HGH Injections For Sale

Clinicians don't cease diagnosing patients once our clinical work is done. Most of us can recall debating whether to point out an atypical mole or another concerning finding to a stranger in public.

Like the doctor back in 2018, who saw a lump on the neck of a woman on TV and reached out via a video on Facebook, which found its way to her. She was eventually diagnosed with thyroid cancer.

Patients even recognize their own experiences and help lead others to clinical care.

And our diagnostic abilities can sometimes prove entertaining when interpreting plotlines in all sorts of storytelling, with endocrinology often making appearances in literature and film.

For instance, much debate has ensued about what Tiny Tim probably suffered from in Dickens's A Christmas Carol; a combination of tuberculosis and rickets makes the most sense to me, as detailed in a report in JAMA.

Malcolm Gladwell pointed out that Goliath in the biblical story probably got his stature and his inability to miss a shepherd boy's slingshot from a pituitary tumor. And the plot of Steel Magnolias revolves around type 1 diabetes.

Most recently, I began to see endocrinology everywhere in probably the most successful series of stories of recent times: the Harry Potter chronicles.

If, like me, you have a Potter-obsessed household, you might have watched the Return to Hogwarts special on HBO earlier this year. One of the observations that piqued my attention was when Emma Watson and Daniel Radcliffe joked about the hormones running rampant as the characters and actors who played them navigated adolescence, growing from children to teens as they made successive movies.

Popular culture has picked up on the comedy of these sometimes awkward pubertal transitions, repeatedly skewered by Saturday Night Live. However, this line made me ponder other less-famous hormones that could explain some of the fantastical findings of the wizarding world.

Hormones invisible chemical messenger are truly magical. They are most famous for sexual development but also empower growth, bone strength, fluid homeostasis, weight, carbohydrate metabolism, salt balance, blood pressure regulation, and any other function you can imagine; indeed, thyroid hormone is crucial for almost every system of the body.

Perhaps, the notable transformation of the main characters through puberty isn't the only hormonal influence we should credit. (This article may contain spoilers: My husband didn't read the Harry Potter series until we read it to our second grader so sadly learned at the age of 37 about the tragedy that befell Dumbledore.)

Just for fun, here are some other hormonal diagnoses that could explain some of the dark arts represented in the series.

Could Hagrid the giant have acromegaly? Clinical signs include enlarged hands and feet as well as excess growth of the ears and nose. A good way to check for these changes is to compare old photographs with the present condition. The actor who plays Hagrid, Robbie Coltrane, looks very different from the character after his transformation. Someone check his IGF-1 the hormone that manages the effects of growth hormone!

Neville Longbottom, the series' late bloomer, is the poster child for teens with constitutional delay of growth and puberty. This often frustrating but benign condition that plagues the "slow developer" tends to run in families and causes those who have it consternation as they wait to grow while their peers surpass them in stature and other ways; it also leads for them to be underestimated, as we witness with Neville in the Harry Potter series.

Voldemort: Depicted without a nose, if He-Who-Must-Not-Be-Named had congenital central abnormalities, he should be screened for central pituitary hormone deficits because the pituitary gland shares common embryology with other midline structures. (His evil has nothing to do with his possible underlying endocrinopathies.)

The Weasley family: if any of these redheaded wizards presented with adrenal insufficiency and rapidly progressive obesity, a POMC (proopiomelanocortin) mutation should be considered.

Nearly Headless Nick's near-decapitation might have affected his thyroid or parathyroid glands Hogwarts physician Madame Pomfrey should pay special attention to his thyroid stimulating hormone and calcium levels, at least if she is willing to take advantage of Muggle remedies.

Moaning Myrtle, who was killed by the Basilisk in the girls' lavatory, continues with tantrums and moans as she haunts the same bathroom at Hogwarts. Could it be that Myrtle's groans and psychiatric overtones were a sign of hypercalcemia, and she was using the facilities as she tried to pass a kidney stone? At the very least causes of polyuria should be investigated, including diabetes insipidus and diabetes mellitus. A unifying diagnosis of never being able to leave the bathroom and vision changes requiring serious glasses like hers would be untreated septo-optic dysplasia or other causes of pituitary malformation or disruption.

