Hope for wannabe writers and a bit of a laugh for anyone

“Our united opinion is entirely against the book.

It is very long and rather old-fashioned.

Does it have to be about a whale?”

                                             From a publisher’s rejection of Herman Melville’s Moby Dick

 

 

                            “The pedestal upon which humans place themselves

in terms of neurological abilities

continues to crumble.”

Professor Malcom Kennedy

                

I always felt an affinity for the T.J. Maxx slogan “never the same place twice.” Indeed, my essential necessities (glasses, pens, cell phone, current book I’m reading, etc.) are truly never the same place twice.

Consider then, the clever Cuttlefish. They are invertebrates and, therefore, have no spine. But their brains are among the largest of the cephalopods, and they can remember “the what, where, and when specific things happened right up to their final days of life, according to new research” as confirmed by the lead study author, Dr Alexandra Schnell from the University of Cambridge. Equally interesting, though not relevant to this study, the amazing Cuttlefish have three hearts, eight arms, blue-green blood, regenerating limbs, and the ability to camouflage and exert self-control.

You’ve probably heard of the Stanford marshmallow test in which a child is offered one marshmallow to eat immediately or, better yet, two marshmallows if the kid can sit with the first untouched treat in an otherwise empty room for twenty minutes in order to get the second one as well.

The cuttlefish were trained to approach a certain part of the tank where two meals were offered.  One entrée was king prawns served hourly, but these are not their favorite dish. The other offer was grass prawns which they much prefer; these were available every three hours in another tank location. Cuttlefish live two years, and the youngsters (a year or less) were tested along with the geriatric bunch (between 1-2 years).  Both groups were easily taught where the prize was no matter how young or old. The elders, however, outdid the young’uns in remembering where the food was left as the locations kept changing after the initial training.

“As they get older,” summarizes Dr. Schnell, “They show signs of declining muscle function and appetite, but it appears that no matter their age, they can remember what they ate, where and when, and use this to guide their future feeding decisions.” On the other hand, our memory center, the two sea-horse shaped hippocampi in the temporal lobes of our brain, deteriorate along with our hearing, our knees, and many other parts, and we tend to lose track of past experiences including the where, when, and who of it all.  Past experiences such as where did I last see my walking shoes and perhaps my prescription glasses are on the radiator in the bathroom.

 

A "Cat in the Hat" moment

Honey, I love you, but this is out of control!

With some difficulty,
I scooped semi-crystallized honey
with a knife
out of the jar
and onto my yogurt.

A large glop fell to the floor
as I reached for a spoon
to scrape off the knife.
that swiped at the blob

that clung to my elbow
and stuck to the table
as I started to eat.

A newspaper clung
to the drips on my sleeve, 

soft sucking noises 

arose from my shoes
as I walked to the sink
'cross honey-streaked floor.

My partner pointed out 

with non-sticky finger
a huge dollop on counter
not even in range
of the gooey affair.

 

Do nine gin-soaked raisins a day keep arthritis pain away?  And what about COVID, could tipsy raisins be a decent anti-inflammatory medicine for the infected?  At least one woman recently vouched for that.

Reading about this raisin product is intriguing, particularly on drunkenraisins.com.  This company’s website promotes their “21^st century recipe” as opposed to the longstanding homemade variety.  The latter involves store-bought golden raisins soaked in any old gin for nine days, then eaten each morning, 9-at-a-time. DrunkenRaisins, however, uses a “Choice Jumbo Golden Raisin”, adds a ‘correct’ juniper berry influenced gin, then marinates the dried fruit in a sealed container with honey and imported cinnamon bark oil.  Each batch takes 10-14 days to finish ‘giving birth to the magic of one of the best anti-inflammatory foods available.”

My mouth is watering, and I don’t even really care for gin.  This goodbye to aching joints habit dates back 100 years.  Now is this placebo or an actual non-steroidal anti-inflammatory drug that needs no rx?  Placebo or not, it could very well be a very pleasant way to dial down arthritic pain.

