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Bones and Alzheimer’s

Bones and Alzheimer’s

Whoever would have thought that bone health could impact the development of dementia?  Until I learned about new research in this regard, I wouldn’t have connected the two.  The operant word here is “health” and that is a function of exercise.  Now, if you’ve read these newsletters in the past you’re probably thinking; Oh boy, here comes another sermon on the value of exercise.  And guess what?  You’re right!

The research connecting the two is from the fields of neuroscience and endocrinology.  It turns out that our bones are an endocrine organ that produces a hormone called osteocalcin.  Osteocalcin acts on many organs in the body including the brain but also on gene expression (the functionality of genes).  Regular exercise promotes bone mass (helping prevent fracture) and the increased mass leads to higher output of osteocalcin. 

At a brain level osteocalcin improves the production of serotonin, dopamine, GABA and other neurotransmitters.  These chemicals are vital to establishing new memories and maintaining previous memories. 

At a genetic level osteocalcin ramps up gene expression (function) of RbAp48.  This gene is critical for protein formation that allows the brain to convert short term memory to long term memory. Research in mice demonstrated that a normal part of aging is reduced osteocalcin production which is also true in humans hence the usual “benign senescent forgetfulness” which is not dementia.  But in mice, experiments knocking out the RbAp48 gene led to very early and rapid onset of dementia.  Injecting RbAp48 into these young, demented mice allowed recovery of memory function.  The next step will be to extend these findings to humans

The T(r)OOTH of the Matter

The T(r)OOTH of the Matter

By:  Sasha Klemawesch, MD

During residency, we had a DDS come do a grand rounds lecture. During it, he advised not rinsing after brushing. I paid no heed to his recommendation at the time since the idea of not rinsing your mouth out after you brush your teeth seemed so bizarre and gross (also probably I was too busy passing notes w my coresident to listen all that closely to a dental lecture – snore!).

The American zeitgeist writ large tends to reinforce the “normality” of swishing and spitting after brushing; picture every couple in every movie you have ever seen standing at the vanity together getting ready for bed; all of them brush, rinse, spit and then smile lovingly at one another (or glare daggers depending on the film).

However, apparently Hollywood and I have gotten it all wrong for decades. My personal dentist recently prescribed fluoride toothpaste and told me to not rinse, eat or drink for at least 15 min after brushing with it, preferrable 30, explaining that were I to do so, I would be giving the fluoride a few mere seconds to try and act before washing it away. You wouldn’t shell out 20 bucks for topical steroids or pain relievers to just immediately scrub them off post-application, would you? When he put it that way it made sense, but I was still Super averse to the notion of not rinsing after brushing; it just seemed so sticky and foreign! However, I assure you, in less than a week, not only did I get over the lack of rinse, but my mouth actually came to feel good and fresh by doing so, and now it’s second nature.

Two other tidbits related to teeth-brushing but non-dental in nature:

(1) Try using your non-dominant hand when brushing next time. Doing so will force your brain to work to establish novel neural pathways which can be especially helpful in delaying cognitive decline as you age.

Second, while the hand swap will benefit brain health, standing on one leg will help your physical health. While seemingly insignificant, if you really force yourself to balance on one leg at a time even for the minute you are brushing your teeth, you are working on balance, core, and leg strength, and those daily minutes will add up. 

I confess, the latter two are coming much more slowly and with greater difficulty than the no-rinsing thing, but I keep trying.

Finally, last teeth-related item; when you finish reading this article, look up and whoever the first person you see is, flash them a big toothy grin. I guarantee both you and they will immediately feel happier by doing so!

TEWL

TEWL

TEWL stands for trans epidermal water loss.  It is the “unperceived” loss of water through our skin, in distinction to the “perceived” loss of water when we sweat.  It is also sometimes called insensible water loss.  It has been known for quite some time that children and adults with eczema have a greater TEWL than normal, but the difference has never been carefully measured.  The Allergy and Asthma Proceedings recently published new research doing just that. 

The measurements were adjusted for body surface area and were 2 ½ times greater in people with eczema than those without.  This water loss leads to excess dryness of the skin which disrupts the barrier function of the skin.  Think of the cracks in the bottom of a dry lake bed.  These micro-cracks in the skin allow ingress of both allergens (such as pollen, dust mites, animal dander) and irritants (such as soap, preservatives in personal care products including their fumes) to get “under the skin” and therefore potentiate the eczema. Two simple strategies work: maintain good hydration and always apply a moisturizer after bathing.

