Thanksgiving Small Bits & Pieces

I’m going to kick off this Doc Gumshoe missive with a little bit of undoubtedly excellent news, albeit information that’s not prone to have an effect on many voters of Gumshoe Nation. In a nutshell, it’s this: on September twenty sixth, the FDA accredited the primary new drug to deal with schizophrenia in additional than 30 years. The drug is Cobenfy (xanomeline/trospium chloride, a fixed-dose mixture treatment. It was initially developed by Lilly (LLY), which offered the license to Karuna Therapeutics. Karuna has since been acquired by Bristol Myers Squibb (BMY).

Dr Tiffany Farchione, director of the FDA’s Division of Psychiatry, stated “This drug takes the primary new method to schizophrenia remedy in a long time. This approval affords a brand new different to the antipsychotic drugs individuals with schizophrenia have beforehand been prescribed. Schizophrenia is a number one reason for incapacity worldwide. It’s a extreme, persistent psychological sickness that’s typically damaging to an individual’s high quality of life.”

For a lot of a long time, remedy of schizophrenia relied on blocking dopamine receptors. Widespread dopamine receptor blockers embody Thorazine (chlorpromazine), Prolixin (fluphenazine), and Haldol (haloperidol). These have been round a very long time. For instance, Thorazine obtained its FDA approval in 1954.

Blocking dopamine receptors has advantages in addition to drawbacks. It reduces signs like hallucinations and paranoia to a degree that sufferers discover livable. However dopamine receptor blockers ceaselessly end in vital weight acquire, such that sufferers taking these medication are likely to have larger charges of cardiac illnesses, leading to decreased life expectancy. And lots of sufferers have discontinued taking these just because these medication made them really feel sluggish and unmotivated.

Cobenfy has an impact on dopamine ranges, however its principal goal is one other neurotransmitter, acetylcholine.

About 25 years in the past, the muscarinic acetylcholine receptor agonist xanomeline (which is without doubt one of the two compounds in Cobenfy) was reported to scale back psychotic signs and enhance cognition in sufferers with Alzheimer’s illness. The antipsychotic and procognitive properties of xanomeline have been subsequently confirmed in a small research of acutely psychotic sufferers with persistent schizophrenia.

The origins of the phrase “schizophrenia” recommend that the important dysfunction is a mind whose totally different capabilities are primarily disjointed – primarily a “break up thoughts.”

Based on the Nationwide Institute of Psychological Well being, schizophrenia is a psychological dysfunction characterised by disruptions in thought processes, perceptions, emotional responsiveness, and social interactions. Though the course of schizophrenia varies amongst people, schizophrenia is often persistent and will be each extreme and disabling.

Schizophrenia is comparatively unusual. Within the US, it impacts between 0.25 and 0.75% of the inhabitants. Nonetheless, it’s a disproportionately costly situation. The monetary burden of schizophrenia consists of the direct value of healthcare, which frequently includes life-long institutionalization, but in addition prices reminiscent of misplaced productiveness, involvement with the felony justice system, and social providers.

Signs of schizophrenia embody psychotic signs reminiscent of hallucinations, delusions, and thought dysfunction (uncommon methods of pondering), in addition to decreased expression of feelings, decreased motivation to perform objectives, issue in social relationships, motor impairment, and cognitive impairment.

The proof supporting Cobenfy as a remedy for schizophrenia is, to this point, quite sparse. There have been solely three managed trials of the drug, and every trial lasted solely 5 weeks. In these trials, Cobenfy decreased the signs of schizophrenia to a manageable degree, with out producing the unwanted effects linked with dopamine receptor blockers reminiscent of cardiac illness or weight acquire. BMY launched outcomes of long-term observational research of Cobenfy, during which sufferers didn’t expertise metabolic adjustments or motion issues reminiscent of affected sufferers taking different medication to regulate schizophrenia.

Pharmaceutical corporations are enthusiastic concerning the Cobenfy outcomes, and are engaged on related drugs which might be efficient in treating such situations as bipolar dysfunction, autism, and Alzheimer’s illness.

BMY has set the wholesale worth of Cobenfy at about $22,500 per yr. It’s anticipated to generate revenues between $3 billion and $5 billion per yr.

