In the definitions of overall health, you can easily understand why any adverse health history is requested if you notice your personal doctor or any other medical professionals. Information requested can include your wellbeing history, family health history, diet, and workout. With respect to the doctor you're seeing, additional information might be requested. Exactly why is this type of comprehensive history vital that you your personal doctor or any other doctor? History supplied by you gives your doctor or doctor the most crucial tool to identify your problem and provide medicine. Quite simply, whenever you offer an honest and finish health history, genealogy, health background, dieting and exercise information you provide your doctor or doctor a look relating to your overall health. Societal values also influence how a person feels about maintaining a particular degree of health. In summary, health means a lot of things. It's a feeling of complete well-being and the lack of disease. Everyone's health falls somewhere on the line between your extremes of excellent health insurance and illness. For that individual, the existence or lack of health is generally not determined exclusively by laboratory test or medical pronouncements but additionally through the expectations produced within his/her particular society.
In my opinion the entire year 2011 is going to be pivotal within the fight to have an affordable and workable Healthcare system that will assist the U . s . States. When we will face the cold hard details and create a obvious knowledge of exactly what a model system appears like, we are able to enjoy better individual health insurance and economic success beyond anyone's belief system to understand. This primary piece of 2012 will construct exactly what a model system appears like and subsequent articles can give additional information of methods we are able to move toward a method that actually works.
By having an ill-created "Obamacare" system taking effect this season, without any benefits for 3 years, it is now time to alter my approach from "fixing" the machine to "saving" the machine. It's not my style to "scare" people into action, but the reality is, if we don't stop this "Obamanation" as a whole, we're destined to become third rate country with economic problems unlike anything our citizens have ever faced. Each and every citizen must become involved now and remain involved for many years because there'll always be individuals seeking capacity to control our way of life. Browse around and find out the signs and symptoms. Already we've debt our grandchildren is going to be having to pay for, unemployment at nothing you've seen prior seen levels and forecast to carry on for a long time, freedoms neutralized or obtained from us, and just what do our leaders inform us? With apparent lies they inform us we're on course, and it'll take many years to make things better (better for who?). We have to do something NOW since the longer we allow these conditions to carry on, the greater devastating they'll be and also the longer it will require to repair them.
So, let us begin with a obvious knowledge of exactly what a workable system appears like. First, a totally free enterprise healthcare system that constantly adjusts to promote conditions will best serve everybody. Quite simply, get politicians and government from the business. Never within our history has any politician/government run program of any sort have you been effective, never!
The First Step to higher health: United nations-elect politicians who claim they'll give a healthcare program for you personally.
Second, every individual must understand they've a person responsibility to consider better proper care of their own health. Eating correctly and exercising routinely is going to do more to enhance a person's health insurance and reduce health problems than any "co-pay health plan".
Second Step to higher health: Purchase only "catastrophic health care insurance options". Everybody must understand that "co-pay plans" aren't actually the things they appear. Diets have the effect of grossly growing costs and therefore are simply financial intends to pre-purchase health care one might or might not need as based on an insurer worker. I believe that eliminating diets would cut back costs up to 70% almost overnight.
Third, go ahead and take profit for lawyers from the industry. Lawyers do nothing to improve healthcare for anybody. Lawyers are simply "vultures" hovering around hospitals searching for possibilities to file a lawsuit someone.
Third Step to higher health: Individually we have to learn to election and elect only politicians who'll support the idea of taking all the profit for lawyers from the industry.
4th, everybody must assume personal responsibility for their. Every person has health issues which are specific on their behalf and individually should result in learning to cope with them. To visualize you can get healthy by visiting a doctor, or perhaps a hospital, or if you take drugs (of any sort), or just being included in medical health insurance, resides inside a fantasy world, it won't happen. Everyone owns something which works to enhance a person's health, and that's our very own body. It had been marvelously produced for everyone everyone and also the better we take proper care of it, the greater the outcomes.
You've got a lot to choose from when you are looking at stepping into shape. There always appears to become a better fitness plan which will really get the body back where it had been or in which you wish it to be. But frankly a number of these hot new fitness plans might not meet your needs exactly or perhaps your fitness goals.
Why don't you create your very own fitness plan rather of attempting every new plan which comes along and wishing to find the best,. You are a distinctive individual with your personal skills and interests. You might also need unique goals and challenges.
1. It's according to your present fitness level – You realize where you are at at this time and also you know your limits. This will be significant because it offers a superior a practical beginning point. It offers a superior the area to enhance and also be without getting another person's expectations set with you.
Your fitness goal, whatever it might be, is exactly what you'll frame your whole fitness program around. It's what's going to inspire you and excited to workout and succeed. That simply does not happen when you are focusing on an objective that another person has looking for you.
4. It supports your schedule – Talking about schedule, whenever you make your own fitness plan you are fitting it to your existence, not the other way round. It might be a practical a part of your existence.
5. It suits your motivation style – What motivates you might be diverse from what motivates another person. With your own personal fitness plan, you develop an agenda that matches your motivation style. It's included in your plan and success is virtually guaranteed.
Whenever you stick to the steps to produce a fitness plan, you are not implementing the simple road. There is a thin line between pushing yourself way too hard and taking it too easy on yourself. For this reason planning is essential. Identify the kinds of activities you like and what you would like to get away from your fitness program – determine what your fitness goals are. Then produce a program that supports you to definitely succeed.
The reason could be to slim down in order to simply look fabulous and healthy. Whatever individuals reasons are, women's health insurance and fitness are essential, here really are a couple of health fitness tips that you should pass.
Let us be honest, we can't begin a fitness regimen just by studying health fitness advice, we must abide by it religiously. It's never easy to begin with an activity unless of course you're really enthusiastic about it. So before involving in the realm of women's health insurance and fitness, make certain you're determined and able to be disciplined. In the end, being healthy is fun!
Now that you've got conditioned the body to maneuver, you can start taking health fitness advice one stage further. Browse over your directory and register in the best gym you've around. Working-out not just provides you with energy, but additionally tones parts of your muscles and makes the body more effective and more powerful. Women's health insurance and fitness is available in great shape therefore it is best to employ a trainer to higher teach you with the requirements of the body. You may also sign up for gym classes like spinning, hip-hop dancing, yoga, and Zumba to boost your projects-out experience. This can be a favorite health fitness tip because it doesn't only cause you to feel healthy, it's also a method that you should make new friends.
Women nowadays are extremely empowered, much more whether it's along with health insurance and fitness. Health fitness advice have the freedom for those and lots of of it's very simple to do. Being fit isn't just about searching good or attractive it's also about taking proper care of the body and swaying it from illnesses. Remember that maintaining women's health insurance and fitness means an extended and healthier existence!
Why Enroll in a Fitness Club?
Be assured that there are plenty of reasons why you need to enroll in a fitness club there is however just one reason why you'll even feel marginally unwilling to enroll in a fitness club and it is known as MEMBERSHIP Charges.
Still, don't allow this dissuade you. In the end, you cannot be prepared to reap all the advantages of joining a fitness club free of charge right?
Fitness clubs keep you motivated. Exercising alone isn't any fun and even if you're avoid a workout buddy, the climate in fitness clubs alone is frequently enough to energise you into 'getting back on track' together with your fitness goals. However, don't be concerned that you simply will not find your personal 'personal space' in fitness clubs. Many people, as if you, understand the atmosphere but they are quick to depart you alone.
Fitness clubs offer savings. There's without doubt that various fitness machines have proven themselves to become very effective. However, to purchase them all would be very expensive! This is actually among the primary reasons to choose a fitness club membership. Sure, you may pay a high amount especially if you are planning for any well-outfitted fitness club, but thinking about that you will get use of numerous equipment, contemplate it a useful investment for your overall fitness goals.
Fitness clubs provide you with use of fitness professionals. Fitness centers worthwhile their salt are staffed with professional nutritionists, dieticians, fitness consultants and private trainers. More often than not, use of this type of person incorporated inside your membership fee so make the most of them!
Fitness clubs offer enjoyable pleasures. Great amenities for example saunas, steam rooms, spacious shower and altering rooms, and possibly a pool are great 'perks' that include a fitness club membership. So exercise and revel in!
All prepared to participate fitness club. Following are a handful of pointers you should think about.
Think about your own fitness goals and just what particular kind of activity really encourages you. For example, if you're more into aerobic workouts, enroll in a fitness club that provides aerobic exercise classes while offering a number of aerobic fitness machines. However, if you are concept of a general workout is swimming be sure that the fitness club includes a great pool.
Location, location, location. The very best fitness club to participate would be to the one which you've ready use of. Trust me, in the event that 'perfect' fitness club is completely across sleep issues of town, odds are, you won't go as frequently while you should and also you might have just wasted money joining it.
Friendly and reliable fitness club staff. Although among the primary factors to participate a fitness club is the plethora of fitness equipment they provide, it is crucial that they've professional staff which are on hand constantly. For example, some fitness clubs claim they have in-house trainers and consultants however, many clients are never in a position to 'consult' together. If you're a novice with fitness equipment or are simply beginning on your fitness goals, this time ought to be big consideration along with you.


text:
Q: How to find highest combination in dataframe I have a data frame that has repeating values in 2 columns and I only want to keep the highest value of each combination. For the following data frame:
df = pd.DataFrame(
np.array([['A', 'B ', 3], ['A', 'B', 6], ['C', 'D', 9],  ['C', 'D', 2], ['C', 'B', 4]]))
df

how would I get this dataframe as a result:
|A|B|6|
|C|D|9|
|C|B|4|

A: Use groupby and aggregate max:
df.groupby([0,1], as_index=False)[2].max()