Perhaps you’ve heard of Lucia DeClerck; she’s recently made headline news.  On her 105^th birthday in January, she was diagnosed with COVID, one day after getting her second Pfizer vaccine.  She isolated for 2 weeks, had very few symptoms, missed her chats with her friends, then went back to her room in a New Jersey nursing home, all the while never missing a single morning dose of her nine golden raisins which she’s been taking for decades.

Was it the vaccine? Prayer and no junk food which she practices daily?  The raisins?  Doesn’t really matter does it…vaccines 1 &2 with rising protection, anti-inflammatory juniper berry phenols toning down an overactive immune system, and/or belief in raisins and religion.  There you have it, whatever ‘it’ is.

Interested?  There are drunken raisin recipes all over the internet, or call DrunkenRaisins.  They’ll ship a super fresh batch to you within 2 to 3 days. 

 Ugh says the retired doctor who got the two-dose Pfizer vaccines in March and just found out this news regarding Delta Variant:

• Pfizer vaccines only effective against Delta at 42%.  Still seems to minimize severe illness, hospitalization, or death.  Other MDs who have gotten the Delta variant tended to have a rather bothersome illness for about 8 days.
• All it takes is less than 5 seconds to catch the darned variant, and the spreader, whether ill or infected without symptoms, tends to infect 8-10 other people.

 

Odoribacteraceae

 

“In people over the age of 100, an enrichment

in a distinct set of gut microbes generate

unique bile acids.”

Professor Kenya Honda

 

New research on the gut microbiome of old folks in Japan was reported in the latest issue of Nature Research. The scientists analyzed the gut bacteria of more than 300 adults in Japan, including 160 over 100 years-old, 112 between 85 and 89, and 47 under 55 years-old. Principal investigator Honda and colleagues found that bacterial isolates in fecal samples from centenarians were often enriched with microbes capable of synthesizing potent bile acids that were not present in the younger groups. Odoribacteraceae strains in particular came out as star producers of isoallo-lithocholic acid (LCA). LCA is a potent antimicrobial against gram-positive, multidrug-resistant strains such as Clostridioides difficile and Enterococcus faecium.

The conclusion of this study, per Prof. Honda: “There are centenarian-specific members of the gut microbiota which, rather than representing a mere consequence of aging, might actively contribute to resistance against pathogenic infection and other environmental stressors.” 

There are a host of responses to this study.  Many readers had their own theories of aging well.  One young lady declared that skinny was the perfect answer, and her daily intake, delivered in anorectic detail, made me cringe.  Another woman, struggling with C. diff unresponsive to various medications, took matters into her own hands.  She announced to her daughter that she needed a stool sample from her. The daughter, first appalled, then complied. The sample was inserted into one end or another (we got no info over which), and mom felt increasingly normal in a gut sort of way within four days!

I’d like to get ahold of a distinct set of those Odori-bugs, but alas, no search on Amazon or Google offered hope for bottles of such supplements just yet.  

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Repurposed Drugs Offer Hope for Preventing/Treating COVID

A new approach to the war on COVID has potential according to a study published in the June 30^th issue of Science Advances. The University of Cambridge is investigating the possibility that a host of drugs, already approved for other uses, may uncover new weapons against this pandemic.  Historically, many drugs originally developed to favorably outwit one disease have proven useful in other ways.  For instance, zidovudine, now known as azidothymidine (AZT), did not work as a cancer drug but 20 years later proved to work well for the prevention and treatment of HIV.

Cambridge researchers used computer models to screen some 2,000 drugs as potential anti-viral treatments.  The researchers narrowed the field down to 200, then chose a subset of 40 to test in the lab using cell lines cultivated from humans and non-human primates; all cell lines were infected with SARS-CoV-2.  Two drugs in particular—proguanil, an anti-malaria drug, and sulfasalazine, a medication for rheumatoid arthritis and ulcerative colitis—successfully stopped COVID viral replication in the cells.

