New Publication on Risk-based Monitoring – Bravo to Vadim Tantsyura

 

Our esteemed data management expert and prolific writer, Vadim Tantsyura has done it again. The publication entitled “Risk-Based Approaches to Data Management and Data Quality: Double Standards or Is It Just Common Sense and Intelligence Taking Over?“ was recently published in Data Basics and co-authored with an international team from the US and Japan.

 

From the introduction: “At a recent Risk-based Monitoring (RBM) conference at University of Tokyo, the authors were asked “Do the various RBM approaches lead to double-standards in processes and quality?“ This report provides several examples when clinical data management (CDM) standard and a so-called best practices can, and perhaps should be deviated from – including such rarely questioned decisions involving database unlock, hard-coding or local laboratory ranges.“

 

For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 165). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website.

 

Joyce Hays, Founder and Editor in Chief of On Target

Jules Mitchel, Editor

 

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Bioelectromagnetic Medicine in the 21st Century

Graphic credit: Geek3 – Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=10618762

 

Electrical phenomena have been studied since antiquity, though progress in theoretical understanding remained slow until the seventeenth and eighteenth centuries. Even then, practical applications for 1) ___ were few, and it would not be until the late nineteenth century that engineers were able to put it to industrial and residential use. The rapid expansion in electrical technology at this time transformed industry and society and gave us the Second Industrial Revolution. In the 18th century, Benjamin Franklin conducted extensive research in electricity, selling his possessions to fund his work. In June 1752 he is reputed to have attached a metal key to the bottom of a dampened kite string and flown the kite in a storm-threatened sky. A succession of sparks jumping from the key to the back of his hand showed that lightning was indeed electrical in nature. He also explained the apparently paradoxical behavior of the Leyden jar as a device for storing large amounts of electrical charge in terms of electricity consisting of both positive and 2) ___ charges. In 1791, Luigi Galvani published his discovery of bioelectromagnetics, demonstrating that electricity was the medium by which neurons passed signals to the 3) ___.

 

Electricity’s extraordinary versatility means it can be put to an almost limitless set of applications which include transport, heating, lighting, communications, medical devices such as deep brain stimulation, the electrocardiogram and many more, computation, and all the e-world’s important new inventions. Electrical power is now the backbone of modern industrial society. Only recently has the critical importance of electromagnetic (EM) field interactions in biology and medicine been recognized. The phenomenon of resonance signaling, shows how specific frequencies, modulate cellular function to restore or maintain health. The application of EM-tuned signals represents more than merely a new tool in information medicine. It can also be viewed in the larger context of EM medicine, the all-encompassing view that elevates the EM over the biochemical. The discovery by Zhadin that ultra small magnetic intensities are biologically significant, suggests that EM signaling is endogenous to 4) ___ regulation, and consequently that the remarkable effectiveness of EM resonance treatments reflects a fundamental aspect of biological systems. The concept that organisms contain mechanisms for generating biologically useful electric signals is not new, dating back to the nineteenth century discovery of currents of injury by Matteucci. The corresponding modern-day version is that ion cyclotron resonance magnetic 5) ___ combinations help regulate biological information. The next advance in medicine will be to discern and apply those EM signaling parameters acting to promote wellness, with decreasing reliance on marginal biochemical remediation and pharmaceuticals. Today, graphene, electricity appears to change stem cells for nerve regrowth. Scientists are combining their expertise to change stem cells for nerve regrowth. Researchers looking for ways to regenerate nerves can have a hard time obtaining key tools of their trade. Schwann cells are an example. They form sheaths around axons, the tail-like parts of 6) ___ cells that carry electrical impulses. They promote regeneration of those axons. And they secrete substances that promote the health of nerve cells. In other words, they’re very useful to researchers hoping to regenerate nerve cells, specifically peripheral nerve cells, those cells outside the brain and spinal 7) ___. But Schwann cells are hard to come by in useful numbers. So researchers have been taking readily available and noncontroversial mesenchymal stem cells (also called bone marrow stromal stem cells that can form bone, cartilage and fat cells) and using a chemical process to turn them, or as researchers say, differentiate them into Schwann cells. But it’s an arduous, step-by-step and expensive process. Researchers at Iowa State University are exploring what they hope will be a better way to transform those stem cells into Schwann-like cells. They’ve developed a nanotechnology that uses inkjet printers to print multi-layer graphene circuits and also uses lasers to treat and improve the surface structure and conductivity of those circuits. It turns out mesenchymal stem cells adhere and grow well on the treated circuit’s raised, rough and 3-D nanostructures. Add small doses of electricity — 100 millivolts for 10 minutes per day over 15 days — and the 8) ___ cells become Schwann-like cells. The findings are featured on the front cover of the scientific journal Advanced Healthcare Materials. According to the authors, there is a huge potential here as the technology could lead to a better way to differentiate stem cells. According to the article, the electrical stimulation is very effective, differentiating 85% of the stem cells into Schwann-like cells compared to 75% by the standard chemical process. The electrically differentiated cells also produced 80 nanograms per milliliter of nerve growth factor compared to 55 nanograms per milliliter for the chemically treated cells. The authors indicated that the results could lead to changes in how nerve injuries are treated inside the 9) ___ and that the results help pave the way for in vivo peripheral nerve regeneration where the flexible graphene electrodes could conform to the injury site and provide intimate electrical stimulation for nerve cell regrowth. The paper also reports several advantages to using electrical stimulation to differentiate stem cells into Schwann-like cells including:

 

1. doing away with the arduous steps of chemical processing

2. reducing costs by eliminating the need for expensive nerve growth factors

3. potentially increasing control of stem cell differentiation with precise electrical stimulation

4. creating a low maintenance, artificial framework for neural damage repairs.

