and become neurons that reconstruct circuits. They instead start pumping out growth factors that enhance the recovery process, allowing new blood vessels and neurons to form. All of this helps make the brain more flexible, giving it a chance to recover after a stroke.
Neuroplasticity is what’s necessary for people who’ve suffered a stroke. It is the ability of the brain to rearrange its circuits, basing the organization on your behaviors.
Benefits of Stem Cell Therapy After a Stroke
Stem cell therapy is minimally invasive. You don’t have to worry about procedures that require long recovery processes or force you to spend time in the hospital. When you get stem cell therapy, the process is fast and can be done as an outpatient treatment.
Stem cells don’t just mask the symptoms of the damage the stroke caused. Experiencing pain after a stroke many times means turning to pain medications, which temporarily give you relief but also have unpleasant side effects. When you turn to stem cell therapy, your brain gets what it needs to start healing.
One of the most important things that stem cell therapy offers is the chance to relieve inflammation. When you suffer an injury of any kind, including a stroke, your body’s natural healing process causes inflammation.
This type of swelling, however, doesn’t allow a regular flow of blood to the injured area. Without the right degree of circulation, the damaged area doesn’t receive nutrients or oxygen, which makes healing more difficult. Stem cells help reduce inflammation, making the process of healing easier.
How the Stem Cell Therapy Process Works
Mesenchymal stem cells (MSCs) have been studied for their potential therapeutic applications in various medical conditions, including stroke. MSCs have several properties that make them attractive candidates for stroke therapy:
- MSCs possess anti-inflammatory properties that can help modulate the immune response and reduce inflammation in the brain following a stroke. Excessive inflammation is a key contributor to secondary damage after a stroke.
- MSCs can modulate the immune system, potentially suppressing harmful immune responses while promoting tissue repair and regeneration.
- MSCs secrete various growth factors and neurotrophic factors that support neuronal survival, growth, and differentiation. These factors can contribute to the repair and regeneration of damaged neural tissue.
- MSCs can stimulate the formation of new blood vessels (angiogenesis), which is crucial for supplying oxygen and nutrients to the damaged brain tissue.
- While the ability of MSCs to differentiate into neurons is limited, they may contribute to neural repair indirectly by interacting with the local environment and supporting the survival of existing neurons.
Is Regenerative Medicine Right for You?
Suffering a stroke can be devastating, leaving you with lasting damage and impacting your quality of life. Along with physical therapy and other treatments your doctor recommends, patients are exploring their options with stem cell therapy. Stem cell therapy and other regenerative medicine options offer the opportunity to give your brain the tools it needs to start healing. By helping reduce inflammation and bringing growth factors to the treatment area, stem cell therapy provides the chance to promote neuroplasticity and start healing.
by admin | Dec 21, 2023 | Lupus, Exosomes, Extracellular Vesicles, Mesenchymal Stem Cells, Regenerative Medicine, Stem Cell Research, Stem Cell Therapy
Systemic lupus erythematosus (SLE) is a common multisystemic autoimmune disease that often results in multi-organ damage when left untreated. Currently affecting over 1.5 million Americans, the etiology and pathogenesis of SLE continue to remain unclear.
At present, glucocorticoids and immunosuppressants are the most prescribed course of therapeutic treatment and mostly as a way to manage and treat symptoms of SLE, not the cause itself.
Considering that the etiology and pathogenesis of SLE are accompanied by immune disorders including abnormal proliferation, differentiation, and activation and dysfunction of T cells, and that mesenchymal stem cells (MSC) and MSC-derived extracellular vesicles (EVs) play important roles in the immunity process, researchers are increasingly turning their attention to MSCs and EVs as potential therapeutic treatment options for SLE.
In this review, Yang et al. examine the immunomodulatory effects and related mechanisms of MSCs and EVs in SLE with hopes of better understanding SLE pathogenesis and guiding biological therapy.
Examining the potential use of MSC and MSC-EVs in SLE treatment the authors found some studies have established that MSCs reduce adverse effects of immunosuppressive drugs and when combined have demonstrated distinct effects on T cell activation and bias.
Additionally, Yang et al. report that MSCs are able to participate in the immune response in two distinct ways: paracrine effect and directly through cell-to-cell interaction. Since reconstruction of immune tolerance and tissue regeneration and repair are required parts of SLE treatment and since MSCs possess high self-renewal ability, rapid expansion in vitro and in vitro, and low immunogenicity, allogeneic MSC transplantation has demonstrated strong evidence for the therapeutic potential of MSC in SLE.
Besides the ability to repair and regenerate tissue, MSCs, and MSC-EVs have strong anti-inflammatory and immunomodulatory effects, making them a potentially ideal treatment option as part of a therapeutic strategy for SLE. Considering that MSC-EVs have similar biological functions with MSCs, but are also considered cell-free, the authors point out that MSC-EVs could be the better choice for SLE treatment in the future.
Despite the potential of MSC and MSC-EVs, Yang et al. point out that genetic modification, metabolic recombination, and other priming of MSCs in vitro should be considered before MSC/MSC-EVs application for SLE treatment. The authors also recommend further clinical evaluation of the time of infusion, appropriate dosage, interval of treatment, and long-term safety of MSC/MSC-EVs in the treatment of SLE before any form of the combination is used as a treatment option.
Source: “Immunomodulatory Effect of MSCs and MSCs-Derived Extracellular ….” 16 Sep. 2021, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481702/.