Here's a post with a similar use case.

redpajama_set_name: RedPajamaStackExchange


This crochet hat pattern features an elegant shell stitch design. It makes a perfect accessory for babies, girls, and women.
Sizes included: Newborn to 3 Months, 3 to 6 Months, 6 to 12 Months, Toddler, 5T to Adult.
Requires worsted weight yarn and size H or i crochet hook.


text:
Evidence Based This post has 11 references
Telomerase, Telomeres & Aging
Written by Puya Yazdi, MD | Last updated: April 21, 2020
SelfDecode Science Team | Written by Puya Yazdi, MD | Last updated: April 21, 2020
SelfHacked has the strictest sourcing guidelines in the health industry and we almost exclusively link to medically peer-reviewed studies, usually on PubMed. We believe that the most accurate information is found directly in the scientific source.
We are dedicated to providing the most scientifically valid, unbiased, and comprehensive information on any given topic.
Our team comprises of trained MDs, PhDs, pharmacists, qualified scientists, and certified health and wellness specialists.
All of our content is written by scientists and people with a strong science background.
Our science team is put through the strictest vetting process in the health industry and we often reject applicants who have written articles for many of the largest health websites that are deemed trustworthy. Our science team must pass long technical science tests, difficult logical reasoning and reading comprehension tests. They are continually monitored by our internal peer-review process and if we see anyone making material science errors, we don't let them write for us again.
Our goal is to not have a single piece of inaccurate information on this website. If you feel that any of our content is inaccurate, out-of-date, or otherwise questionable, please leave a comment or contact us at [email protected]
Note that each number in parentheses [1, 2, 3, etc.] is a clickable link to peer-reviewed scientific studies. A plus sign next to the number "[1+, 2+, etc...]" means that the information is found within the full scientific study rather than the abstract.
Every time cells divide, chromosomes get a little bit shorter. That's why cells have telomeres – non-coding sequences of DNA that sit at the ends of chromosomes and protect genes from damage. Read on to learn more about telomerase, telomeres, and their role in aging.
What is Telomerase?
Telomeres are sequences of DNA at the ends of each chromosome. They don't code for anything; instead, their job is to protect DNA from damage while it's being copied. Each time cells divide, DNA duplicates, and telomeres get shorter [1].
When telomeres are too short to protect DNA, cells enter a state called senescence: they stop dividing. Ultimately, if these cells trigger the DNA damage response (DDR), they will be tagged for death [1, 2].
Telomerase is an enzyme that adds more nucleotides to the end of the telomere, elongating them. This allows cells to divide and grow for longer [1].
Telomerase is an enzyme that lengthens telomeres, the sequences of protective DNA at the ends of chromosomes.
What is the CST Complex?
The CST complex is a structure that helps to protect your chromosomes from damage. CST doesn't stand for a longer name; instead, it's an abbreviation of the three proteins making up the complex: CTC1, STN1, and TEN1 [3, 4].
The CST complex is what's called "evolutionarily conserved," meaning that it's almost identical across species as distantly related as humans and yeast. When a single gene, protein, or protein complex is common to so many species, researchers can be fairly sure it's important [3].
But what does it do? The CST complex appears to have two major functions:
Physically protecting telomeres (and the rest of the chromosome) from damage [3]
Regulating the telomerase enzyme by both supporting its function & putting a limit on how often it can bind to DNA [5, 3]
In short, the CST complex's job is to make sure telomeres don't get too short or too long, and it's probably been doing this job for hundreds of millions of years [3].
CST in Humans
Humans have multiple mechanisms to protect our telomeres, including the CST complex and another protein complex called shelterin [3, 6].
Of these, shelterin is considered more important; it is the major obstacle protecting your telomeres from damage. However, if certain components of shelterin (POT1 and TPP1) are missing or reduced, the CST complex is there to pick up the slack, so to speak [3, 6].
Recent research has also shown that the CST complex helps your cells safely lengthen your telomeres during cell division. Thus, if any single protein in the CST complex isn't functioning well, telomeres could get dangerously short, resulting in premature aging [5].
Telomeres and the Science of Aging
Researchers have long suspected that shortening telomeres are among the causes of aging.
In adult tissues, there isn't enough telomerase to keep up with cell division. Gradually, throughout the human lifespan, telomeres get shorter and shorter, and more and more cells enter senescence. Thus, older people can't grow and regenerate their tissues as effectively as younger people [1, 2].
Short telomeres have also been linked with degenerative diseases and premature aging in humans. In this light, many researchers have attempted to discover whether activating telomerase and elongating telomeres can prevent or delay aging in humans and animals [1, 2, 7].
Gene Therapy for Mice
Telomere extension has already worked as an anti-aging strategy in animal models.
In one memorable study, middle-aged and older mice (one and two years old) were treated with gene therapy that increased their TERT expression. Those that received the treatment lived for 13-24% longer than those without, and there were no apparent side effects of the procedure [7].
However, animal research is infamously difficult to reproduce in humans. Over the decades, many mouse and rat studies have produced spectacular results which then never become relevant to human health. Researchers are hard at work trying to find the key to human longevity, but they haven't found it yet.
Cells with shortened telomeres can't divide, and mice that received gene therapy to increase TERT expression lived longer. Thus, shortening telomeres may play a role in aging.
How Much Telomerase is Best?
Given what we've just discussed, you might think that the answer is simple: the more active your telomerase (and the longer your telomeres), the better. However, there is no scientific consensus on the ideal range of telomerase activity or the ideal telomere length [1].
Telomere length is a strange and controversial field of research, and long telomeres seem to have positive and negative effects, depending on the study and the frame of reference. Most notably, dangerous cancer cells tend to have high telomerase activity and unusually long telomeres [8, 1].
Some genetic variants, like rs2736100, are especially confusing. The homozygous 'AA' genotype, which reduces telomerase activity, is linked with testicular cancer and progressive scarring of the lungs [9, 10].
In this variant, the 'C' allele seems to increase telomerase activity and lengthen the telomeres, so you might think it would increase longevity. However, people with even one copy of the 'C' allele developed glioma, a type of dangerous brain cancer, 60% more often than those who don't [9, 10].
Possible Interactions in Cancer Cells
To recap: many variants that increase TERT activity are also linked with cancer, but gene therapy to increase TERT in mice hasn't caused cancer. Why this discrepancy? Researchers have not reached a consensus, but there are a few possible answers.
One possibility raised by researchers is that TERT doesn't itself increase cancer risk, but instead amplifies the effect of other genes and mutations that do by allowing unlimited cell proliferation the tumor cells. A hallmark of cancer cells is that they can divide and proliferate indefinitely, and TERT mutations are among the most likely mechanisms behind this ability [11, 1].
TERT variants may also have other effects on tumor cells and future studies will be needed to fully understand their role in cancer.
Longer telomeres and more telomerase activity have been linked to cancer. Most likely because this allows the cancer cells to keep dividing.
Check out our post on TERT (the gene that codes for telomerase) on SelfDecode to learn more.
Optimize Your Lab Results to Strengthen Your Immune System!
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Analyze My Labs
Puya Yazdi
Dr. Puya Yazdi is a physician-scientist with 14+ years of experience in clinical medicine, life sciences, biotechnology, and nutraceuticals.
As a physician-scientist with expertise in genomics, biotechnology, and nutraceuticals, he has made it his mission to bring precision medicine to the bedside and help transform healthcare in the 21st century.He received his undergraduate education at the University of California at Irvine, a Medical Doctorate from the University of Southern California, and was a Resident Physician at Stanford University. He then proceeded to serve as a Clinical Fellow of The California Institute of Regenerative Medicine at The University of California at Irvine, where he conducted research of stem cells, epigenetics, and genomics. He was also a Medical Director for Cyvex Nutrition before serving as president of Systomic Health, a biotechnology consulting agency, where he served as an expert on genomics and other high-throughput technologies. His previous clients include Allergan, Caladrius Biosciences, and Omega Protein. He has a history of peer-reviewed publications, intellectual property discoveries (patents, etc.), clinical trial design, and a thorough knowledge of the regulatory landscape in biotechnology.He is leading our entire scientific and medical team in order to ensure accuracy and scientific validity of our content and products.
The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease. Information is shared for educational purposes only. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition.
Joe Cohen, CEO
Joe Cohen won the genetic lottery of bad genes. As a kid, he suffered from inflammation, brain fog, fatigue, digestive problems, anxiety, depression, and other issues that were poorly understood in both conventional and alternative medicine.
Fisetin Potential Benefits + Foods, Dosage & Side Effects
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Align your health hacks with your genes for optimal health & cognitive function.
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redpajama_set_name: RedPajamaCommonCrawl


text:
L'hôtel de la croix d'or est un bâtiment historique situé dans la ville de Montbéliard dans le Doubs.

Histoire
L'hôtel de la croix d'or a été construit de 1619 à 1625.

Il fut une propriété du prince Léopold-Frédéric de Wurtemberg jusqu'à ce qu'il le vende en 1654.

L'édifice e été attesté comme auberge entre 1662 et 1730.

Il devint par la suite la maison d'un notable local, Pierre-Joseph Beurnier. À sa mort, et selon le testament qu'il a laissé, le bâtiment est légué à la ville et est transformé en hospice pour orphelins en 1770. Cet acte a été approuvé par le duc Charles II de Wurtemberg et a servi dans un premier temps à accueillir douze jeunes filles pauvres et orphelines.
L'édifice servira d'hospice jusqu'en 1945.

