More on Science
Michael Hunter, MD
3 years ago
5 Drugs That May Increase Your Risk of Dementia
While our genes can't be changed easily, you can avoid some dementia risk factors. Today we discuss dementia and five drugs that may increase risk.
Memory loss appears to come with age, but we're not talking about forgetfulness. Sometimes losing your car keys isn't an indication of dementia. Dementia impairs the capacity to think, remember, or make judgments. Dementia hinders daily tasks.
Alzheimers is the most common dementia. Dementia is not normal aging, unlike forgetfulness. Aging increases the risk of Alzheimer's and other dementias. A family history of the illness increases your risk, according to the Mayo Clinic (USA).
Given that our genes are difficult to change (I won't get into epigenetics), what are some avoidable dementia risk factors? Certain drugs may cause cognitive deterioration.
Today we look at four drugs that may cause cognitive decline.
Dementia and benzodiazepines
Benzodiazepine sedatives increase brain GABA levels. Example benzodiazepines:
Diazepam (Valium) (Valium)
Alprazolam (Xanax) (Xanax)
Clonazepam (Klonopin) (Klonopin)
Addiction and overdose are benzodiazepine risks. Yes! These medications don't raise dementia risk.
USC study: Benzodiazepines don't increase dementia risk in older adults.
Benzodiazepines can produce short- and long-term amnesia. This memory loss hinders memory formation. Extreme cases can permanently impair learning and memory. Anterograde amnesia is uncommon.
2. Statins and dementia
Statins reduce cholesterol. They prevent a cholesterol-making chemical. Examples:
Atorvastatin (Lipitor) (Lipitor)
Fluvastatin (Lescol XL) (Lescol XL)
Lovastatin (Altoprev) (Altoprev)
Pitavastatin (Livalo, Zypitamag) (Livalo, Zypitamag)
Pravastatin (Pravachol) (Pravachol)
Rosuvastatin (Crestor, Ezallor) (Crestor, Ezallor)
Simvastatin (Zocor) (Zocor)
This finding is contentious. Harvard's Brigham and Womens Hospital's Dr. Joann Manson says:
“I think that the relationship between statins and cognitive function remains controversial. There’s still not a clear conclusion whether they help to prevent dementia or Alzheimer’s disease, have neutral effects, or increase risk.”
This one's off the dementia list.
3. Dementia and anticholinergic drugs
Anticholinergic drugs treat many conditions, including urine incontinence. Drugs inhibit acetylcholine (a brain chemical that helps send messages between cells). Acetylcholine blockers cause drowsiness, disorientation, and memory loss.
First-generation antihistamines, tricyclic antidepressants, and overactive bladder antimuscarinics are common anticholinergics among the elderly.
Anticholinergic drugs may cause dementia. One study found that taking anticholinergics for three years or more increased the risk of dementia by 1.54 times compared to three months or less. After stopping the medicine, the danger may continue.
4. Drugs for Parkinson's disease and dementia
Cleveland Clinic (USA) on Parkinson's:
Parkinson's disease causes age-related brain degeneration. It causes delayed movements, tremors, and balance issues. Some are inherited, but most are unknown. There are various treatment options, but no cure.
Parkinson's medications can cause memory loss, confusion, delusions, and obsessive behaviors. The drug's effects on dopamine cause these issues.
A 2019 JAMA Internal Medicine study found powerful anticholinergic medications enhance dementia risk.
Those who took anticholinergics had a 1.5 times higher chance of dementia. Individuals taking antidepressants, antipsychotic drugs, anti-Parkinson’s drugs, overactive bladder drugs, and anti-epileptic drugs had the greatest risk of dementia.
Anticholinergic medicines can lessen Parkinson's-related tremors, but they slow cognitive ability. Anticholinergics can cause disorientation and hallucinations in those over 70.
5. Antiepileptic drugs and dementia
The risk of dementia from anti-seizure drugs varies with drugs. Levetiracetam (Keppra) improves Alzheimer's cognition.
One study linked different anti-seizure medications to dementia. Anti-epileptic medicines increased the risk of Alzheimer's disease by 1.15 times in the Finnish sample and 1.3 times in the German population. Depakote, Topamax are drugs.
Bob Service
3 years ago
Did volcanic 'glasses' play a role in igniting early life?
Quenched lava may have aided in the formation of long RNA strands required by primitive life.