And though Dolores Umbridge doesn't have an obvious endocrine disorder, she seems like the kind of person who would visit an endocrine office after doing loads of "her own research" and arrive with a list of labs she demands.

Severus Snape provides a good opportunity to point out someone with excessively greasy skin and abnormal sweating (hyperhidrosis) as an adult, symptoms that perhaps would be best managed by our colleagues in dermatology.

The Dementors: These demons clearly work for insurance companies, tormenting the young wizards with denials and prior authorization requests.

Enzyme names sound a lot like spell incantations. Iodothyronine deiodinase? HMG CoA reductase? Future authors looking for new spells need look no further than their closest endocrine textbook.

Please note, I consider all my patients to be miraculous and worthy of admiration these comparisons are all in good fun and in no way diminish the weight of these conditions.

As Rubeus Hagrid himself said, "I am what I am, an' I'm not ashamed. 'Never be ashamed,' my ol' dad used ter say, 'there's some who'll hold it against you, but they're not worth botherin' with.'"

Like magic, endocrinology can't be seen with the naked eye, but it's everywhere we look, if only we choose to look.

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Harry Potter's World Similar to the Magic of Endocrinology - Medscape

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This weeks top articles:

FDA authorizes Moderna, Pfizer-BioNTech COVID-19 vaccines for children down to 6 months of age

The FDA today announces the EUA of both Moderna and Pfizer-BioNTech COVID-19 vaccines for use in children aged 6 months and older.

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Must-read news from the week of June 13 - Contemporary Pediatrics

Scientists demonstrate that they can control the properties of lab-grown plant material, which could enable the production of wood products with little waste.

Because of deforestation, the world loses about 10 million hectares of forest an area about the size of Iceland each year. At that rate, some researchers predict the worlds forests could disappear in 100 to 200 years.

A hectare is an area equal to a square with 100-meter sides, or 10,000 m2, and is primarily used in the measurement of land. One hectare contains about 2.47 acres and an acre is about 0.405 hectares. 100 hectares makes one square kilometer.

In an effort to provide an environmentally friendly and low-waste alternative, researchers at MIT have pioneered a tunable technique to generate wood-like plant material in a lab, which could enable someone to grow a wooden product like a table without needing to cut down trees, process lumber, etc.

These researchers have now demonstrated that, by adjusting certain chemicals used during the growth process, they can precisely control the physical and mechanical properties of the resulting plant material, such as its stiffness and density.

They also show that, using 3D bioprinting techniques, they can grow plant material in shapes, sizes, and forms that are not found in nature and that cant be easily produced using traditional agricultural methods.

In an effort to provide an environmentally friendly and low-waste alternative, researchers at MIT have pioneered a tunable technique to generate wood-like plant material in a lab. Credit: Courtesy of the researchers

The idea is that you can grow these plant materials in exactly the shape that you need, so you dont need to do any subtractive manufacturing after the fact, which reduces the amount of energy and waste. There is a lot of potential to expand this and grow three-dimensional structures, says lead author Ashley Beckwith, a recent PhD graduate.

Though still in its early days, this research demonstrates that lab-grown plant materials can be tuned to have specific characteristics, which could someday enable researchers to grow wood products with the exact features needed for a particular application, like high strength to support the walls of a house or certain thermal properties to more efficiently heat a room, explains senior author Luis Fernando Velsquez-Garca, a principal scientist in MITs Microsystems Technology Laboratories.

Joining Beckwith and Velsquez-Garca on the paper is Jeffrey Borenstein, a biomedical engineer and group leader at the Charles Stark Draper Laboratory. The research is published recently in the journal Materials Today.

To begin the process of growing plant material in the lab, the researchers first isolate cells from the leaves of young Zinnia elegans plants. The cells are cultured in liquid medium for two days, then transferred to a gel-based medium, which contains nutrients and two different hormones.

Adjusting the hormone levels at this stage in the process enables researchers to tune the physical and mechanical properties of the plant cells that grow in that nutrient-rich broth.

In the human body, you have hormones that determine how your cells develop and how certain traits emerge. In the same way, by changing the hormone concentrations in the nutrient broth, the plant cells respond differently. Just by manipulating these tiny chemical quantities, we can elicit pretty dramatic changes in terms of the physical outcomes, Beckwith says.