Les façades et les toitures, l'escalier de la tour avec sa rampe en fer forgé ainsi que le plafond peint du grand salon au premier étage font l'objet d'une inscription au titre des monuments historiques depuis le .

Architecture

Notes et références

Voir aussi

Article connexe
 Liste des monuments historiques de Montbéliard

Liens externes

Monument historique à Montbéliard
Monument historique inscrit en 1977
Hôtel particulier monument historique dans le Doubs

redpajama_set_name: RedPajamaWikipedia


On Wednesday 9th July, Models Own where running a giveaway on their Twitter giving 3 lucky people the chance to win either their 'Polish For Tans' collection and their 'Summer Hypergels' or a £10 e-voucher. Like 800 other Models Own fans, I retweeted their tweet and I was lucky enough to be selected for the main prize of the 10 nail polishes.
Being a huge fan of Models Own nail polishes I was so happy to have been selected so thought I would share with you the beautiful polishes I have won.
Here we have the 'Polish For Tans' collection and I absolutely love the colours for during the summer months.
And here we have the "Summer Hypergels' which are perfect colours for me as I love wearing Pinks/Red shades.
If you would like to see some of my previous posts featuring Models Own then take a look here and here.


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Q: Node Webkit shows uncaught nodejs error when using angularJS I have been building and debugging an Angular.JS application for several months now running from a browser without any issues whatsoever, however I am now in the stages of packaging it to run in node wrapper. When i created my package.json and ran the folder from nw.exe I get an error that says:
Uncaught node.js Error

    ReferenceError: angular is not defined
        at file:///C:/wamp/www/Maintenence/ng/ng-init.js:2:11

now the code line it has a problem with in ng-init.js is
var app = angular.module('MaintenenceApp', ['ngRoute']);

It doesnt like angular in angular.module and once I received this error I went to the angular.js docs to make sure i hadnt done something wrong here and according to https://docs.angularjs.org/guide/module this code is 100% correct.
what could be causing this error. as i mentioned, it runs perfectly in a web browser with no errors in js console.
package.json
{
    "main": "index.html",
    "name": "Maintenence Manager",
    "version": "0.0.1",
    "window": {
        "toolbar": false,
        "frame"  : true
    }
}

here is the order of my scripts in the head of index.html index.html
<didnt seem important to show css links and such but jquery is also in the page>
<script type="text/javascript" src="//code.angularjs.org/1.3.0-rc.0/angular.js"></script>
<Script type="text/javascript" src="//code.angularjs.org/1.3.0-rc.0/angular-route.js"></Script>
<script type="text/javascript" src="ng/ng-init.js"></script>

Thanks in advance.

A: As it turns out, Node Webkit doesn't support src="//url.com" which i use so the http/https thing doesn't become in issue.
Replacing the urls for the scripts with src="http://url.com" fixed my issue.


Bachelor's degree in Computer Science, Engineering, Management Information Systems or related area.
Ability to multi-task, and be mindful of deadlines.
Self-motivated and ability to remain focused on assigned projects.
Compensation Package ranges from PHP30,000-PHP50,000 depending on the interview assessment and years or expertise.


text:
Disney Channel Releases Trailer for Myrna Velasco's Animated Series "Star Wars Resistance"
Posted on August 20, 2018 by Tom Castaneda
Myrna Velasco is joining the resistance…
Disney Channel has released a new trailer for its upcoming animated show Star Wars Resistance, featuring the Mexican American actress.
"Can you imagine what it's like to be an ace pilot?" Kazuda Xiono ("Kaz") asks in the new trailer. Audiences will follow Kaz and some familiar Star Wars faces as he does just that — become a top pilot, not to mention spying on the rising threat of the First Order for the Resistance.
In the hour-long premiere, Poe and BB-8 assign Kaz to go undercover on the Colossus, a massive aircraft home to new aliens, droids, and other creatures. He makes new friends, like Poe's old buddy Yeager, as well as a battered astromech droid called Bucket. With challenges like dangerous sky races and keeping his mission a secret from his newfound crew, Kaz is in over his head as he tries to avoid the danger of the First Order.
Star Wars Rebels showrunner Dave Filoni created the series, which will see Oscar Isaac reprising his big screen role as pilot Poe Dameron, while Christopher Sean voices Kaz. Gwendoline Christie will return to voice the villainous Captain Phasma, and Rachel Butera plays General Leia Organa.
In addition to Velasco, other supporting voice actors include Suzie McGrath, Scott Lawrence, Josh Brener, Donald Faison, Jim Rash and Bobby Moynihan.
The adventure series will have a one-hour premiere on Sunday, October 7 at 10:00 pm ET/PT on Disney Channel, DisneyNOW, and Disney Channel VOD, with further airings on Disney XD.
Velasco's credits include Elena of Avalor, Descendants: Wicked World and Modern Family.
This entry was posted in Entertainment and tagged Christopher Sean, Descendants: Wicked World, Disney Channel, Disney Channel VOD, Disney XD, DisneyNOW, Donald Faison, Elena of Avalor, Gwendoline Christie, Jim Rash, Josh Brener, Modern Family, Myrna Velasco, Oscar Isaac, Rachel Butera, Scott Lawrence, Star Wars, Star Wars Rebels, Star Wars Resistance, Suzie McGrath by Tom Castaneda. Bookmark the permalink.


