Stifle injuries and treatments – Tri-State Livestock News

In the past, an injury to the stifle joint of a horse may have certainly ended his or her career or usefulness. Now, with the ever-evolving science of veterinary medicine, afflictions to the joint have a much higher chance of being treated or even healed.

One of the reasons a stifle injury gives apprehension to horse owners is the complicated nature of the joint said Scott Cammack, D.V.M. He practices at Northern Hills Veterinary Clinic in Sturgis, South Dakota, with several other specialists.

Cammack explains that its treatment is much more involved than similar injuries. For example, an injury to the hock can often be resolved by fusing the bottom two joints (the hock consists of four total). Because it is a low-motion joint, the horse will still be sound and function after fusion.

The stifle, on the other hand, is a high-motion joint. Its got a lot of things going on in there. It doesnt have the capacity to be fused and still be sound. I would consider that they are more serious. They are more prone to long-term issues than a hock is, in my mind, he said.

According to Dr. Cammack, the stifle is anatomically similar to a human knee. All the parts are similar to your knee. Just as athletes injure their knees, they injure themselves. They have a patella, theyve got meniscuses, theyve got anterior and posterior cruciate ligaments, theyve got collateral ligaments. One major difference is that humans have one patellar ligament coming off the kneecap, while horses have three. Therefore, horses can have very unique issues.

One condition, often found in younger horses (aged 2-6) is the intermittent upward fixation of the patella or simply a catchy stifle. Dr. Cammack describes this condition: The locking mechanism of the stifle is inappropriately keeping the leg in the locked, extended position. They cant bend their leg and it only bends at the fetlock. That one is one that we treat in different ways. Sometimes, well do a procedure where we put a needle in the medial patellar ligament and we split it a little bit and cause it to thicken up and tighten up a little bit to help correct that. So thats a pretty simple procedure.

Another condition found in younger horses is OCD (osteochondrosis) lesions, a developmental issue. According to Dr. Cammack, they are cyst-like lesions on the bone. Some of them fill in and some require surgery. We saw one just the other day. A four year old had large cysts up in the bone. All they did was turn the horse out and waited. That one filled in on its own, but thats not common. Usually youre injecting the cyst or putting a screw across it or various treatments for something like that.

On the other hand, older horses may have very different afflictions in the joint. He said, In my mind, youre going to see more of the soft tissue injuries in your younger horses and more of the osteoarthritis in the older horses.

Older horses are going to be more prone to seeing arthritis in their stifle, which might be secondary to an injury it had had way back when. They injured a collateral ligament and it wasnt diagnosed, or they have some instability from ligament damage and then it healed some and they got by with it. Years down the road, youre seeing the arthritis, the osteoarthritis in there.

Stifle injuries are often seen in performance horses in various disciplines. When you start getting into any disciplines where theyre having to run hard, turn hard, stop hard, spin. We see it more in the reined cow horses and the reiners and the barrel horses, Dr. Cammack said. However, injuries can occur on the ranch or in other disciplines, as well. Certainly any horse can catch some bad ground or find a hole in the ground or something that can cause them injury.

Interestingly, younger horses may be more prone to injuries that occur in the arena. We are doing our futurities and so much heavy training on them when theyre young and they dont have the muscle memory and the skillset to have their leg in the right place at the right time with that amount of force on it.

Dr. Cammacks procedure for examining horses includes a flex test, where the joint is stressed momentarily to determine the location of any potential weaknesses in the joints. The end goal is to determine how to optimize the horses performance without masking any problems. If the horse deals with chronic issues, the typical injection of HA (hyaluronic acid), a type of steroid, may be administered, costing around $175.

For other injuries, different types of injections may do the trick. Theres certainly a lot more going on with regenerative medicine than there used to be, Dr. Cammack said. Using PRP (platelet-rich plasma) can help the joint heal itself. Youre taking the blood and processing it and pulling out platelet-rich plasma. Its going to have healing factors and certain proteins that can help the joint get better. This may cost around $250.

Theres another one called pro-stride, which is another form of PRP, but its a more concentrated form of PRP. Its more like $450. If youre getting into stem cells, that goes right up. We just pull the bone marrow or the fat, depending on which form were doing and we send it in. With that sample that we send in, we have to send $2,300 to the laboratory. That one can be in excess of $2,500 to do stem cells, Dr. Cammack said. Its an exciting area.

Cammack has devoted his professional career to the study of equines and particularly their joints and movement.

When I was in college, I started working at this clinic with Dr. Margie Jones. I developed a strong affinity for equine work and did a year internship with an equine surgeon in California, but he did a sports medicine practice and then I got in the deep pool of sports medicine and developed a deep love for it, he said.

More severe injuries to the stifle may involve surgeries, which range vastly in involvement and price.

This article serves as a brief overview of a very large field of veterinary study. Dr. Cammack devotes much of his practice and time to learning more about the equine, attending the yearly American Association of Equine Practitioners conferences, and expanding into regenerative medicine.