It took a long time for life to emerge. Microbes were present 3.7 billion years ago, just a few hundred million years after the 4.5-billion-year-old Earth had cooled enough to sustain biochemistry, according to fossils, and many scientists believe RNA was the genetic material for these first species. RNA, while not as complicated as DNA, would be difficult to forge into the lengthy strands required to transmit genetic information, raising the question of how it may have originated spontaneously.
Researchers may now have a solution. They demonstrate how basaltic glasses assist individual RNA letters, also known as nucleoside triphosphates, join into strands up to 200 letters long in lab studies. The glasses are formed when lava is quenched in air or water, or when melted rock generated by asteroid strikes cools rapidly, and they would have been plentiful in the early Earth's fire and brimstone.
The outcome has caused a schism among top origin-of-life scholars. "This appears to be a great story that finally explains how nucleoside triphosphates react with each other to create RNA strands," says Thomas Carell, a scientist at Munich's Ludwig Maximilians University. However, Harvard University's Jack Szostak, an RNA expert, says he won't believe the results until the study team thoroughly describes the RNA strands.
Researchers interested in the origins of life like the idea of a primordial "RNA universe" since the molecule can perform two different functions that are essential for life. It's made up of four chemical letters, just like DNA, and can carry genetic information. RNA, like proteins, can catalyze chemical reactions that are necessary for life.
However, RNA can cause headaches. No one has yet discovered a set of plausible primordial conditions that would cause hundreds of RNA letters—each of which is a complicated molecule—to join together into strands long enough to support the intricate chemistry required to kick-start evolution.
Basaltic glasses may have played a role, according to Stephen Mojzsis, a geologist at the University of Colorado, Boulder. They're high in metals like magnesium and iron, which help to trigger a variety of chemical reactions. "Basaltic glass was omnipresent on Earth at the time," he adds.
He provided the Foundation for Applied Molecular Evolution samples of five different basalt glasses. Each sample was ground into a fine powder, sanitized, and combined with a solution of nucleoside triphosphates by molecular biologist Elisa Biondi and her colleagues. The RNA letters were unable to link up without the presence of glass powder. However, when the molecules were mixed with the glass particles, they formed long strands of hundreds of letters, according to the researchers, who published their findings in Astrobiology this week. There was no need for heat or light. Biondi explains, "All we had to do was wait." After only a day, little RNA strands produced, yet the strands continued to grow for months. Jan Paek, a molecular biologist at Firebird Biomolecular Sciences, says, "The beauty of this approach is its simplicity." "Mix the components together, wait a few days, and look for RNA."
Nonetheless, the findings pose a slew of problems. One of the questions is how nucleoside triphosphates came to be in the first place. Recent study by Biondi's colleague Steven Benner suggests that the same basaltic glasses may have aided in the creation and stabilization of individual RNA letters.
The form of the lengthy RNA strands, according to Szostak, is a significant challenge. Enzymes in modern cells ensure that most RNAs form long linear chains. RNA letters, on the other hand, can bind in complicated branching sequences. Szostak wants the researchers to reveal what kind of RNA was produced by the basaltic glasses. "It irritates me that the authors made an intriguing initial finding but then chose to follow the hype rather than the research," Szostak says.
Biondi acknowledges that her team's experiment almost probably results in some RNA branching. She does acknowledge, however, that some branched RNAs are seen in species today, and that analogous structures may have existed before the origin of life. Other studies carried out by the study also confirmed the presence of lengthy strands with connections, indicating that they are most likely linear. "It's a healthy argument," says Dieter Braun, a Ludwig Maximilian University origin-of-life chemist. "It will set off the next series of tests."
Sara_Mednick
3 years ago
Since I'm a scientist, I oppose biohacking
Understanding your own energy depletion and restoration is how to truly optimize
Hack has meant many bad things for centuries. In the 1800s, a hack was a meager horse used to transport goods.
Modern usage describes a butcher or ax murderer's cleaver chop. The 1980s programming boom distinguished elegant code from "hacks". Both got you to your goal, but the latter made any programmer cringe and mutter about changing the code. From this emerged the hacker trope, the friendless anti-villain living in a murky hovel lit by the computer monitor, eating junk food and breaking into databases to highlight security system failures or steal hotdog money.
Now, start-a-billion-dollar-business-from-your-garage types have shifted their sights from app development to DIY biology, coining the term "bio-hack". This is a required keyword and meta tag for every fitness-related podcast, book, conference, app, or device.