 

A key to making it all work is the graphene inkjet printing process which takes advantages of graphene’s wonder-material properties — it’s a great conductor of electricity and heat, it’s strong, stable and biocompatible — to produce low-cost, flexible and even wearable electronics. However, once graphene electronic circuits were printed, they had to be treated to improve electrical conductivity. That usually meant high temperatures or chemicals. Either could damage flexible printing surfaces including plastic films or paper. The authors solved the problem by developing computer-controlled 10) ___ technology that selectively irradiates inkjet-printed graphene oxide. The treatment removes ink binders and reduces graphene oxide to graphene — physically stitching together millions of tiny graphene flakes. The process makes electrical conductivity more than a thousand times better.

 

There are also new possibilities to think about. The technology, for example, could one day be used to create dissolvable or absorbable nerve regeneration materials that could be surgically placed in a person’s body and wouldn’t require a second surgery to remove.

 

Sources: Iowa State University; Suprem R. Das, Metin Uz, Shaowei Ding, Matthew T. Lentner, John A. Hondred, Allison A. Cargill, Donald S. Sakaguchi, Surya Mallapragada, Jonathan C. Claussen. Stem Cell Differentiation: Electrical Differentiation of Mesenchymal Stem Cells into Schwann-Cell-Like Phenotypes Using Inkjet-Printed Graphene Circuits (Adv. Healthcare Mater. 7/2017). Advanced Healthcare Materials, 2017; 6 (7) DOI: 10.1002/adhm.201770032; Iowa State University. “Graphene, electricity used to change stem cells for nerve regrowth.”; 10 April 2017: sciencedaily.com/releases; ncbi.nlm.nih.gov/pubmed; Wikipedia

 

ANSWERS: 1) electricity; 2) negative; 3) muscles; 4) cell; 5) field; 6) nerve; 7) cord; 8) stem; 9) body; 10) laser

 

Benjamin Franklin’s Contributions to Health and Medicine

Benjamin Franklin Drawing Electricity from the Sky c. 1816 at the Philadelphia Museum of Artby Benjamin West; Google Cultural Institute; Public Domain; Wikipedia Commons

 

Benjamin Franklin took a great interest in health-related topics. In his day, many beliefs about health and disease were based on superstition. Franklin applied Enlightenment reasoning to his study of various afflictions and came up with some astonishingly accurate hypotheses. Here are just a few of Franklin’s theories and accomplishments in the fields of health, physical fitness, and medicine.

Common cold: In the 18th century, most people believed that wet clothing and dampness in the air caused the common cold. However, Franklin observed that sailors, who were constantly wearing wet clothing, remained healthy. After considering the matter on and off for several years, he eventually concluded: “People often catch cold from one another when shut up together in small close rooms, coaches, &c. and when sitting near and conversing so as to breathe in each other’s transpiration.“ Before the knowledge of viruses and germs, Franklin had determined that the common cold was passed between people through the air. Franklin’s views on the cause of the common cold indicate that he was sympathetic to the view that it could result from some causative agent or agents transmitted from one person to another. In writing to Benjamin Rush, the eminent Philadelphia physician best known for his strong advocacy of blood-letting, Franklin commented thus.

 

[I] am glad to hear that [Dr. Cullen] speaks of Catarrhs or Colds by contagion. I have long been satisfy’d from Observation, that besides the general Colds now termed Influenza’s, which may possibly be spread by Contagion as well as by a particular Quality of the Air, People often catch Cold from one another when shut up together in small close Rooms, Coaches, &c. and when sitting near and conversing so as to breathe in each others Transpiration, the Disorder being in a certain State. As to Dr. Cullen’s Cold or Catarrh a frigore, I question whether such an one ever existed. (Franklin 1773a; 1773b).

 

Lead poisoning: Franklin learned first-hand from the printing business that working with warm lead type caused his hands to become exceptionally stiff and sore. He discovered that some typesetters who warmed their type sometimes lost the complete use of their hands. Franklin decided to work with cold type from that point on. Years later, he visited a hospital in France that treated patients suffering from what was then called the “dry gripes“ or “dry belly ache.“ In analyzing the list of patients, Franklin deduced that all of them were in professions where they were exposed to large quantities of lead. He corresponded with others interested in this health issue, exchanging observations and insights about the illness. Franklin concluded: “I have long been of the opinion that that distemper [dry gripes] proceeds always from a metallic cause only, observing that it affects among tradesmen those that use lead, however different their trades, as glazers, type-founders, plumbers, potters, white lead-makers and painters.“ Franklin’s observations were among the earliest to link health problems with exposure to lead.

 

Pennsylvania Hospital: A friend of Franklin, Dr. Thomas Bond, came up with the idea of establishing a public hospital. Bond was unable to raise the money, so he turned to Franklin, who mounted a public relations and information campaign in support of a hospital. The colonial government finally agreed and the hospital was founded in 1751. The hospital’s mission was to serve the mentally ill, along with providing medical care to poor citizens who could not afford a private physician. The Pennsylvania Hospital is considered to be the first public hospital in the United States. While raising money for the hospital, Franklin came up with a new idea for combining public (government) money with private donations, which created the first matching grant.

 

Electricity and paralysis: Franklin experimented with giving electrical shocks to individuals who had paralysis in their limbs due to a stroke or other cause. He wired the patients to Leyden jars and sent electrical shocks to the paralyzed limbs. Franklin observed improvement in many of the patients, but reported that most relapsed after several days. Although he was initially excited about the possibilities, he wrote that he “never knew any advantage from electricity in palsies that was permanent.“ Modern medical doctors stimulate immobile muscles with electrical impulses to help prevent atrophy.