Another study, this one from the Tokyo University of Science, has also come up with a duo of drugs with great promise, perhaps even better than the Cambridge findings. These researchers also tested a panel of already approved drugs in similarly infected cell model cultures. They found a different duo of drugs that effectively blocked the virus: the anti-inflammatory drug cepharanthine and the HIV viral protease* inhibitor nelfinavir. Cepharanthine inhibited SARS-CoV-2 entry into host cells by blocking viral entrance into target cells while nelfinavir suppressed viral replication through protease inhibition.

This picture shows that cepharanthine in the upper left-hand corner sporting fashionable pale turquoise and grey blocks the ugly brown COVID spike from entering the cell. In the lower left-hand corner, a lump of lovely lime green nelfinavir enters the cell and rips apart the protease which stops viral reproduction. The color choices are for artistic purposes and do not represent the actual cells, virions, or drugs.

__

*Protease is an enzyme that breaks down proteins into shorter molecules called peptides which allows the virus to construct new proteins in order to replicate new virions inside the host cell.

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I like coffee a lot even though I can hardly taste it!  My dentist can’t stand the coffee stains on the inner surfaces of my teeth; apparently stains are good places for bad biofilms.  Biofilms are ‘communities’ of bacteria co-existing perhaps with a dash of fungi, a smidgen of bacteriophages, and volunteer viruses. They are held together by extracellular polymeric substances (EPS) and tethered to inert surfaces such as teeth, catheters, prostheses, and implants. Home for the wee beasties becomes long-term quarters in what one article on PubMed.gov calls “the biofilm lifestyle.”  More on biofilms in an upcoming post. Meanwhile, for the sake of my dentist, I dilute my morning coffee with water, or drink it with soy milk. I still can’t taste it, and I still love it.

 But let’s move on to important coffee news.  Researchers from the University of South Australia have found that drinking too much coffee can contribute to osteoarthritis, joint disease, and obesity. This same group determined that six cups a day was the absolute safe level of consumption. Another study, conducted at the Australian Centre for Precision Health at the South Australian Health and Medical Research Institute, was based on 17,702 participants aged 37 to 73 and their relationship with coffee. Principal investigator Kitty Pham declared “We consistently found that higher coffee consumption was significantly associated with reduced brain volume” and increased risk of dementia. They declare “Rethink your drink” if your consumption comes even close to six cups a day. Earlier studies declared coffee drinking protects the brain from dementia. What is it then: A good-for-the-brain drink or bad? Six cups too much or just fine?

 To end on an up-note, a prospective study over 12 years determined that coffee does not cause cardiac arrhythmias. Analyzing data from UK Biobank, the investigators determined “each additional cup of habitual coffee consumed was associated with a 3% lower risk of incident arrhythmia.” That sounds completely ridiculous to me, but it was printed in JAMA in July of this year, so could it be so?

I’m down to one diluted cup per day.  Heaven forbid they ever investigate dark chocolate!

 

 

Oh Yuck

We’re not even safe in our beds!  A Medical Microbiology lecturer at the University of Westminster, Manal Mohammed gives us too much information when it comes to bedtime. She notes:

1.    We shed around 5 million skin cells each night in bed. (How can they know this?) The microscopic dust mites have a field day eating those old dead cells. The mite droppings can cause itching, allergies, and asthma.

2.    Those dead cells, along with saliva, sweat, and dandruff, is the perfect environment for bacteria, viruses and fungi.

3.    Gram negative bacteria like Staph aureus and E. Coli can find their way into your bed!

 Ick, ick, ick.  Care to know more? You can find her complete article at:

https://theconversation.com/your-bed-probably-isnt-as-clean-as-you-think-a-microbiologist-explains-163513

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From “The Week” Magazine

“Health officials in Seoul banned gyms from playing music with a tempo faster than 120 beats per minute, on the grounds that such music inspires gymgoers to exercise and breathe harder, thus raising the risk of spreading COVID.”

 

What is PM2.5 and Why Do I Itch?