Eisai and Eli Lilly conceal instances of mind accidents linked to their Alzheimer’s medication

Clearly, these are genuinely dreadful information gadgets. The medication in query are Eisai’s Leqembi (lecanemab) and Eli Lilly’s Kisunia (donanemab). The NY Occasions not too long ago devoted greater than a full web page to this case, describing a number of instances during which sufferers taking these medication skilled mind accidents, which might have been anticipated primarily based on their genetic profiles.

In 2021, Eisai put out a name for volunteers to take part in a medical trial of their experimental drug lecanemab (then known as BAN2401) for the remedy of Alzheimer’s illness. Almost 2,000 individuals answered the decision. Eisai sought particularly to incorporate people whose genetic profiles made them particularly inclined to develop Alzheimer’s. However these identical people have been extra inclined to mind bleeding or swelling in the event that they obtained the drug.

Eisai made a public assertion that each one volunteers could be given a genetic take a look at to determine the precise people who have been at explicit threat for mind accidents. Nonetheless, Eisai didn’t inform these trial volunteers that they have been at particularly excessive threat of experiencing these mind accidents. It has been revealed {that a} whole of 274 volunteers joined the trial unaware that they have been at elevated threat. Two of those volunteers died of their mind accidents, and greater than 100 others skilled mind bleeding or swelling.

On July 6, 2023, the FDA granted accelerated approval to Leqembi/lecanemab for the remedy of Alzheimer’s, noting that its modest profit outweighed its dangers. The advantages of Leqembi/lecanemab for the remedy of Alzheimer’s are certainly modest. Therapy with the drug slows cognitive decline for a number of months solely.

An identical scenario has emerged with regard to Eli Lilly’s anti-Alzheimer’s drug Kisunia (donanemab). Lilly selected to not inform 289 volunteers in a medical trial of donanemab that their genetic profiles made them particularly susceptible to mind accidents. A few quarter of volunteers within the Kisunia trials skilled mind swelling or bleeding.

The FDA granted approval to Kisunia nearly precisely a yr after Leqembi’s FDA blessing – July 2, 2024.

In each the Leqembi and Kisunia trials, volunteers first needed to signal consent types that stated that individuals with sure genetic traits confronted larger dangers of mind accidents from receiving the medication, and that contributors within the trial could be given genetic exams for these traits. However they have been advised that they’d not be told as to the outcomes.

Primarily, the volunteers in these trials have been anticipated to go forward and take part within the trials with out understanding whether or not they have been at elevated threat for mind harm. The individuals conducting the trial would know, however the trial topics wouldn’t know.

Each Leqembi/lecanemab and Kisunia/donanemab are BACE inhibitors (beta-site amyloid precursor protein cleaving enzyme inhibitors), that means that they aim amyloid beta, a type of plaque that clogs mind connections. The unlucky Aduhelm/aducanumab (from Biogen), which was taken off the market resulting from its poor efficiency in addition to the tendency to end in mind bleeds, can be a BACE inhibitor.

Mind bleeding and mind swelling is particularly prevalent in individuals with the APOE4 gene. About 40% of people with two copies of the gene skilled mind bleeding, and about 35% skilled mind swelling. This gene is extremely correlated with Alzheimer’s illness. Folks with one copy of APOE4 have double or triple the danger of creating Alzheimer’s illness, whereas individuals with two copies have an eight- to twelvefold improve in threat.

It ought to be identified that the profit these BACE inhibitors ship is minimal. It slows the onset of dementia in sure Alzheimer’s sufferers for lower than a yr earlier than the illness resumes its harmful course.

The annual value of Leqembi/lecanemab is $26,500. For Kisunia/donanemab it’s $32,000. Evidently, neither Eisai nor Lilly need to allow unlucky particulars, such because the frequency of mind bleeds, to intrude with their gross sales prospects.

A drug-free nasal spray could defend towards respiratory infections

The nasal spray we’re discussing is a gel-like spray formulated with out lively pharmaceutical components. It has but to be examined in people, however the researchers say it created a protecting coating that lasted for as much as eight hours within the nasal cavities of mice. If the spray’s security and efficacy are confirmed in people, the analysis workforce stated the method might play an essential function in lowering respiratory illnesses and safeguarding public well being towards new threats.

The nostril is a standard passage into the physique for a lot of viruses and micro organism. Most respiratory infections, reminiscent of flu and COVID, are transmitted when an individual inhales tiny droplets of fluid that carry the pathogen. As soon as they get contained in the nostril, the viral or bacterial particles contained in the droplets infect the cells that line the nasal cavity. These pathogens replicate and journey additional down the respiratory tract of the contaminated particular person, typically reaching the lungs, the place they’ll trigger bronchitis and pneumonia. Pathogens can be launched again into the air when an contaminated particular person sneezes, coughs, laughs, sings, talks, and even simply breathes out and in.

