Regulatory Affairs at Target Health


Target Health now represents 36 companies at FDA from all over the world. Our regulatory team is led by Glen Park, PharmD with terrific support from Mary Shatzoff MS, who just returned to Target Health after a brief hiatus, and Adam Harris MS, Tony Pinto MA, Lydia Battaglia and Carlos Figueroa. Jules Mitchel, MBA, PhD also supports all aspects of regulatory affairs and consults with the team as needed. Programs include but not limited to: orphan diseases, oncology, gastroenterology, dermatology, endocrinology, neurology and wound healing. Target Health provides regulatory agency, strategic planning, FDA meetings, eCTD publishing and all regulatory submissions.


The Survivor Tree


A Callery pear tree became known as the “Survivor Tree“ after enduring the September 11, 2001 terror attacks at the World Trade Center. In October 2001, the tree was discovered at Ground Zero severely damaged, with snapped roots and burned and broken branches. The tree was removed from the rubble and placed in the care of the New York City Department of Parks and Recreation. After its recovery and rehabilitation, the tree was recently returned to the Memorial. New, smooth limbs extended from the gnarled stumps, creating a visible demarcation between the tree’s past and present. Today, the tree stands as a living reminder of resilience, survival and rebirth.





Before                                                                                     After


ON TARGET is the newsletter of Target Health Inc., a NYC-based, full-service, contract research organization (eCRO), providing strategic planning, regulatory affairs, clinical research, data management, biostatistics, medical writing and software services to the pharmaceutical and device industries, including the paperless clinical trial.


For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. 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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Human Microbiome


Diagram of the human body showing the relative abundances of various types of microbes in each region. “ “Skin Microbiome20169-300” by Darryl Leja, NHGRI


The scientific study of microbiology, which led to important discoveries such as Louis Pasteur’s “germ theory of disease,“ grew out of society’s desire to eradicate infectious diseases.


The human microbiome is composed of the microbes, as well as their genes and genomes, that live in and on the human 1) ___. These resident microbes maintain our immune systems, contribute to the digestion of our food, and act as first line of defense against pathogens. There are many diseases that may be the result of disturbed microbiomes; however, microbiome-based medical treatments and applications are not completely mainstream and will be a part of future preventative 2) ___. Advances in medicine, now view humans and microbes as a co-evolved system for the mutual benefit of both the host and resident 3) ___. Most of the microbes we come in contact with are not germs, but beneficial microbes that digest many things in our diet – like vegetables – that we could not digest without microbial enzymes. They provide energy for our metabolism, make essential vitamins, and act as a first line of defense against potential pathogens.


The human microbiome is primarily composed of bacteria, but also includes numerous and diverse viruses, fungi and protozoa. The human body is made up of about 10 times more microbial cells (~1014) than human cells (~1013). It is thought that there are millions more microbial genes than human genes in this human microbiome system. Scientists now believe that infants are sterile (free of microbes) in the womb and receive their first inoculum of microbes from the mother during natural childbirth (not C-section). This inoculum goes on to colonize the newborn and initiate a succession of events leading to the development of the child’s own 4) ___. The newborn relies on this maternal vaginal microbial inoculum and the additional inoculum of microbes from mother’s breast milk for microbial colonization of all exposed surfaces in and on the infant’s body (e.g., oral, nasal/airways, gut, urogenital, skin). This is a dynamic process in which microbial abundances increase from effectively zero at birth to over six orders of magnitude (more than a million times) within just the first few weeks of life, with wide swings in the microbial membership of these communities until the microbiota largely stabilize in composition and numbers after approximately three years of life.




The characteristics of human microbiota change over time in response to varying environmental conditions and life stages. Image courtesy: US National Library of Medicine. Image source: Ottman N, Smidt H, de Vos WM and Belzer C (2012)


The newborn’s gut microbiota trigger development and maturation of the newborn’s 5) ___ system. Although there is still a great deal of research needed to understand precisely what happens in this developmental process, it appears the maturing immune system relies on the presence of microbial communities, and especially the presence of these early microbes, to distinguish “self“ from “nonself.“ It is these particular microbes that shape our immune systems. Once the immune system has matured, it will consult its “memory banks“ if another microbe is encountered in order to determine if this microbe is considered “self“ or “nonself“ and to mount defenses against the microbe if it is recognized as a pathogen. Most of these microbes are growing in our large 6) ___, but each region of our body has its own distinct community of microbes living in or on it. For example, we have a particular kind of microbial community that prefers to grow on skin or in the nose. Our mouths have a rich mixture of microbes, with specific microbes that prefer teeth versus those that prefer gums. Even though the tongue is in constant contact with the roof of the mouth, microbes growing on the roof of the mouth are, very different from those growing on the tongue. Current research is grappling with which factors regulate microbial colonization in areas of the body that are just millimeters apart.


