Guest writer Gary Conkling started writing stories as a child and publishing them on his own hand-cranked printing press. Little did he know digital technology would make it possible to repeat the task asan adult by publishing his own blog, Life Notes. He is a journalist by trade who has worked in the trenches of public affairs at the federal, state, regional and local levels. But he also is an observer of life occurring around him. This piece is from his blog, found at https://garyconklinglifenotes.wordpress.com.

Science can be described as the continuous study of what we dont know but wished we did.

Thats why science is discomfiting for humans who believe they know all the answers. Scientists like answers, too, but mostly because they raise even more questions.

At its core, science thrives on exploration, from ancient civilizations digging ditches to redirect water and clambering into boats to see whats over the horizon, and in more recent times from dissecting cadavers to understand human anatomy to discovering the connection between sewage and pathogens.

Mankind has long stared into the sky to see whats out there and understand how it affects Earth. Sky explorers continue making discoveries such as black holes.

Despite their name, black holes are actually dense objects with intense gravitational fields that make it hard for objects and light to escape.

Astronomers believe, at least for now, that jumping into a black hole in space is a one-way trip. But no one knows for sure because we lack the means to reach a black hole since the closest one is 1,600 light years away.

Humans have intuitively understood the importance of the sun to life on Earth. What astronomers have learned is that our sun is a very old ball of energy that holds 99.8 percent of our solar systems mass.

Astronomers predict the sun will burn through its existing hydrogen supply and then expand, engulfing Mercury, Venus and eventually Earth on its journey to becoming a giant red star. Luckily, astronomers estimate the sun has enough hydrogen to keep burning for another 5 billion years.

The science of cells is even more jaw-dropping. Biologists believe cells are the fundamental unit of what we call life. This had led to the scientific fields of cellular and molecular biology.

These biologists now routinely uncover new knowledge about genetics, immunology and neurobiology by learning the relationships within cells of DNA, RNA and protein synthesis.

There are parallel scientific discoveries regarding atomic matter and its properties that govern space, time, energy and matter in the observable universe.

Scientists have uncovered the existence of what physicists call antimatter, which consists of antiparticles with the same mass as matter but with the opposite sign. What sounds like worthless knowledge is actually critical to medical tomography, better known as PET scans.

Quantum mechanics is perhaps the most disruptive discovery by physicists.

Albert Einsteins insight gave us the theory of relativity, but he was never able to combine it with a provable field theory. Einstein wanted to believe how our universe operates was predictable through direct observation.

Physicists have learned matter and light at atomic and subatomic levels have predictable patterns that can be harnessed in things such as integrated circuits, but also can be altered by random events. The course of Earth and its universe is not a foregone conclusion.

That was demonstrated when NASAs DART spacecraft successively slammed into an asteroid, redirecting it onto a new course. This was planned intervention.

At the quantum level, most intervention is unplanned and often unnoticed. Our best evidence of this randomness is human disease, which may affect some people but not others, even among family members.

Scientists examining a random meteorite made a surprising discovery. Even though the meteorite consisted of nickel and iron, common minerals on Earth, they had cooled a million years or so in space, congealing into something not found on Earth tetrataenite.

It turns out tetrataenite is ideal for high-end magnets used in electric vehicles and space shuttle turbines. And scientists have figured out how to replicate tetrataenite in laboratories, which holds the prospect of displacing rare earths that must be mined and processed.

Science may seem like it has reduced life to a soulless existence. Atoms, antimatter and black holes dont provide satisfying stories about life, survival or after-life. In fact, science challenges many religious beliefs, ancient myths and human historical accounts.

Challenging what some accept as truth doesnt need to shatter a belief in a greater power. Scientists have uncovered a great deal about how our universe works but not how it all got its start. The Big Bang Theory explains how the universe is behaving, not why the Big Bang occurred.

What we know is that scientists discover a lot of things that travel well in our everyday lives.

Space exploration best exemplifies the upside of science. In support of space travelers, NASA and various corporations have innovated devices now commonly used in terrestrial life, such as air purifiers, workout machines, flame-retardant clothing, camera phones, invisible braces, solar cells, better tires and baby food.

Scientists may be on to an even more novel, climate-friendly ideas, such as chicken meat without chickens, which the Food and Drug Administration has just given the nod to go forward to a market near you. Slaughter-free, lab-grown chicken meat, referred to as cultivated meat, originated with California cardiologist Dr. Uma Valeti, who was inspired by stem cells used to repair human hearts.

If you can grow heart cells, Valeti reasoned, you can grow chicken meat. Ten years later, he was proven right.

A taste-tester who tried his cultivated meat commented, It tastes like chicken. Valetis quick response, It is chicken.

Thats why chicken brands are salivating to get his laboratory recipe. And its why science can defy everyday logic and understanding.

Brian Greene, a professor of physics and mathematics, is renowned for his breakthrough discoveries in superstring theory, which is an attempt to model fundamental forces of nature as vibrating super-symmetrical strings. Its basically an effort to resolve the theory of relativity with the realities of quantum physics.

However, Greene ventures into a more problematic field the meaning of the universe.

In his latest book, Until the End of Time, Greene uses scientific knowledge to trace the origin of the universe and the human place within that universe. He writes in his preface: Although obscured by mist here and fog there, the panorama is becoming sufficiently clear that we cogitating creatures can glean more fully than ever before how we fit into the grand expanse of time.

Greene wrote that before he knew about chicken meat without chickens.

People with religious beliefs often view science as anti-religious, even as an attack on religion. The tension between scientific inquiry and religious zealotry is real. Scientists focus on questions while zealots settle for answers, sometimes based on dubious evidence or misconstrued history.

There is a path through the tension, though. Scientists dont have to dismiss a greater force and zealots have to rely on faith rather than crypto-facts.

We could someday figure out how the universe truly works, but still never know how it came to be. The desire and for many the desperate need to know there is something larger out there larger than life as we know it can yield an emotional calm and an enhanced ability to deal with very real and present distress.

It also would help if scientists and zealots played by the same rules.

Questions are not disbelief. Probabilities are safer to cling to than facts in assessing the universe. The scientific method and faith are not incompatible.

The branch of science we call archaeology has unearthed the remains of creatures long ago gone extinct and capable civilizations that vanished.

Contemporary religions rarely acknowledge their existence or their successes and failures. Their religions and gods are reduced to pagan rites, despite their reigns that lasted for centuries and may have grown out of the early struggles of post-evolutionary humans.

Their achievements in building grand temples and practical waterworks are overlooked behind the smudge of time covering their history-revealing wall paintings and rock carvings. Their migrations are just lost legends. But like space, we are learning little by little about our forebears on Earth.

It was just 75 years ago that scientists in a New Jersey lab invented the transistor, which created the foundation for what we now call the Digital Age and a fierce global competition to manufacture advanced semiconductors.

The US Department of Energy just announced a scientific breakthrough to mimic the sun by using nuclear fusion to create more energy than it consumed, raising the prospect of a limitless zero-carbon energy source to replace fossil fuels in the battle against climate change.

Science isnt perfect. Neither is our pantheon of perceptions about God.

Believing in something larger than our human selves is something scientists and people of faith have in common. If both were honest, they would admit they have more questions than answers and that faith can help people abide lifes travails.