Bio-hacking involves bypassing your body and mind's security systems to achieve a goal. Many biohackers' initial goals were reasonable, like lowering blood pressure and weight. Encouraged by their own progress, self-determination, and seemingly exquisite control of their biology, they aimed to outsmart aging and death to live 180 to 1000 years (summarized well in this vox.com article).
With this grandiose north star, the hunt for novel supplements and genetic engineering began.
Companies selling do-it-yourself biological manipulations cite lab studies in mice as proof of their safety and success in reversing age-related diseases or promoting longevity in humans (the goal changes depending on whether a company is talking to the federal government or private donors).
The FDA is slower than science, they say. Why not alter your biochemistry by buying pills online, editing your DNA with a CRISPR kit, or using a sauna delivered to your home? How about a microchip or electrical stimulator?
What could go wrong?
I'm not the neo-police, making citizen's arrests every time someone introduces a new plumbing gadget or extrapolates from animal research on resveratrol or catechins that we should drink more red wine or eat more chocolate. As a scientist who's spent her career asking, "Can we get better?" I've come to view bio-hacking as misguided, profit-driven, and counterproductive to its followers' goals.
We're creatures of nature. Despite all the new gadgets and bio-hacks, we still use Roman plumbing technology, and the best way to stay fit, sharp, and happy is to follow a recipe passed down since the beginning of time. Bacteria, plants, and all natural beings are rhythmic, with alternating periods of high activity and dormancy, whether measured in seconds, hours, days, or seasons. Nature repeats successful patterns.
During the Upstate, every cell in your body is naturally primed and pumped full of glycogen and ATP (your cells' energy currencies), as well as cortisol, which supports your muscles, heart, metabolism, cognitive prowess, emotional regulation, and general "get 'er done" attitude. This big energy release depletes your batteries and requires the Downstate, when your subsystems recharge at the cellular level.
Downstates are when you give your heart a break from pumping nutrient-rich blood through your body; when you give your metabolism a break from inflammation, oxidative stress, and sympathetic arousal caused by eating fast food — or just eating too fast; or when you give your mind a chance to wander, think bigger thoughts, and come up with new creative solutions. When you're responding to notifications, emails, and fires, you can't relax.
Downstates aren't just for consistently recharging your battery. By spending time in the Downstate, your body and brain get extra energy and nutrients, allowing you to grow smarter, faster, stronger, and more self-regulated. This state supports half-marathon training, exam prep, and mediation. As we age, spending more time in the Downstate is key to mental and physical health, well-being, and longevity.
When you prioritize energy-demanding activities during Upstate periods and energy-replenishing activities during Downstate periods, all your subsystems, including cardiovascular, metabolic, muscular, cognitive, and emotional, hum along at their optimal settings. When you synchronize the Upstates and Downstates of these individual rhythms, their functioning improves. A hard workout causes autonomic stress, which triggers Downstate recovery.
By choosing the right timing and type of exercise during the day, you can ensure a deeper recovery and greater readiness for the next workout by working with your natural rhythms and strengthening your autonomic and sleep Downstates.
Morning cardio workouts increase deep sleep compared to afternoon workouts. Timing and type of meals determine when your sleep hormone melatonin is released, ushering in sleep.
Rhythm isn't a hack. It's not a way to cheat the system or the boss. Nature has honed its optimization wisdom over trillions of days and nights. Stop looking for quick fixes. You're a whole system made of smaller subsystems that must work together to function well. No one pill or subsystem will make it all work. Understanding and coordinating your rhythms is free, easy, and only benefits you.
Dr. Sara C. Mednick is a cognitive neuroscientist at UC Irvine and author of The Power of the Downstate (HachetteGO)
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Greg Lim
3 years ago
How I made $160,000 from non-fiction books
I've sold over 40,000 non-fiction books on Amazon and made over $160,000 in six years while writing on the side.
I have a full-time job and three young sons; I can't spend 40 hours a week writing. This article describes my journey.
I write mainly tech books:
Thanks to my readers, many wrote positive evaluations. Several are bestsellers.
A few have been adopted by universities as textbooks:
My books' passive income allows me more time with my family.
Knowing I could quit my job and write full time gave me more confidence. And I find purpose in my work (i am in christian ministry).