 

Exercise: As an avid swimmer in his youth, Franklin learned the joys of exercise. He was one of the earliest supporters of regular exercise as a way of maintaining one’s health. He especially believed in outdoor exercise with lots of fresh air. In a letter to his son William, Franklin outlined a complete program of vigorous exercise, which Franklin contended would help prevent disease. Franklin rightly believed that the more strenuous the exercise, the higher the degree of body warmth. He commented that when he exercised vigorously with dumbbells that both his heart rate and temperature rose. Today we know that regular cardiovascular exercise can prevent a variety of ailments.

 

Swimming: Franklin grew up near the ocean in Boston and began swimming at a young age. On his first trip to London in 1724, he often swam in the Thames River and entertained observers with the “ornamental“ maneuvers he performed in the water. While in London, Franklin considered taking a job as a full-time swimming instructor. For his early encouragement of the sport of swimming, Franklin was posthumously inducted into the International Swimming Hall of Fame. In a 1747 letter to his parents, Benjamin Franklin noted:

 

“I apprehend I am too busy in prescribing, and meddling in the Dr’s sphere, when any of you complain of ails in your letters: but as I always employ a physician myself when any disorder arises in my family and submit implicitly to his orders in everything, so I hope you consider my advice, when I give any, only as a mark of my good will, and put no more of it in practice that happens to agree with what your Dr. directs.“

 

After giving this assurance that he did not mean to play the physician, Franklin continued with advice about remedies for bladder stone and gravel. In fact, throughout his life he dispensed such advice and wrote knowledgeably on a number of health-related issues. Franklin played many roles during his long life: printer and publisher, civic activist, revolutionary and statesman, scientist and philosopher, diplomat, and sage. Given the significance of his political and civic activities and his experimentation with electricity, it is little wonder that Franklin’s medical interests have attracted less attention. Nonetheless, despite his lack of formal training, medicine was prominent among Franklin’s interests. His writings ranged over a number of topics, from treatment of the common cold to promotion of exercise and a moderate diet. With his connections to prominent physicians on both sides of the Atlantic and with his published works widely read, Franklin’s thoughts on health and medicine found a broad contemporary audience. He was also a medical activist and inventor, championing smallpox inoculation, taking a leading role in founding Pennsylvania Hospital (the first such institution in the British North American colonies), and inventing devices like bifocal glasses.

 

Born in Boston in 1706, Benjamin Franklin was the youngest son of 17 children. He came to Philadelphia in 1723, after leaving an apprenticeship with his brother, a printer. By the 1730s, Franklin was owner of his own printing house, publishing a popular newspaper and almanac, and a civic activist. He retired from printing in 1748 to pursue other interests and later gained international fame for his experiments with electricity. Franklin spent the latter portion of his life in politics and diplomacy. He served in the Pennsylvania Assembly and spent 15 years in London as a colonial agent. He was also a member of the legislative bodies crucial to the founding of the United States, serving as a delegate to the Continental Congress and, later, the oldest participant in the Constitutional Convention. Franklin signed both the Declaration of Independence and the Constitution, and was sent to France as the first diplomat from the USA. Such diverse interests and activities were not unusual for the time. Many educated men were active or interested in politics, civic or social improvement, and scientific exploration. These pursuits rose out of a social consciousness born of the Enlightenment. This movement valued reason and observation as the means to knowledge and improved social organization. An Enlightenment temperament, such as that shown by Franklin, had a high regard for rationality, valued self-discipline and social consciousness, and desired to generate progress by increase of learning. In his roles as scientist and purveyor of information, Franklin was an active citizen in the eighteenth-century medical world. His contemporaries sought healthcare and medical advice from a wide variety of sources and most medical care was provided in the home from family members or – for the wealthy – servants. Sources of counsel about health, disease and medicine included popular health manuals, almanacs, newspapers and cookbooks. The adages and poetry in Poor Richard’s Almanac, the entire contents of which were authored by Franklin, served to instruct the masses at the same time they entertained. Through his almanac and other writings, Benjamin Franklin exerted his greatest influence on the medical sphere. With numerous well-informed correspondents – including physicians and scientists on two continents – and, as a skilled writer, he was capable of writing letters, articles, collections of sayings and other works filled with medical commentary. These covered a wide range of subjects including electrical treatments for paralysis.

 

Medical uses of electricity were much discussed during Franklin’s lifetime. It was known, from early in the eighteenth century, that an electrical shock could cause involuntarily twitching and contraction of muscles. Many people thus hoped that ?electrical fire’ would provide a cure for paralysis. They believed that sending a charge through the affected limbs might increase blood flow, regenerate muscle and restore movement or physical control. Franklin was doubtful about the usefulness of electrical treatment for palsy and paralysis and never promoted himself as an electrical therapist. Nonetheless, because of his reputation as an electrical innovator, he was from time to time contacted by people seeking electrical therapy. Using an electrostatic generator (in which electrical charge was created by rubbing material against a mounted glass ball or cylinder turned by a crank) and a Leyden jar (which stored the electrical energy), Franklin obliged those patients who came to him desiring electrical therapies. He described these treatments in a letter to Sir John Pringle, dated 21 December 1757.

 

“Some years since.a number of paralytics were brought to me from different parts of Pennsylvania and the neighboring provinces, to be electris’d, which I did for them, at their request. My method was, to place the patient first in a chair on an electric stool, and draw a number of large strong sparks from all parts of the affected limb or side. Then I fully charg’d two 6 gallon glass jars, each of which had about 3 square feet of surface coated and I sent the united shock of these thro’ the affected limb or limbs, repeating the stroke commonly three times each day.