 

PM refers to particulate matter that hangs in the air creating haze and off-color sunshine.  The 2.5 refers to the size of these particles, which is 2.5 microns or less, which are produced by vehicle exhaust, burning fuels (wood, oil, coal), and wildfires. They are easily carried over long distances. As you can well imagine, such tiny particles can pass deep into lungs and through blood vessel walls into the bloodstream thus increasing risk for heart and lung disease. Several thousand of the smaller particles could fit on the period at the end of this sentence. What came as a surprise to me as I investigated this hazardous air-borne matter was its effect on the skin.

 “These pollutants often contain chemical compounds that act like keys, allowing them to slip past the skin’s outer barrier and penetrate into cells, where they can disrupt gene transcription, trigger oxidative stress or cause inflammation.” 

 Past studies have found a link between atopic dermatitis (AD, aka eczema) and air pollution in cities with high background levels of PM2.5 from cars and industry.  The latest study, published in April of this year in JAMA Dermatology, was conducted by researchers in San Francisco as they perused medical records from November, 2018.  At that time, a serious wildfire nearby (Camp Fire), while extinguished in about two weeks, caused a notable increase in the number of clinic visits for itching and new rashes in both pediatric and adult populations. The authors of the study concluded that even short-term exposure to high PM2.5 environmental particulate matter is associated with increased skin woes, and the majority of new patients scratching n’ rashing had no history of dermal disorders.

 Ugh, walked this morning through the PM2.5 haze, and now I’m itching all over! Little red itchy bumps on the forearm; PM2.5 or creepy little noseeums (a catch-all name for 5,000 species of tiny biting flies)?

 

Here Comes Delta!

 

Q:  Why is the Delta Variant so transmissible?

A:  Because people infected with it carry a viral load of roughly 1,000 times higher than those infected with the original coronavirus strains.

 

Understatements of the Pandemic

 “Putting it all together, Delta’s really difficult to stop.”

                        Benjamin Cowling, University of Hong Kong

 

“This virus has surprised us.”

                        Emma Hodcraft, University of Bern

 

Kanopy.com

 A free streaming site is yours by signing up through your local library.  City librarians were available by phone at the Denver Public Library (and others, I assume, throughout the country).  Denver libraries are finally open; what a pleasure to browse for books rather than wait at the curb for one's order.

For a good laugh, Kanopy streams the silly movie “What We Do in the Shadows 2014.”  Not the series which is mildly funny through the first episode but then collapses into plain stupid, watch the movie!  It is also available on YouTube for $2.99.  A wide range of other movies, both short (and well-done) and long.

 

“There’s always a little bit of tension around

these issues of, well, is the drug going

to work, or not.”

Dr. Robert Shafer, Stanford infectious disease specialist

 

Good news from a phase 2 investigation pitting Molnupiravir (an oral antiviral agent still in clinical trials) against SARS-CoV-2.  After years of testing this-a-vir and that-a-vir in various labs, Molnupiravir and Remdesivir proved most likely to succeed.  Here’s the background story followed by the test results.

RNA viruses rely on their RNA-dependent polymerase (RdRP)* to stitch together  viral messenger RNA.  The sequenced mRNA in turn produces various proteins used for the production of new virions as the invading virus overtakes host cells. What’s needed for halting viral reproduction is a reliable RdRp inhibitor. Many those-a-virs created in labs have been tested against SARS-CoV-2. A successful compound will plop itself into the developing viral sequence causing mutations in the proteins and…hurray! no new offspring created. Remdesivir showed strong inhibition in lab and animal trials, and was subsequently approved for treatment in patients. Unfortunately, while it works well in toning down the severity of the illness thus speeding recovery, it requires IV infusion in a hospital setting and doesn’t reduce deaths in difficult cases. 

There are currently 246 antivirals in development. Creating antiviral meds is rather tricky, the difficulty being how to stop propagation of more virions produced within the host cell without killing the cell itself. Merck’s Molnupiravir, originally developed by Emory University then bought by Ridgeback Bio that sold it to Merck, originally targeted Influenza for Phase 1 animal trials. The drug proved to be effective at curbing flu infections in mice, guinea pigs, ferrets and human-airway organoids (human cells grown in petri dishes into viable tissues).. 