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Study reveals how skin cells prepare to heal wounds – Jill Lopez

A team of University of California, Irvine researchers have published the first comprehensive overview of the major changes that occur in mammalian skin cells as they prepare to heal wounds. Results from the study provide a blueprint for future investigation into pathological conditions associated with poor wound healing, such as in diabetic patients.

"This study is the first comprehensive dissection of the major changes in cellular heterogeneity from a normal state to wound healing in skin," said Xing Dai, PhD, a professor of biological chemistry and dermatology in the UCI School of Medicine, and senior author. "This work also showcases the collaborative efforts between biologists, mathematician and physicists at UCI, with support from the National Institute of Arthritis & Musculoskeletal & Skin Diseases-funded UCI Skin Biology Resource-based Center and the NSF-Simons Center for Multiscale Cell Fate Research.

The study, titled, "Defining epidermal basal cell states during skin homeostasis and wound healing using single-cell transcriptomics," was published this week inCell Reports.

"Our research uncovered at least four distinct transcriptional states in the epidermal basal layer as part of a 'hierarchical-lineage' model of the epidermal homeostasis, or stable state of the skin, clarifying a long-term debate in the skin stem cell field," said Dai.

Using single-cell RNA sequencing coupled with RNAScope and fluorescence lifetime imaging, the team identified three non-proliferative and one proliferative basal cell state in homeostatic skin that differ in metabolic preference and become spatially partitioned during wound re-epithelialization, which is the process by which the skin and mucous membranes replace superficial epithelial cells damaged or lost in a wound.

Epithelial tissue maintenance is driven by resident stem cells, the proliferation and differentiation dynamics of which need to be tailored to the tissue's homeostatic and regenerative needs. However, our understanding of tissue-specific cellular dynamics in vivo at single-cell and tissue scales is often very limited.

"Our study lays a foundation for future investigation into the adult epidermis, specifically how the skin is maintained and how it can robustly regenerate itself upon injury," said Dai.

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Study reveals how skin cells prepare to heal wounds - Jill Lopez

One Upside of the Coronavirus Shutdown, Maybe? Fewer Voter Initiatives – Lost Coast Outpost

Voters fill out their ballots on Nov. 6, 2018, at The Salvation Army in San Jose. Photo by Dai Sugano, Bay Area News Group

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California voters may experience a small silver lining amid the coronavirus pandemic: a shorter November ballot, featuring fewer of the statewide propositions that often put voters in the middle of confusing industry fights.

Initiative proponents have until the end of April to collect the signatures they need to put their ideas on the ballot and with millions of Californians staying home, and practicing social distancing when they go out, it may be impossible for some campaigns to collect enough signatures in time.

People arent out in public, and those who are out in public arent inclined to approach a stranger, take a pen, and stand within 6 feet to put something on the ballot, said Brian Brokaw, a Democratic political consultant who has been involved in several potential ballot measures.

Normally presidential election years attract a slew of initiatives, as campaigns particularly those pushing liberal ideas seek approval from a larger and more diverse electorate. Though we wont know until July exactly how many propositions will be on the ballot, it appears likely that it will be a lot less than in 2016, when Californians voted on 17 statewide ballot measures. Political insiders estimate the final number for 2020 will be in the range of six to 10.

Thats good news for election officials, who could face lower costs for printing and mailing shorter ballots, and for voters who may find the decision-making easier when faced with fewer proposals, said Kim Alexander, president of the nonprofit California Voter Foundation.

Sometimes voting in California can feel like youre taking a test voters can be intimidated by the length and complexity of the ballot, she said. So it could help encourage voter participation if we have fewer complex initiatives sprouting out of special-interest fighting.

People arent out in public, and those who are out in public arent inclined to approach a stranger, take a pen, and stand within 6 feet to put something on the ballot. Brian Brokaw, political consultant

So far four measures have qualified for the November ballot, one measure has submitted signatures that are being verified, and another eight have collected at least 25% of the necessary signatures. (Depending on what type of law an initiative would change, it needs either about 623,000 valid signatures or about 997,000 valid signatures.)

Several campaigns have stopped collecting signatures because of the coronavirus shutdown, including those pushing initiatives to allow sports betting, tax plastic packaging to fund environmental programs, continue funding stem cell research and expand Californias data privacy law.

None of them are officially calling it quits. Some may already have enough signatures to make it on the ballot, while others are hoping they can resume collecting signatures in time to get more.

Because the health and wellbeing of Californians is foremost, we paused paid signature gathering efforts for the time being, said Jacob Mejia, a spokesman for the Pechanga Indian tribe that is backing the measure to permit sports betting. Tribal leadership remains committed to bringing this proposal to voters in November and are monitoring developments closely and assessing all options.

But the odds of getting back on the street with pens and clipboards any time soon seem slim, as Gov. Gavin Newsom has said the order to stay home to curb the spread of coronavirus may last two to three months.

Everything is on hold until its safe, said Dan Newman, a spokesman for the plastic recycling measure.