In a way, these growing plant cells behave almost like stem cells researchers can give them cues to tell them what to become, Velsquez-Garca adds.

They use a 3D printer to extrude the cell culture gel solution into a specific structure in a petri dish, and let it incubate in the dark for three months. Even with this incubation period, the researchers process is about two orders of magnitude faster than the time it takes for a tree to grow to maturity, Velsquez-Garca says.

Following incubation, the resulting cell-based material is dehydrated, and then the researchers evaluate its properties.

They found that lower hormone levels yielded plant materials with more rounded, open cells that have lower density, while higher hormone levels led to the growth of plant materials with smaller, denser cell structures. Higher hormone levels also yielded plant material that was stiffer; the researchers were able to grow plant material with a storage modulus (stiffness) similar to that of some natural woods.

Another goal of this work is to study what is known as lignification in these lab-grown plant materials. Lignin is a polymer that is deposited in the cell walls of plants which makes them rigid and woody. They found that higher hormone levels in the growth medium causes more lignification, which would lead to plant material with more wood-like properties.

The researchers also demonstrated that, using a 3D bioprinting process, the plant material can be grown in a custom shape and size. Rather than using a mold, the process involves the use of a customizable computer-aided design file that is fed to a 3D bioprinter, which deposits the cell gel culture into a specific shape. For instance, they were able to grow plant material in the shape of a tiny evergreen tree.

Research of this kind is relatively new, Borenstein says.

This work demonstrates the power that a technology at the interface between engineering and biology can bring to bear on an environmental challenge, leveraging advances originally developed for health care applications, he adds.

The researchers also show that the cell cultures can survive and continue to grow for months after printing, and that using a thicker gel to produce thicker plant material structures does not impact the survival rate of the lab-grown cells.

I think the real opportunity here is to be optimal with what you use and how you use it. If you want to create an object that is going to serve some purpose, there are mechanical expectations to consider. This process is really amenable to customization, Velsquez-Garca says.

Now that they have demonstrated the effective tunability of this technique, the researchers want to continue experimenting so they can better understand and control cellular development. They also want to explore how other chemical and genetic factors can direct the growth of the cells.

They hope to evaluate how their method could be transferred to a new species. Zinnia plants dont produce wood, but if this method were used to make a commercially important tree species, like pine, the process would need to be tailored to that species, Velsquez-Garca says.

Ultimately, he is hopeful this work can help to motivate other groups to dive into this area of research to help reduce deforestation.

Trees and forests are an amazing tool for helping us manage climate change, so being as strategic as we can with these resources will be a societal necessity going forward, Beckwith adds.

Reference: Physical, mechanical, and microstructural characterization of novel, 3D-printed, tunable, lab-grown plant materials generated from Zinnia elegans cell cultures by Ashley L. Beckwith, Jeffrey T. Borenstein and Luis F. Velsquez-Garca, 7 March 2022, .DOI: 10.1016/j.mattod.2022.02.012

This research is funded, in part, by the Draper Scholars Program.

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MIT Pioneers Technology To Grow Customizable Wood Products in the Lab With Little Waste - SciTechDaily

By Diana Outlaw, Associate Professor, Biological Sciences, Mississippi State University

To my fellow parents and community members in rural America,

After the schools closed in March, 2020, we sat out the remainder of the 2020-2021 school year, opting to keep our exceptional child safe at home. Its not so much that we were worried about her being more vulnerable to Covid but that her poor adaptive skills and general lack of hygiene awareness made us extremely apprehensive about the germ-ridden cesspool of an elementary school.

You see, Arya has encephalopathy, essentially widespread brain damage that affects every aspect of her functioning, from her cognitive level to her understanding of time, from understanding her bodys cues to being able to find something that is right in front of her. She can be trained, but she doesnt understand why. She learns through repetition, and her reasoning is always circular.

We had no choice for the 2021-2022 school year except to send her back. But we practiced with masks, and she showed us that she was exceptionally compliant. One upside of perseverance! We got her vaccinated as soon as she was eligible, and she was thrilled. She gets a subcutaneous growth hormone shot every day, so needles are not a big deal to her.