Present nasal sprays provide restricted safety towards respiratory pathogens as a result of they’ve a single mechanism of safety. They both neutralize pathogens or block their entry into the cells lining the nostril, they usually carry out each duties with restricted efficacy.

The projected new drug-free nasal spray was developed to dam germs in 3 ways — the spray types a gel-like matrix that enhances the seize of respiratory droplets, immobilizes the germs, blocking their transport into the nasal lining, and successfully neutralizes the germs, stopping an infection. The nasal spray, known as Pathogen Seize and Neutralizing Spray (PCANS), was developed with nonpharmaceutical components already utilized in accredited nasal sprays or listed within the FDA’s Usually Acknowledged as Secure (GRAS) record.

The researchers designed the formulation and studied its skill to seize respiratory droplets in a 3D-printed duplicate of the human nasal passages. The experiments confirmed that when administered into the nasal cavity mannequin, the spray captured twice as many droplets as naturally occurring mucus produced as a part of the physique’s innate protection system.

The researchers examined the spray’s protecting results towards a pressure of influenza in mice. The spray was quickly activated following administration into the nostril and lasted as much as eight hours. A single dose might successfully block an infection from an influenza virus at 25 occasions the deadly dose of the virus. Which means the spray was able to keeping off an infection even when animals have been uncovered to a heavy load of the virus. Based on the investigators, virus ranges within the lungs of pretreated animals have been decreased by practically 100% p.c, in contrast with virus ranges within the lungs of nontreated animals.

The nasal spray was developed by Harvard Medical Faculty researchers working with Brigham and Ladies’s Hospital. The data above got here from a Harvard Medical Faculty launch.

It might be anticipated that the builders of the nasal spray could be extremely captivated with its advantages. Doc Gumshoe’s skeptical flip of thoughts poses a query: even when this superb drug-free nasal spray completed in human topics outcomes corresponding to these in mice, would extraordinary people be prone to routinely spray a gel coating into their nasal passages to guard themselves towards pathogens? People who had ceaselessly skilled higher respiratory illnesses, or who had been warned that they have been at elevated threat for higher respiratory illnesses may use this gadget. Such individuals may take up the behavior of a every day dose of this nostril spray, kind of as a routine follow, like brushing their enamel. I emphasize the phrase “may” in that sentence. It might rely, to a substantial diploma, on what the nostril spray felt like once you press the button or squeeze the tube. Extra considerably, it will depend upon whether or not these people perceived precise enchancment: did spraying gel of their noses truly end in fewer instances of colds or the flu?

At this second, the protecting nasal spray is a good distance from the medical trials that will be essential to fulfill the FDA and get the nasal spray accredited as a medical gadget. Designing medical trials themselves could be a problem. The trial would wish to enlist voluntary topics, a few of whom could be spraying a placebo of their noses. Then, to be able to confirm the efficacy of the nasal spray in stopping an infection, the topics – together with these within the placebo arm – must be uncovered to pathogens, to be able to confirm that the nasal spray decreased an infection. Due to this fact, some trial topics would undoubtedly expertise precise infections. Based mostly on the experimental proof that the gel captured twice as many respiratory droplets as naturally occurring mucus, those that obtained the actual nasal spray would presumably expertise infections at half the speed, however they’d be uncovered to infectious viruses and micro organism, and if the an infection price matched that within the mice, maybe half of the topics would truly get sick. And the an infection price within the placebo group could be twice as excessive.

There could also be methods round this, nevertheless it strikes this observer as a protracted, lengthy shot.

Making an attempt to make sense of lengthy COVID

Sure, COVID 19 continues to be with us, though a lot much less of a menace. The newest figures for deaths, hospitalizations, emergency division visits, and optimistic exams are means, means down. There have been 444 deaths within the US resulting from COVID in the course of the week ending November 3. This was about 1.0% of all of the deaths within the US at that time. And solely 0.5% of the emergency division visits have been resulting from COVID. Listed below are some mortality figures going again to the beginning of the epidemic to offer some perspective concerning the present state.