Science isnt perfect. Religion isnt infallible.

Another point of mutual intersection between science and religion is history. Galileos proclamation that Earth circles the sun turned him into a religious pariah, but opened the window to a more accurate picture of our universe. Think how limited our world would be if we still clung to the belief Earth was flat?

In 1910, zoologist George Murray Levick went to Antarctica to study a penguin colony. Through photography, he observed male birds having sex with other male birds.

Fearing blowback, Levick omitted those observations and photographs from his official report, even though same-sex animal behavior and human behavior had been studied as far back as the 1700s.

Homosexual and bisexual animal behavior has since been chronicled and studied in more than 1,000 species, including mammals. Ironically, the prevalence of homosexual animal behavior conflicts with Darwinian evolutionary theory that stressed reproductive ability as critical to survival.

Today scientists still arent certain what leads to homosexuality. One thing is scientifically known, though: Homosexuality and bisexuality arent moral choices.

They could even be in some species a key to their evolutionary success. Do we have to wait a century or longer to recognize homosexuality can be as determined as human DNA? Couldnt scientists and religious believers agree we have more consequential things to worry about in our world?

Finally, science can inform us about history. Vaccination saves lives. People with black skin arent mentally inferior. Females can be as accomplished as men in operating rooms and sports fields. And yet cult-like groups make false claims about vaccines, women continue to be oppressed by patriarchies and Black people remain undervalued much of this in the name of quasi-religious doctrines.

Humans face massive challenges climate change, artificial intelligence and gene-editing technology. These challenges, among others, represent opportunities for scientists and moralists to cooperate and point to directions that are humane in the face of fundamental change.

We should be at the point where we can say scientists arent always right, and neither are religious leaders. We all have a lot to learn about the human condition. And we have a long way to go to improve the human condition for everyone, including suffering or impoverished people.

Surely that could be a mutual rallying point for scientists and religious leaders. All it would take is some humility that we may never know everything to know in our universe, and that a dose of genuine faith can do more good than harm.

More:
Conklin: Where science and religion intersect - News-Register

The bispecific antibody teclistamab-cqyv (Tecvayli) showed promising efficacy and safety in patients with relapsed/refractory multiple myeloma (MM) with a well-tolerated safety profile in data from the phase 1/2 MajesTEC-1 trial (NCT04557098). These results led to the October 2022 FDA approval of the B-cell maturation antigen (BCMA)-directed, CD3 T-cell engager, for adult patients with relapsed or refractory MM who have received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

The approval was based on 110 patients among whom the overall response rate was 61.8% (95% CI, 52.1%-70.9%) with a complete response rate of 28.2%. The estimated duration of response rate at 6 and 9 months was 90.6% (95% CI, 80.3%95.7%) and 66.5% (95% CI, 38.8%-83.9%), respectively.2

Teclistamab is a highly effective therapy for relapsed/refractory MM that rivals the efficacy of [chimeric antigen receptor] CAR T-cell therapy, but ultimately is a lot simpler to administer and will be more readily available than CAR T-cell therapies, Alfred L. Garfall, MD, said.

In an interview with OncologyLive, Garfall, director of autologous hematopoietic stem cell transplantation and an assistant professor of medicine at the Hospital of the University of Pennsylvania in Philadelphia, discussed the durability of responses teclistamab elicited and how it will change the treatment regimen for relapsed/refractory MM.

Despite all the progress with new MM therapies that have been developed over the past [couple of] decades, unfortunately most patients are expected to relapse. We need new therapies to address the needs of patients who are progressing despite all the best currently available therapies.

What is impressive about teclistamab is the high response rate as a single agent in patients who have become refractory to the most commonly available therapies for MM. In the patient population studied in a pivotal trial, approximately 65% of patients responded to teclistamab and those responses tended to be very durable [with a] median duration of response of approximately 18 months. That is quite impressive.

Among the therapies that we give on an ongoing basis for MM, there are some specific toxicities in the early week or two of teclistamab therapy. For patients who respond and handle those toxicities as most patients do, there is very little cumulative toxicity. Compared with the typical therapies that are being given to patients in this advanced setting, which often entail multiple agents being given continuously over a long period typically once [the patients] get through the initial couple of weeks, they have very good quality of life on teclistamab with very little cumulative toxicity.

Despite receiving it continuously in many cases for several years, patients usually continue to feel well with very little toxicity that affects quality of life. There are some toxicities to be aware of as patients are exposed to it over time; the main things are immune suppression and risk of infection. In my experience, this is such a breath of fresh air for patients who have been on myeloma therapy continuously for years with sophisticated agents that are much better than chemotherapy but still take their toll after [months] of continuous exposure.

We are used to conventional monoclonal antibody therapies for cancer having a single specificity for target on the surface of the cancer cell and binds to that target. A T-cellengaging bispecific antibody such as teclistamab has 1 arm binding to a cell surface target on the surface of the MM cell, in this case BCMA, but with the other arm it binds to a T cell, CD3. By having that dual specificity, the drug can bring together a myeloma cell and a T cell and force T-cell recognition of the myeloma cell, activating the T cell.

This is a mechanism that was first exploited with a drug called blinatumomab [Blincyto], which is an anti-CD19/CD3-bispecific T-cell engager approved for treatment of acute lymphoblastic leukemia. Teclistamab is the first bispecific antibody approved that exploits [this] mechanism of action but does so in the format of a full-length antibody. That means that it has a much longer half-life and so it can be given with intermittent dosing, as opposed to the requirement for continuous intravenous infusion, which is the case for the prior generation of bispecific T-cell engagers, such as blinatumomab.

With almost any MM therapy you are concerned about immunosuppressive effects, and...this drug does have some immunosuppressive effects. Almost all patients who were on it for [an extended time] develop low IgG, which is expected from the effect of the drug on normal plasma cells. Patients treated at our center have all received intravenous immunoglobulin if theyve been on the drug for long enough to develop low immunoglobulin levels.

It was also clear in MajesTEC-1 that there may be an increased risk of opportunistic infections. There was some pneumocystis pneumonia that was seen on the study and as a result we have started giving our patients pneumocystis prophylaxis. There was even a case of progressive multifocal leukoencephalopathy. These infections often occurred in patients who had been on the drug for a [long time] whose myeloma was under very good control, suggesting that there is an immune suppressive effect of teclistamab. Now, the benefit for these patients was clear in terms of their control over myeloma and many of these infections can be [potentially] prevented with measures such as pneumocystis prophylaxis.

Teclistamab is going to be a workhorse for us and patients with heavily relapsed/ refractory disease, in line with its FDA approval. [With] the availability to give it quickly and the excellent safety and efficacy profile, it will be the therapy of choice for many patients in those late lines of therapy. This will be easier for centers to use compared with the complexity of CAR T-cell therapies, even if [those] are a bit more potent.

There is also potential with teclistamab fixed-duration therapy, especially if it is used earlier [during] MM therapy. So far in the clinical trials, it has been given [via] continuous dosing, but we have all had patients who have had to stop it for one reason or another, often for infection. In those patients, at least my experience is that they seldom progress after it stopped even for many months. That raises the possibility that patients could receive fixed courses of this drug, especially earlier on in MM therapy and get the best of both worldsthe upside of its potent antimyeloma activity without the downside of infection risks that may come with long-term exposure.