Researchers believe that what is eaten, combined with our hormones, bodily fluids, skin oils, genetic makeup, where we live, and many other factors, contribute to the colonization and growth of these microbes. Bathing, shampooing, washing hands, brushing teeth remove some microbes, which eventually grow back; however, too much washing may deplete valuable microbes, which could weaken the immune system. Each of us has a personal, group of microbial species and strains making each person’s microbiome 7) ___. Routine practices, including the use of antibiotics, may alter the human microbiome by reducing nontargeted bacteria and creating antibiotic resistant strains. Scientists are concerned about human behaviors that may disturb this delicate system. Antibiotic use is just one example of a common medical practice that may be altering the human microbiome by reducing, removing, or changing fundamental elements.


Antibiotics have been in broad use for treating infectious diseases in humans for over 70 years. As with vaccines, antibiotics have proven to be a very important medical advance, effectively eliminating many infectious diseases that have plagued human history. Today, as a result of antibiotics and vaccines, children do not die of the infectious diseases that killed them even 50 years ago. However, routine use of 8) ___ may cause collateral damage to our microbial flora in two ways: through the unintended death of nontargeted bacteria and through the emergence of antibiotic-resistant bacteria. Antibiotics can have unintended consequences and kill off beneficial bacteria in our microbiomes that are not the original target of the antibiotic?so-called “nontarget bacteria.“ There is thought to be a relationship between the disturbance of the human microbiome through antibiotic use and the unexpected rise in autoimmune 9) ___ and allergies, particularly in Western countries. Autoimmunity is the failure of our own immune systems to distinguish “self“ from “nonself.“ This failure can lead to an immune response being mounted against our own cells and tissues. Examples of autoimmune diseases include rheumatoid arthritis, lupus, diabetes and celiac disease. The current line of thinking is that loss of normal microbiome constituents through antibiotic use may remove the necessary trigger for normal immune system development. As a result, an underdeveloped immune system might possibly allow autoimmune diseases to develop. Currently, much research is being conducted to better understand the relationship between the human microbiome and autoimmune diseases, and to find better treatments and cures.


The “disappearing microbiota hypothesis“ postulates that, as a consequence of routine customs in modern societies – such as clean water, sanitation, caesarean birth and antibacterial soaps – practiced over many generations, the normal inoculum on which the newborn is dependent for microbiome and immune system development has become depleted in the mother. This hypothesis further suggests that we might be losing key members of our normal microbiome, generation after generation, because of the increasingly impoverished microbiomes of mothers, resulting in a cumulative loss of the normal microbiota needed to support human health. Whether this hypothesis is supported awaits rigorous scientific testing, but it does help frame the question of why we are currently seeing epidemics in 10) ___autoimmune diseases that have been relatively rare throughout human history. Perhaps disturbances to our microbiome are key to understanding why these diseases are increasing; in turn, this understanding may lead to the treatment and, ultimately, prevention of such diseases. (Part 2 next week.)


ANSWERS: 1) body; 2) medicine; 3) microbes; 4) microbiome; 5) immune; 6) intestine; 7) unique; 8) antibiotics; 9) diseases; 10) autoimmune


Antonie van Leeuwenhoek (1632-1723)


Portrait of Antonie van Leeuwenhoek (1632-1723)



Editor’s note: We give thanks to all the scientists and great thinkers, who, throughout history, ignored the derision of many, and courageously continued focused exploration of great ideas.  They have been the drivers of human progress.


The Secretary of the Royal Society, London, wrote the following letter to van Leeuwenhoek, on the 20th of October, 1676; Dear Mr. Anthony van Leeuwenhoek, Your letter of October 10th has been received here with amusement. Your account of myriad “little animals“ seen swimming in rainwater, with the aid of your so-called “microscope,“caused the members of the society considerable merriment when read at our most recent meeting. Your novel descriptions of the sundry anatomies and occupations of these invisible creatures led one member to imagine that your “rainwater“ might have contained an ample portion of distilled spirits–imbibed by the investigator. Another member raised a glass of clear water and exclaimed, “Behold, the Africk of Leeuwenhoek.“ For myself, I withhold judgment as to the sobriety of your observations and the veracity of your instrument. However, a vote having been taken among the members (accompanied, I regret to inform you, by considerable giggling) it has been decided not to publish your communication in the Proceedings of this esteemed society. However, all here wish your “little animals“ health, prodigality and good husbandry by their ingenious “discoverer.