 

The first thing observed was an immediate greater sensible warmth in the lame limbs that receiv’d the stroke than in the others. The limbs too were found more capable of voluntary motion and seem’d to receive strength. These appearances gave great spirits to the patients, and made them hope a perfect cure; but I do not remember that I ever saw any amendment after the fifth day: Which the patients perceiving, and finding the shocks pretty severe, they became discourag’d, went home and in a short time relapsed; so that I never knew any advantage from electricity in palsies that was permanent.’

 

Although Franklin’s patients found no permanent cure for their paralysis, he continued to receive requests for aid – one even from Pringle himself, who requested Franklin’s presence in 1767 at the treatments administered to the daughter of a nobleman. Franklin also concerned himself with medical problems more removed from his own scientific expertise. He wrote about lead poisoning on several occasions, in particular about a disease known as the dry-gripes (or dry-bellyache) that had plagued Europe and the colonies for years. Franklin had not yet left Boston when, in 1723 the Massachusetts colonial legislature passed a bill outlawing the use of lead in the coils and heads of stills. Observance of this law led to vastly decreased incidence of the dry-gripes, as the population drank less and less lead-contaminated rum. In a letter to his friend, Philadelphia physician Cadwalader Evans, Franklin wrote that he was certain that the symptoms known as dry-bellyache were always the result of lead exposure, whether in food or drink or from exposure through trades that used lead. In his correspondence with Dr George Baker, Franklin advanced this idea and thus helped Baker discover the aetiology of the Devonshire Colic, a condition the symptoms of which included weakened muscles, loss of weight and pallor. It was widespread in Baker’s native Devonshire; Baker suspected lead-contaminated cider was the cause, and his discussions with Franklin helped confirm his hypothesis. Baker eventually found that millwheels that were used to crush the apples were bound together with poured molten lead. He credited Franklin with his assistance in this discovery on several occasions.

 

Franklin’s scientific activities and medical acumen was respected on both sides of the Atlantic by physicians, scientists and, in one case, royalty. During Franklin’s time in Paris, he participated in the discrediting of the medical cult surrounding Mesmerism. Franz Anton Mesmer arrived in Paris in 1778, promoting his new principle of healing known as animal magnetism. His treatments attracted many followers, but also the scepticism of French physicians, who regarded Mesmer as a fraud. In March 1784, Louis XVI appointed a commission to investigate Mesmer’s claims. Four physicians and five eminent scientists were on the commission, including Franklin, who was chosen to preside over their investigation. The Commission observed one of Mesmer’s disciples, a Dr D’Eslon, at Franklin’s home in Passy, outside Paris. D’Eslon attempted to magnetize several patients chosen by the Commission, as well as members of Franklin’s own household, and the subjects reported feeling no change. In the Commission’s report, written by Franklin, Mesmer was declared a fraud, as no reasonable proof of animal magnetism could be determined. Franklin felt that any cures made were a product of imagination, and the report he authored led to Mesmer’s disgrace.

 

Throughout his lifetime, Franklin produced many lighter writings on health related topics as well. His advice in Poor Richard’s Almanac includes Franklin’s most famous advice on health, including such maxims as:

 

Early to bed and early to rise, makes a man healthy, wealthy and wise

Be not sick too late, nor well too soon

Time is an herb that cures all diseases

Eat to live and not live to eat.

 

Franklin promoted a moderate diet, exercise, and self-control in all things, and sometimes even followed his own advice. In his youth, Franklin was influenced to try vegetarianism after reading Thomas Tryon’s Way to Health and Happiness; he later returned to eating meat. He exercised frequently, favoring swimming and endorsing it not only as good exercise but also as a method to open pores, hydrate the body and maintain cleanliness. In his old age, Franklin continued to exercise, lifting and swinging weights when his health no longer allowed him to swim or walk. Many of Franklin’s medical writings showed the same spirit of public activism that characterized his civic and national projects. He repeatedly used his skills with pen and press in support of innovations that could make a difference in the public health. Most significant, perhaps, was his lifelong endorsement of smallpox inoculation. Inoculation spread rapidly in North America and Europe after its introduction into western medicine in the 1720s. The practice involved exposing healthy individuals to the disease by abrading the skin and introducing a small amount of morbid matter. Typically the patient would contract a similarly mild instance of the disease and, once recovered, would have permanent immunity. Cases contracted the natural way would often leave victims disfigured and had a significant mortality rate. Franklin wrote articles promoting inoculation and its safety as early as 1731. His support of inoculation grew after the heartbreaking loss of his 6-year-old son, Francis Folger Franklin, to smallpox in 1736. Franklin had planned to inoculate the boy at the time of an outbreak, but was unable to do so because the child was in a weakened state from another illness. Critics of inoculation suggested that Franklin’s son had been a victim of the procedure, and Franklin was forced to publish an article in his paper, The Pennsylvania Gazette, insisting that his son had contracted a natural case of the disease. Throughout his life, Franklin monitored the success of inoculation in several colonial cities, and shared information with his correspondents about the procedure’s extremely low mortality rates and the decreased smallpox incidence that resulted. The statistics he compiled were useful for Some Account of the Success of Inoculation for the Small-pox in England and America, a pamphlet he wrote with physician William Heberden. While in London, Franklin encouraged Heberden to write briefly on the value of inoculation and to include instructions by which any educated layman could inoculate his own family. Franklin wrote the preface and had 1500 copies printed and sent to the colonies for free distribution.