See more here:
Teclistamab Demonstrates Exciting Efficacy in Relapsed or ... - OncLive

Michael J. Fallon, MD, radiation oncologist, University of Wisconsin Carbone Cancer Center, discusses supportive care considerations for patients with relapsed/refractory multiple myeloma.

The use of infection prophylaxis continues to evolve with the addition of new therapies, such as anti-BCMA CAR T-cell therapies and bispecific T-cell engagers, since these agents have different effects on the immune system that clinicians are still working to understand, Fallon says. Although the National Comprehensive Cancer Networkguidelines have started to integrate the use of infection prophylaxis with these agents; however, the current recommendations only fit specific conditions for a patient, and more clarity is needed to know when this intervention is appropriate, Fallon explains. In the past, supportive care considerations for patients who received an autologous stem cell transplant were well defined, and improvements to guidelines will be made for newer therapies, according to Fallon, who adds that, in general, patients have less infections with T-cell redirecting therapies compared with other treatments.

Immunizations continue to be a cost burden to patients. For example, patients within the Medicare population are only allowed 2 lifetime doses of a pneumococcal injection, and patients with relapsed/refractory multiple myeloma will likely need up to 4 injections, Fallon explains. For patients who are post transplant, they may require up to 6 injections, and oftentimes, these patients will need to pay out of pocket for these vaccines, Fallon says.

Additionally, tertiary centers will provide some of these injections; however, patients must also rely on the local community hospitals and clinics to provide the injections, Fallon explains. Coordinating these series of vaccines between different health-care systems can also present a challenge for patients with multiple myeloma, Fallon adds.

Bone health remains the most impactful adverse event (AE) for patients with relapsed/refractory multiple myeloma, as they can experience walking difficulties, pain, and numbness, Fallon says. These AEs can be detrimental to a patient's quality of life. It is important that clinicians remain vigilant with medications to maintain bone health medications and ensure fractures do not happen, Fallon concludes.

Go here to see the original:
Dr. Fallon on Supportive Care Considerations in R/R Multiple ... - OncLive

By Jim ThompsonHCP columnist

Elliott Winton came into my life unexpectedly around Valentines Day, 2000 when I was diagnosed with Non-Hodgkins Lymphoma. We usually have an appointment to see each other this time of year, and I just saw him again on Feb. 13.

He is in his early 80s, and I am 72. Back when we met, he was in his 50s in the prime of his career, and I was 49. Today, he works at Emorys Winship Cancer Center on Mondays and Grady Hospital (the Saint Elsewhere of Atlanta) on Tuesdays. He is not accepting new patients.

I have written about our travels together before, but I think it is appropriate to relate them again, if for no other reason than to encourage others who have had surprises since the last time I related this journey. Dr. Winton tells me I am in a select group only a few of his patients have stayed around so long, despite the great advances in cancer research in the last quarter century. Think how sad that must be for him.

This years reunion felt a bit different. It was as if one of us might not be around for our already appointed get-together next year, at 9 a.m. Feb. 12, 2024. Of course, we should all live each day as if it might be our last.

The winter of 2006-07 was our toughest together. The chemo was messing up my kidneys and Dr. Winton told me I was within hours of being put on dialysis.

Mr. Thompson, you have got to drink more water and pee, pee, pee! I remember him saying one night about 11 p.m. (I have no idea when he slept, he always seemed to be at the hospital).

But I followed his instructions. I thought I would drown. It probably also helped that three doctors, with a deer-in-the-headlights look, came to my room that night and told me they were my renal team and there to start my prep for dialysis by morning if nothing changed. Things changed. I am sure I never drank so much water in 12 hours before or since.

That was also the winter I decided I was not a statistic. In the middle of the night, I would be on my laptop, looking up data and information on Burkitts Lymphoma, the type I had that time. I had an epiphany when looking at the longevity charts. I realized that every dot on those curves represented people, and I decided I would be one of those people out on the end with longevity, not on the other end of that chart.

Laura was a trooper that winter, too. They would try to let me out of the hospital for a few days for each holiday, but I often would not be home more than a few hours before my temperature shot up, and I had to go back in. Despite my protests, Laura would not take no for an answer, and we would be headed back to Emory. From Thanksgiving to Easter, I spent every holiday in the hospital as well as a lot of time in between.

Then there was February of 2017. I knew I was sick again and made an appointment to see Dr. Winton and his sidekick, Jessica Neeley (I cant say enough good things about her, either. I am convinced she has no life outside the Winship Cancer Center).

Laura and I show up, and Dr. Winton does not like what he sees. He wants to do a PET-Scan right now. He starts calling all the CT-Scanner locations in the Emory system. He finds me an opening within an hour at their downtown location (it usually takes a week or two to get an appointment at any of these which speaks to the clout of Dr. Winton).

Laura and I go straight from Dr. Wintons office to the scanner. When I get off the scanner, the technician said, Dr. Winton called and wants you to wait here for a few minutes.

Unusual. In a few minutes, Dr. Winton calls.

Mr. Thompson, dont go home, come back here, we have a bed for you on E6 (the famous cancer floor at Emory hospital) and we are going to admit you right now.

Yes, sir. What else could I say?

That spring and summer, we prepped and I had an autologous stem cell transplant. It had its ups and downs, too, but Dr. Winton had to stand aside and turn me over the bone marrow transplant team. Yet, he and Jessica came to see me several times during that ordeal, even though they were not my official team at the time. They often came on Sunday afternoons when they got their own rounds done early.

Of course, readers of this column know me and know God is an important part of my life. Ive been given, so far, an extra 23 years. I wake up every morning asking the Lord what he wants me to do with these days. I didnt beat cancer. He did, and I need to follow His leading on what to do with all this extra time.

For those of you who read my previous columns on these experiences with a detached, "that is something that happens to others, but have now found it has happened to you" attitude, be encouraged. Your dot on the longevity curves may be at the same place mine has been. But I will be happy to talk to you, no matter where your dot on the curve winds up. See below for how to reach me.

Jim Thompson, formerly of Marshall, is a graduate of Hillsboro High School and the University of Cincinnati. He resides in Duluth, Ga. and is a columnist for The Highland County Press. He may be reached at [emailprotected]

Read more from the original source:
Happy Valentine's Day - The Highland County Press

Stretch the shelf-life of your grapes with these tips.

Larisa Davydova/Getty Images

No matter the variety, grapes make for a delicious snack, especially when theyre spread across a beautiful charcuterie board (theyre of course also delicious in liquid form, if you catch my drift). But grapes also happen to be a pricier produce item, and can spoil quite quickly if not stored properly. It can also be difficult to pick the perfect bunch of grapes since theyre so tightly clustered together.

Still, there are a few things to look out for when examining grapes at the grocery store. Its always important to make sure theyre firm, plump, and attached to the stem. If you pick up a bag with loose grapes rolling around at the bottom, thats a good indicator that they may be quicker to spoil. And while this may seem like common knowledge, you should also avoid grapes that are moldy, watery, and shriveled at the stem. However, if you see a whiteish coating on a bunch of grapes, thats totally fine. Its called bloom, which is a naturally occurring substance that protects grapes from moisture loss.