He said the campaign will try to get on the 2022 ballot if it cant resume gathering signatures very soon.

Newsom said this week that companies that are paid to gather signatures for ballot initiatives have asked him to extend the deadlines for submitting signatures so they can have more time to qualify for the November ballot. He was noncommittal, saying only that the question is one of many things hes processing in response to the pandemic.

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CALmatters.org is a nonprofit, nonpartisan media venture explaining California policies and politics.

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One Upside of the Coronavirus Shutdown, Maybe? Fewer Voter Initiatives - Lost Coast Outpost

Reviewing CRYO-CELL International (OTCMKTS:CCEL) and Harsco (OTCMKTS:HSC) – Redmond Register

CRYO-CELL International (OTCMKTS:CCEL) and Harsco (NYSE:HSC) are both small-cap medical companies, but which is the superior business? We will contrast the two companies based on the strength of their dividends, profitability, analyst recommendations, risk, valuation, institutional ownership and earnings.

Insider & Institutional Ownership

91.7% of Harsco shares are owned by institutional investors. 54.0% of CRYO-CELL International shares are owned by insiders. Comparatively, 1.8% of Harsco shares are owned by insiders. Strong institutional ownership is an indication that endowments, large money managers and hedge funds believe a stock is poised for long-term growth.

CRYO-CELL International has a beta of -0.25, suggesting that its share price is 125% less volatile than the S&P 500. Comparatively, Harsco has a beta of 2.27, suggesting that its share price is 127% more volatile than the S&P 500.

Analyst Recommendations

This is a breakdown of recent recommendations for CRYO-CELL International and Harsco, as provided by MarketBeat.

Harsco has a consensus price target of $26.67, suggesting a potential upside of 321.27%. Given Harscos higher possible upside, analysts clearly believe Harsco is more favorable than CRYO-CELL International.

Earnings & Valuation

This table compares CRYO-CELL International and Harscos revenue, earnings per share and valuation.

Harsco has higher revenue and earnings than CRYO-CELL International.

Profitability

This table compares CRYO-CELL International and Harscos net margins, return on equity and return on assets.

Summary

Harsco beats CRYO-CELL International on 8 of the 12 factors compared between the two stocks.

About CRYO-CELL International

Cryo-Cell International, Inc. engages in the cellular processing and cryogenic cellular storage with a focus on the collection and preservation of umbilical cord blood stem cells for family use. It provides cord tissue service that stores a section of the umbilical cord tissue, a source of mesenchymal stem cells that are used in regenerative medicine to treat a range of conditions, including heart, kidney, ALS, wound healing, and auto-immune diseases. The company also manufactures and sells PrepaCyte CB processing system, a technology used to process umbilical cord blood stem cells. It stores approximately 500,000 cord blood and cord tissue specimens worldwide. The company markets its cord blood stem cell preservation services directly to expectant parents, as well as by distributing information through obstetricians, pediatricians, childbirth educators, certified nurse-midwives, and other related healthcare professionals. Cryo-Cell International, Inc. was founded in 1989 and is headquartered in Oldsmar, Florida.

About Harsco

Harsco Corporation provides industrial services and engineered products worldwide. The company operates in three segments: Harsco Metals & Minerals, Harsco Industrial, and Harsco Rail. The Harsco Metals & Minerals segment provides on-site services of material logistics, product quality improvement, and resource recovery for iron, steel, and metals manufacturing; and value added environmental solutions for industrial co-products, as well as produces industrial abrasives and roofing granules. The Harsco Industrial segment manufactures and supplies custom-engineered and manufactured air-cooled heat exchangers for the natural gas, natural gas processing, and petrochemical industries; industrial grating products, such as metal bar grating configurations for industrial flooring, and safety and security applications in the energy, paper, chemical, refining, and processing industries. It also offers heat transfer products, such as boilers and water heaters for commercial and institutional applications; and high-security fencing products. The Harsco Rail segment designs and manufactures safety systems for transportation and industrial applications; and equipment, after-market parts, and services for the maintenance, repair, and construction of railway track. It serves private and government-owned railroads, and urban mass transit systems. Harsco Corporation was founded in 1853 and is headquartered in Camp Hill, Pennsylvania.

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Reviewing CRYO-CELL International (OTCMKTS:CCEL) and Harsco (OTCMKTS:HSC) - Redmond Register

Blood donors in high demand – Dominion Post – The Dominion Post

As COVID-19 restricts residents from leaving their homes, Monongalia County is faced with a lack of blood donors.

The American Red Cross is facing a severe blood shortage due to an unprecedented number of blood drive cancellations during this coronavirus outbreak, said Jason Keeling, executive director of the American Red Cross local chapter.

Nationally, 7,000 Red Cross blood drives have been canceled with 63 being canceled in West Virginia.

Due to the cancellations, West Virginia is down 1,800 pints of blood from its typical intake, which would usually be enough to save up to 600 lives.

Keeling said contributions from the public are now desperately needed to save lives.