 

Franklin did more than just write about medical matters. Most of his inventions provided practical solutions to everyday problems, and Franklin brought that same inventive spirit into the medical realm. His medical creations were uncomplicated and made to be immediately useful, like the flexible catheter he designed for his brother John, who suffered from bladder stone and urinary retention. Franklin designed a device in 1757, had it made by a local silversmith, and sent it to John in Boston, with a letter detailing its design and use. The catheter was made from silver wire, coiled with joints to allow flexibility, and covered with gut. Most famous among his contributions to medical care were Franklin’s ?double spectacles’, better known as bifocals. He himself was probably wearing these spectacles as early as the 1750s, during his time in London. In several letters to London philanthropist, George Whatley, Franklin stated that he had created bifocals to avoid awkward shifting between his regular and reading glasses. Cutting his other glasses and having half of each lens placed in the same frame, Franklin believed, make my eyes as useful to me as ever they were. The first written record of his bifocals design, is a letter to George Whatley:

 

“I had formerly two Pair of Spectacles, which I shifted occasionally, as in travelling I sometimes read, and often wanted to regard the Prospects. Finding this Change troublesome, and not always sufficiently ready, I had the Glasses cut, and half of each kind associated in the same Circle. By this means, as I wear my spectacles constantly, I have only to move my Eyes up or down, as I want to see distinctly far or near, the proper Glasses being always ready.“ (Franklin 1785).

 

Franklin also served the Philadelphia medical scene with his skills as an organizer and philanthropist. In 1751 Franklin’s friend, Dr Thomas Bond, began a campaign to raise money for what would be the first voluntary hospital in the colonies. Bond had little success raising money and turned to Franklin for assistance. Franklin supported the idea completely and agreed to become a subscriber. His involvement had the desired effect, and once he was involved in the project funds were raised easily. He then petitioned the Pennsylvania Assembly for support and convinced the legislators to match the voluntary funds if he and Bond could solicit ?2000 from citizens of the colony. The founders used the Assembly’s promise of matching funds to encourage private donors, and the necessary sum was soon raised. Pennsylvania Hospital received its charter in May 1751 and, in 1756, the first patients were admitted to the hospital’s building at Eighth and Pine Streets. Franklin served on the hospital’s board for a number of years, and sought support from abroad for the institution during his time in London. Franklin enjoyed good health. While most images of Franklin show him in prosperous middle age or as an elderly statesman, he was a strong and active youth. As a young man, Franklin’s most serious afflictions were respiratory illnesses. He was thus very interested in the common cold and its causes. He dismissed the popular notion that changes in temperature, particularly exposure to cold air, made people apt to catch cold. He suggested instead that putrid matter in the air was responsible. Because of this belief, Franklin championed proper ventilation as essential to good health, noting that:

 

?I am persuaded that no common Air from without, is so unwholesome as the Air within a close Room, that has been often breath’d and not changed.’

 

Franklin advocated as much exposure to fresh air as possible and frequently slept with an open window. He enjoyed a daily air bath to cleanse his skin. This involved sitting naked in his chambers with the windows open. Other than frequent respiratory problems, Franklin suffered two common eighteenth-century complaints: gout and pain from bladder stones. These were largely nuisance diseases in Franklin’s middle years, and he was fortunate to enter his seventies still active and mentally focused. His gout attacks began in his forties and continued intermittently for the rest of his life – with occasional attacks in his knees, feet and hands so severe as to render him bedridden. He often returned to a simple diet when dealing with this problem and he believed that exposing his afflicted limbs to fresh air was also helpful. As late as 1783, at the age of 76, Franklin faced gout attacks philosophically, noting:

 

?I have been lately ill with a Fit of the Gout, if that may indeed be called a Disease; I rather suspect it to be a Remedy; since I always find my Health and Vigor of Mind improv’d after the Fit is over.’

 

As he advanced into his eighties, Franklin’s health increasingly failed. His bladder stone grew, causing him pain in movement and curtailing the active life he had enjoyed before then. The stone was probably sizable by the time it began to cause Franklin difficulty, and it only grew larger. Late in his life, he noted that he could actually feel the weight of the stone moving in his body when he rolled over in bed or shifted position. Franklin’s stone was too large for surgery by the time it caused him the greatest suffering. With the high risks of any procedure where cutting was involved, and his advanced age making the operation even more dangerous, Franklin chose to manage the stone as best he could with diet and gentle exercise. In a 1787 letter to the Comte de Buffon, a friend and fellow sufferer, Franklin noted that he had ?tried all the noted Prescriptions for diminishing the Stone, without procuring any good Effect. But observing Temperance in Eating, avoiding wine and Cyder, and using daily the Dumb Bell, which exercises the upper Part of the Body without much moving the Parts in contact with the Stone, I think I have prevented its Increase’.

 

In his final years, Franklin took opium to combat the severe pain resulting from the stone and he was often bedridden. He died 17 April 1790, after suffering a bout of pneumonia and pleurisy.

 

With the breadth of his commentary, and the useful products of his inventiveness, Franklin’s medical legacy continues to the present. His wit and wisdom on diet, health care and moderate living, as written in Poor Richard’s Almanac, is still part of the public consciousness. Almost immediately after his death, authors began quoting and reprinting Franklin’s advice to give their own works legitimacy and to boost sales. We may now be able to quantify the calories burned during exercise or the nutritional content in our diet, but Franklin’s advice, made long before such activities were possible or even understood, still rings true in its simplicity. In a larger sense, Franklin’s medical legacy is similar to the legacy of the Enlightenment world in which he lived – a legacy of public health initiatives and ideas about improvement through moderation and human enterprise. Franklin’s thoughts and inventions fit squarely into this heritage, from his campaign against smallpox that paved the way for acceptance of vaccination (announced by Edward Jenner within a decade of Franklin’s death) to his invention of spectacles that could serve two purposes simultaneously. Because his thoughts on health and medicine depended so much upon people taking an active role in remaining healthy and improving society, the medical world of Benjamin Franklin will continue to have relevance and influence for years to come.