:13 Foods That (Basically) Never Spoil

Now that you know how to pick out a stellar bunch, keep reading for tips on how to store grapes so you can enjoy them for weeks at a time.

Have you ever walked into someones kitchen and noticed a big, beautiful bowl of grapes on the counter? While grapes may make for a convenient grab-and-go snack when stored this way, this is the quickest way for grapes to lose their moisture and crispness.

Instead, whole grapes should be washed, patted dry, and then stored in a well-ventilated container in the crisper drawer of your refrigerator. This will allow them to last for up to three weeks. Youll want to avoid putting them into an airtight container or plastic bag, since that prevents air circulation. You could also keep whole grapes in the bag they came in if you dont have a proper food storage container.

:How to Store Strawberries So They Won't Spoil Quickly

If you have leftover cut up grapes, theres no need to toss them just yet! Cut grapes can be stored in an airtight container in the refrigerator for up to 48 hours. If you notice the edges start to dry up and brown, thats finetheyre still safe to eat.

Use any leftover cut grapes as a yogurt or oatmeal topping, or as a bite-sized snack.

Yes, you can freeze grapes. And if youve never had frozen grapes, what are you waiting for?! They make for such a quick and delicious snack or dessertbasically like an all-natural, bite-sized freeze pop.

:Does Flour Go Bad? Here's When You Should Replace Your Baking Staples

To freeze, simply rinse and dry your grapes and spread them out on a lined baking sheet. Place them in the freezer for a few hours or overnight, and once theyre frozen, you can put them in a storage container so theyre easily accessible. Just make sure that your grapes arent clumped together on the baking sheet, otherwise they will freeze together (which I guess isnt the worst thing). If youre feeling especially fancy, you can roll your frozen grapes in coarse sugar to add some extra sweetness. Just make sure you enjoy them immediately!

For more Real Simple news, make sure to sign up for our newsletter!

Read the original article on Real Simple.

See original here:
How to Store Grapes So They Stay Firm and Fresh - AOL

William Haseltine

It is becoming increasingly clear that we have misunderstood SARS-CoV-2, the virus that causes COVID-19. Many people, including some experts in the scientific community, deemed the pandemic over with the release of the mRNA vaccines. The beliefor perhaps it was hope in disguisewas that with the development of the vaccines, we could go back to living our lives as usual, back to a semblance of pre-pandemic normalcy. This simply is not so, as evidenced by surging cases around the world and the continued onslaught of variant after variant.

Even the latest approach, trying to play catch-up with variants by updating our vaccines to match the dominant circulating strain, is a losing game; we will always be one step behind, forced to adapt to the cards we are dealt rather than dictating the playing field. This should come as no surprise. Across the globe, highly skilled influenza researchers have been battling for decades to develop long-lasting, broadly neutralizing flu shots. Although plenty of progress has been made, we still have yearly flu seasons, some of which are plagued by low vaccine efficacyin 2021/2022, the vaccine was only 36% effective at preventing influenza cases requiring medical attention.1

At this point, we seem to have accepted that we will be living with COVID-19 for the foreseeable future; such complacency is very dangerous. Living with the virus is no different from living with a pet lion; there is never any guarantee of safety. We know SARS-CoV-2 can change rapidly, we know it can become far more virulent, and we have no idea of the determinants of pathogenesis.

Our single-minded reliance on vaccines, at the expense of developing novel drug therapies, has left us fighting with one hand tied behind our back. Our current antivirals are anemic at best: they are either no longer effective, like most monoclonal antibodies, or they simply cannot prevent infection in the first place. If we ever hope to control COVID-19, we need to join the battle fully. This means a dramatic increase in resources to fund drug development efforts. The problem is not a lack of tools; it is a lack of political, scientific, and economic will. It is time to change that.

What follows is a summary of the shortcomings of our currently available antiviral drugs as well as a brief overview of some promising, up-and-coming contenders.

1. Monoclonal Antibodies (mAbs)

Monoclonal antibodies are antibodies designed to target a specific antigen or even a specific region of an antigen, usually the spike protein. Once the antibodies bind to the antigen, they either block it from being able to bind to our cells or mark it for destruction by other immune cells. As such, they work well in instances where they correctly match up to the antigen at handsuccessfully neutralizing the virus and inhibiting infectionbut suffer from the same major issues as vaccines: viral resistance and viral mutation.2 With repeat or extended exposure to a certain antibody, SARS-CoV-2 will eventually mutate to escape the immune system, rendering the antibody ineffective and even in the absence of resistance, run-of-the-mill viral mutation can have the same effect.

Monoclonal antibodies come with the additional drawback of needing to be administered intravenously or subcutaneously by a healthcare professional. None of the currently available options come in an oral format, as a pill. This means people with mild-to-moderate diseasenot bad enough to warrant hospitalizationoften do not receive treatment and, while sick, run the risk of infecting others. Practically speaking, monoclonal antibodies simply cannot be used prophylactically; they may help you once youre in the hospital, but they wont be able to stop you from ending up there in the first place.

2. Paxlovid

Paxlovid is a kinase inhibitor that interferes with the main protease (Mpro) of SARS-CoV-2; it is highly efficacious, safe, and is taken orally. Early clinical trial results confirmed its promise, indicating a near-90% reduction in the risk of COVID-19related hospitalizations and deaths.3 Even in a highly vaccinated population, the drug was able to reduce hospitalization or death by 44% in adults over 50 years of age.4 And unlike monoclonal antibodies, viral resistance and viral variation pose less of an issue for Paxlovid because the main protease is a highly conserved region of the SARS-CoV-2 genome. Whereas the spike protein can undergo large structural changes without too heavy of a sacrifice on viral fitness, this is simply not true of the main protease.5

So what are the drawbacks? First on the list is a phenomenon that has been termed Paxlovid rebound. This occurs when, following a full course of the medication and apparent clearance of the virus, symptoms suddenly return. Although this may happen even in the absence of antiviral treatmentsone preprint indicates that up to 10% of infections are followed by a rebound in symptoms and 12% by a rebound in viral levels it is more common in those treated with Paxlovid.6,7 The main limitation facing Paxlovid, however, is its inability to prevent infection.8 As such, it cannot be used in a pre- or post-exposure context, cannot avert onward transmission, and cannot contain the pandemic. It is a great start and points us in the right direction, but it is not the final solution.

3. Remdesivir

Remdesivir is a nucleoside analogue that works by inhibiting RNA-dependent RNA polymerasethe enzyme that builds up viral RNA chains during replication. Despite being a nucleotide analogue, it does not carry the mutagenic risk of molnupiravir; rather than being incorporated into the viral genome and then introducing errors, it works by being incorporated into the viral genome and then stalling the inclusion of any additional nucleosides.

Still, remdesivir suffers from other issues. First and foremost is the problem of low efficacy. Results from the World Health Organization (WHO) Solidarity Trial, a randomized trial that enlisted roughly 3,000 people, concluded that remdesivir has no significant effect on patients with COVID-19 who are already being ventilated.9 For hospitalized patients not requiring ventilation, remdesivir had only a small, nonsignificant effect on death or progression to ventilation.

Another major drawback of remdesivir is the fact it must be administered intravenously across the span of multiple days. As with monoclonal antibodies, this significantly limits its practicality for everyday use. It also means that it cannot be used in a prophylactic capacity.