It inhibits the nations ability to have blood supply available for those that need it most such as cancer patients and those needing emergency procedures, Keeling said.

The Centers for Disease Control encourages anyone who is healthy even if they are social distancing to donate.

Keeling said additional precautionary measures are being taken to protect staff and those who choose to donate. He said everyone who comes in to donate is having their temperature taken first and using social distancing.

Those who have traveled abroad to China, Hong Kong, Macau, Iran, Italy and South Korea within the last 28 days are asked not to donate.

Hospitals, including WVU Medicine, have been working through the shortage to ensure those who need donations the most are not left without them.

Aaron Shmookler, assistant professor in the WVU department of pathology, anatomy, and laboratory medicine said WVU Medicine has postponed or canceled elective surgeries to avoid any complications.

Hematopoietic stem cell transplants, which is often used to treat cancer, have also been delayed. Schmookler said many of the blood products for this type of cellular therapy come from donors living outside the United States, which has made it difficult to administer the products to those who need them.

We have routine blood orders not being filled to 100%, Schmookler said. Although generally we have maintained stock of our inventory, over time a dwindling blood supply will make it more difficult to provide transfusion support when clinically indicated.

WVU Medicine has continued to treat patients with complex medical issues, including hemorrhagic shock, postpartum bleeding, surgery, cancer, and heart disease. Schmookler said blood has never been denied to those who need it.

In the case that the COVID-19 pandemic continues to escalate, and the blood supplies continue to diminish, Schmookler said it would force hospitals to make a difficult decision.

This coordinated effort is essential to ensure that the best clinical and laboratory decisions are made for each patient who needs blood, he said. The worst possible plan would be having to make very, very difficult and complex ethical decisions on who receives those last precious units of available blood. I am certainly hopeful for the best.

Several local blood drives are still scheduled for the coming weeks, and residents are encouraged to register by visiting http://www.redcrossblood.org.

Morgantown Red Cross drives will be held 9 a.m.-6 p.m. Monday and Tuesday, 11 a.m.-5 p.m. Wednesday, noon-5:30 p.m. Thursday and noon-5 p.m. Friday at the Morgantown Red Cross office.

From noon-4 p.m. April 7, an additional drive will be held at the Fresh Harvest Church in Morgantown.

I implore everyone who is healthy and eligible to please donate blood, Schmookler said. Call your local blood donation center, make an appointment, and help me and my professional clinical and laboratory colleagues in the hospital care for our relatives, our loved ones, and our friends.

By Gabriella Brown

TWEET @DominionPostWV

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Blood donors in high demand - Dominion Post - The Dominion Post

Reversing The Ageing Process With Stem Cell Therapy – Version Weekly

It is a universally acknowledged fact that the majority of women refuse to age, the moment they reach the age of 40. The desire to turn back the clock is something that gets automatically etched on their minds, after hitting middle age. Making a wise choice from the wide range of anti-ageing solutions available for women can be a highly baffling affair, but understanding the skins needs is equally crucial.

So what exactly is ageing, that every person, especially women dread? It can be regarded as a complex process resulting in accrual changes in a persons body over. a period of time. Ageing occurs in fractions, because the stem cells which have the ability to renew themselves grow old as DNA gets damaged and changes occur in the overall physiology. As time passes by and people age, the majority of the cells present in their bodies get replaced and the ability of the body to produce more new cells gradually declines, Thus, anti-ageing retards the degeneration process of the body.

Post an anti-ageing fat stem cell treatment the skin shows prominent signs of turning softer while the body notices a remarkable surge of energy, resulting in improved sleeping and breathing patterns, controlled sugar levels, rebalanced hormones, increased metabolism, average weight loss and fading age spots. This all seems possible owing to the insertion of 30-50 million supercharged active stem cells.

Ageing is indeed complex, as its causes have not yet been completely understood. A big part of ageing occurs when the body is being attacked by inflammation and oxidative stress. Even though it is said that ageing is a natural process which is unavoidable, there is still scope to maintain health and stay young for both preventing age-related diseases and to enjoy the benefits of youth.

The desire to be younger is not exactly a new idea. The concept of anti-ageing has kept humankind occupied since ages, with the idea about staying healthy and fit with age and improving the quality of life. So with the rising evidence about the association of ageing diseases with adult stem cell exhaustion, it will not be surprising to witness an elevation of interest towards restoring the adult stem cell function to improve these conditions and to turn back the clock!

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Reversing The Ageing Process With Stem Cell Therapy - Version Weekly

4 relationship problems that can be linked back to early childhood – Big Think

Fear of abandonment can stem from childhood loss or childhood maltreatment.

Photo by Koldunova Anna on Shutterstock

"Powerful experiences can alter the functioning of an adult brain, but with children, traumatic events may change the entire framework of their brain." - Dr. Bruce Perry, Senior Fellow of the Child Trauma Academy.

Fear of abandonment can stem from childhood loss - the death of a parent or loved one - but it can also stem from maltreatment during childhood. Maltreatment or neglect as a child can be difficult to pinpoint, especially if that mistreatment isn't physical but more of an emotional nature.