 

Lisa Gensel; The Royal Society of Medicine; pbs.org/benfranklin/l3l; http://www.jameslindlibrary.org/articles/benjamin-franklins-1706-1790-place-in-the-history-of-medicine/; Twin Cities Public Television, Inc.Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1299336/

 

Zika Virus Persists the CNS and Lymph Nodes of Rhesus Monkeys

 

According to a study published online in the journal Cell (28 April 2017), Zika virus (CREDIT: National Institute of Allergy and Infectious Diseases) can persist in cerebrospinal fluid (CSF), lymph nodes and colorectal tissue of infected rhesus monkeys for weeks after the virus has been cleared from blood, urine and mucosal secretions. The image is a transmission electron microscope image of negative-stained, Fortaleza-strain Zika virus (red), isolated from a microcephaly case in Brazil.

 

For the study, the authors infected 20 rhesus monkeys with Zika virus and noted that although virus was cleared from peripheral blood within 7-10 days, Zika virus was detected in the CSF for up to 42 days and in lymph nodes and colorectal biopsies for up to 72 days. Immunologic data showed that the emergence of Zika virus-specific neutralizing antibodies correlated with the rapid control of the virus in plasma. However, Zika-specific antibodies were not detected in CSF, which could be why the virus remained in CSF longer. The authors also found that viral persistence in CSF correlated with the activation of the mechanistic target of rapamycin (mTOR) pathway, which has been shown to be related to the development of brain tissue and brain malformations.

 

According to the authors, the findings suggest that persistent virus in the central nervous system may contribute to the neurological issues associated with Zika virus infection. Although Zika virus usually causes mild or no symptoms in people, it has been associated with neurological disorders in children and adults and can cause severe fetal defects, such as microcephaly, if an infected pregnant woman passes the virus to her fetus. The authors note it is possible that if the virus can persist in the central nervous system and other tissues in humans with Zika infection, more extensive neurologic and lymphoid disease than currently appreciated may be occurring.

 

Outcomes After Diagnosis Of Mild Cognitive Impairment in a Large Autopsy Series

 

A study recently reported the Annals of Neurology (2017;81:549-559), was performed to determine clinical and neuropathological outcomes following a clinical diagnosis of mild cognitive impairment (MCI). For the study, data were drawn from a large autopsy series (N=1,337) of individuals followed longitudinally from normal or MCI status to death, derived from 4 Alzheimer Disease (AD) Centers in the United States.

 

Study participants had a mean follow-up was 7.9 years. Of the 874 individuals ever diagnosed with MCI, final clinical diagnoses were varied: 39.2% died with an MCI diagnosis, 46.8% with a dementia diagnosis, and 13.9% with a diagnosis of intact cognition. The latter group, however, had pathological features resembling those with a final clinical diagnosis of MCI. In terms of non-AD pathologies, both primary age-related tauopathy (p<0.05) and brain arteriolosclerosis pathology (p<0.001) were more severe in MCI than cognitively intact controls. Among the group that remained MCI until death, mixed AD neuropathologic changes (ADNC; >1 comorbid pathology) were more frequent than “pure“ ADNC pathology (55% vs 22%); suspected non-Alzheimer pathology comprised the remaining 22% of cases. A majority (74%) of subjects who died with MCI were without “high“-level ADNC, Lewy body disease, or hippocampal sclerosis pathologies; this group was enriched in cerebrovascular pathologies. Subjects who died with dementia and were without severe neurodegenerative pathologies tended to have cerebrovascular pathology and carry the MCI diagnosis for a longer interval.

 

The authors concluded that MCI diagnosis usually was associated with comorbid neuropathologies. However, less than one-quarter of MCI cases showed pure AD at autopsy.

 

FDA Approves Drug to Treat ALS

 

Amyotrophic lateral sclerosis (ALS), commonly referred to as Lou Gehrig’s disease, is a rare disease that attacks and kills the nerve cells that control voluntary muscles. Voluntary muscles produce movements such as chewing, walking, breathing and talking. The nerves lose the ability to activate specific muscles, which causes the muscles to become weak and leads to paralysis. ALS is progressive, meaning it gets worse over time. The Centers for Disease Control and Prevention estimates that approximately 12,000-15,000 Americans have ALS. Most people with ALS die from respiratory failure, usually within three to five years from when the symptoms first appear.

 

The FDA has approved granted approval of Radicava (edaravone) to Mitsubishi Tanabe Pharma America, Inc. to treat patients with ALS. Radicava is administered with an initial treatment cycle of daily intravenous infusions for 14 days, followed by a 14-day drug-free period. Subsequent treatment cycles consist of dosing on 10 of 14 days, followed by 14 days drug-free. The efficacy of edaravone was demonstrated in a six-month clinical trial conducted in Japan. In the trial, 137 participants were randomized to receive edaravone or placebo. At Week 24, individuals receiving edaravone declined less on a clinical assessment of daily functioning compared to those receiving a placebo. The most common adverse reactions reported by clinical trial participants receiving edaravone were bruising (contusion) and gait disturbance. Radicava is also associated with serious risks that require immediate medical care, such as hives, swelling, or shortness of breath, and allergic reactions to sodium bisulfite, an ingredient in the drug. Sodium bisulfite may cause anaphylactic symptoms that can be life-threatening in people with sulfite sensitivity.