4. Molnupiravir

Molnupiravir works by inserting errors into the viral genome.10 These errors are then copied during replication, and when enough of them accrue, viral proteins end up with too many mutations to properly function, incapacitating the virus. The main issue facing molnupiravir is low efficacy. It was initially touted to reduce the risk of hospitalization and death by up to 50%, but this number dropped down to 30% by the end of the full clinical trial.11,12 Since then, new data from the largest randomized trial of molnupiravir, which enlisted a total of 26,000 individuals, indicate that molnupiravir offers no reduction in the frequency of COVID-19associated hospitalizations or deaths in high-risk vaccinated adults.13 Whether you take molnupiravir or you take a placebo, your odds are the same.

The low efficacy is further problematized by a dubious safety profile. Owing to a shared intermediate required in both the synthesis of viral RNA as well as human DNAribonucleoside 5-diphosphatemolnupiravir may pose a mutagenic threat to humans: instead of introducing errors only to viral RNA, the drug may also lead to host DNA mutations.14 Long term, this could result in the growth of cancerous tumors and even birth defects, either through mutated sperm precursor cells or if given directly to pregnant women.

Molnupiravirs mechanism of action also carries the risk of spawning new viral variants. Recall that its entire modus operandi is, essentially, destruction via mutation. Certain scenarios, some as banal as a person forgetting to finish their full course of medication, may bring about all of the mutation with none of the destruction. The risk of such viral mutations following treatment with molnupiravir is especially acute in immunocompromised patients, where new variants can form as quickly as a day or two.15

New Drugs, Familiar Mechanisms

Many of the novel COVID-19 drugs making their way through the development and trial pipeline are based on the same broad strategies as the antivirals discussed above. They take advantage of the same viral weaknesses but try to improve on the limitations of their predecessors.

Take, for example, the kinase inhibitor Xocova. Developed by Japanese pharmaceutical company Shionogi, it works in the same way as Paxlovid, by inhibiting the main protease (Mpro) of SARS-CoV-2. Early efficacy data, albeit based on a very small sample size, indicates robust antiviral activity, with a rapid decrease in viral RNA titers compared with placebo.16 That said, time until relief of symptoms was similar between the two groups.

Another group of Japanese researchers developed and tested main protease inhibitors that include fluorine atoms to increase cell membrane permeability and binding affinity for the pocket of Mpro. The team also replaced the digestible amide bond with a surrogate structure to improve biostability. The modified compounds outperformed nirmatrelvir in mouse models.17

Then there is VV116, an oral remdesivir derivative.18 Like its parent compound, it works by inhibiting the RNA-dependent RNA polymerase. Unlike its parent compound, however, VV116 matches Paxlovid in efficacy, enabling clinical recovery from mild-to-moderate COVID-19 in the same amount of time.19 And crucially, where remdesivir must be delivered via injection or intravenous drip, VV116 can be taken orally, expanding its potential reach.

Despite small improvements, such up-and-coming antivirals represent a mostly lateral move. True, they expand our arsenal of treatments against COVID-19 and help decrease the risk of viral resistance, but ultimately they differ from our current antivirals in degree, not in kind. Like Paxlovid, molnupiravir, monoclonal antibodies, and remdesivir, none of them will work prophylacticallythey can only treat, not prevent.

Exploiting Vulnerabilities: Strategies for Prophylactic Drug Design

With an eye toward prevention, its clear we need to diversify our lines of attack against SARS-CoV-2. What follows is a broad overview of strategies that may yield more success in the pursuit of prophylactic antivirals.

COVID-19 begins when SARS-CoV-2 first encounters cells in the upper airway that express a suitable attachment site, the angiotensin converting enzyme 2 (ACE 2). But entry into the target cells requires much more than surface attachment; after the virus has attached itself to ACE2, it still needs to fuse with the host cell membrane in order to inject its genetic material into the cytoplasm, where replication can begin. To fuse with the host membrane, SARS-CoV-2 depends on certain human enzymesfurin, transmembrane serine proteases (TMPRSSs), and cathepsins (CTSs)to cleave its spike (S) protein. Inhibition of ACE2-binding or of membrane fusion blocks viral entry, short circuiting infection before it ever gets a foothold.

Binding and fusion are complex processes with many moving parts, rendering them sites of potential failure. Scientists have begun exposing these vulnerabilities and leveraging them to their advantage.

1. Potential therapies targeting the human ACE2 receptor of the viral spike protein

A massive survey of 2,900 FDA-approved drugs revealed that carvedilol, a beta blocker used to treat high blood pressure and heart failure, may also prove useful against SARS-CoV-2.20 To test its suitability, researchers exposed human lung cells (A549-ACE2) to carvedilol for two hours before infecting them with SARS-CoV-2. After two days of incubation, they checked the cells for the presence of SARS-CoV-2 spike protein, used as a marker of infection. At a half-maximal effective concentration of 4.1M, carvedilol successfully cleared infection. Further, assessment of two large COVID-19 databases indicated that carvedilol-use was associated with a 17% lower risk of a COVID-19 positive test result. Although the exact mechanism of action through which carvedilol inhibits SARS-CoV-2 entry into cells is unknown, the researchers suggest this may happen through disruption of spike proteinACE2 interactions.

Another candidate, aloperine, comes by way of a medicinal plant called Sophora alopecuroides L. Isolated from the seeds of the plant, aloperine and its various derivatives have previously been shown to impair viral entry of HIV-1 and influenza.21 A recent study indicates that aloperines antiviral activity extends to SARS-CoV-2, successfully inhibiting entry into host cells in vitro.22 Compound 5, one of many aloperine-derivatives, proved especially effective, capable of limiting viral entry not only against pseudotyped viruses with the D614G variant of the spike protein, but also against Delta and Omicron variants. Confocal microscopy suggests that compound 5 inhibits viral entry before fusion to the cell or endosomal membrane.

Then there are a variety of ACE2 decoys, which mimic the receptor protein and trick the virus into binding to them instead of binding the real thing.23 Once the SARS-CoV-2 spike protein binds to the decoy, it undergoes irreversible structural changes that prevent it from being able to bind to ACE2 down the line, effectively blocking viral entry. ACE2 decoys come with the added benefit of being broadly-neutralizing; whereas SARS-CoV-2 evolves to escape monoclonal antibodies, evolution selects for ACE2 affinity. Thus, viral resistance to ACE2 decoys would come at the expense of its ability to bind ACE2, impairing infectivity and overall viral fitness. ACE2 decoys remain effective against the Omicron family of SARS-CoV-2.

2. Therapies targeting viral membrane fusion

In addition to fusing with the cell membrane directly, SARS-CoV-2 can inject its genetic material into cells by being absorbed into the cell in a vesicle, a process known as endocytosis, and then fusing with the membrane of the endosome once inside the cell. Obatoclax, an experimental drug for the treatment of cancers, was found to deliver a double strike against SARS-CoV-2, blocking both direct membrane fusion as well as endocytosis; it blocks direct membrane fusion by reducing furin activity and it blocks endocytosis by reducing the activity of cathepsin L.24 In vitro, obatoclax retained its potency against the spike proteins of different variants, including Alpha, Beta, and Delta. The study was performed prior to the emergence of Omicron.