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DHEA / Pregnenolone Capsules
Home » Compounding » DHEA / Pregnenolone Capsules
Overview Of DHEA / Pregnenolone Capsules
Dosage Power Of DHEA / Pregnenolone Capsules
Multiple Strengths
Dehydroepiandrosterone (DHEA) is a C19 steroid also known as 5-androsten-3 beta-ol-17-one. DHEA and DHEAS (an active, sulfated form of DHEA), are endogenous hormones secreted by the adrenal cortex in primates and a few non-primate species in response to ACTH. DHEA is a steroid precursor of both androgens and estrogens, and thus is often called 'the mother hormone'. Endogenous DHEA is thought to be important in several endocrine processes, but current medical use of DHEA is limited to controlled clinical trials. In 1997, Pharmadigm, Inc. received an orphan drug designation to enroll patients with thermal burns who require skin-grafting into trials using injectable DHEAS, known as PB-005. Researchers continue to investigate the role of both endogenous and exogenous DHEA in CNS, psychiatric, endocrine, gynecologic and obstetric, immune, and cardiovascular functions. GeneLabs Technologies, Inc., submitted an NDA in September 2000 for its proprietary DHEA product, called prasterone (Prestara™, formerly known Aslera™ or GL-701). Prasterone appears to attentuate some symptoms of mild-to-moderate systemic lupus erythematosus (SLE) and may increase bone density based on evidence from two phase III studies in women; studies in men with SLE are ongoing. The FDA placed Prestara™ under a 6-month priority review status in October 2000; on April 19, 2001 the FDA stated that although the drug showed advantages over placebo in one study, the advantages were not statistically significant. Additional data were submitted to the FDA following a 'not approvable' letter on June 26, 2001. On September 2, 2002, the FDA issued an 'approvable' letter for the Prestara™ product, but the agency has asked for additional clinical trial data regarding the drug's effects on bone mineral density before granting final approval for SLE. The manufacturer began a confirmatory phase III trial in early 2003; the primary endpoint will be measurement of bone mineral density of the lumbar spine; the trial is targeted for completion at the end of 2003. In October 2004, the manufacturer released information that Prestara™ therapy did not meet the primary end point in the confirmatory trial. In August 2003, Paladin Labs Inc., received orphan drug designation from the FDA for prasterone, dehydroepiandrosterone, DHEA, under the brand name Fidelin™, for adrenal insufficiency.
Exogenously administered DHEA is sold as a nutritional supplement in health and drug stores and many older individuals are using it to 'maintain the vitality of their youth'. There is currently no objective, well-controlled, large-scale, scientific evidence to back claims that taking DHEA combats the signs or symptoms of aging, diabetes, neurologic disease, sexual dysfunction, or heart disease. Some athletes abuse DHEA believing that it can enhance the body's synthesis of testosterone; the potential action of DHEA as an anabolic steroid has lead to the prohibition of supplementation in competitive sport, even though evidence of anabolic effects in athletes is lacking. DHEA is also abused by athletes in an attempt to normalize the testosterone:epitestosterone ratio. However, the sensitivity and specificity of currently available testing for athletic 'doping' can readily identify the presence of banned substances, including testosterone. Because of DHEA's complex physiologic actions, more than 500 scientific articles investigating it have been published since 1993. Many of the short-term trials of DHEA to date have lacked the rigor and statistical applications needed to support therapeutic claims. Most claims will need to be confirmed by large-scale, properly conducted, and controlled studies. In 1984, the FDA banned the non-prescription (OTC) sale of exogenous DHEA due to concern over hepatotoxicity (hepatitis and hepatic tumors) as noted in animal studies. The FDA formally relegated DHEA to a Category II OTC ingredient at that time (i.e., not generally recognized as safe and effective). However in 1994, the passage of the US Dietary Supplement Health and Education Act (DSHEA) allowed DHEA to be marketed as a nutritional or dietary supplement.
Pregnenolone, also referred to as 5-pregnenolone or pregn-5-en-3β-ol-20-one, is a 21-carbon endogenous steroid. It is biosynthesized from cholesterol and is a precursor and a metabolic intermediate to the gonadal steroid hormones and adrenal corticosteroids, including estrogen, progesterone, testosterone, dehydroepiandrosterone (DHEA), cortisol, and cortisone. Pregnenolone is also biosynthesized from cholesterol within the central nervous system and the peripheral nervous system, which lends its classification as a neurosteroid.
Synthetic pregnenolone is sold as a supplement. It is not FDA-approved and there is little data on the safety and efficacy of long-term use of pregnenolone. Pregnenolone should be taken under the supervision of a physician.
Preliminary research shows that pregnenolone enhances learning and memory and can even reverse memory deficits in rodents. However, human studies have produced contradictory results.
Initial research shows that pregnenolone has significant anti-inflammatory properties.
Dysregulation of pregnenolone has been observed in patients with schizophrenia, bipolar disorder, depression, and Alzheimer's disease. This data leads researchers to look at the potential of exogenous pregnenolone to treat patients with these conditions.
Early human trials show that pregnenolone significantly improves SANS scores in patients diagnosed with schizophrenia compared to placebo. Early human trials suggest that pregnenolone may improve depressive symptoms in patients diagnosed with bipolar disorder.
Endogenous DHEA is a complex hormone, and researchers still have much to discover in regards to its physiologic effects in males and females. Less is known regarding the mechanisms of action of exogenously administered DHEA.
CNS actions: Both DHEA and DHEAS may be synthesized de-novo by the central nervous system, and concentrations of DHEA and DHEAS are higher in the brain than in other organs. The two neurohormones appear to have excitatory activity at both GABA and NMDA receptors.
Dermatologic actions after burn injury: Animal studies have suggested that DHEA and DHEAS expedite the re-epithelialization of donor skin-graft sites.
Endocrine actions: Endogenous DHEA is synthesized by the conversion of cholesterol via CYP11A1 to pregnenolone, followed by CYP17 conversion to DHEA and then to DHEAS via dehydroepiandrosterone sulfatransferase. The synthesis of DHEA occurs exclusively in the adrenal cortex in women, while in men 10—25% of DHEA is synthesized by the testes and roughly 80% of the DHEA comes from the adrenal glands. DHEA is converted via hydrosteroid dehydrogenases and aromatase into androstenedione, testosterone, and estradiol by peripheral tissues. DHEA is of only minor importance as an androgenic substance itself. The production rate of DHEA by the body changes dramatically throughout life, typically peaking at adrenarche, the adrenal contribution to the onset of puberty. In males, DHEA serum levels are high in neonates right after birth, rapidly fall within 5 months, then begin to rise at the age of 9 years. Endogenous DHEA concentration then peaks again in males at roughly the 20th—30th years of life. In females, DHEA serum levels are high in neonates right after birth, rapidly fall within 5 months, then begin to rise at the age of 7 years. Endogenous DHEA concentration then peaks again in females at roughly the 20th and 40th year of life. DHEA levels decline steadily after the fifth decade in both males and females. DHEAS concentrations in males and females follow similar patterns. The administration of DHEA supplements results in different hormonal concentration changes in males and females; the actions are dependent on the dose, formulation and route of administration, and age of the person receiving the DHEA.
Hemostasis: Inhibition of platelet aggregation by exogenous DHEA has been demonstrated in vivo in humans; DHEA either prolonged or completely inhibited the rate of arachidonate-stimulated platelet aggregation after 14 days of administration. The degree of inhibition of platelet aggregation was noted to be time and dose dependent.
Immunologic actions: Because SLE occurs more frequently in women than men and because SLE is known to worsen during pregnancy, a hormonal etiology is suspected for this disease. DHEA up-regulates interleukin-2 (IL-2) production by T-lymphocytes in murine lupus models and reverses the clinical autoimmune disease. Lower endogenous levels of DHEA and DHEAS have been noted in both male and female patients with lupus at the time of diagnosis. Chronic corticosteroid treatment, which may cause adrenal atrophy, contributes to reduced DHEA levels in these patients. Supplementation of DHEA in SLE may augment immune system activity and potentially offset the undesired effects of chronic corticosteroid use in these patients. Exact mechanisms of DHEA on immune function are not yet clear. DHEA has been shown to increase the numbers of natural killer cells in aging women. Serum DHEA levels are observed to be reduced in patients with AIDS or age-related immunodeficiency, suggesting that DHEA may serve as a marker of the integrity of the immune system. No studies to date have shown that DHEA supplementation augments currently available therapies for AIDS.
Pregnenolone plays a crucial role in processes throughout the body, including neurogenic growth. It's role as a substrate makes it crucial in the production of steroid hormones and adrenal corticosteroids and therefore highlights its importance in the regulation of bodily processes. It is also a precursor to other neurosteroids, including pregnenolone sulfate and allopregnanolone.
As a neurosteroid, pregnenolone modulates neurotransmission via the neuronal membrane and provokes structural changes in neurons and in astrocytes. Neurosteroids, including pregnenolone, have a modulating effect on neural excitability and synaptic plasticity. Pregnenolone is an excitatory neurosteroid and can act as an allosteric modulator of neurotransmitter receptors, such as GABAA, NMDA, and sigma receptors.
Pregnenolone is a ligand of the microtubule-associated protein 2 (MAP2) for the stimulation of the polymerization of microtubules. It is also a N-methyl-d-aspartate (NMDA) NMDA ligand. It is a negative allosteric modulator of the GABAA receptor and the CB1 receptor, and is an agonist of the σ1 receptor and the pregnane X receptor.
As a nutritional supplement, DHEA is most commonly administered by the oral route. Many DHEA products available as nutritional supplements contain varied amounts of DHEA and do not appear to be manufactured according to good manufacturing processes (GMP). Using HPLC techniques, one study found that only 7 out of the 16 assayed products contained DHEA within a 10% variation of the labeled content.Some products contained no detectable DHEA.
The literature is lacking in pharmacokinetic studies using serial serum sampling of DHEA after supplementation. In the body, DHEA and DHEAS are widely distributed, converted to the sex hormones in peripheral tissues, and appear to cross the blood-brain barrier. The serum pharmacokinetic parameters and metabolism of DHEA and DHEAS following administration may vary among persons of different sex and age groups and the dose or route of administration. Quantification of DHEA to aide in detection of abuse by athletes may soon be accomplished. Gas chromatography-mass spectrometry (GC-MS) can evidently detect DHEA metabolites in the urine within 8 hours of a single oral dose of 50 mg. Within 24 hours, 50—75% of an oral DHEA dose is recovered as glucuronide and sulfate conjugates, androsterone, and etiocholanone in the urine.
Oral Route: Micronization appears to enhance oral absorption and may influence the metabolic conversion of DHEA to the various sex hormones in men and women. After oral dosing, elevations in serum concentrations of DHEA and DHEAS, above endogenous levels, persist for 12 hours.
Pregnenolone can be administered orally, subcutaneously, intravenously, intranasally, and topically/transdermally. Oral pregnenolone has high metabolism and low bioavailability. It is lipophilic and readily crosses the blood brain barrier.
There is very limited data on the pharmacokinetics of exogenous pregnenolone. Oral pregnenolone is metabolized in preference to allopregnanolone, rather than other hormones biosynthesized from pregnenolone substrate, such as cortisol or DHEA. One study observed that three hours after oral consumption of a single dose of 400mg of pregnenolone, pregnenolone serum levels increased by approximately 60%. Two hours after this dose, allopregnanolone serum levels tripled. An earlier study shows that a single oral dose of 175mg of pregnenolone approximately doubled pregnenolone serum levels over the course of four to eight hours.
One study observed the effects of exogenous pregnenolone on patients diagnosed with schizophrenia or schizoaffective disorder. Participants were given eight weeks of oral pregnenolone–with an escalating fixed-dose approach, where patients took 500mg per day for the last four weeks. Serum levels of pregnenolone and certain downstream metabolites were measured. Treatment with oral pregnenolone elevated pregnenolone serum levels fourfold, pregnenolone sulfate serum levels tripled, and allopregnanolone serum levels increased fivefold. Furthermore, treatment with oral pregnenolone elevated progesterone serum levels more than fourfold and DHEAS levels by approximately 16%. In this study, exogenous pregnenolone did not increase serum levels of testosterone, free testosterone, cortisol, DHEA, estradiol, or androstenedione levels.
Your health care provider needs to know if you have any of these conditions: breast cancer (men or women); cancer of the lining of the uterus (endometrial cancer); diabetes or high blood sugar; immune system problems; infertility; liver disease; post-menopause; prostate cancer or an enlarged prostate gland; rheumatoid arthritis; uterine cancer; vaginal bleeding or menstrual problems; vaginal cancer; an unusual or allergic reaction to progesterone, DHEA, soy, other medicines, foods, dyes, or preservatives; pregnant or trying to get pregnant; breast-feeding. Visit your doctor or health care professional for regular checks on your progress. Women should inform their doctor if they wish to become pregnant or think they might be pregnant. There is a potential for serious side effects to an unborn child. DHEA use is banned in competitive sports. Both college (NCAA) and olympic (USOC) committees do not allow DHEA use among athletes.
NOTE: DHEA has not yet been evaluated by the Food and Drug Administration. Nutritional supplement products containing DHEA are not intended to diagnose, treat, cure, or prevent any disease. Consumers should also be informed that rigid quality control standards are not required for nutraceuticals and substantial variability can occur in both the potency and the purity of these products.
Dehydroepiandrosterone (free and sulfate) test systems measure dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) in urine, serum, plasma, and amniotic fluid. These measurements are used in the diagnosis and treatment of DHEA-secreting adrenal cancers. It is unclear at this time if supplementation with DHEA would result in false-positives of these tests. The effect of DHEA on hormone-dependent tumors in males and females is unknown. Many hormonal agents with androgenic or estrogenic activity are contraindicated for use in persons with various hormonally-dependent neoplasms. Some data suggests an association between elevated endogenous DHEA and DHEAS serum concentrations and the development of breast cancer andovarian cancer in women. As with other hormones, DHEA supplementation in a woman with undiagnosed abnormal vaginal bleeding, endometrial cancer, endometrial hyperplasia, uterine cancer, or vaginal cancer is not recommended. DHEA may stimulate the growth of cancerous tissue and should not be used in male patients with either breast or prostate cancer. Male patients with symptoms of prostatic hypertrophy or erectile dysfunction that have not been medically evaluated should not take DHEA supplements. Because the incidence of some hormonally-dependent cancers naturally increases with age, "andropausal" men and post-menopausal women should approach DHEA supplementation with caution. It is recommended that a qualified healthcare prescriber's recommendations be sought prior to DHEA supplementation. Benefit versus risk should be determined individually. Women taking DHEA should receive an annual clinical breast examination and pelvic examination and regular mammograms as recommended by their healthcare professional. Men taking DHEA should receive annual physical examinations, including prostate examination or PSA levels, as recommended by their healthcare provider.
Dehydroepiandrosterone, DHEA is contraindicated for use in children <= 18 years of age. Because endogenous DHEA, DHEAS, and androstenedione serum concentrations are related to the onset of puberty, there is concern that the use of DHEA supplements in children or adolescents would interfere with natural growth and sexual maturation.
Females of childbearing age with infertility due to hyperandrogenism or chronic anovulation should not take DHEA supplements. The relationship of DHEA and DHEAS to ovulation and fertility is complex and still poorly understood. However, women with hirsutism and infertility or polycystic ovary syndrome (PCOS) are commonly found to have elevated endogenous DHEA or DHEAS serum concentrations on assay. Women with higher serum levels of endogenous DHEAS and who are receiving fertility treatments have been noted to have higher rates of ovarian hyperstimulation syndrome (OHSS) associated with their treatments. DHEA may also induce changes in the normal menstrual cycle in women of childbearing age.
Dehydroepiandrosterone, DHEA should be considered a pregnancy category X drug, similar to other androgenic hormones. Studies of the role of endogenous fetal and maternal DHEA in pregnancy indicate that the ratio of DHEA or DHEAS to other hormones in the serum or placenta may influence the processes of fetal development, parturition, and labor. Endogenous DHEA and DHEAS appear to be important in the functional development of the adrenal cortex and other endocrine activities in the fetus; it is assumed that exogenous DHEA supplementation to a pregnant woman could potentially have deleterious effects on fetal development or viability. The androgenic effects of DHEA could potentially result in masculinization of a female fetus. No controlled trials of DHEA in primate or human gestation exist. Do not administer DHEA to a pregnant woman.
DHEA is a hormone and should not be supplemented in a lactating woman who is breast-feeding her infant. Most hormones are excreted in breast milk. Like other androgenic hormones, it is possible that DHEA could inhibit lactation. It is unknown what effect DHEA would have on the breast-feeding infant.
Dehydroepiandrosterone, DHEA should be considered contraindicated for use in patients with hepatic disease, hepatitis,hepatocellular cancer, or jaundice. In 1984, the FDA banned the non-prescription (OTC) sale of DHEA due to concern over its ability to cause hepatotoxicity. DHEA supplements are now able to be sold as "nutritional supplements" secondary to the US Dietary Supplement Health and Education Act (DSHEA) of 1994, and are no longer regulated as drugs outside of clinical trials. Transient drug-induced hepatitis has been reported in association with the use of DHEA nutritional supplements. Because both estrogens and androgens may exacerbate acute intermittent or variegate hepatic porphyria, DHEA, which has androgenic actions, should be used with caution in patients with these diseases.
Treatment of patients with diabetes mellitus with DHEA is currently not warranted. The role of endogenous DHEA in relationship to insulin resistance is not clear. DHEA and DHEAS may not be mediators of insulin action. Long-term trials evaluating the effectiveness and safety of exogenous DHEA supplementation in patients with diabetes are currently unavailable. Patients with diabetes mellitus who are pursuing the use of DHEA supplements should see a qualified health care professional.
DHEA treatment of patients with human immunodeficiency virus (HIV) infection should be approached with caution. DHEA may possess immunomodulating effects, perhaps by enhancing the secretion of IL-2 from activated T cells as demonstrated in murine models. While this suggests that DHEA may play a role in the function of the immune system, the role of DHEA supplementation in the treatment of human HIV infection, especially acquired immunodeficiency syndrome (AIDS), has not yet been determined. Safety and efficacy have not been established.
Most non-essential hormones are discontinued several weeks prior to major surgery where feasible. DHEA may inhibit platelet aggregation, an effect that may be important to consider during surgical procedures. The decision of when to resume DHEA after surgery would be based on the perceived additional risk from DHEA use and the need for DHEA therapy.
Soy oil is the raw product from which many DHEA supplements are manufactured. Cholesterol from soy oil is converted into DHEA. DHEA products should be used cautiously in patients with a history of allergies to soy-containing foods or who exhibit immediate-type soya lecithin hypersensitivity.
One of the functions of endogenous DHEA is to inhibit the enzyme glucose-6-phosphate dehydrogenase. Use DHEA with caution in patients with G6PD deficiency.
Prasterone (DHEA) should be used with caution in patients with bipolar disorder. One case report exists of the appearance of mania in a predisposed patient consuming large doses of a DHEA supplement on a routine basis. Until more information is known, clinicians should be aware that emotional lability or changes in mood may occur in selected patients.
There is little data on the long-term effects of oral pregnenolone. Since pregnenolone is a precursor to estrogen, its use is contraindicated in patients diagnosed with or at risk for estrogen-dependent cancers, including breast, endometrial, ovarian, and prostate. Research shows that high levels of estrogen may also contribute to a number of health concerns and conditions, including endometriosis, cardiovascular disease, lupus erythematosus, neurodegenerative diseases like Alzheimer's, and seizure disorders.
High levels of DHEA, a pregnenolone-derived neurosteroid, might worsen psychiatric disorders and increase the risk of mania in people who have mood disorders. Pregnenolone is contraindicated in patients taking DHEA, patients with higher than normal levels of DHEA, and patients who have been diagnosed with or who are at risk for psychiatric disorders and mania.