Week ending 09/14/2024 – 563 deaths resulting from COVIDWeek ending 08/31/2024 – 663 deaths resulting from COVIDWeek ending 05/18/2024 – 336 deaths resulting from COVIDWeek ending 01/27/2024 – 2,131 deaths resulting from COVIDWeek ending 01/17/2023 – 3,870 deaths resulting from COVIDWeek ending 01/15/2022 – 19,078 deaths resulting from COVIDWeek ending 01/19/2021 – 25,974 deaths resulting from COVID

The parade of variants continues. Presently, the dominant variant nationwide is KP.3.1.1, which accounts for 52% of instances, adopted by XEC, with 28% of instances, and MC.1, with 6% of instances. The unique Omicron variant has been changed by subvariants, together with LB.1, KP.2, and KP.3. As I’ve tediously famous, because the virus mutates, essentially the most “profitable” variants – profitable when it comes to their very own survival as a viral species – are the variants that allow the human illness sufferer to outlive and go the virus on to different. A virus that kills its victims shortly is doomed to extinction.

All in all, COVID as an acute an infection is receding. However what continues to have an effect on plenty of individuals, and trigger quite a lot of concern to the healthcare group, is lengthy COVID, which continues to be a puzzle. Lengthy COVID signs are much like the signs of an acute COVID an infection. Generally reported lengthy COVID signs included fatigue, mind fog, muscle ache, joint ache, again ache, headache, sleep disturbance, lack of odor or style, and gastrointestinal signs.

The CDC’s criterion for lengthy COVID is that the virus that causes COVID-19 is “current for no less than three months as a steady, relapsing and remitting, or progressive illness state that impacts a number of organ methods.”

Based on the CDC, estimates of the prevalence of lengthy COVID fluctuate resulting from totally different research standards, signs investigated, affected person populations, and timing of when signs are assessed. In 2022, 6.9% of adults and 1.3% of kids (roughly 17 million and 1 million, respectively) in america reported ever experiencing lengthy COVID. The newest figures I might discover, dated February fifteenth of this yr, ranged from 1.9% within the US Virgin Islands to 10.6% in West Virginia. These are clearly outliers; general, the prevalence remained on the identical degree because it had been in 2022.

I ought to add right here that an AI-enabled method, developed by Mass Basic Brigham, means that lengthy COVID prevalence is way larger – about 22%. The algorithm used was developed by drawing nameless affected person information from the medical data of practically 300,000 sufferers throughout 14 hospitals and 20 group well being facilities within the Mass Basic Brigham system. That algorithm might determine extra individuals who ought to be receiving take care of this debilitating situation.

Whereas lengthy COVID can happen in anybody who will get the coronavirus an infection, some individuals or teams of individuals are at larger threat of creating lengthy COVID. These embody ladies, individuals with underlying situations, individuals who skilled extra extreme outcomes of COVID-19, and other people of Hispanic ethnicity.  Roughly 1 in 4 adults with lengthy COVID reported experiencing vital limitations of their every day exercise.

A research carried out by a workforce of researchers at Brigham and Ladies’s Hospital targeted particularly on lengthy COVID. Researchers discovered individuals with wide-ranging lengthy COVID signs have been twice as prone to have SARS-CoV-2 proteins of their blood, in comparison with these with out lengthy COVID signs.

The workforce discovered that 43% of these with lengthy COVID signs affecting three main methods within the physique – the cardiovascular, digestive, and respiratory methods – examined optimistic for COVID viral proteins inside 1 to 14 months of their preliminary optimistic COVID take a look at. However solely 21% of those that didn’t report any lengthy COVID signs examined optimistic for the COVID virus on this identical interval.The hope expressed by the researchers is that by figuring out a subset of people that have a reservoir of the coronavirus of their our bodies, it could be attainable to deal with these individuals with efficient antivirals to alleviate their signs.

The research analyzed 1,569 blood samples collected from 706 people, together with 392 contributors from the Nationwide Institutes of Well being-supported Researching COVID to Improve Restoration (RECOVER) Initiative, who had beforehand examined optimistic for a COVID an infection. Utilizing SIMOA, an ultrasensitive take a look at for detecting single molecules, researchers seemed for complete and partial proteins from the SARS-CoV-2 virus. Additionally they analyzed information from the contributors’ lengthy COVID signs, utilizing digital medical chart info or surveys that have been gathered similtaneously the blood samples have been taken.

Researchers identified that it’s attainable {that a} persistent an infection explains some however not all the lengthy COVID signs. If that is so, testing and remedy might help in figuring out sufferers who could profit from different remedies.