Arya is in a self-contained classroom, which means that most if not all of her classmates also have poor adaptive skills. Which translates to mean the most vulnerable students in the school, which further translates to the families of her classmates being more vulnerable than most because they are often the only care and safety that her classmates have. If one of their family members gets sick, the children will suffer.

Literally, the kids had no class to go to, so that meant that someone had to be home caring for those kids, probably missing work, missing income, missing food.

But, one night earlier this year, I got a text from Aryas teacher, informing me that everyone in Aryas class (students, teachers, aides) had been in close contact with someone who had tested positive for Covid. In that moment I was beyond upset for my own family, and for the families of the rest of the students in the class.A caregiver goes down, and ward of the state may be the only choice for these kids. Everyone had to quarantine for five days, which really meant seven because it was a three-day weekend. Literally, the kids had no class to go to, so that meant that someone had to be home caring for those kids, probably missing work, missing income, missing food. The reality is that no one will likely ever know what the impact was. And, my cynical side believes that no one cares.

Let me just get really clear and blunt here. I am a privileged, well-educated white woman with multiple safety-nets. I can work from home and have all the benefits as a salaried state university employee. So, we quarantined and I worked when I could, with zero concern about our livelihood. Zero. Oktibbeha County in Mississippi, like most of Mississippi is rural, with limited internet access, limited access to transportation, limited access to health care. In a study examining the early impact of the pandemic in Mississippi, which has the poorest score of all 50 states on the economic hardship index, . . [taking] into account unemployment, dependency, education, income, crowded housing, and poverty,1 rural Mississippians had significantly higher case rates and mortalities than non-rural Mississippians. In this context of rurality and poverty, essential employees at the university and in the community had no choice over the course of the pandemic. They couldnt work at home. They couldnt be home to make sure their kids got their schoolwork done.For most of the families in Aryas class, another 5 day quarantine has real, and quite likely economic, consequences consequences that could be prevented with widespread vaccination.

For most of the families in Aryas class, another 5 day quarantine has real, and quite likely economic, consequences consequences that could be prevented with widespread vaccination.

So please if you can, get vaccinated, and get your kids vaccinated.We Can Do This! For yourselves, for kids and families like those of Aryas classmates.The caregivers of vulnerable children thank you very much. For more information about vaccinations, go to vaccines.gov.

1Zhang, L., Mcleod, S. T., Vargas, R., Liu, X., Young, D. K., & Dobbs, T. E. (2020). Subgroup comparison of Covid-19 case and mortality with associated factors in Mississippi: findings from analysis of the first four months of public data.Journal of biomedical research,34(6), 446457. https://doi.org/10.7555/JBR.34.20200135

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Commentary: The Importance of Covid Vaccination in Rural Schools - Daily Yonder

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Crinetics Pharmaceuticals, Inc. (NASDAQ:CRNX) is a great speculative biotech play to look into. That's because it is expected that it will release results from two phase 3 studies under the PATHFNDR program in 2023. Both studies, known as PATHFNDR-1 and PATHFNDR-2, are using paltusotine for the treatment of patients with Acromegaly. One study is switching patients from injectable standard of care (SOC) treatments and the other is targeting untreated patients. Both of these randomized trials will be important, because they will be needed for the company to be able to file a New Drug Application (NDA) to the FDA for approval thereafter. A prior phase 2 study, known as ACROBAT, showed that patients were able to maintain hormone suppression even after switching from SOC injections to paltusotine.

Paltusotine is also being explored for use in treating patients with neuroendocrine tumors and carcinoid syndrome in phase 2 testing. Another important program would be the use of CRN04777 which was shown to be safe/tolerable in patients with congenital hyperinsulinism in a phase 1 study. Crinetics is in the process of initiating a phase 2 study using CRN04777 for this patient population in the 2nd half of 2022. With proof of concept established in phase 2 for paltusotine for Acromegaly, plus a major readout from a late-stage study for this program in 2023, these are the reasons why I believe this biotech is a great speculative biotech play to look into.