An additional approach to blocking cathepsin Lmediated entry of SARS-CoV-2 involves the use of the RNA-editing tool Genome-wide Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas13. With the help of CRISPR-Cas13, researchers knocked down cathepsin L messenger RNA (mRNA) in the lungs of mice, significantly reducing viral entry.25 To deliver the CRISPR-Cas13 specifically to the lungsleaving cathepsin L untouched in the spleen and the liverthey engineered lung-selective lipid nanoparticles (LNPs). Both prophylactic and therapeutic administration of the lung-specific CRISPR-Cas13dbased therapy effectively inhibits lethal SARS-CoV-2 infection in mice. Significantly, this approach inhibited infection not only against wild-type SARS-CoV-2 and against the Delta variant, but also against SARS-CoV-1, the cause of the 2003 SARS outbreak.

Cathepsin L is one of the two main proteases that SARS-CoV-2 depends on for viral entry into host cells. The other, as mentioned above, is TMPRSS2. A group of German scientists tested nafamostat mesylate, a kinase inhibitor that targets TMPRSS2 and is approved for treatment of pancreatitis in Japan, for its ability to block SARS-CoV-2 infection. Indeed, the compound strongly suppressed viral entry in vitro.26 A separate study, using kinase inhibitors to simultaneously block TMPRSS2 and cathepsin B, yielded similar results, with a reduction of viral load to 0.036% in ACE2-expressing human induced pluripotent stem cells.27 These results held up against multiple variants.

As much as we would like to pretend otherwise, the COVID-19 pandemic does not end where vaccines begin. At least not the current vaccines. XBB.1.5 is just the latest reminder that, as long as SARS-CoV-2 continues to spread and mutate we will continue to see waves of infection.

This is not to say that vaccines do not have their place in the fight against COVID-19, they clearly do, but rather that they are not the panacea that many hoped and that some claimed they would be. Vaccination is one protective strategy, but we cannot put all of our eggs in a single basket. And if we do, we should not be surprised when they end up cracking. Vaccines protect against the worst of COVID-19, but they do so only for a limited duration and against a limited number of variants. This wont change anytime soon.

What can we do to help improve our odds against SARS-CoV-2? We need to actively expand our arsenal of anti-COVID-19 drugs. In particular, it should have dawned on us that we need to develop combinatorial drug therapies that can be used prophylactically, to prevent infection and stop onward transmission. We still do not have a vaccine for human immunodeficiency virus (HIV), for example, but new infections and deaths continue to decline.28 We owe this largely to antiretroviral therapy (ART) and pre-exposure prophylactic (PrEP) medication. Antiretrovirals help those who are HIV positive suppress viral loads to undetectable levels. Undetectable = untransmittable, meaning they cannot pass the virus on to others.29 Similarly, pre-exposure prophylactic (PrEP) medication helps protect those at high-risk of exposure to HIV. As long as it is taken as prescribed, it prevents the virus from taking hold in the body.

If we hope to ever contain SARS-CoV-2, we need to pursue a similar strategy. My recommendation is the following: in the United States, a warp-speed-like project between government, industry, and academia and a minimum of five billion, or up to ten billion, additional dollars per year to fund such collaborations.30 A similar commitment to public health and drug development must be echoed by others, especially the European Union and China. We also need to make sure we have global clinical trial capabilities in place, so that wherever outbreaks occur, we are prepared to test novel drugs on the spot. It is time to fight the battle with both hands, not just one.

References

William R. Haseltine, PhD, is chair and president of the think tank ACCESS Health International, a former Harvard Medical School and School of Public Health professor and founder of the universitys cancer and HIV/AIDS research departments. He is also the founder of more than a dozen biotechnology companies, including Human Genome Sciences.

Read more here:
Can We Still Contain, and Possibly Eliminate, COVID-19? Yes, and ... - Inside Precision Medicine

What is positron emission tomography (PET)?

Positron emission tomography (PET) is a type of nuclear medicine procedure that measures metabolic activity of the cells of body tissues. PET is actually a combination of nuclear medicine and biochemical analysis. Used mostly in patients with brain or heart conditions and cancer, PET helps to visualize the biochemical changes taking place in the body, such as the metabolism (the process by which cells change food into energy after food is digested and absorbed into the blood) of the heart muscle.

PET differs from other nuclear medicine examinations in that PET detects metabolism within body tissues, whereas other types of nuclear medicine examinations detect the amount of a radioactive substance collected in body tissue in a certain location to examine the tissue's function.

Since PET is a type of nuclear medicine procedure, this means that a tiny amount of a radioactive substance, called a radiopharmaceutical (radionuclide or radioactive tracer), is used during the procedure to assist in the examination of the tissue under study. Specifically, PET studies evaluate the metabolism of a particular organ or tissue, so that information about the physiology (functionality) and anatomy (structure) of the organ or tissue is evaluated, as well as its biochemical properties. Thus, PET may detect biochemical changes in an organ or tissue that can identify the onset of a disease process before anatomical changes related to the disease can be seen with other imaging processes such as computed tomography (CT) or magnetic resonance imaging (MRI).

PET is most often used by oncologists (doctors specializing in cancer treatment), neurologists and neurosurgeons (doctors specializing in treatment and surgery of the brain and nervous system), and cardiologists (doctors specializing in the treatment of the heart). However, as advances in PET technologies continue, this procedure is beginning to be used more widely in other areas.

PET may also be used in conjunction with other diagnostic tests, such as computed tomography (CT) or magnetic resonance imaging (MRI) to provide more definitive information about malignant (cancerous) tumors and other lesions. Newer technology combines PET and CT into one scanner, known as PET/CT. PET/CT shows particular promise in the diagnosis and treatment of lung cancer, evaluating epilepsy, Alzheimer's disease and coronary artery disease.

Originally, PET procedures were performed in dedicated PET centers, because the equipment to make the radiopharmaceuticals, including a cyclotron and a radiochemistry lab, had to be available, in addition to the PET scanner. Now, the radiopharmaceuticals are produced in many areas and are sent to PET centers, so that only the scanner is required to perform a PET scan.

Further increasing the availability of PET imaging is a technology called gamma camera systems (devices used to scan patients who have been injected with small amounts of radionuclides and currently in use with other nuclear medicine procedures). These systems have been adapted for use in PET scan procedures. The gamma camera system can complete a scan more quickly, and at less cost, than a traditional PET scan.

PET works by using a scanning device (a machine with a large hole at its center) to detect photons (subatomic particles) emitted by a radionuclide in the organ or tissue being examined.

The radionuclides used in PET scans are made by attaching a radioactive atom to chemical substances that are used naturally by the particular organ or tissue during its metabolic process. For example, in PET scans of the brain, a radioactive atom is applied to glucose (blood sugar) to create a radionuclide called fluorodeoxyglucose (FDG), because the brain uses glucose for its metabolism. FDG is widely used in PET scanning.

Other substances may be used for PET scanning, depending on the purpose of the scan. If blood flow and perfusion of an organ or tissue is of interest, the radionuclide may be a type of radioactive oxygen, carbon, nitrogen, or gallium.