Pregnenolone may cause rapid heart beat. Pregnenolone is contraindicated in patients diagnosed with or at risk for arrhythmia.
Pregnenolone is contraindicated in patients diagnosed with or at risk for liver or kidney disease.
Smoking increases the risk of cardiovascular disease in women taking menopausal hormone therapy. Smoking increases testosterone levels in men by as much as 15% compared to patients who do not smoke. Although more research is needed to fully understand how smoking impacts hormone levels, it is recommended that patients interested in taking pregnenolone should cease smoking before taking pregnenolone.
DHEA should be considered a pregnancy category X drug, similar to other androgenic hormones. Studies of the role of endogenous fetal and maternal DHEA in pregnancy indicate that the ratio of DHEA or DHEAS to other hormones in the serum or placenta may influence the processes of fetal development, parturition, and labor. Endogenous DHEA and DHEAS appear to be important in the functional development of the adrenal cortex and other endocrine activities in the fetus; it is assumed that exogenous DHEA supplementation to a pregnant woman could potentially have deleterious effects on fetal development or viability. The androgenic effects of DHEA could potentially result in masculinization of a female fetus. No controlled trials of DHEA in primate or human gestation exist. Do not administer DHEA to a pregnant woman.
There is little data on the use of pregnenolone tablets in women who are pregnant or breastfeeding. As such, it is difficult to determine a drug-associated risk of adverse developmental outcomes. Women who are pregnant or breast-feeding should avoid using this product.
NOTE: High concentrations of anastrozole inhibited metabolic reactions catalyzed by cytochromes P450 (CYP) 1A2, 2C8/9, and 3A4. Anastrozole did not inhibit CYP2A6 or the polymorphic CYP2D6 in human liver microsomes. Per the manufacturer, it is unlikely that anastrozole administered at the recommended dose will inhibit the metabolism of cytochrome P450-mediated drugs given concomitantly.
In a study in male volunteers (n=16), anastrozole did not alter the warfarin pharmacokinetics (Cmax or AUC), and did not alter warfarin anticoagulant activity as measured by prothrombin time, activated partial thromboplastin time, and thrombin time of both R- and S-warfarin.
Anastrozole and tamoxifen should not be administered together. Clinical and pharmacokinetic results from the ATAC study demonstrate that concurrent administration of anastrozole and tamoxifen results in a reduction of anastrozole plasma levels by 27% compared to those achieved with anastrozole alone. However, coadministration did not affect the pharmacokinetics of tamoxifen or N-desmethyltamoxifen.
The goal of anastrozole therapy is to decrease circulating estrogen concentrations and inhibit the growth of hormonally-responsive cancers. Anastrozole should not be given concurrently with any estrogens or estrogen-containing products, including combined oral contraceptives, as these could interfere with the pharmacologic action of anastrozole. In addition, in women receiving long-term aromatase inhibitor therapy, atrophic vaginitis due to estrogen suppression is common; atrophic vaginitis due to aromatase inhibitor therapy is sometimes treated with vaginal estrogen as the systemic exposure of estrogen from vaginal preparations is thought to be low. In a recent study of 7 women on aromatase inhibitor therapy, estrogen concentrations rose significantly after the addition of vaginally administered estrogen for atrophic vaginitis. Estrogen concentrations increased from a mean baseline level of < 5 pmol/l to 72 pmol/l at 2 weeks and to < 35 pmol/l at 4 weeks. Although the study was small, estrogen concentrations rose significantly in 6/7 patients. Clinicians should be aware that serum estrogen concentrations may increase with the use of vaginal estrogen preparations; alternative treatments for atrophic vaginitis in patients taking aromatase inhibitors should be considered.
Androstenedione is an important metabolic precursor for androgens and estrogens in both males and females. Androstenedione supplements should not be given concurrently with any aromatase inhibitors, as androstenedione could interfere with the pharmacologic action of the aromatase inhibitor. Conversely, aromatase inhibitors (e.g., aminoglutethimide, anastrozole, exemestane, letrozole, testolactone, vorozole) could interfere with biotransformation of androstenedione in both males and females; the enzyme aromatase converts androstenedione to estrone.
Prasterone, dehydroepiandrosterone, DHEA is converted via hydrosteroid dehydrogenases and aromatase into androstenedione, testosterone, and estradiol by peripheral tissues. Prasterone or DHEA supplements should not be given concurrently with any aromatase inhibitors, as DHEA could interfere with the pharmacologic action of the aromatase inhibitor and compromise aromatase inhibitor effectiveness. Conversely, aromatase inhibitors (e.g., aminoglutethimide, anastrozole, exemestane, letrozole, testolactone, vorozole could interfere with biotransformation of DHEA.
DHEA / Pregnenolone Capsules Side Effects & Reactions
NOTE: Many prasterone, dehydroepiandrosterone, DHEA preparations contain a variety of other ingredients, including minerals, vitamins, hormones and/or herbs, and each individual component may need to be evaluated for the presence of drug interactions. Only drug interactions pertaining to DHEA are discussed in this monograph.
Prasterone, dehydroepiandrosterone, DHEA is converted via hydrosteroid dehydrogenases and aromatase into androstenedione, testosterone, and estradiol by peripheral tissues. DHEA is a weak androgen that has complex hormonal effects. It is unclear what actions prasterone, dehydroepiandrosterone, DHEA would have on other exogenous hormonal regimens (e.g., androgens, estrogens, oral contraceptives, or progestins). Either additive or antagonistic effects could potentially occur. The mechanisms or results of interactions with DHEA and other hormones may be multifactorial and dependent on the sex and age of the individual being treated, the indication for hormone use, the route by which DHEA is given, and the length of concomitant use. Concurrent use of DHEA with any of these hormonal regimens is not recommended at this time.
Prasterone, dehydroepiandrosterone, DHEA is converted via hydrosteroid dehydrogenases and aromatase into androstenedione, testosterone, and estradiol by peripheral tissues. DHEA is a weak androgen that has complex hormonal effects. It is unclear what actions prasterone, dehydroepiandrosterone, DHEA would have on other exogenous hormonal regimens. It would seem prudent to not administer DHEA with infertility or hormonal cancer treatments such as GnRH analogs (cetrorelix, ganirelix, goserelin, histrelin, leuprolide, or triptorelin) since DHEA may theoretically interfere with these therapies.
Prasterone, dehydroepiandrosterone, DHEA is converted via hydrosteroid dehydrogenases and aromatase into androstenedione, testosterone, and estradiol by peripheral tissues. DHEA is a weak androgen that has complex hormonal effects. The action of 5-alpha reductase inhibitors (i.e., dutasteride, finasteride) could potentially be antagonized by DHEA administration. 5-alpha-reductase inhibitors have anti-androgenic effects on the prostate gland that may be antagonized by the androgenic effects of DHEA on these tissues. Avoid concurrent use.
Drug interactions with Saw palmetto, Serenoa repens have not been specifically studied or reported. Saw palmetto extracts appear to have antiandrogenic effects. The antiandrogenic effects of Saw palmetto, Serenoa repens would be expected to antagonize the actions of androgens; it would seem illogical for patients taking androgens to use this herbal supplement.
Corticosteroids blunt the adrenal secretion of endogenous DHEA and DHEAS, resulting in reduced DHEA and DHEAS serum concentrations. The impact of exogenous prasterone, dehydroepiandrosterone, DHEA administration on the safety or efficacy of chronic corticosteroid treatment regimens is not yet clear. The administration of DHEA to patients on corticosteroids should only be done under the observation of a qualified health care professional.
Prasterone, dehydroepiandrosterone, DHEA appears to have anti-platelet effects, which may prolong bleeding times. Inhibition of platelet aggregation by DHEA has been demonstrated in vivo in humans; the rate of arachidonate-stimulated platelet aggregation was prolonged or completely inhibited. In addition, DHEA is converted to androgens and estrogens within the human body and thus may affect hemostasis via androgenic or estrogenic effects. Estrogens increase the production of clotting factors VII, VIII, IX, and X.Androgens, such as testosterone, increase the synthesis of several anticoagulant and fibrinolytic proteins. Because of these potential, varied effects on coagulation, patients receiving DHEA concurrently with anticoagulants (e.g., warfarin or heparin) or other platelet inhibitors, including aspirin, ASA should be monitored for side effects or the need for dosage adjustments.
Concurrent use of antidiabetic agents with prasterone, dehydroepiandrosterone, DHEA is currently not warranted. The role of endogenous DHEA in relationship to insulin action or glucose intolerance is not clear. Endogenous levels of DHEA and DHEAS may be regulated by insulin and may not mediate insulin action. It is unclear what effect DHEA supplementation would have on glycemic control. Trials evaluating the effectiveness and safety of exogenous DHEA supplementation in combination with antidiabetic agents are currently unavailable.
Prasterone, dehydroepiandrosterone, DHEA is converted via hydrosteroid dehydrogenases and aromatase into androstenedione, testosterone, and estradiol by peripheral tissues. Prasterone or DHEA supplements should not be given concurrently with any aromatase inhibitors, as DHEA could interfere with the pharmacologic action of the aromatase inhibitor and compromise aromatase inhibitor effectiveness. Conversely, aromatase inhibitors (e.g., aminoglutethimide, anastrozole, exemestane, letrozole, testolactone, vorozole) could interfere with biotransformation of DHEA.
Prasterone, dehydroepiandrosterone, DHEA may inhibit the metabolism of triazolam, and other benzodiazepines (e.g., alprazolam, estazolam, midazolam) which undergo CYP3A4-mediated metabolism. In one study of elderly volunteers, half of the patients received DHEA 200 mg/day PO for 2 weeks, followed by a single dose of triazolam 0.25 mg. Triazolam clearance was reduced by close to 30% in the DHEA-pretreated patients vs. the control group; however, the effect of DHEA on CYP3A4 metabolism appeared to vary widely among subjects. While more study is needed, benzodiazepine-induced CNS sedation and other adverse effects might be increased in some individuals if DHEA is co-administered.
Prasterone, dehydroepiandrosterone, DHEA is a weak androgen that has complex hormonal effects. Androgens are known to stimulate erythropoiesis.58 Despite the fact that endogenous generation of erythropoietin is depressed in patients with chronic renal failure, other tissues besides the kidney can synthesize erythropoietin, albeit in small amounts. Concurrent administration of androgens can increase the patient's response to epoetin alfa, reducing the amount required to treat anemia. Because adverse reactions have been associated with an abrupt increase in blood viscosity, this drug combination should be avoided, if possible. Further evaluation of this combination needs to be made.
In vitro, both genistein and daidzein inhibit 5 alpha-reductase isoenzyme II, resulting in decreased conversion of testosterone to the potent androgen 5-alpha-dihydrotestosterone (DHT) and a subsequent reduction in testosterone-dependent tissue proliferation. The action is similar to that of finasteride, but is thought to be less potent. Theoretically, because the soy isoflavones appear to inhibit type II 5-alpha-reductase, the soy isoflavones may counteract the activity of the androgens.
There is very little data on the effects of long-term use of pregnenolone. Limited studies where pregnenolone is administered for four to twelve weeks show that pregnenolone is well-tolerated. One study recorded mild side effects, including mild restlessness, mild muscle pain/stiffness, and mild cold extremities.
Pregnenolone may cause side effects similar to those known for testosterone, including acne, hair loss, aggressiveness, irritability, increased levels of estrogen, and hair growth on the face in women. In some cases, which would call for immediate termination of use, it may cause rapid heartbeat, blurred vision, and dizziness. This list may not include all possible adverse reactions or side effects.
Store this medication in its original container at 68°F to 77°F (20°C to 25°C) and away from heat, moisture and light. Keep all medicine out of the reach of children. Throw away any unused medicine after the beyond-use date. Do not flush unused medications or pour down a sink or drain.
You can order DHEA / Pregnenolone Capsules from MediLab's compounding pharmacy in the following Florida regions:
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Marx CE, Bradford DW, Hamer RM, Naylor JC, Allen TB, Lieberman JA, Strauss JL, Kilts JD. Pregnenolone as a novel therapeutic candidate in schizophrenia: emerging preclinical and clinical evidence. Neuroscience. 2011;191:78-90.
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Wellman M, Shane-McWhorter L, Orlando PL et al. The role of dehydroepiandrosterone in diabetes mellitus. Pharmacotherapy 1999;19:582-591.
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Mungenast F, Thalhammer T. Estrogen Biosynthesis and Action in Ovarian Cancer. Front Endocrinol (Lausanne). 2014;5:192.
Bosland MC. The Role of Estrogens in Prostate Carcinogenesis: A Rationale for Chemoprevention. Rev Urol. 2005;7(Suppl 3):S4–S10.
Deroo BJ, Korach KS. Estrogen receptors and human disease. J Clin Invest. 2006;116(3):561–570.
Serdar E. Bulun SE, Monsavais D, Pavone ME, Dyson M, Xue Q, Attar E, Tokunaga H, Su EJ. Role of Estrogen Receptor-β in Endometriosis. Nat Med. 2012;18(7):1016–1018.
Howard BV, Rossouw JE. Estrogens and Cardiovascular Disease Risk Revisited: the Women's Health Initiative. Curr Opin Lipidol. 2013;24(6):493–499.
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SANTA FE ART INSTITUTE AND "THE ART OF CHANGE:" A NIGHT OF FILM, MUSIC AND ART CELEBRATING CATALYTIC ARTISTS THAT CHANGE THE WORLD
Santa Fe, NM, September 25, 2019 — Beneath a serene, star-filled evening sky on September 6th, Santa Fe Art Institute (SFAI) hosted "The Art of Change: A Night of Film, Music and Art Celebrating Catalytic Artists that Change the World." The evening was a cross disciplinary art experience that featured a mixed media exhibit, an […]
Hummingbird Media, Inc. ⋅ Published: October 2, 2019
Santa Fe, NM, September 25, 2019 — Beneath a serene, star-filled evening sky on September 6th, Santa Fe Art Institute (SFAI) hosted "The Art of Change: A Night of Film, Music and Art Celebrating Catalytic Artists that Change the World." The evening was a cross disciplinary art experience that featured a mixed media exhibit, an exclusive screening of a new Prince documentary film by Director Kirk Fera, and an intimate performance by Belling The Cat: Brian Hardgroove's newly minted rock ensemble which also scored music for the film. During the event, a sensational multi-room audio experience was delivered by Sennheiser.
The new movie, entitled "Mr. Nelson: On the North Side," describes how Prince found security, musical opportunities and encouragement while growing up in North Minneapolis at a local community center called The Way. The intimate screening included a thoughtful Q&A with Director Kirk Fera and Brian Hardgroove, moderated by Director Chris Eyre (Smoke Signals and Skins), followed by an outdoor musical performance by Hardgroove's Belling The Cat.
Wireless system heard 'round the world
SFAI guests were invited to listen to a custom stereo feed of the performance through a pair of Sennheiser MOMENTUM headphones, while moving freely throughout the facility. This was made possible through a Sennheiser evolution wireless G4 system, which broadcast a stereo mix to 26 different G4 wireless receiver packs which were connected to the headphones. The set-up consisted of a single Sennheiser ew IEM G4 transmitter coupled with an A 5000-CP passive antenna, which then broadcast the stereo signal to 26 IEM G4 stereo receivers.
Throughout the evening, Sennheiser evolution 900 series microphones graced the stage, ensuring that instrument and vocal performances were captured with detail, fidelity and power. Several Sennheiser e 935 cardioid microphones handled vocal duties, while a 906 super-cardioid was used on guitar amplifiers. The drum kit, played by Hardgroove himself, featured an e 901 on the kick drum, e 904s on the snare and toms, and e 914s on the hi-hat and as overheads.
"I love that the Art Institute has been able to partner with a world class musician and producer like Brian Hardgroove, who brings his passion, expertise and perfectionism to Santa Fe," commented Jamie Blosser, Executive Director of SFAI. "Having Sennheiser products here to accompany our guest experience exemplifies the amazing quality that all artists strive for. We support many local artists, as well as national and international artists, and they are all blown away by what is going on right here in Santa Fe. This work has something of a ripple effect around the world."
Keeping it in Santa Fe
Hardgroove, a longtime collaborator with Sennheiser, was asked by Director Kirk Fera to score the new film after having worked with him on an earlier film by Fera entitled Find Your Groove. For Hardgroove, it was all about getting the right people in the room and making it happen in an inspiring location: "It was important for me to keep this project in Santa Fe after we agreed to do the score," he says. "Kirk agreed to this and once we assembled everybody in the room we listened to Kirk's cues and just let the inspiration run."
"I fell in love with the Santa Fe community itself through Brian, and when we went into the studio, it was genius," adds Fera. "I would give the band a cue — each one from different time period and varying in length — and these guys nailed it. The music in this film is really special to me, and the creative spirit of everyone coming out together in Santa Fe made the film so much better in the end."
"We've done many projects with Brian over the years — he is a true visionary who has pulled all of this together," said David Missall, Development & Application Engineering, Sennheiser. "We are very pleased to have contributed to the successful outcome of this event by helping provide a superior audio experience for guests and friends of the SFAI."
To learn more about SFAI's events and programming, please visit https://sfai.org.
About Sennheiser
Shaping the future of audio and creating unique sound experiences for customers – this aim unites Sennheiser employees and partners worldwide. Founded in 1945, Sennheiser is one of the world's leading manufacturers of headphones, loudspeakers, microphones and wireless transmission systems. Since 2013, Sennheiser has been managed by Daniel Sennheiser and Dr. Andreas Sennheiser, the third generation of the family to run the company. In 2018, the Sennheiser Group generated turnover totaling €710.7 million. www.sennheiser.com
This section of Pro Sound Network, "The Wire," contains original press releases that reflect the views of the industry organizations issuing them. Releases are not reviewed or edited by Pro Sound News editorial staff.
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In a 'winner takes all' contest at Colney Lane last Wednesday, UEA Men's Football I suffered a heart-breaking 3-2 defeat to Loughborough II which confirmed their relegation from Midlands 1A Division.
The hosts went in to the game with the knowledge that a win would keep alive their survival hopes and would be enough to leapfrog their opponents, despite them having a game in hand. But the visitors snatched a priceless victory that extends the gap between the two sides to four points with UEA only have one game to play, confirming their demotion before this week's Derby Day encounter.
In an evenly contested tie, UEA were their own worst enemy at times. Loughborough were gifted the lead early on after a long throw wasn't dealt with by the UEA defence, allowing the away player to direct a low shot past the 'keeper, beating him at his near post.
Though they fought their way back into the match towards the end of the first half when Neil Hurren latched on to a well crafted chipped through ball and poked past the 'keeper, Loughborough were once again handed the lead on a plate after the interval. After centre-back Daniel Morphew had slashed a clearance skywards, he then hauled down the striker to award the visitors perhaps the most blatant penalty you're ever likely to see. The resulting spot-kick was dispatched with certified aplomb into the bottom right hand corner by their central midfielder, giving the home side an uphill struggle once more.
Nevertheless, UEA deserve plenty of credit for battling back into the game. This time it was the away side who caused their own downfall, failing to deal with a goal mouth scramble in their own penalty area which was eventually curled home into the bottom corner from just outside the six-yard box by Chuka Obi.
Seconds later, Simon Beeson did well to turn his man and began running through on goal, only to be dragged to the floor by the Loughborough defender. Had the decision been given, the referee would have been given no option but to send off the player. Despite the justified cries from the UEA players, the referee waved away their appeals – a turning point that swung the match back in the favour of UEA's opponents.
What came next was a moment of pure genius – and unfortunately for the U's it came from Loughborough's talented winger. The number seven collected the ball midway into the UEA half, pulled off a sublime 'Zidane turn' to beat two players, dropped a shoulder to beat another, then showed an electric turn of pace to force his way into the penalty area where he then unleashed a stunning left footed drive across the goalkeeper and into the top corner.
Cue euphoric celebrations from Loughborough, while the UEA players could only stand completely stunned. It was a goal worthy of winning any game, and unlike the other two goals there was absolutely nothing that could have been done to prevent it.
Understandably, the goal seemed to have knocked the stuffing out of the home side. They tried to press for a late equaliser, but it was the visitors who came closest to scoring as they looked a constant threat on the counter with UEA forcing men forwards in the late stages. Despite a flurry of late free-kicks, throw-ins and corners, Loughborough held firm for the all important three points.
UEA will hope their luck is in store next week, when they come against bitter rivals Essex in the much awaited-for Derby Day encounter.