I'm always eager to write. When work is a dread or something bad happens, writing gives me energy. Writing isn't scary. In fact, I can’t stop myself from writing!
Writing has also established my tech authority. Universities use my books, as I've said. Traditional publishers have asked me to write books.
These mindsets helped me become a successful nonfiction author:
1. You don’t have to be an Authority
Yes, I have computer science experience. But I'm no expert on my topics. Before authoring "Beginning Node.js, Express & MongoDB," my most profitable book, I had no experience with those topics. Node was a new server-side technology for me. Would that stop me from writing a book? It can. I liked learning a new technology. So I read the top three Node books, took the top online courses, and put them into my own book (which makes me know more than 90 percent of people already).
I didn't have to worry about using too much jargon because I was learning as I wrote. An expert forgets a beginner's hardship.
"The fellow learner can aid more than the master since he knows less," says C.S. Lewis. The problem he must explain is recent. The expert has forgotten.”
2. Solve a micro-problem (Niching down)
I didn't set out to write a definitive handbook. I found a market with several challenges and wrote one book. Ex:
- Instead of web development, what about web development using Angular?
- Instead of Blockchain, what about Blockchain using Solidity and React?
- Instead of cooking recipes, how about a recipe for a specific kind of diet?
- Instead of Learning math, what about Learning Singapore Math?
3. Piggy Backing Trends
The above topics may still be a competitive market. E.g. Angular, React. To stand out, include the latest technologies or trends in your book. Learn iOS 15 instead of iOS programming. Instead of personal finance, what about personal finance with NFTs.
Even though you're a newbie author, your topic is well-known.
4. Publish short books
My books are known for being direct. Many people like this:
Your reader will appreciate you cutting out the fluff and getting to the good stuff. A reader can finish and review your book.
Second, short books are easier to write. Instead of creating a 500-page book for $50 (which few will buy), write a 100-page book that answers a subset of the problem and sell it for less. (You make less, but that's another subject). At least it got published instead of languishing. Less time spent creating a book means less time wasted if it fails. Write a small-bets book portfolio like Daniel Vassallo!
Third, it's $2.99-$9.99 on Amazon (gets 70 percent royalties for ebooks). Anything less receives 35% royalties. $9.99 books have 20,000–30,000 words. If you write more and charge more over $9.99, you get 35% royalties. Why not make it a $9.99 book?
(This is the ebook version.) Paperbacks cost more. Higher royalties allow for higher prices.
5. Validate book idea
Amazon will tell you if your book concept, title, and related phrases are popular. See? Check its best-sellers list.
150,000 is preferable. It sells 2–3 copies daily. Consider your rivals. Profitable niches have high demand and low competition.
Don't be afraid of competitive niches. First, it shows high demand. Secondly, what are the ways you can undercut the completion? Better book? Or cheaper option? There was lots of competition in my NodeJS book's area. None received 4.5 stars or more. I wrote a NodeJS book. Today, it's a best-selling Node book.
What’s Next
So long. Part II follows. Meanwhile, I will continue to write more books!
Follow my journey on Twitter.
This post is a summary. Read full article here
Aaron Dinin, PhD
2 years ago
The Advantages and Disadvantages of Having Investors Sign Your NDA
Startup entrepreneurs assume what risks when pitching?
Last week I signed four NDAs.
Four!
NDA stands for non-disclosure agreement. A legal document given to someone receiving confidential information. By signing, the person pledges not to share the information for a certain time. If they do, they may be in breach of contract and face legal action.
Companies use NDAs to protect trade secrets and confidential internal information from employees and contractors. Appropriate. If you manage a huge, successful firm, you don't want your employees selling their information to your competitors. To be true, business NDAs don't always prevent corporate espionage, but they usually make employees and contractors think twice before sharing.
I understand employee and contractor NDAs, but I wasn't asked to sign one. I counsel entrepreneurs, thus the NDAs I signed last week were from startups that wanted my feedback on their concepts.
I’m not a startup investor. I give startup guidance online. Despite that, four entrepreneurs thought their company ideas were so important they wanted me to sign a generically written legal form they probably acquired from a shady, spam-filled legal templates website before we could chat.
False. One company tried to get me to sign their NDA a few days after our conversation. I gently rejected, but their tenacity encouraged me. I considered sending retroactive NDAs to everyone I've ever talked to about one of my startups in case they establish a successful company based on something I said.