The radionuclide is administered into a vein through an intravenous (IV) line. Next, the PET scanner slowly moves over the part of the body being examined. Positrons are emitted by the breakdown of the radionuclide. Gamma rays called annihilation photons are created when positrons collide with electrons near the decay event. The scanner then detects the annihilation photons, which arrive at the detectors in coincidence at 180 degrees apart from one another. A computer analyzes those gamma rays and uses the information to create an image map of the organ or tissue being studied. The amount of the radionuclide collected in the tissue affects how brightly the tissue appears on the image, and indicates the level of organ or tissue function.

In general, PET scans may be used to evaluate organs and/or tissues for the presence of disease or other conditions. PET may also be used to evaluate the function of organs, such as the heart or brain. The most common use of PET is in the detection of cancer and the evaluation of cancer treatment.

More specific reasons for PET scans include, but are not limited to, the following:

To diagnose dementias (conditions that involve deterioration of mental function), such as Alzheimer's disease, as well as other neurological conditions such as:

Parkinson's disease. A progressive disease of the nervous system in which a fine tremor, muscle weakness, and a peculiar type of gait are seen.

Huntington's disease. A hereditary disease of the nervous system which causes increasing dementia, bizarre involuntary movements, and abnormal posture.

Epilepsy. A brain disorder involving recurrent seizures.

Cerebrovascular accident (stroke)

To locate the specific surgical site prior to surgical procedures of the brain

To evaluate the brain after trauma to detect hematoma (blood clot), bleeding, and/or perfusion (blood and oxygen flow) of the brain tissue

To detect the spread of cancer to other parts of the body from the original cancer site

To evaluate the effectiveness of cancer treatment

To evaluate the perfusion (blood flow) to the myocardium (heart muscle) as an aid in determining the usefulness of a therapeutic procedure to improve blood flow to the myocardium

To further identify lung lesions or masses detected on chest X-ray and/or chest CT

To assist in the management and treatment of lung cancer by staging lesions and following the progress of lesions after treatment

To detect recurrence of tumors earlier than with other diagnostic modalities

Read the original here:
Positron Emission Tomography (PET) | Johns Hopkins Medicine

Pet Finders Pet Adoption, Best pet classifieds site, Buy sell Pet

For a better experience please change your browser to CHROME, FIREFOX, OPERA or Internet Explorer.

Animal & Pet Search Engine

Search Keyword

Select Category Select Category

Location Select Location United States Aberdeen Alabama Anacortes Anniston Arizona Arkansas Asbury Park Auburn Augusta Avondale Bainbridge Bainbridge Belen Bellevue Bellingham Binghamton Bisbee Blairsville Bloomfield Boca Raton Bremerton California Carmel Carrollton Casa Grande Chickasaw Claremont Clovis Carmel Connecticut Durham Florida Hollywood Manchester Miami New Jersey New Mexico New York North Carolina Tucumcari Washington

Dozens of new postings are added every day. Let's find our new pet friend

We are loving pets...

The best way to save a beloved pet is to keep them out of the shelter system. Rehoming a dog or cat is a better kind of pet adoption, in every way.

Pet Blog

The care conditions of the pet dogs gain a healthier structure day by day. Accordingly, the life span of the dogs has also been extended. Ho...

One of the most important problems experienced by dog owners, especially in the summer, emerges as the problem of biting and flitting. Bec...

Please enter your phone number and we will call you back soon

We will call you back soon

Please enter valid phone number

Read more:
Pet Finders Pet Adoption, Best pet classifieds site, Buy sell Pet

pet, any animal kept by human beings as a source of companionship and pleasure.

While a pet is generally kept for the pleasure that it can give to its owner, often, especially with horses, dogs, and cats, as well as with some other domesticated animals, this pleasure appears to be mutual. Thus, pet keeping can be described as a symbiotic relationship, one that benefits both animals and human beings. As the keeping of pets has been practiced from prehistoric times to the present and as pets are found in nearly every culture and society, pet keeping apparently satisfies a deep, universal human need.

The history of pets is intertwined with the process of animal domestication, and it is likely that the dog, as the first domesticated species, was also the first pet. Perhaps the initial steps toward domestication were taken largely through the widespread human practice of making pets of captured young wild animals. Eventually, a working relationship developed between the dogs and their human captors. The dog was swifter, had stronger jaws, and was better at tracking prey; therefore, it could be of great use in hunting and guarding duties. From human beings, on the other hand, the dogs were assured of a constant supply of food as well as warmth from the fire. There is indirect evidence that the dog may have been domesticated and kept as a pet since Paleolithic times, as can be surmised from the paintings and carvings that archaeologists have found in ancient campsites and tombs. In Mesopotamia, dogs that look remarkably like the present-day mastiff were shown participating in a lion hunt. Domestic pets were often depicted in the scenes of family life in ancient Egypt; hunting dogs of the greyhound or saluki type accompany their master to the chase, and lap dogs frequently sit under the chair of their master or mistress.

Next to the dog, horses and cats are the animals most intimately associated with human beings. Surprisingly, both these animal groups were domesticated rather late in human history. There is no evidence that horses were domesticated in Paleolithic or Mesolithic times, but by about 2000 bce horses used in chariot battles were an established phenomenon throughout the Middle East. It seems that riding astride horses was a practice developed a few centuries later (see horsemanship). The cat too does not seem to have been domesticated as a pet until the New Kingdom period (about the 16th century bce) in Egypt. This is all the more strange as the ancient Egyptians had tamed many types of animals, such as lions, hyenas, monkeys, the Nile goose, and dogs, since the Old Kingdom period. But once cats were finally domesticated, their popularity was enormous. Gradually, the cat became one of the most universally worshiped animals.

As has been noted, the primary bond distinguishing a pet-and-owner relationship is affection. As useful as many of these animals are, what differentiates a pet from other economically useful livestock is the degree of contact between the animals and human beings. Often, this relationship has been unabashedly sentimentalized in myth, art, and literature. The affection between Alexander the Great and his favourite horse, Bucephalus, has become legendary, while in the modern age the popularity of such canine motion-picture stars as Rin Tin Tin and Lassie is further evidence of the importance placed on the relationship between owner and pet.

The pet-and-owner relationship, however, is not only founded on companionship; since the earliest period of domestication, pets have fulfilled practical, economic ends. Catching other animals to feed their human masters is one of the most fundamental uses of pets, and not only dogs have served in this capacity but cats, hyenas, and lions have also been used for hunting. The aristocratic, rather arcane sport of falconry made use of the natural talent of hawks to aid in hunting game birds. Pets have also been used for the purpose of guardingeither other livestock, the home or territory of their owners, or the owners themselves. Any pet that has a sharp sense of smell or hearing and that makes a loud noise when aroused can be used as a guard, although dogs are the best-known examples. It is thought that the Nile goose, a favourite household pet of the ancient Egyptians, may have served such a purpose. The herding and guarding of livestock is another practical use of pets, in particular the dog. Over the centuries, many specialized breeds of dog have been developed to suit this purpose.

Often, pets have been used as a source of food when other sources become scarce. This has been the case with dogs throughout their history of domestication in both the Old World and the New World. Guinea pigs, domesticated as pets in the New World, also assured a stable food supply.