SteamJet recently attended the SmallSat conference in Logan, Utah. SmallSat is an internationally recognized conference on small satellites held annually on the campus of Utah State University. The conference is focused on providing a forum for the best minds in the small satellite community to explore new trends and directions, review recent successes, and introduce new and innovative technologies relevant to the market.
The SteamJet propulsion system was introduced and well received from both potential customers and industry professionals. The tuna can shape factor, the safety features and overall design quality and performance were greatly appreciated by industry experts, raising the interest of many key players in using our system for their future missions.
"The feedback we received from the small satellite community was extremely good. We committed to creating a really safe and compact propulsion system since day one, which are essential features in the small satellite market. We had a lot of interest around our product, so we are now pushing product development and testing to make it ready for space." said SteamJet's Director, Marco Pavan.
Following this year's success, SteamJet is looking forward to #SMALLSAT 2019!


"Programmed Genome Processing in Ciliates" by Aaron David Goldman, Elizabeth M. Stein et al.
The ciliates are a group of protists distinguished by the hair-like cilia on their cell surfaces. Ciliates also possess two types of nuclei, a germline micronucleus and a somatic macronucleus. The micronuclear genome contains segmented genes divided by spacer sequences of DNA that are removed to generate the macronuclear genome during development. For some species, certain micronuclear gene segments can be reordered and/or inverted with respect to their final gene sequence in the macronucleus. This chapter explores the similarities of and differences between micronuclear genomes and the processes of macronuclear development across different ciliate species.
Goldman, Aaron David, Elizabeth M. Stein, John R. Bracht, and Laura F. Landweber. "Programmed Genome Processing in Ciliates." In Discrete and Topological Modeling in Molecular Biology, edited by Natasa Jonoska and Masahico Saito, 273-287. Berlin, Germany: Springer, 2014.