Paltusotine is being developed for the treatment of patients with Acromegaly. This is a differentiated treatment option for patients, because it is being developed as an oral treatment. Current standard of care (SOC) treatment options used are injections. Acromegaly is a type of hormonal disorder that occurs when your pituitary gland produces too much growth hormone during adulthood. What happens is that bones and other parts of the body become enlarged. The enlarged parts of the body that are possible for those who have Acromegaly are:

In Adulthood though, height is something that doesn't change for someone who has Acromegaly. It is a rare disorder in that there are fewer than 20,000 U.S. cases per year. The key is that these patients are able to bring growth hormone and IGF-1 levels to a normal level. If this can be accomplished only then can these patients have a normal life expectancy.

The thing is that this program has come a long way. Why is that? Well, that's because a phase 1 study using paltusotine was initiated back in 2018. Since then, it has really done well to advance the use of this drug for the treatment of patients with Acromegaly. After that, it has been able to advance two separate phase 2 studies recruiting patients with Acromegaly.

These two studies are the phase 2 ACROBAT Edge and ACROBAT Evolve studies. Any patient who finished either of these studies were then enrolled into the phase 2 Open-Label Extension (OLE) study known as ACROBAT Advance. The good thing here is that Crinetics released some positive long-term data from this particular OLE study back on November 8, 2021. It was shown that with a cut off date of August 31, 2021 41 patients had gone through and received paltusotine for a total of 51 weeks.

A really good thing about this study is that only 4 patients ended up discontinuing from the study. The main takeaway that you should know about this study is that patients taking paltusotine ended up achieving lower median serum insulin-like growth factor-1 ((IGF-1)) levels compared to the washout period. A washout period is where patients take no drug whatsoever. This signifies that the drug was able to do a good job at lowering IGF-1 levels. Not only that, but it was able to maintain such levels for an extended period of time similar to that which was achieved on prior SRL therapy for up to 51 weeks.

There are two important things to explain here. The first of which is that SRL therapy is a standard of care (SOC) treatment option for these patients with Acromegaly. SRL stands for somatostatin-receptor ligand and is responsible for slowing down the production of hormones, especially the growth hormone and serotonin. While it works well, there are a few issues with it. They are:

Secondly, the main problem with Acromegaly goes to what I stated above in the definition of it. That is, if a therapy can fully lower serum insulin-like growth factor-1 ((IGF-1)) levels to normal, then these patients can be treated properly. It's hard to say whether or not the drug will be successful, but it is important to note that about 41 out of 49 (84%) of the eligible patients decided to remain in the ACROBAT Advance study.

With achieving such great success in the IGF-1 biomarker data from several phase 2 studies with paltusotine in treating patients with Acromegaly, it has already been able to advance a phase 3 program known as PATHFNDR. It had dosed the first patient in the phase 3 PATHFNDR-1 in June of 2021. This late-stage study is expected to enroll up to a total of 52 patients with Acromegaly who are at the time of study entry biochemically controlled.

What does that mean? It means that these patients have insulin-like growth factor-1 ((IGF-1)) 1.0x upper limit of normal (ULN). They achieve this while on other standard of care (SOC) treatment options like octreotide or lanreotide (synthetic version of stomatostatin) depot monotherapy. Patients for this phase 3 PATHFNDR-1 study are randomized to receive 1:1 to receive once daily oral paltusotine or placebo for a total of 9 months. The main thing to note here is that these patients are switching off of SOC injection treatment over to paltusotine. The primary endpoint for the study is going to be the proportion of patients who will be biochemically controlled during at least weeks 32 to 36. The only major downside at the moment for this particular program is that results from this late-stage study with paltusotine are not expected to be released until 2023. There is also a second phase 3 randomized double-blind placebo-controlled study known as PATHFNDR-2. This study is similar to the other late-stage study, but instead is treating patents who have not been treated. In essence, there are two criteria for recruiting in this late-stage study. These two stipulations are:

The primary endpoint will be the average IGF-1 1.0x ULN at weeks 22 to 24. Again, this will be the use of paltusotine compared to placebo. This is another study, which is expected to have data released in 2023.