Pets have also been used to eliminate animal pests. The rat-catching ability of cats is celebrated in fairy tales such as Puss n Boots and Dick Whittington, as is the snake-catching talent of the mongoose in Rudyard Kiplings Rikki-tikki-tavi.

Finally, pets themselves have become a self-perpetuating industry, bred for a variety of purposes, including their value as breeding animals. Pets that are bred for aesthetic purposes may have full-fledged show careers. Other pets may be bred for racing or other competitive sports, around which sizable industries have been built.

Animals kept as pets can be classified according to the type of premises or habitat they usually occupy. Dogs, cats, and birds such as canaries and parakeets are kept as household pets. Other birds, such as jays, magpies, and members of the crow family, are kept in aviaries. When kept as pets, reptiles and amphibians frequently require special conditions of heat and moisture. For this reason, they are best kept in glassed enclosures called vivaria. The most common vivarium pets are snakes, lizards, turtles, frogs, and toads. Many people keep fish as aquarium pets. Fishes constitute a completely separate section of the pet world, and an international industry exists for catching, breeding, transporting, and supplying stock. Hutch, or cage, pets can be kept indoors or outdoors under protected conditions. These pets include rabbits, guinea pigs, rats, mice, hamsters, gerbils, and, recently, chinchillas. Paddock pets are those that must be stabled outdoors and include such animals as horses, ponies, donkeys, and mules. Several kinds of insects are also kept as pets. These include walking-stick insects (kept in simple containers at room temperature) and ants (kept in artificial nests).

Of increasing concern is the sale of exotic pets (e.g., jaguars, alligators, ocelots, monkeys, apes, kinkajous, etc.). Rarely are the owners of such pets able to provide the basic nutritional or habitat needs of these animals; most of the animals soon die or are sent to a zoo. Furthermore, in order to obtain the young, which are considered most desirable as pets, many adults of the wild species are killed, seriously depleting populations already endangered. Several countries have passed laws to prohibit the importation of endangered species as pets, but an active black market flourishes.

Original post:
Pet | Definition, Types, History, & Facts | Britannica

2016 psychological thriller film directed by Carles Torrens

Pet is a 2016 psychological thriller film directed by Carles Torrens, written by Jeremy Slater, and starring Dominic Monaghan, Ksenia Solo, Jennette McCurdy, and Nathan Parsons.[4][5][6] The film premiered at South by Southwest on March 11, 2016 [7][8] and was released to theaters on December 2, 2016 by Orion Pictures and Samuel Goldwyn Films.

Seth is a severely introverted man who works at an animal control center. He has developed an obsession with Holly, a waitress and former high school classmate of his, after he saw her writing in her journal on the bus. Seth seeks advice from security guard Nate, who tells him to be confident and approach her. Seth extensively researches Holly's online profiles and tries to ask her out, but she rebuffs him. At home, Holly tells her friend Claire about Seth, and takes a drunken phone call from her ex-boyfriend Eric.

Holly receives a bouquet at work the next day, and, assuming they are from Eric, goes to the bar where he works. Seth, who has been following her, confronts her, leading to a physical confrontation when he refuses to accept her rejection. Eric attacks Seth, but Seth is able to steal Holly's journal, which he spends the next several days reading. At work, Seth discovers a trapdoor to a room in an abandoned wing of the animal shelter, where he sets about constructing a steel cage. He follows Holly home, breaks into her apartment, and kidnaps her.

After awakening in the cage, Holly vows to survive, speaking to an image of Claire. Seth informs Holly that he loves her and has imprisoned her to "save" her. Through reading Holly's journal, Seth has learned that Eric slept with Claire, which Holly confronted the latter about during a car ride. In her anger, Holly continued accelerating the car until they were hit by a truck. Although injured, Claire had survived, but Holly fatally stabbed her with a glass shard; Claire's death was attributed to the crash. Since then, Holly has committed a series of gruesome murders and written about them in her journal, leading to Seth finding a "purpose" in life by preventing Holly from hurting anyone else.

Over the next several days, they engage in psychological mind games against each other as Holly begins to slip details to draw Seth in. Seth maintains that Holly committed the other murders out of guilt for not being caught over Claire, but Holly counters that she kills simply for pleasure. A suspicious Nate follows Seth and discovers Holly. She deliberately distracts Nate so that Seth has time to overpower him. At Holly's urging, he smashes Nate's skull with a cinder block, then follows her instructions to dispose of the body.

The police become suspicious of Seth's role in Nate's disappearance. Holly convinces him that he can save her if he proves his love to her by cutting off his finger. He does, but this leads to Holly grabbing his knife and threatening to kill herself if he doesn't release her. She says she finally believes that he loves her before slitting his throat.

Some time later, Holly is back together with Eric, and the "fictional" events from her journal are being published by a vanity press. Holly finds evidence that Eric has been cheating again, but declines to hurt him. Instead, she travels to a warehouse, where it is revealed that Seth is being kept in a cage, still alive but horribly mutilated and tortured; she thanks him for "saving" her by allowing her to take out all of her murderous impulses on him instead.

It was announced in August 2015 that filming had begun with actors Dominic Monaghan, Ksenia Solo, Jennette McCurdy, and Nathan Parsons.[4][5][6]

The film premiered at the March 2016 South by Southwest Film festival.[7][8][9]

Pet was released to nine theatres on December 2, 2016 with total gross of $8,004.[10][11] It was set for a June 16, 2017 theatrical opening in Spain.[12]

Reviews for Pet have been mixed, with critics alternatively praising the subversive themes and strong leading performances, or lamenting the implausible twists. The review aggregator website Rotten Tomatoes reported that 56% of critics have given the film a positive review based on 18 reviews, with an average rating of 5.16/10.[13] On Metacritic, the film has a weighted average score of 48 out of 100 based on 8 critics, indicating "mixed or average reviews".[14] Reviews that have criticized the twists include Screen Anarchy, which wrote "Without spoiling anything more, the twists push past the merely unlikely into a strange minefield of 'what in the world?'",[15] and RogerEbert.com, which noted "The rank, idiotic implausibilities continue to mount..."[16]

The Hollywood Reporter gave the bottom line of "This graphically violent horror thriller features too many plot twists for its own good", but the review has also words of praise for the direction and cast: "Still, the film is engrossing, thanks to the directors skill at delivering sustained tension, and the excellent performances."[17]

An entirely positive review came from The A.V. Club's Alex McCown, who stated: "Part of the wicked fun of Pet, a dark little exercise in sadism and black humor, is how it upends the traditional conventions of the 'wronged woman turns the tables on her abuser' narrative. (...) The films zigs where you expect a depraved zag, resulting in a smart and unsettling tale."[18]

Another overall positive review has been given by Katie Walsh of Los Angeles Times, who wrote: "The constant power flipping allows for some interesting explorations of both the misogyny and misandry demonstrated by the main characters, and the way they justify their actions through the philosophical lens of love and sacrifice. 'Pet' is a modern-day fable of unchecked desire that descends quickly into a bloody, morbid cautionary tale."[19]

Francisco Marinero of El Mundo rated Pet 2 out 5 stars, writing that the film, which as usual in American independent pictures stars a "nondescript guy sadly alone in domestic routines", "is conceived as a function of the bombshells in its writing and characters", favouring gruesomeness over suspense.[20]

Link:
Pet (film) - Wikipedia