One of many questions raised by the research is why greater than half of sufferers with wide-ranging lengthy COVID signs examined unfavourable for persistent viral proteins.

Dr David Walt, principal investigator on the research noticed that the discovering famous above suggests there may be possible a couple of reason for lengthy COVID. For instance, one other attainable reason for lengthy COVID signs might be that the virus harms the immune system, such that immune dysfunction continues after the virus is cleared.

Dr Walt and his workforce are at the moment conducting follow-up research to higher perceive whether or not an ongoing an infection is behind some individuals’s lengthy COVID signs. They’re analyzing blood samples and symptom information in bigger teams of sufferers, together with individuals of broad age ranges and people with compromised immune signs. It might be essential to determine people who usually tend to have persistent virus of their our bodies, resulting in lengthy COVID.

The coronavirus inflicting COVID will not be distinctive in staying within the physique and inflicting ongoing signs months after the preliminary acute an infection. Animal research have discovered Ebola and Zika proteins in tissues post-infection and these viruses have additionally been related to post-infection sickness.

My tackle this matter is that, whereas acute COVID infections are a lot much less frequent and infrequently trigger critical sickness or dying, they’ll and do result in lengthy COVID, which is an final result to be assiduously averted. Due to this fact, cautious people (my spouse and myself) proceed to put on masks in some public locations, together with the road on the pharmacy to select up our drugs and medical amenities.

Who is aware of when – if ever! – it’ll actually and actually be over.

A Division of Power regulation might drastically change our mild bulbs

That regulation might have a big opposed impact on the well being of many individuals within the US, particularly epileptics and migraineurs.

The regulation is scheduled to take impact in July 2028, and it’s targeted completely on vitality effectivity, as one would anticipate of a regulation coming from the Division of Power. The related assertion is as follows:

“The adopted requirements, that are expressed in minimal lumens (“lm”) output per watt (“W”) of a lamp or lamp efficacy (“lm/W”). These requirements apply to all merchandise manufactured in, or imported into, america beginning on July 25, 2028.”

At current, the one mild bulbs (“lamps,” within the official DOE parlance) that will meet these requirements are the LEDs that emit mild within the 460 – 495 nm (nanometer) vary. A nanometer, by the way in which, is a billionth of a meter. Mild in that vary is emphatically on the blue finish of the spectrum, ranging into the ultraviolet.

However mild at that frequency has clear and distinct points. Within the night, it messes up our circadian rhythms. Our mind thinks it’s nonetheless broad daylight, undoubtedly not time to fall asleep. Blue mild suppresses the manufacturing of melatonin, which helps us fall asleep and keep asleep. We’ve got all been advised that staring into our pc screens or watching tv within the half-hour or so earlier than bedtime is a really unhealthy concept, as a result of the blue mild will make it tougher to get night time’s sleep.

Past the circadian rhythm subject that impacts us all, blue LED mild is a serious public well being subject for epileptics and migraineurs, lots of whom are extraordinarily delicate to the standard of sunshine and easily can not tolerate blue LED mild. Yellow and white LEDs, though problematic, are extra acceptable, however the LEDs on the blue finish of the spectrum are past what these individuals can tolerate.

For these people, even temporary publicity to unnatural mild, significantly on the blue finish of the spectrum, can set off epileptic seizures and migraine complications. And a migraine is rather more and far worse than a foul headache. Along with the pounding ache, a migraine can convey on different signs, reminiscent of extreme nausea and vomiting, in addition to excessive sensitivity to any mild, such that the migraineur must shelter in a darkish room.

The prevalence of migraines within the US inhabitants is surprisingly excessive – nearly 10% of males and about 21% of girls report migraines or exceptionally extreme complications throughout a three-month interval.

What we’d like is mild whose frequencies are extra evenly distributed over the seen spectrum, not concentrated on the blue finish. Sure, broader spectrum mild bulbs are much less vitality environment friendly, however they’re more healthy and far, rather more nice.

It’s price mentioning that we people, together with all different creatures whether or not animal or vegetable, developed with incandescent mild, and I don’t imply Edison mild bulbs. The solar and all the celebs in our cosmos emit incandescent mild, as do candles and torches and cooking fires. Incandescence is mild produced by any scorching or burning matter.