PLE

PLE

PLE stands for protein losing enteropathy and was the subject of a review article in a recent issue of The New England Journal of Medicine. PLE is a syndrome not a specific disease and can occur for a wide variety of reasons.  The problem is caused by the loss of plasma proteins through the intestines (they “leak” out).  In general terms it is caused by illnesses that damage the intestinal lining or that block the intestinal lymphatic drainage.

The resultant loss of proteins causes a drop in oncotic pressure which lead to edema. The loss of immune proteins causes a greater predilection to infections.  The most common cause for PLE is inflammatory bowel disease such as regional enteritis or Crohn’s disease.  But for our purposes, food allergy, eosinophilic enteritis, and gluten sensitivity are all potential causes.  All three of these conditions can cause inflammation in the GI tract and if its is severe enough to cause disruption of the GI tract mucosa and PLE.  Clues to this possibility include “GI tumult”, edema in the ankles/legs, and a low albumin and/or globulin on blood work.  Correcting the cause of inflammation fixes the PLE.

Zorro Returns

Zorro Returns

A recent issue of the New England Journal of Medicine had an editorial (not a research paper) titled “Strategic Masking to Protect Patients from all Respiratory Viral Infections”.   It was written by four Harvard physicians whose specialty is epidemiology and public health. 

The authors preamble alludes to the understandable mask wearing pushback/mask use fatigue in both the general population and in healthcare workers.  That’s very understandable.  We are all sick of constraints.  But the focus of the article is with the first word: “strategic”.  They make a rational argument for what they call strategic masking.  Myriads of studies during the Covid 19 pandemic came to diverse findings on mask benefit.  From “doesn’t seem to do much” to “has a major impact on transmission”.  The authors point out that the naysay findings are probably due to inappropriate mask type or improper use.  How many times have you seen people wearing a mask covering their mouth but not their nose.  Duh!  Collating all the data it seems that there is up to a 60 to 70% effectiveness of preventing viral transmission with masking.  This includes the SARS-COV-2 virus along with other pesky viruses: influenza, RSV, human metapneumovirus, parainfluenza and rhinovirus.  One fifth of patients hospitalized for pneumonia have a viral pathogen not a bacterial one.  Influenza alone accounts for 50 to 60 thousand deaths a year in the US.

The strategies they offer are several.  One is to consider mask use in public places and health care facilities during months of the year with high viral illness.  Another is to consider universal masking in health care settings when patients being attended to are at a higher risk due to age or underlying premorbid conditions.

My own personal experience does not constitute science.  But prior to Covid-19 and mask use this aging physician was catching two to three viral respiratory infections a year.  Since my mask use over the past 4 years, I have not been sick. 

Ice Cream Therapy

Ice Cream Therapy

Finally, a medical therapy I can relate to.  I love ice cream.  Actually, it’s not a medical therapy, but a safe mechanism to “test the waters” in alpha-gal syndrome.  This newsletter has previously discussed this uncommon condition that unfortunately is becoming more common.  By way of reminder the syndrome is the new onset of anaphylaxis due to eating meat.  It is a strange condition in that the allergic symptoms occur suddenly (hives, swelling, throat constriction) but are delayed 3 to 6 hours from the meat ingestion.  It’s kind of similar to touching a hot stove and then feeling the sudden pain hours later.  The reason it develops is due to allergic sensitization from a tick bite.  The other peculiar aspect of the syndrome is that the allergic issue usually doesn’t develop for several months after the tick bite.  Thus, people often don’t associate the two.  The tick saliva contains a molecule called alpha-gal which is also found in meat, especially beef and pork.  The diagnostic test is to draw blood and see if there are antibodies to alpha-gal.  An antibody level greater than .10 IU/L makes the diagnosis “possible” and a level greater than 2 IU/L is definitive. 

If a patient avoids further tick bites this antibody level can decrease over time.  Once it has decreased enough then the likelihood for reaction goes away.  So it is in this setting that the ice cream test comes in to play.  High fat ice cream has a very small amount of alpha-gal, so if ingesting it turns out to be safe, then the patient can feel greater comfort returning to meat. 