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News » Pregnancy News
Pregnancy-Induced Hypertension and Effects on Offspring Health
Amos Grünebaum
According to a new study published in the journal PLoS One, offspring born to mothers with pregnancy-induced hypertension (PIH) in the first trimester were less likely to have health issues later in life. Late in pregnancy PIH had the opposite effect. The research was completed by researchers at the University of Copenhagen.
Researchers reviewed medical records for more than 750,000 births. Offspring were followed for up to 30 years and health issues were noted. According to the research, the human body has not moved past all of its hunter-gatherer roots. First-trimester PIH was associated with improved health outcomes for offspring. Researchers believe the risk to maternal health in the first trimester is offset by these improved offspring health outcomes.
When women experienced PIH in the second or third trimester, the results were not the same. Offspring showed signs of increased health risks in these cases - reinforcing the play of natural selection in human reproduction.
Source: Hollegaard B, Byars SG, Lykke J, Boomsma JJ. Parent-offspring conflict and the persistence of pregnancy-induced hypertension in modern humans. PLoS One. 2013;8(2):e56821. doi: 10.1371/journal.pone.0056821. Epub 2013 Feb 25.
pregnancy induced hypertension (PIH)
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Sarah is the mother of 2 children. After a difficult birth, Sarah's son Avi was admitted to the neonatal intensive care unit (NICU), and later passed away. Her second child, Lila, was born 18 months later, and is now a happy, healthy seven-year-old. From her experience, Sarah is passionate about empowering parents faced with life's most fragile and difficult of moments.
Sarah received a Bachelor of Science in Neurobiology and Physiology from Purdue University, and a Master of Arts in Philanthropic Studies from the Indiana University Lilly Family School of Philanthropy. She is employed with the Indiana University Foundation.
Gina joins the Project Sweet Peas board as Vice President and offers vast experience and knowledge. After her own experience with the NICU, Gina wanted a way to give back and pay it forward.
Gina received her JD from University of Pittsburgh School of Law and currently practices at Walsh, Barnes, Collis & Zumpella, P.C.
Corin is the Treasurer and Co-Founder of Project Sweet Peas and a Division Coordinator for the Southern New England division. Corin is the mother of five children. Her first child, Gabriel, spent 55 days in the NICU before he passed away in the loving arms of his parents. Gabriel is the inspiration and drive behind her passion to make sure NICU and bereaved families receive the support that they need.
Corin received an Associates in Baking and Pastry Arts from Johnson and Wales University and has returned to college to pursue a degree in Social Work. In addition to raising her four children at home and attending night classes, she is currently serving as Secretary on the Women & Infants NICU Advisory Committee, and an active volunteer at the hospital.
Chris serves as the Director of Grant Development. His son Adrian Burke "AB" was born at 23 weeks and after 131 days in the NICU has continued to grow and thrive. Out of gratitude for the community that offered unwavering support during Adrian's hospital stay, Chris and his wife Jes have worked to identify opportunities to give back to the NICU community. Chris is motivated to identify and capture funding to ensure that Project Sweet Peas can continue engaging and supporting this community.
Chris received a Bachelor of Science in Business Management from Athens State University and is currently completing a Master's in Business Analytics at the University of Alabama at Huntsville. He is employed as a Program Manager for Hexagon Safety & Infrastructure.
Megan resides in Pittsburgh, PA with her husband and daughter. She is happy to bring several years of professional writing and communications experience to the Project Sweet Peas team. Several of Megan's friends' children have stayed in the NICU, and she is proud to work with an organization that supports families going through difficult situations.
Diane is a Board Advisor and a Division Coordinator for our Southern New England division, which was created in honor of her twin boys, Justin and Collin, who were born prematurely at 33 weeks and spent 6 weeks in the NICU. Diane, along with her husband, sons, and daughter Ashlyn, aspire to pay it forward to other NICU families.
Diane received a Bachelor of Science in Business Administration from Northeastern University and a Masters in Business Administration from Suffolk University. She is currently employed with the University of Massachusetts Medical School.
Janice is a Board Advisor and a Division Coordinator for our New Hampshire division, which was created in memory of Aiden and to honor Adam. Her grandsons were born at 26w 4d. Adam spent 103 days in the NICU. Sadly, Aiden passed after his first few hours of life. After this experience Janice became passionate about giving back to the families who are faced with this difficult journey in the NICU.
Kate is the Co-Founding President for Project Sweet Peas. Kate was a major contributor in the creation of Project Sweet Peas in memory of Shannon Crawford (01/16/07-01/19/07), who passed away from two birth defects (CDH & HLHS). Kate remains an active volunteer.