The actual high quality of incandescent mild sources, which can’t be matched by LEDs, is that it emits mild all through your complete steady spectrum. LED producers could make mild bulbs that mimic your complete spectrum, mixing diodes that emit radiation at a spread of factors, from the ultraviolet to the infrared. However irrespective of what number of diodes the LED accommodates, it is not going to be a steady spectrum like incandescent mild. Elements of the spectrum can be lacking, and what we’re in a position to see illuminated by LEDs is not going to cowl your complete seen spectrum.

In Rockland, Maine, there may be an artwork museum, the Farnsworth, which homes a superb assortment of the works of Andrew Wyeth. The Wyeth work are illuminated by LEDs – all aside from one portray which is adjoining to a big window that allows the portray to be lit by daylight. The distinction between the LED-lit work and the one portray close to the window is big. The LED-lit work look drab as compared.

It is perhaps attainable to make LEDs which can be superior to those within the Farnsworth, however absence of your complete seen spectrum can be a deficit. I want to assume that sooner or later the Authorities, whether or not the Division of Power or the Division of Well being and Human Companies, will come to understand that mild bulbs that span the seen spectrum are, no less than in some instances, a necessity.

Power-efficient mild bulbs that emit a nice mild that may be tolerated by epileptics and migraineurs and are sympathetic to the wants of our circadian rhythms ought to, I deeply hope, turn out to be accessible effectively earlier than that dire date in 2028.

Transient remark: is Lesstranol the reply to elevated ldl cholesterol?

A daily reader and web buddy despatched a bit about this complement with the query “Is there something to this?”

My reply is a cautious “possibly.”

The commercial selling Lesstranol will not be a wild overstatement. Right here is the principal assertion of Lesstranol’s worth:

“After a long time of treating 1000’s of sufferers with unhealthy levels of cholesterol, I got here to the conclusion that there needed to be a neater all-natural means to assist my sufferers help their levels of cholesterol. After meticulous analysis, I recognized 1 all-natural key nutrient that helps preserve each regular ldl cholesterol and triglyceride ranges whereas selling optimum LDL/HDL steadiness and cardiovascular well being.

This key nutrient is Purple Yeast Rice. Historic Chinese language healers believed purple yeast rice might promote good blood circulation. Immediately, trendy scientists know that it accommodates monacolins, substances identified to advertise regular levels of cholesterol. These monacolins cease the motion of the HMG-CoA reductase, an enzyme that helps make ldl cholesterol.”

Certainly, purple yeast rice can have a helpful impact on levels of cholesterol. Right here’s what the Mayo Clinic says about it:

“Analysis reveals that purple yeast rice containing appreciable quantities of monacolin Ok can decrease your whole blood ldl cholesterol degree, your low-density lipoprotein (LDL, or “unhealthy”) ldl cholesterol degree and your triglyceride degree.

Whereas the complement is mostly thought of secure, it’d carry the identical potential unwanted effects as statin ldl cholesterol medication.

Purple yeast rice may cost lower than a statin. Nonetheless, with a complement, there’s much less assurance concerning high quality and the way a lot lively ingredient is definitely within the product. Some purple yeast merchandise may comprise solely small quantities of monacolin Ok and doubtlessly have little impact on levels of cholesterol.”

And who is aware of how a lot of that monocolin Ok is within the Lesstranol complement. As has been ceaselessly identified in these items, dietary supplements are completely unregulated. There isn’t any means of understanding what is definitely within the Lesstranol tablets. Talking for myself, if I had elevated ldl cholesterol (which, fortunately, I don’t!), I’d observe the recommendation of my doctor, which might possible level me to a statin.

* * * * * * * *

In previous Doc Gumshoe epistles, we have now mentioned elevated ldl cholesterol and methods of managing that situation, and in addition famous the introduction of recent statins. Is it maybe time to muster up an outline of that image?  Please let me know!

I used to be solely in a position to cowl a number of of the latest developments on this installment, so within the subsequent one I’ll decide up the place I left off and produce you extra bits and items.

Within the meantime, thanks for all feedback and benefit from the holidays, in addition to the non-holidays. Michael Jorrin (aka Doc Gumshoe).

[ed note: Michael Jorrin, who I dubbed “Doc Gumshoe” many years ago, is a longtime medical writer (not a doctor) and shares his commentary with Gumshoe readers once or twice a month. He does not generally write about the investment prospects of topics he covers, but has agreed to our trading restrictions.  Past Doc Gumshoe columns are available here.]