I guess I can justify my nightly ice cream dessert as a proof that I’m not developing alpha-gal.

Mosquito Advisory

Mosquito Advisory

The Florida Department of Health has issued a statewide mosquito advisory.  In the past two months there has been an increasing number of malaria cases in the state.  Malaria is transmitted by infected Anopheles mosquitos.  The Florida cases have all been due to these mosquitos transmitting Plasmodium vivax.  So far, there have been no deaths but several people required hospitalization. 

The health department recommends reducing the chance for bites by wearing long pants and sleeves and using repellant (either on skin or on clothing) especially at dawn and dusk when mosquitos are most active.  They also recommend “cover and drain” measures to eliminate standing water where mosquitos breed:  garbage cans, house gutters, buckets, pool covers, flowerpots and plastic children’s pools. 

The symptoms of malaria include; fever, chills, sweats, nausea, vomiting and headache and should prompt individuals to seek immediate medical treatment. 

New Strategy for Lyme

New Strategy for Lyme

I’ve been privileged to be in the medical field since the discovery of Lyme disease and witness the ongoing research to understand it and to treat it.  I happened to be an intern at Yale when a mother returned her child to the medical center insisting that the original diagnosis of juvenile rheumatoid arthritis, they had received on their initial visit might not be correct.  After her first visit, she returned home to Old Lyme, Connecticut and by talking to neighbors found out that several other children in her neighborhood had gone to Yale and received the same “rare diagnosis”.  A team of epidemiologists was dispatched to Old Lyme and indeed found a number of additional cases. 

Thus, the research ball started rolling.  I’ve often thought the illness should have been named after that intrepid mother rather than the town. 

Lyme disease is caused by the bacteria Borrelia burgdorferi.  Initially, the bacteria and the disease were limited to New England but have spread throughout the eastern states including Florida.

A vaccine for humans was developed and became available in 1998.  But since consumer demand was low it went out of production in 2002.  But because of increasing cases in the US a new vaccine is undergoing clinical trials by Pfizer pharmaceuticals. 

Meanwhile, a different strategy is being implemented, a vaccine for mice.  Mice are one of the most important reservoir hosts for Lyme disease.  Living in the wild they transfer the bacteria via the ticks they carry and the ticks’ progeny.

The mouse vaccine is in edible pellets.  It’s interesting that both the human vaccine and the mouse pellet vaccine contain a protein called OspA which is found on the surface of B.burgdorferi.  The OspA spurs antibody production in the vaccine which in turn prevents infection. 

A recent five-year study done in New York state using the mouse pellets found a 23% reduction in infected ticks after two years of distributing the pellets and a 76% reduction after five years. 

Tezepelumab-ekko 

Tezepelumab-ekko 

Tezepelumab-ekko (Tezspire) is the first and only biologic agent approved by the FDA for severe asthma that is not limited to a specific asthma phenotype. 

Biologic agents have ben a true god-send in terms of helping patients with severe asthma.  The underlying cause for asthma is inflammation.  But the cause of the inflammation varies from patient to patient.  This variability is where the term phenotype comes into play.  Identifying the specific immune mechanism that instigates the inflammation and thus the asthma has proven extremely useful.  There are already a number of biologic agents that are extremely effective but to date they tend to target a single specific inflammatory mediator.  In most cases that is all that is required.  However, asthmatic inflammation can sometimes be multifactorial or what is referred to as a cascade effect.  Think of dominoes falling into one another.  This is where Tezepelumab-ekko can have utility.

Of course, every coin has two sides.  With its broader impact on immune modulators there is also a potential for reducing desirable immune function.  If a patient had a helminth infection this could worsen.  Also, live vaccines must be avoided. 

Leatherman Drug

Leatherman Drug

My favorite companion on woodland hikes (other than my wife and dogs) is my Leatherman, the ultimate multitool.  It seems that the biologic agent dupilumab (Dupixent) is also becoming a multitool.  It was initially approved by the FDA for people with severe eczema (atopic dermatitis).  It works by preventing the inflammatory eosinophils from entering the skin.  But since eosinophils also cause other types of allergic inflammation dupilumab’s role has expanded to include severe asthma, chronic rhinosinusitis with polyposis, eosinophilic esophagitis, and urticaria.  It is both an expensive and potent medicine so it is not considered a first line treatment for any of these conditions.