 

The FDA granted this drug orphan drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

 

K A L E  C A E S A R !!!

This is one of the most delicious salads on the planet, whether you make it with romaine or with kale. I’ve been making Caesar salad for years and if I do say so, myself, my recipe is one of the best. Take it from me, there is no bottled Caesar dressing, that can equal the one you make yourself. Also, for some reason, some restaurants stopped using anchovies and even eliminated garlic. Without these two ingredients (and all of the others, too) you may have some kind of salad, don’t know what you would call it; but it ain’t Caesar. ©Joyce Hays, Target Health Inc.

 

Get all of the ingredients together in one place. Use fresh! Fresh garlic is better than garlic powder. Fresh lemon is better than bottled. Freshly grated parmesan is better than bought and freshly baked croutons taste much better than store bought. ©Joyce Hays, Target Health Inc.

 

 

Ingredients

 

The Dressing

 

3 anchovy fillets packed in oil, drained

4 fresh garlic cloves

Pinch Kosher salt

1 large egg yolk (boil egg for 1 minute and not longer)

Zest of 1/2 fresh lemon

2 Tablespoons fresh lemon juice, plus more (to your taste)

3/4 teaspoon Dijon mustard

2 Tablespoons excellent olive oil

2 Tablespoons canola oil

6 Tablespoons finely grated FRESH Parmesan

Pinch black pepper

Worchester sauce (one drop)

 

The Croutons

 

1 cup torn 1″ (bite-size) pieces old bread, with crusts

1 Garlic clove, squeezed

2 teaspoons olive oil

 

The Kale

 

1 large head of kale, leaves separated, washed three times, dried with paper towel. Then leaves torn by hand, put into a bowl and set aside.

 

Even though the plastic bag may say, pre-washed, I always rinse any leafy veggie under cold water, two or three times. Here’s the kale a dark beautiful green – has lots of healthy magnesium; just what you want for good health. I would say, that I tore the leaves too much; better a little larger. ©Joyce Hays, Target Health Inc.

 

 

The Cheese

 

1 cup FRESHLY GRATED Parmesan, grate it yourself & leave extra on the dining table, so more can be added after serving. Although, you can buy pre-grated parmesan, it’s quite bland compared with the cheese you grate yourself, freshly grated for each recipe.

 

Directions

 

The Croutons, certainly, can be made the day before. Otherwise, make them first, before you make the dressing. Can you buy packaged croutons? Of course, but try to make them yourself. The flavor is so much better. If you’re going to make a really great Caesar salad, you might as well make great tasting croutons. There is simply no comparison! Once you taste the richness of your own croutons, you’ll never buy them again. They’re not a peripheral ingredient, they make the salad better. That’s why they’re in the recipe.

 

1. Preheat oven to 375 degrees.

2. In a medium bowl, add the 2 teaspoons olive oil and the squeezed juice of one fresh garlic clove. Stir

3. Tear or cut any left-over bread, you have, into (1 inch) bite size pieces, enough for 1 cup (press the bread down a bit, in the measuring cup). Then put the pieces of bread, into the bowl with oil/garlic. My favorite bread for croutons is day old (or older) sour dough bread.

4. Now, toss the bread pieces or cubes and be sure that the bread cubes are all covered (as much as possible) with the oil mixture. Let them sit for a while to absorb the oil, like 30 to 60 minutes. Stir them around every once in a while

5. Arrange croutons on a baking sheet or large pan and bake, tossing occasionally, until golden, 10-15 minutes. Watch them carefully. Just a little too long in the oven, and they will burn and won’t be useable for the salad. When golden, remove from oven and set aside to cool.

 

Croutons are about to go into the oven. You can see that some pieces have more oil than others. Doesn’t matter. Once added to the salad, dressing will rub onto the croutons and they’ll be delicious. ©Joyce Hays, Target Health Inc.

 

Out of the oven, crisp, crunchy and delicious; ready to be added to the salad. These are a hundred times better than store-bought. ©Joyce Hays, Target Health Inc.

 

 

The Dressing

 

1. Use a large wood salad bowl and make the dressing in the bottom of this bowl.

2. Boil one large egg for one minute and remove from heat after 1 minute. Immediately run the egg under cold water. Then carefully crack it open, so as not to break the yolk. You have to separate the yolk from the egg white and use only the yolk in this recipe. Separate and put the yolk into a small container, ready to use in the dressing. This is a precaution worth taking, to prevent salmonella. Never use a completely raw egg.

 

You’ve got to boil the one egg, for 1 minute and not longer. This is a short cautionary step, so as not to get salmonella. ©Joyce Hays, Target Health Inc.

 

 

3. Now, mash all the garlic and anchovies, right in the wood salad bowl, with a fork. Evenly mash, so you get a smooth paste.

 

Starting to mash the garlic and anchovies in our wooden salad bowl. This wooden bowl is devoted to Caesar salad, only. By doing this, over time, the garlic and oil season the wood. In Santa Fe, at one of our favorite restaurants, we ran into a chef who did the same thing, tableside. Used a favorite wood salad bowl for Caesar salad only. Four Seasons restaurant always had same bowl for their Caesar Salads, made tableside. This beautiful space with unequaled delicacies, was where Target Health Inc. held the first-second-third and fourth annual Holiday Parties. In the first few years, our numbers were small but our goals were not; Four Seasons fulfilled our needs nicely. That great restaurant is gone now, but not forgotten. ©Joyce Hays, Target Health Inc.