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Academy Announces the 2020 Oscar Nominations
With the wide range of movies released in 2019, the nominations for this year's awards are very vast.
Kourtni Weldon and Jazzmyn Roman|January 13, 2020
Emily Lara
This morning the 92nd Academy Awards nominees were announced. Many of the most beloved movies from the past year are nominated in multiple categories, leaving movie-goers full of anticipation of which will be named the "Best" in each category.
Joker, one of the most talked about films of 2019, is nominated in 11 different categories. The lead actor of the film, Joaquin Phoenix, was nominated for "Performance by an actor in a leading role" for his performance as Arthur Fleck, also known as Joker. The film was also nominated in categories such as "Achievement in music written for motion pictures" for the movie's original score written by Hildur Guðnadóttir, and "Best motion picture of the year."
Other films nominated for "Best motion picture of the year" include Once Upon A Time… In Hollywood, which received mixed reviews, as well as Ford v Ferrari, which was received well by critics.
"I thought [Ford v Ferrari] was a really good movie," junior Lilya Ocampo said. "The race car driver was casted perfectly. I couldn't see anyone else playing that character, and all the music and sound in the movie was amazing as well."
2019 was a great year for film, including setting a new record for the world's top grossing film of all time with the release of Avengers: Endgame, which is nominated for the award for "Achievement in visual effects."
"Endgame definitely deserved a nomination," senior Katelyn Goldstein said. "I liked how action packed it was and how it incorporated all the superheroes in that realm of movies."
The Academy is also recognizing the outstanding animated films from the previous year, nominating films such as How To Train Your Dragon: The Hidden World and Toy Story 4.
"Disney always makes good movies," junior Emma Allen said. "I'm not surprised it got a nomination. It definitely deserved it, although I wasn't a huge fan of the ending."
Other movies nominated for multiple awards this year include Little Women (critically praised as a fun and thoughtful adaptation of Louisa May Alcott's novel), 1917 (the Golden Globe winner for best picture) and the Irishman (Netflix's three-hour epic). The list of nominees this year are diverse in all categories, and audiences are creating all kinds of buzz surrounding who they believe will win this year. Be sure to tune into the 92nd Academy Awards on February second to see which movies will take home the most prestigious awards of the season.
Click here to view the full list of nominations.
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Oatmeal is known for its beneficial nourishing and soothing properties and it still remains as a very popular natural skin care ingredient. Oatmeal is great for exfoliating your face (because of its grainy texture) and for the preparation of homemade face masks; oats can effectively absorb and remove the dirt and impurities from skin surface.
Natural Scrubs made with Oats mixed with other fruits can help treat many skin conditions, as well as rejuvenate and sooth dry and itchy skin; Today I am reviewing a facial scrub from Juicy Chemistry – Peach & Strawberry Oats Face Scrub which suits even the sensitive skin. Picture itself look so tempting right! This scrub is made of oats, peach & strawberry.
Product claims : Improves skintone and texture. Fights dull and flaky dryness. Absorbs excess dirt, oil and bacteria.
I am a big fan of natural skin care products. First thing I noticed about this product is how wonderful it smell. After a tired day @ work, this is so awesome to use. I used this during my stay in Kerala.
I mix this with water to make a thick paste. Gently, in circular motions, massage your clean face with this scrub to exfoliate your skin; massage for 1-2 minutes, avoiding the eye area. Rinse with warm and then, cold water (cold water will help close your pores).
I loved the strawberry + peach smell it has and it really made my face soft and clean. Scrub is not harsh at all. As it has no harmful ingredients – Its completely safe to use everyday too. If used everyday, A tub lasts for more than a month. My skin never felt dry after using this. I am not saying it improves skin tone and all..However, my skin never had any breakouts or something . It's a nice everyday scrub.
Use a wooden applicator to take the product each time. This ensure the products remain fresh. It's safest to take the products with an applicator.
Follow Juicy Chemistry here for ordering the products. Juicy Chemistry Ships worldwide. If you decide to order and don't know which products suit your skin type, You can direct message Juicy Chemistry, The Wonderful Megha Asher will respond to all your queries and help you choose the products that best suit your skin type.
**Products send by the brand. However my review is honest & unbiased as always.
It is !! Do try them!