Antonie Philips van Leeuwenhoek was a Dutch tradesman and scientist. He is commonly known as “the Father of Microbiology“, and considered to be the world’s first microbiologist. He is best known for his work on the improvement of the microscope and for his contributions towards the establishment of microbiology. Raised in Delft, Netherlands, Leeuwenhoek worked as a draper in his youth, and founded his own shop in 1654. He made a name for himself in municipal politics, and eventually developed an interest in lens making. Using his handcrafted microscopes, he was the first to observe and describe single-celled organisms, which he originally referred to as animalcules, and which are now referred to as microorganisms. He was also the first to record microscopic observations of muscle fibers, bacteria, spermatozoa, and blood flow in capillaries (small blood vessels). Leeuwenhoek did not author any books; his discoveries came to light through correspondence with the Royal Society, which published his letters.


Antonie van Leeuwenhoek was born in Delft, Dutch Republic, on October 24, 1632 of Dutch ancestry. His father, Philips Antonysz van Leeuwenhoek, was a basket maker who died when Antony was five years old. His mother, Margaretha (Bel van den Berch), came from a well-to-do brewer’s family, and married Jacbon Jansz Molijn, a painter, after Philips’ death. Antony had four older sisters, Margriete, Geertruyt, Neeltge, and Catharina. Little is known of his early life; he attended school near Leyden for a short time before being sent to live in Benthuizen with his uncle, an attorney and town clerk. He became an apprentice at a linen-draper’s shop in Amsterdam at the age of 16. He married Barbara de Mey in July 1654, with whom he would have one surviving daughter, Maria (four other children died in infancy). That year he returned to Delft, where he would live and study for the rest of his life. He opened a draper’s shop, which he ran throughout the 1650s. His status in Delft grew throughout the following years, although he would remain an obscure figure outside of the city. He received a lucrative municipal title as chamberlain for the Delft sheriffs’ assembly chamber in 1660, a position which he would hold for almost 40 years. In 1669 he was named a surveyor by the Court of Holland; later he would become a municipal “wine-gauger“ in charge of the city’s wine imports.


Leeuwenhoek was a contemporary of another famous Delft citizen, painter Johannes Vermeer, who was baptized just four days earlier. It has been suggested that he is the man portrayed in two of Vermeer’s paintings of the late 1660s, The Astronomer and The Geographer. However, others argue that there appears to be little physical similarity. Because they were both relatively important men in a city with only 24,000 inhabitants, it is likely that they were at least acquaintances. Also, it is known that Leeuwenhoek acted as the executor of the will when the painter died in 1675. While running his draper’s shop, Leeuwenhoek began to develop an interest in lens making, although few records exist of his early activity. Leeuwenhoek’s interest in microscopes and a familiarity with glass processing led to one of the most significant, and simultaneously well-hidden, technical insights in the history of science. By placing the middle of a small rod of soda lime glass in a hot flame, Leeuwenhoek could pull the hot section apart to create two long whiskers of glass. Then, by reinserting the end of one whisker into the flame, he could create a very small, high-quality glass sphere. These spheres became the lenses of his microscopes, with the smallest spheres providing the highest magnifications.



Microscopic section through one-year-old Ash tree (Fraxinus) wood, drawing made by Leeuwenhoek


After developing his method for creating powerful lenses and applying them to study of the microscopic world, Leeuwenhoek introduced his work to his friend, the prominent Dutch physician Reinier de Graaf. When the Royal Society in London published the groundbreaking work of an Italian lensmaker in their journal Philosophical Transactions of the Royal Society, de Graaf wrote to the journal’s editor Henry Oldenburg with a ringing endorsement of Leeuwenhoek’s microscopes which, he claimed, “far surpass those which we have hitherto seen“. In response the Society published in 1673 a letter from Leeuwenhoek, which included his microscopic observations on mold, bees, and lice.