Brain development, according to this Child Welfare Information Gateway study, is actually the process of creating, strengthening and discarding connections among the neurons we're born with.

These connections are called synapses and they organize the brain by forming neural pathways that connect various parts of the brain governing everything we do.

The growth of each region of the brain depends largely on receiving stimulation for that area - think of it as a muscle that needs to be exercised in order to grow strong and be useful. Leaving that muscle unattended, not giving it movement and strength, will eventually lead it to atrophy, making it a deterrent for your entire body to function properly.

This is how maltreatment works. To remedy this issue in your relationship, work on exercising that "attachment muscle", allowing yourself to become more vulnerable and open with your partner.

An inability to commit to the relationship can be really difficult to overcome.

Photo by Motortion Films on Shutterstock

This 2016 study by Winston and Chicot offers proof to the theory that parental inconsistency and lack of love can lead to long-term mental health problems as well as to reduced overall potential and happiness later in life.

The human brain is made of over 100 billion brain cells that each connect to over 7000 other brain cells - it's an extremely complex system. And yet - by the age of 3, a child's brain has reached more than 90% of its adult size.

The experiences that a baby has within the first three years of life lay the ground for how their brain is wired well into adulthood. While it's possible for us to "re-learn" things as adults and change the framework of our brains this way - there is much importance laid on the connection and relationship that an infant has with their caregiver.

Longitudinal studies have proven that a child's inability to form and maintain healthy relationships throughout life may be significantly impaired by having an insecure attachment to a primary caregiver during their early development years.

To address this common relationship problem, consider how you view attachment, dedication and loyalty in relationships - there is a good chance you are already very committed to your partner but simply fear the "label" of being so invested in a relationship.

Entitlement can be an unrealistic, unmerited and inappropriate sense of how you should be treated and what you deserve.

Image by Artur Szczybylo on Shutterstock

Entitlement, defined as an unrealistic, unmerited or inappropriate expectation of favorable living conditions and treatment by others, can also stem back to the experiences we have during childhood. To remedy this issue in a relationship can be quite difficult, as entitlement is an inherently selfish quality.

According to Better Help, there are two main reasons why people act entitled in relationships - they are either overcompensating for never getting what they want or are so used to getting what they want that they can't even entertain the possibility of not getting what they want.

Overcompensating for past wrongs - an example being a child who grows up lacking the toys, games, and clothes owned by their peers may grow up to believe they are entitled to what they missed out on.

A habit of getting what they want all the time - an example being a child who was given whatever they asked for without reason which can lead them to believe they should always get what they ask for even if it's not realistic.

Childhood emotional neglect is a deep and long lasting wound that can impact all future relationships.

Photo by rawf8 on Shutterstock

Childhood emotional neglect is a deep and long-lasting would that isn't always easily detectable. In fact, many times, these feelings of worthlessness and defectiveness that children feel aren't imposed by parents who mean harm to their child.

According to Good Therapy, there are four different kinds of parenting styles that can lead to your child feeling worthless or defective.

Authoritarian parents: they want their children to follow the rules but have very little time or inclination to listen to their child's feelings or needs.

Permissive parents: they have a very laid back attitude about child-rearing, but they may be too laid back - which may let children do what they wish and "fend for themselves." This can lead to children feeling as though they "aren't worthy of their parent's time" and in the future, they may feel unworthy of their romantic partner's time as well.

Narcissistic parents: they feel as though the world (and their children) revolve around them, placing their own needs and desires above those of their children. Adults who were raised by narcissistic parents may always allow their partner's needs and wants to overshadow their own, feeling as though they are not worthy of having their own needs met.

Addressing issues of self-worth often involve therapy, self-help programs and a lot of time to heal and retrain your brain in how you view yourself.

"Our brains are sculpted by our early experiences. Maltreatment is a chisel that shapes a brain to contend with strife but at the cost of deep, enduring wounds." - Teicher, 2000.

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About Stem Cell Center

The Stem Cell Center Network, a division of Global Stem Cells Groupis a unique international network of medical practices, dedicated to bringing Stem Cell therapies to the patients who need them.

Our physicians are experts in their fields who wanted to broaden their horizons and embrace Stem Cell treatments as the future of modern and regenerative medicine. Each medical practitioner in our network is dedicated to providing the best treatments and contributing to the global store of knowledge and research. By joining our network, they are able to fulfil this mission. Once a physician joins our network, we provide all the training, equipment and support they need to set up, run and market their Stem Cell practice. They enjoy geographic and specialization exclusivity, as well as a strong network of patient referrals. Each physician in our network is also invited to become a member of our faculty and the Global Stem Cell Foundation, where they can contribute to the worlds growing Stem Cell store of knowledge.