Two of the other three NDAs were from nearly identical companies. Good thing I didn't sign an NDA for the first one, else they may have sued me for talking to the second one as though I control the firms people pitch me.
I wasn't talking to the fourth NDA company. Instead, I received an unsolicited email from someone who wanted comments on their fundraising pitch deck but required me to sign an NDA before sending it.
That's right, before I could read a random Internet stranger's unsolicited pitch deck, I had to sign his NDA, potentially limiting my ability to discuss what was in it.
You should understand. Advisors, mentors, investors, etc. talk to hundreds of businesses each year. They cannot manage all the companies they deal with, thus they cannot risk legal trouble by talking to someone. Well, if I signed NDAs for all the startups I spoke with, half of the 300+ articles I've written on Medium over the past several years could get me sued into the next century because I've undoubtedly addressed topics in my articles that I discussed with them.
The four NDAs I received last week are part of a recent trend of entrepreneurs sending out NDAs before meetings, despite the practical and legal issues. They act like asking someone to sign away their right to talk about all they see and hear in a day is as straightforward as asking for a glass of water.
Given this inflow of NDAs, I wanted to briefly remind entrepreneurs reading this blog about the merits and cons of requesting investors (or others in the startup ecosystem) to sign your NDA.
Benefits of having investors sign your NDA include:
None. Zero. Nothing.
Disadvantages of requesting investor NDAs:
You'll come off as an amateur who has no idea what it takes to launch a successful firm.
Investors won't trust you with their money since you appear to be a complete amateur.
Printing NDAs will be a waste of paper because no genuine entrepreneur will ever sign one.
I apologize for missing any cons. Please leave your remarks.
Muthinja
3 years ago
Why don't you relaunch my startup projects?
Open to ideas or acquisitions
Failure is an unavoidable aspect of life, yet many recoil at the word.
I've worked on unrelated startup projects. This is a list of products I developed (often as the tech lead or co-founder) and why they failed to launch.
Chess Bet (Betting)
As a chess player who plays 5 games a day and has an ELO rating of 2100, I tried to design a chess engine to rival stockfish and Houdini.
While constructing my chess engine, my cofounder asked me about building a p2p chess betting app. Chess Bet. There couldn't be a better time.
Two people in different locations could play a staked game. The winner got 90% of the bet and we got 10%. The business strategy was clear, but our mini-launch was unusual.
People started employing the same cheat engines I mentioned, causing user churn and defaming our product.
It was the first programming problem I couldn't solve after building a cheat detection system based on player move strengths and prior games. Chess.com, the most famous online chess software, still suffers from this.
We decided to pivot because we needed an expensive betting license.
We relaunched as Chess MVP after deciding to focus on chess learning. A platform for teachers to create chess puzzles and teach content. Several chess students used our product, but the target market was too tiny.
We chose to quit rather than persevere or pivot.
BodaCare (Insure Tech)
‘BodaBoda’ in Swahili means Motorcycle. My Dad approached me in 2019 (when I was working for a health tech business) about establishing an Insurtech/fintech solution for motorbike riders to pay for insurance using SNPL.
We teamed up with an underwriter to market motorcycle insurance. Once they had enough premiums, they'd get an insurance sticker in the mail. We made it better by splitting the cover in two, making it more reasonable for motorcyclists struggling with lump-sum premiums.
Lack of capital and changing customer behavior forced us to close, with 100 motorcyclists paying 0.5 USD every day. Our unit econ didn't make sense, and CAC and retention capital only dug us deeper.
Circle (Social Networking)
Having learned from both product failures, I began to understand what worked and what didn't. While reading through Instagram, an idea struck me.
Suppose social media weren't virtual.
Imagine meeting someone on your way home. Like-minded person
People were excited about social occasions after covid restrictions were eased. Anything to escape. I just built a university student-popular experiences startup. Again, there couldn't be a better time.
I started the Android app. I launched it on Google Beta and oh my! 200 people joined in two days.
It works by signaling if people are in a given place and allowing users to IM in hopes of meeting up in near real-time. Playstore couldn't deploy the app despite its success in beta for unknown reasons. I appealed unsuccessfully.
My infrastructure quickly lost users because I lacked funding.
In conclusion
This essay contains many failures, some of which might have been avoided and others not, but they were crucial learning points in my startup path.
If you liked any idea, I have the source code on Github.
Happy reading until then!