Hopefully paltusotine does well in these studies for Acromegaly. However, things are looking good in that Crinetics has already been able to establish a partnership with a Japanese pharmaceutical company by the name of Sanwa Kagaku Kenkyusho Co., Ltd. (Known as "Sanwa") for paltusotine. Crinetics received $13 million as an upfront payment and then also may be eligible to earn milestone payments relating to certain development, regulatory and commercial goals being met. If paltusotine achieves marketing approval in Japan, then it will also be able to receive tiered royalties on net product sales. Sanwa will have the right to develop and commercialize the drug for Acromegaly/neuroendocrine tumors in Japan. That's okay though, because it will be responsible for all costs of every single study done in Japan for it. This means that Crinetics won't have to worry about funding or spending money to run these studies in that specific territory. Not only that, but it still retains rights for paltusotine outside of Japan. What does this do? Well, it provides the ability for it to attempt to make another partnership for the drug in another territory besides Japan. If that doesn't happen, then it retains full rights for the drug in the rest of the territories.

According to the 10-Q SEC Filing, Crinetics Pharmaceuticals had cash, cash equivalents and investments of $319.7 million as of March 31, 2022. This is a lot of cash on hand, however, there is one important thing to consider here and that is that this amount does not include the most recent cash offering it had enacted in April of 2022. That is when it sold a total of 5,625,563 shares of its common stock at a price of $22.22 per share. It received roughly $125 million in gross proceeds from the common stock offering. It believes that it has enough cash on hand to fund its operations into the 2nd half of 2024. This means I don't anticipate another cash raise for quite some time. I believe that if it does enact another cash raise it will choose to do so by at least mid-2023 or thereafter. The only way it would want to raise earlier than expected is if market conditions worsen even further or it has a strategic transaction it wants to accomplish. Other than both of these situations, it won't need to raise cash for quite some time.

There are a few risks that investors should be aware of before investing in Crinetics Pharmaceuticals. The first risk involves the PATHFNDR program itself. While it achieved success with the primary endpoint using paltusotine in Acromegaly in a prior phase 2 study, there is no guarantee that the same will be done in either one of the two ongoing PATHFNDR studies. Results from either one of these studies won't be known until 2023.

The second risk involves the use of CRN04777 for congenital hyperinsulinism. A phase 1 study completed the safety portion and was shown to be tolerable. There was also some proof of concept evidence of being able to achieve dose-dependent suppression of glucose or sulfonylurea-induced insulin secretion as well. The next step is for the biotech to speak to regulators and initiate a phase 2 study using CRN04777 for congenital hyperinsulinism to confirm efficacy. This mid-stage study is expected to start in the 2nd half of 2022. One caveat from its main program is that paltusotine is also being developed to treat patients with neuroendocrine tumors as well in a phase 2 study. This provides another shot on goal, just in case the drug doesn't succeed in the two ongoing PATHFINDR studies for Acromegaly.

The final conclusion is that Crinetics Pharmaceuticals is a great speculative biotech play to look into. That's because it has already established proof of concept of being able to achieve normal hormone and IGF-1 levels in a phase 2 study. The two ongoing PATHFNDR studies using paltusotine for patients with Acromegaly may ultimately prove this finding.

At least the biotech has been advancing its pipeline providing additional shots on goal. Paltusotine is also being used to treat patients with neuroendocrine tumors as well. It has already done some leg work in showing that CRN04777 is safe and provides dose-dependent suppression of glucose or sulfonylurea-induced insulin secretion in a phase 1 study. A phase 2 study using this drug for the treatment of patients with congenital hyperinsulinism is expected to start in the 2nd half of 2022. It has even been able to spin out a company known as Radionetics oncology, which will be focused on advancing nonpeptide precision radiotherapeutics for the treatment of patients with cancer. This company was spun out from Crinetics nonpeptide platform.

Another drug in Crinetics pipeline is CRN04894, which is an ACTH antagonist. It is being developed to treat patients with Congenital adrenal hyperplasia and Cushing's Disease. Based on proof of concept established in phase 2 for paltusotine in Acromegaly, plus many other drugs being advanced in the pipeline for additional shots on goal, these are the reasons why I believe this is worth a look as a speculative biotech play. The two trial readouts from the phase 3 PATHFNDR studies provide major inflection points for Crinetics.

Originally posted here:

Crinetics: Late-Stage Acromegaly Disease Studies Will Be Inflection Point (NASDAQ:CRNX) - Seeking Alpha