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About Stem Cell Center

From Bats to Human Lungs, the Evolution of a Coronavirus – The New Yorker

There are endless viruses in our midst, made either of RNA or DNA. DNA viruses, which exist in much greater abundance around the planet, are capable of causing systemic diseases that are endemic, latent, and persistentlike the herpes viruses (which includes chicken pox), hepatitis B, and the papilloma viruses that cause cancer. DNA viruses are the ones that live with us and stay with us, Denison said. Theyre lifelong. Retroviruses, like H.I.V., have RNA in their genomes but behave like DNA viruses in the host. RNA viruses, on the other hand, have simpler structures and mutate rapidly. Viruses mutate quickly, and they can retain advantageous traits, Epstein told me. A virus thats more promiscuous, more generalist, that can inhabit and propagate in lots of other hosts ultimately has a better chance of surviving. They also tend to cause epidemicssuch as measles, Ebola, Zika, and a raft of respiratory infections, including influenza and coronaviruses. Paul Turner, a Rachel Carson professor of ecology and evolutionary biology at Yale University, told me, Theyre the ones that surprise us the most and do the most damage.

Scientists discovered the coronavirus family in the nineteen-fifties, while peering through early electron microscopes at samples taken from chickens suffering from infectious bronchitis. The coronaviruss RNA, its genetic code, is swathed in three different kinds of proteins, one of which decorates the viruss surface with mushroom-like spikes, giving the virus the eponymous appearance of a crown. Scientists found other coronaviruses that caused disease in pigs and cows, and then, in the mid-nineteen-sixties, two more that caused a common cold in people. (Later, widespread screening identified two more human coronaviruses, responsible for colds.) These four common-cold viruses might have come, long ago, from animals, but they are now entirely human viruses, responsible for fifteen to thirty per cent of the seasonal colds in a given year. We are their natural reservoir, just as bats are the natural reservoir for hundreds of other coronaviruses. But, since they did not seem to cause severe disease, they were mostly ignored. In 2003, a conference for nidovirales (the taxonomic order under which coronaviruses fall) was nearly cancelled, due to lack of interest. Then SARS emerged, leaping from bats to civets to people.The conference sold out.

SARS is closely related to the new virus we currently face. Whereas common-cold coronaviruses tend to infect only the upper respiratory tract (mainly the nose and throat), making them highly contagious, SARS primarily infects the lower respiratory system (the lungs), and therefore causes a much more lethal disease, with a fatality rate of approximately ten per cent. (MERS, which emerged in Saudi Arabia, in 2012, and was transmitted from bats to camels to people, also caused severe disease in the lower respiratory system, with a thirty-seven per cent fatality rate.) SARS-CoV-2 behaves like a monstrous mutant hybrid of all the human coronaviruses that came before it. It can infect and replicate throughout our airways. Thats why it is so bad, Stanley Perlman, a professor of microbiology and immunology who has been studying coronaviruses for more than three decades, told me. It has the lower-respiratory severity of SARS and MERS coronaviruses, and the transmissibility of cold coronaviruses.

One reason that SARS-CoV-2 may be so versatile, and therefore so successful, has to do with its particular talent for binding and fusing with lung cells. All coronaviruses use their spike proteins to gain entry to human cells, through a complex, multistep process. First, if one imagines the spikes mushroom shape, the cap acts like a molecular key, fitting into our cells locks. Scientists call these locks receptors. In SARS-CoV-2, the cap binds perfectly to a receptor called the ACE-2, which can be found in various parts of the human body, including the lungs and kidney cells. Coronaviruses attack the respiratory system because their ACE-2 receptors are so accessible to the outside world. The virus just hops in, Perlman told me, whereas its not easy to get to the kidney.

While the first SARS virus attached to the ACE-2 receptor, as well, SARS-CoV-2 binds to it ten times more efficiently, Kizzmekia Corbett, the scientific lead of the coronavirus program at the National Institutes of Health Vaccine Research Center, told me. The binding is tighter, which could potentially mean that the beginning of the infection process is just more efficient. SARS-CoV-2 also seems to have a unique ability, which SARS and MERS did not have, to use enzymes from our human tissueincluding one, widely available in our bodies, named furinto sever the spike proteins cap from its stem. Only then can the stem fuse the virus membrane and the human-cell membrane together, allowing the virus to spit its RNA into the cell. According to Lisa Gralinski, an assistant professor in the Department of Epidemiology at the University of North Carolina at Chapel Hill, this supercharged ability to bind to the ACE-2 receptor, and to use human enzymes to activate fusion, could aid a lot in the transmissibility of this new virus and in seeding infections at a higher level.

Once a coronavirus enters a personlodging itself in the upper respiratory system and hijacking the cells hardwareit rapidly replicates. When most RNA viruses replicate themselves in a host, the process is quick and dirty, as they have no proofreading mechanism. This can lead to frequent and random mutations. But the vast majority of those mutations just kill the virus immediately, Andersen told me. Unlike other RNA viruses, however, coronaviruses do have some capacity to check for errors when they replicate. They have an enzyme that actually corrects mistakes, Denison told me.