 

 

4. Next, with a small whisk, add the egg yolk and whisk it into the garlic/anchovy paste; or continue to use the fork.

5. Now, add the lemon zest, 2 Tablespoons of fresh lemon juice and whisk; then add the mustard and 1 drop of Worchester sauce, whisk again

6. Next, add the extra virgin olive oil and whisk it into the dressing.

7. Add the canola oil drop by drop, while you whisk it into the dressing.

8. Finally, add the freshly grated parmesan and black pepper (to your taste). Taste to see if the dressing needs more of anything (to your taste). With the anchovies, you may decide not to use any salt. You might want more lemon juice. This is the time to taste and decide. I don’t think you need salt, since the anchovies are salty enough.

9. Whisk the dressing so it’s thick and glossy.

 

Freshly grated parmesan means doing it yourself. There’s no substitute. Buying a container that reads “freshly grated“ simply is NOT. After a while, you’ll see, there’s something satisfying about doing it yourself. ©Joyce Hays, Target Health Inc.

 

Make the dressing completely in the bottom of your salad bowl. Then add the kale leaves. ©Joyce Hays, Target Health Inc.

 

 

10. If you want, you can make the dressing 1 day ahead; however, I think serving right after making the dressing is the very best way to make Caesar salad.

11. Just before serving, add the croutons and toss. Then add additional freshly grated parmesan and serve.

 

Add the freshly baked croutons to the kale, with dressing underneath. Now, it’s time to toss. ©Joyce Hays, Target Health Inc.

 

I always add to the table, a dish with extra, freshly grated parmesan, just in case I didn’t use enough in the dressing. ©Joyce Hays, Target Health Inc.

 

Tossing the salad. Just about to serve it. Will add more parmesan in a minute. ©Joyce Hays, Target Health Inc.

 

The proof is in the eating. ©Joyce Hays, Target Health Inc.

 

We’re trying a super-Tuscan wine, Tignanello – which is a blend of 80% Sangiovese, 15% Cabernet Sauvignon, and 5% Cabernet Franc, from the highly regarded Antinori Estate of fine wines. Scroll down to read more about the history of this wine, worth trying, if you haven’t already. ©Joyce Hays, Target Health Inc.

 

We started our meal with glasses of full bodied Tignanello, a blend with complex aromas and a long finish, worth paying attention to. Then the Caesar salad, which if made correctly, makes a bold statement to your taste buds. We thought that a white wine, would not push back enough and that this red would be the best to accompany the Caesar. This particular recipe is so-o good, that I made it my whole meal with seconds and thirds. Jules likes more than one dish at dinner, so I created another meatless recipe, experimenting with him for the first time. I call it a Mushroom Medley with Marsala; served with a nice chewy twisted pasta called, Gemelli. I would say that New Yorkers (following the lead of California) are now trending toward more and more meatless meals.

I took a chance that the richness of the mushrooms would combine well with the Tignanello wine, and the two were made for each other. This whole meal was simple but beyond delicious. Call us OCDers, but for the thousandth time, we had our yummy lo-cal jello cake for dessert, slathered with cool whip.

 

BTW, just to go back to the Caesar: I never promised you a low-cal salad. Sorry 

At Manhattan’s Signature Theater, where THI is a Patron, saw a new play by one of New York’s young talented playwrights, Annie Baker, called Antipodes, which for me, echoed Samuel Beckett. A year ago, we saw Annie Baker’s The Flick, which won that year’s Pulitzer prize. The Flick ran for three hours, but with excellent theater, time is never an issue and we loved this play. Antipodes, is a mind bender and an allegory (in my opinion) and I love art, like this, that compels you to cogitate more than you might do, otherwise. We’ve also seen Annie Baker’s play, John, with a surprise ending. Keep a lookout for the keen talent of Annie Baker, often working with young, equally talented NYC director, Sam Gold.

 

More about Tuscan wines from the Antinori Estate:

Gemelli Pasta

 

Giovanni di Piero Antinori joined the Florentine Guild of Vintners in 1385, beginning an oenological legacy that has lasted over 26 generations. Throughout the company’s history, it has remained family-owned and operated. Today, Marchese Piero Antinori directs the long-lived family vision, and his three daughters participate in various activities with the firm.

Famed wine consultant Giacomo Tachis began his celebrated tenure with Antinori in 1961, a year that witnessed the inception of new vinification techniques (controlled temperatures, aging in bottle, and barrels comprising a range of types and styles) and the beginning of a revisionist period in the concept of Chianti (which was later actualized in various methods utilized to maximize extraction and aroma). This dynamic period of experimentation continued over the course of several years, with some of the pivotal initiatives including the use of maloactic fermentation for red wines, aging in barrique, and planting of several non-indigenous varietals.

The most tangible and compelling evocation of these progressive efforts, of course, is captured in Antinori’s extensive portfolio, which features some of Italy’s most revered and sought-after bottlings.

Piero Antinori desired not to recreate a Bordeaux-style claret, but rather, to convey the versatility and finesse of the noble Sangiovese.

Drawing upon the consummate skill of Giacomo Tachis, Antinori realized his conception in the form of the second official Super-Tuscan – Tignanello – debuting in 1971 as a blend of 80% Sangiovese, 15% Cabernet Sauvignon, and 5% Cabernet Franc. While second in the Super-Tuscan timeline, its conception entailed several inaugural efforts: It was the first modern wine of Chianti to contain a nontraditional grape – Cabernet Sauvignon – while omitting white grapes, and the premiere wine to be aged in small barrels.

 

From Our Table to Yours

 

Bon Appetit!