Van Leeuwenhoek wrote his letters to the Royal Society by hand in Dutch, the only language he knew, before publication in the Philosophical Transactions


Leeuwenhoek’s work fully captured the attention of the Royal Society, and he began regularly corresponding with the Society regarding his observations. He had at first been reluctant to publicize his findings, regarding himself as a businessman with little scientific, artistic, or writing background, but de Graaf urged him to be more confident in his work. By his death in 1723, he had written 190 letters to the Society, detailing his findings in a wide variety of fields, centered around his work in microscopy. He only wrote letters, in his own colloquial flavor of Dutch; he never published a proper scientific paper. He had strongly preferred to work alone, distrusting the sincerity of those who offered their assistance. The letters were translated into Latin or English by the German Oldenburg, who learnt Dutch in order to be able to do so. Despite the initial success of Leeuwenhoek’s relationship with the Royal Society, this relationship was soon severely strained. In 1676, his credibility was questioned when he sent the Royal Society a copy of his first observations of microscopic single-celled organisms. Previously, the existence of single-celled organisms was entirely unknown. Thus, even with his established reputation with the Royal Society as a reliable observer, his observations of microscopic life were initially met with both skepticism and open ridicule. Eventually, in the face of Leeuwenhoek’s insistence, the Royal Society arranged for Alexander Petrie, minister to the English Reformed Church in Delft, Benedict Haan, at that time Lutheran minister at Delft, and Henrik Cordes, then Lutheran minister at the Hague, accompanied by Sir Robert Gordon and four others to determine whether it was in fact Leeuwenhoek’s ability to observe and reason clearly, or perhaps the Royal Society’s theories of life itself that might require reform. Finally in 1677 Leeuwenhoek’s observations were fully vindicated by the Society. Leeuwenhoek was elected to the Royal Society in February 1680 on the nomination of William Croone, a then-prominent physician. Leeuwenhoek was “taken aback“ at the nomination, which he considered a high honor, although he did not attend the induction ceremony in London, nor did he ever attend a Royal Society meeting. By the end of the 17th century, Leeuwenhoek had a virtual monopoly on microscopic study and discovery. His contemporary Robert Hooke, an early microscope pioneer, bemoaned that the field had come to rest entirely on one man’s shoulders. He was visited over the years by many notable individuals, such as Russian Tsar Peter the Great.


To the disappointment of his guests, Leeuwenhoek refused to reveal the cutting-edge microscopes he relied on for his discoveries, instead showing visitors a collection of average-quality lenses. An experienced businessman, Leeuwenhoek realized that if his simple method for creating the critically important lens was revealed, the scientific community of his time would likely disregard or even forget his role in microscopy. He therefore allowed others to believe that he was laboriously spending most of his nights and free time grinding increasingly tiny lenses to use in microscopes, even though this belief conflicted both with his construction of hundreds of microscopes and his habit of building a new microscope whenever he chanced upon an interesting specimen that he wanted to preserve. He made about 200 microscopes with different magnification. He was visited by Leibniz, William III of Orange and his wife, the Amsterdam burgemeester (the mayor) Johan Huydecoper, the latter very interested in collecting and growing plants for the Hortus Botanicus Amsterdam and all gazed at the tiny creatures. Nicolaes Witsen sent him a map of Tartaria and a mineral found near the origin of the river Amur. In 1698 Leeuwenhoek was invited in the boat of Tsar Peter the Great. On the occasion Leeuwenhoek presented the Tsar an “eel-viewer“, so Peter could study the blood circulation, whenever he wanted.




Leeuwenhoek’s microscopes


Leeuwenhoek made more than 500 optical lenses. He also created at least 25 microscopes, of differing types, of which only nine survived. His microscopes were made of silver or copper frames, holding hand-made lenses. Those that have survived are capable of magnification up to 275 times. It is suspected that Leeuwenhoek possessed some microscopes that could magnify up to 500 times. Although he has been widely regarded as a dilettante or amateur, his scientific research was of remarkably high quality. The microscopes were relatively small devices, the biggest being about 5 cm long. They are used by placing the lens very close in front of the eye, while looking in direction of the sun. The other side of the microscope had a pin, where the sample was attached in order to stay close to the lens. There were also three screws that allowed the viewer to move the pin, and the sample, along three axes: one axis to change the focus, and the two other axes to navigate through the sample. Leeuwenhoek maintained throughout his life that there are aspects of microscope construction “which I only keep for myself“, in particular his most critical secret of how he created lenses. For many years no-one was able to reconstruct Leeuwenhoek’s design techniques. However, in 1957 C.L. Stong used thin glass thread fusing instead of polishing, and successfully created some working samples of a Leeuwenhoek design microscope. Such a method was also discovered independently by A. Mosolov and A. Belkin at the Russian Novosibirsk State Medical Institute.