It was Denisons lab at Vanderbilt that first confirmed, in experiments on live viruses, the existence of this enzyme, which makes coronaviruses, in a sense, cunning mutators. The viruses can remain stable in a host when there is no selective pressure to change, but rapidly evolve when necessary. Each time they leap into a new species, for example, they are able to hastily transform in order to survive in the new environment, with its new physiology and a new immune system to battle. Once the virus is spreading easily within a species, though, its attitude is, Im happy, Im good, no need to change, Denison said. That seems to be playing out now in humans; as SARS-CoV-2 circles the globe, there are slight variations among its strains, but none of them seem to affect the viruss behavior. This is not a virus that is rapidly adapting. Its like the best car in the Indy 500. Its out in front and there is no obstacle in its path. So there is no benefit to changing that car.

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From Bats to Human Lungs, the Evolution of a Coronavirus - The New Yorker

Leronlimab Used in Seven Patients with Severe COVID-19 Demonstrated Promise with Two Intubated Patients in ICU, Removed from ICU and Extubated with…

VANCOUVER, Washington, March 27, 2020 (GLOBE NEWSWIRE) -- CytoDyn Inc. (OTC.QB: CYDY), (CytoDyn or the Company"), a late-stage biotechnology company developing leronlimab (PRO 140), a CCR5 antagonist with the potential for multiple therapeutic indications, announced today the three-day results post-leronlimab treatment of the first four patients under an Emergency Investigational New Drug (EIND) granted by the U.S. Food and Drug Administration (FDA). A total of seven patients have been enrolled thus far under EIND in the same leading medical center in the New York City area.

The treatment with leronlimab is targeted as a therapy for patients who experience respiratory complications as a result of contracting SARS-CoV-2 causing the Coronavirus Disease 2019 (COVID-19). Leronlimab is believed to provide therapeutic benefit by enhancing the immune response while mitigating the cytokine storm that leads to morbidity and mortality in these patients.

Bruce Patterson, M.D., Chief Executive Officer and founder of IncellDx, a diagnostic partner and advisor to CytoDyn, said, IncellDx has developed specific companion diagnostic tests to determine the efficacy and dosing of leronlimab in these severe cases of COVID-19. We found that patients with severe COVID-19 disease are in the midst of immunologic chaos which includes the cytokine storm. Our companion diagnostics showed that after three days of therapy, the immune profile in these patients approached normal levels and the levels of cytokines involved in the cytokine storm were much improved.

Jacob Lalezari, M.D., Interim Chief Medical Officer of CytoDyn, commented, These preliminary results give hope that leronlimab may help hospitalized patients with COVID-19 recover from the pulmonary inflammation that drives mortality and the need for ventilators. A leading medical center in the heart of the New York City epidemic was instrumental in giving the preliminary data.

Nader Pourhassan, Ph.D., President and Chief Executive Officer of CytoDyn said: We are extremely pleased for the coronavirus patients under the care of the treating medical team and that the FDA is so responsive to advance our Phase 2 clinical trial. I am very hopeful that leronlimab can help to reduce the rate of mortality among COVID-19 patients with severe symptoms of ARDS and to assist our government to fight this battle.

About Coronavirus Disease 2019SARS-CoV-2 was identified as the cause of an outbreak of respiratory illness first detected in Wuhan, China. The origin of SARS-CoV-2 causing the COVID-19 disease is uncertain, and the virus is highly contagious. COVID-19 typically transmits person to person through respiratory droplets, commonly resulting from coughing, sneezing, and close personal contact. Coronaviruses are a large family of viruses, some causing illness in people and others that circulate among animals. For confirmed COVID-19 infections, symptoms have included fever, cough, and shortness of breath. The symptoms of COVID-19 may appear in as few as two days or as long as 14 days after exposure. Clinical manifestations in patients have ranged from non-existent to severe and fatal. At this time, there are minimal treatment options for COVID-19.

About Leronlimab (PRO 140) The FDA has granted a Fast Track designation to CytoDyn for two potential indications of leronlimab for deadly diseases. The first as a combination therapy with HAART for HIV-infected patients and the second is for metastatic triple-negative breast cancer.Leronlimab is an investigational humanized IgG4 mAb that blocks CCR5, a cellular receptor that is important in HIV infection, tumor metastases, and other diseases, including NASH.Leronlimab has completed nine clinical trials in over 800 people, including meeting its primary endpoints in a pivotal Phase 3 trial (leronlimab in combination with standard antiretroviral therapies in HIV-infected treatment-experienced patients).

In the setting of HIV/AIDS, leronlimab is a viral-entry inhibitor; it masks CCR5, thus protecting healthy T cells from viral infection by blocking the predominant HIV (R5) subtype from entering those cells. Leronlimab has been the subject of nine clinical trials, each of which demonstrated that leronlimab could significantly reduce or control HIV viral load in humans. The leronlimab antibody appears to be a powerful antiviral agent leading to potentially fewer side effects and less frequent dosing requirements compared with daily drug therapies currently in use.