But then along came March, 2020 and the onset of SARS-CoV-2 which completely changed their plans. A successful test with ferrets proved that Molnupiravir blocked both developing cases as well as ferret to ferret transition. They went on to a Phase 2 safety trial with 202 outpatients with early symptoms of SARS-CoV-2. Those who received 400 or 800 mg. daily were completely free of virus by Day 5. Only 11.1% of the placebo group had similar clearance. Phase 2/3 testing is underway with results expected in September.

Here’s hoping!!

 By the way, I began publishing my e-mail newsletter again.  If you would like to receive this type of information via e-mail, please feel free to send me your e-mail to denverdoconline@gmail.com.  There will be overlap between the newsletter and the blog.  I will not share your e-mail with anyone, and you can always unsubscribe by replying to the newsletter with 'unsubscribe.'

Best wishes,

DenverDoc

 

Oops, I forgot to include the illustration that goes with yesterday's post.

 

I spend hours on the internet reading various e-magazines, often going down a path of interest leading me far from my goal—namely getting a thought-provoking newsletter to you more or less every two weeks.  Yesterday, I found this study in the journal ‘Brain Communications’ about how near-death experiences (NDE) in humans may have an evolutionary origin; it’s a definite read and share investigation.  Let’s start with thanatosis (feigned death or ‘playing possum’) as it occurs in animals under attack by predators. 

An artist created the above cartoon from a real-life video involving an impala who goes limp after being caught by a cheetah who then is bullied by a hyena thus allowing the impala to make a get-away.  If you would like to see the actual dramatic footage from Africa, check out: https://www.youtube.com/watch?v=JqlGjX1MtVg.  After that, google ‘thanatosis’ or ‘thanatosis in insects’ to see an enormous array of animals, and insects, many on their backs with feet in the air, feigning death when threatened by those higher on the food chain. Another interesting link is found at https://www.thoughtco.com/why-some-animals-play-dead-373909.

 The authors of this study define NDEs as “unique conscious, self-related emotional, spiritual and mystical unexplained experiences occurring in life-threatening situations or situations that may feel life-threatening, including cardiac arrests, traffic accidents, physical assaults and drug abuse.”

They searched for examples of encounters between humans and big animals including sharks, and heard or read testimonials from survivors of mass executions, genocide, or terrorists attacks for examples of thanatosis or NDEs. After compiling their data, they concluded that thanatosis occurs across a wide range of creatures from arthropods to humans, and that playing dead or going into an NDE sort of dream or trance was definitely associated with survival.  See below for an archived account of a human/lion interaction in the 19^th century, and a few other such stories are included in the material in “Brain Communications”.

 You can skim or read the entire study material at https://academic.oup.com/braincomms/article/3/3/fcab132/6307709 .  Next newsletter I will include the physiology that accompanies human and probably other animal species when flight is not an option but feigning death or entering a dreamlike state may be a life saver. And the NDEs associated with “out-of-body experiences, feeling one with the universe, feeling peace and acceptance, sometimes even joy, and visual and auditory hallucinations, including seeing bright lights, being in a tunnel and meeting spirits or ancestors” can become a life-changing memory.

 Interested in reading the entire study?  Visit: https://academic.oup.com/braincomms/article/3/3/fcab132/6307709.

 Thanks for reading, double thanks for feedback!

 DenverDoc

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Developing… not on the market yet

A recently-tested new topical goo for atopic dermatitis (AD) suggests that a combination of cannabidiol (CBD) and aspartame applied regularly to the itchy, inflamed, scaley skin of AD alleviates or clears all those symptoms in a satisfying sort of way.  The trial included 57 people who were randomized to control group, CBD cream alone, or the new combo.  Researchers used the ISGA score (investigator’s static global score) to record baseline symptom assessment compared to change after 2 weeks of use. ISGA scores range from 0 (no trouble at all) to 4 (a hot mess of skin misery).  After 14 days, 50% of the group receiving CBD/aspartame scored 0-1, down 2-3 points from the start of the trial whereas the CBD and control group participants scored the satisfying ISGA 0-1 in just 20% and 15% respectively.

CBD-enriched creams have proven success in multiple dermatological problems including AD, acne, psoriasis, skin cancer, pruritus, and pain.  But who thought aspartame was an effective dermal soother? 

Aspartame apparently has analgesic functions that are similar to those of nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen. A rodent trial in 2015 exposed the mice to topical 2, 4-dinitrofluorobenzene thus creating the mousy version of AD. Sucrose in the mice’s drinking water did nothing to soothe the itch and inflammation whereas drinking aspartame in water inhibited ear swelling and skin eruptions.  Please note, the International Sweeteners Association does not recommend adding aspartame to your drinking water based on other not-so-successful animal studies.

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A Scientist’s Fashion Tip

“Once you can accept the universe as matter expanding into nothing that is something, wearing stripes with plaid comes easy."

Albert Einstein

Make the Most of Your Calcium Intake

What you need to know about calcium

• Recommended daily intake of calcium is 1200 mg for women over 50.  This should be roughly ½ from diet and ½ from supplements.
• You can only absorb 500 mg of calcium at a time.
• Calcium supplements require stomach acid to dissolve, so they should be taken with a meal.  The food stimulates secretion of acid.  The exception:  calcium citrate dissolves without acid.
• Once dissolved, a small amount of calcium can be absorbed in the intestine alone, but vitamin D is required for calcium to be actively absorbed in useful quantities.
• Calcium and D are necessary, but not sufficient for best bone health.  The two alone may increase bone density, but at best really just reduce the rate of bone loss.  The recommended daily dose is 2,000 IU of vitamin D3.  Some people absorb D better than others; a blood test to check for adequate D levels is recommended.
• Accelerated bone loss among women during the peri-menopausal period occurs between the ages of 40 to 54 years, and then stabilizes.  A second period of accelerated bone loss begins at age 70 among women, notably in the total hip, which can lead to a substantial drop in bone density and strength by age 75 years.  This loss is associated with the increased incidence of hip fractures. 
• If your calcium intake is less than your body needs, parathyroid glands imbedded in the thyroid gland are activated to produce parathormone (PTH).  This hormone stimulates osteoclasts to breakdown bone in order to release calcium.  Blood levels of calcium are maintained in a narrow normal range, and bone reserve is tapped when levels fall at the expense of bone density.  
•  Use of potent meds to control acid reflux or gastritis such a Prilosec (omeprazole) interferes with calcium dissolution and absorption contributing to low blood levels of calcium.

My Trainer, My Desk

Everybody get on your feet,
You make me nervous
When you're in your seat
-----Jerry Jeff Walker


    
     What on earth would our Ice Age ancestors think?  Genetically identical to our 21st century selves, they were perfectly suited to a life of obligatory physical exercise, periodic famine, and unrelenting cold.  We, on the other hand, no longer running from predators or chasing our dinner, pass our days on the job and at leisure slouched in our chairs, inert, well-fed, and warm.
     My Fitbit, a pedometer-plus, tallies steps, stairs, and calories. Gizmos within know when I am active and know when I am not.  After a day at home or at work, add housework or laundry plus a walk and a trip to the store, I might manage to reach the 10,000 step goal. Syncing with Fitbit on-line turns daily data into a pie chart of motion, gray for sedentary with blue, yellow, and pink for light, moderate and heavy action.  Alas, my so-called busy day is awash in inert--big yawning gray, a thin slice of sky, a sliver of sun, and one slash of pink.
     Perhaps it's time for on beyond Fitbit. A smart--and very pricey!--desk might be the next best thing to a personal trainer.  For several thousand dollars, you can buy a work station at stirworks.com that greets you by name, gently nags you to move, keeps a log of your day, week, and month, and advises you how long until you're next scheduled to fidget.  When you've been too still for too long, the thing takes a 'whisperbreath', heaving beneath your laptop like an impatient dog past due for a walk.
     Sit-stand workstations are today’s medical news; studies prove they decrease on-the-job sedentary behavior (SB), may or may not affect productivity, and mostly don’t cause workplace injuries.  Ingenius, creepy, or just a sign of our times?