In the setting of cancer, research has shown that CCR5 may play a role in tumor invasion, metastases, and tumor microenvironment control. Increased CCR5 expression is an indicator of disease status in several cancers. Published studies have shown that blocking CCR5 can reduce tumor metastases in laboratory and animal models of aggressive breast and prostate cancer. Leronlimab reduced human breast cancer metastasis by more than 98% in a murine xenograft model. CytoDyn is, therefore, conducting aPhase 1b/2 human clinical trial in metastatic triple-negative breast cancer and was granted Fast Track designation in May 2019.

The CCR5 receptor appears to play a central role in modulating immune cell trafficking to sites of inflammation. It may be crucial in the development of acute graft-versus-host disease (GvHD) and other inflammatory conditions. Clinical studies by others further support the concept that blocking CCR5 using a chemical inhibitor can reduce the clinical impact of acute GvHD without significantly affecting the engraftment of transplanted bone marrow stem cells. CytoDyn is currently conducting a Phase 2 clinical study with leronlimab to support further the concept that the CCR5 receptor on engrafted cells is critical for the development of acute GvHD, blocking the CCR5 receptor from recognizing specific immune signaling molecules is a viable approach to mitigating acute GvHD. The FDA has granted orphan drug designation to leronlimab for the prevention of GvHD.

About CytoDynCytoDyn is a late-stage biotechnology company developing innovative treatments for multiple therapeutic indications based on leronlimab, a novel humanized monoclonal antibody targeting the CCR5 receptor. CCR5 appears to play a critical role in the ability of HIV to enter and infect healthy T-cells.The CCR5 receptor also appears to be implicated in tumor metastasis and immune-mediated illnesses, such as GvHD and NASH. CytoDyn has successfully completed a Phase 3 pivotal trial with leronlimab in combination with standard antiretroviral therapies in HIV-infected treatment-experienced patients. CytoDyn plans to seek FDA approval for leronlimab in combination therapy and plans to complete the filing of a Biologics License Application (BLA) in the first quarter of 2020 for that indication. CytoDyn is also conducting a Phase 3 investigative trial with leronlimab as a once-weekly monotherapy for HIV-infected patients. CytoDyn plans to initiate a registration-directed study of leronlimab monotherapy indication. If successful, it could support a label extension. Clinical results to date from multiple trials have shown that leronlimab can significantly reduce viral burden in people infected with HIV with no reported drug-related serious adverse events (SAEs). Moreover, a Phase 2b clinical trial demonstrated that leronlimab monotherapy can prevent viral escape in HIV-infected patients; some patients on leronlimab monotherapy have remained virally suppressed for more than five years. CytoDyn is also conducting a Phase 2 trial to evaluate leronlimab for the prevention of GvHD and a Phase 1b/2 clinical trial with leronlimab in metastatic triple-negative breast cancer. More information is atwww.cytodyn.com.

Forward-Looking StatementsThis press releasecontains certain forward-looking statements that involve risks, uncertainties and assumptions that are difficult to predict. Words and expressions reflecting optimism, satisfaction or disappointment with current prospects, as well as words such as believes, hopes, intends, estimates, expects, projects, plans, anticipates and variations thereof, or the use of future tense, identify forward-looking statements, but their absence does not mean that a statement is not forward-looking. The Companys forward-looking statements are not guarantees of performance, and actual results could vary materially from those contained in or expressed by such statements due to risks and uncertainties including: (i)the sufficiency of the Companys cash position, (ii)the Companys ability to raise additional capital to fund its operations, (iii) the Companys ability to meet its debt obligations, if any, (iv)the Companys ability to enter into partnership or licensing arrangements with third parties, (v)the Companys ability to identify patients to enroll in its clinical trials in a timely fashion, (vi)the Companys ability to achieve approval of a marketable product, (vii)the design, implementation and conduct of the Companys clinical trials, (viii)the results of the Companys clinical trials, including the possibility of unfavorable clinical trial results, (ix)the market for, and marketability of, any product that is approved, (x)the existence or development of vaccines, drugs, or other treatments that are viewed by medical professionals or patients as superior to the Companys products, (xi)regulatory initiatives, compliance with governmental regulations and the regulatory approval process, (xii)general economic and business conditions, (xiii)changes in foreign, political, and social conditions, and (xiv)various other matters, many of which are beyond the Companys control. The Company urges investors to consider specifically the various risk factors identified in its most recent Form10-K, and any risk factors or cautionary statements included in any subsequent Form10-Q or Form8-K, filed with the Securities and Exchange Commission. Except as required by law, the Company does not undertake any responsibility to update any forward-looking statements to take into account events or circumstances that occur after the date of this press release.

CYTODYN CONTACTSInvestors: Dave Gentry, CEORedChip CompaniesOffice: 1.800.RED.CHIP (733.2447)Cell: 407.491.4498dave@redchip.com

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Leronlimab Used in Seven Patients with Severe COVID-19 Demonstrated Promise with Two Intubated Patients in ICU, Removed from ICU and Extubated with...