Replica of microscope by Leeuwenhoek


Leeuwenhoek used samples and measurements to estimate numbers of microorganisms in units of water. He also made good use of the huge lead provided by his method. He studied a broad range of microscopic phenomena, and shared the resulting observations freely with groups such as the English Royal Society. Such work firmly established his place in history as one of the first and most important explorers of the microscopic world. He was one of the first people to discover cells, along with Robert Hooke. Leeuwenhoek’s main discoveries are the:


infusoria (protists in modern zoological classification), in 1674

bacteria, (e.g., large Selenomonads from the human mouth), in 1676

vacuole of the cell.

spermatozoa in 1677.

banded pattern of muscular fibers, in 1682.


In 1687 he reported his research on the coffee bean. He roasted the bean, cut it into slices and saw a spongeous interior. The bean was pressed, and an oil appeared. He boiled the coffee with rain water twice, set it aside. Like Robert Boyle and Nicolaas Hartsoeker, Leeuwenhoek was interested in the dried cochineal, trying to find out if the dye came from a berry or an insect.


Leeuwenhoek was also a Dutch Reformed Calvinist. He often referred with reverence to the wonders God designed in making creatures great and small. He believed that his amazing discoveries were merely further proof of the great wonder of God’s creation. Leeuwenhoek’s discovery that smaller organisms procreate similarly to larger organisms challenged the contemporary belief, generally held by the 17th-century scientific community, that such organisms generated spontaneously. The position of the Church on the exact nature of the spontaneous generation of smaller organisms was ambivalent.




Antonie van Leeuwenhoek is buried in the Oude kerk in Delft


By the end of his life, Leeuwenhoek had written approximately 560 letters to the Society and other scientific institutions concerning his observations and discoveries. Even when dying, Leeuwenhoek kept sending letters full of observations to London. The last few also contained a precise description of his own illness. He suffered from a rare disease, an uncontrolled movement of the midriff, which is now named Van Leeuwenhoek’s disease. He died at the age of 90, on August 26, 1723 and was buried four days later in the Oude Kerk (Delft).

In 1981 the British microscopist, Brian J. Ford found that Leeuwenhoek’s original specimens had survived in the collections of the Royal Society of London. They were found to be of high quality, and were all well preserved. Ford carried out observations with a range of microscopes, adding to our knowledge of Leeuwenhoek’s work.


Reduced Incidence of Prevotella and Other Fermenters in Intestinal Microflora of Autistic Children


High proportions of autistic children suffer from gastrointestinal (GI) disorders, implying a link between autism and abnormalities in gut microbial functions. Increasing evidence from recent high-throughput sequencing analyses indicates that disturbances in composition and diversity of gut microbiome are associated with various disease conditions. However, microbiome-level studies on autism are limited and mostly focused on pathogenic bacteria.


As a result, a study published online in PLOS 1 (3 July 2013), was performed to define systemic changes in gut microbiome associated with autism and autism-related GI problems. The study recruited 20 neurotypical and 20 autistic children accompanied by a survey of both autistic severity and GI symptoms. By pyrosequencing the V2/V3 regions in bacterial 16S rDNA from fecal DNA samples, a comparison was made of gut microbiomes of GI symptom-free neurotypical children with those of autistic children mostly presenting GI symptoms. Unexpectedly, the presence of autistic symptoms, rather than the severity of GI symptoms, was associated with less diverse gut microbiomes. Further, rigorous statistical tests with multiple testing corrections showed significantly lower abundances of the genera Prevotella, Coprococcus, and unclassified Veillonellaceae in autistic samples. These organisms are intriguingly versatile carbohydrate-degrading and/or fermenting bacteria, suggesting a potential influence of unusual diet patterns observed in autistic children. However, multivariate analyses showed that autism-related changes in both overall diversity and individual genus abundances were correlated with the presence of autistic symptoms but not with their diet patterns.


Taken together, autism and accompanying GI symptoms were characterized by distinct and less diverse gut microbial compositions with lower levels of Prevotella, Coprococcus, and unclassified Veillonellaceae.


Precocious GEM: Shape-Shifting Sensor Can Report Conditions from Deep in the Body


Novel geometrically encoded magnetic sensors (GEMs), developed by researchers from NIST and NIH, respond to local biochemical conditions such as a change in acidity near inflammation sites – by changing their shape and response to radio frequencies. Credit: Kelley/NIST PML



Scientists working at the National Institute of Standards and Technology (NIST) and the National Institutes of Health (NIH) have devised and demonstrated a new, shape-shifting probe, about one-hundredth as wide as a human hair, which is capable of sensitive, high-resolution remote biological sensing that is not possible with current technology. If eventually put into widespread use, the design could have a major impact on research in medicine, chemistry, biology and engineering. Ultimately, it might be used in clinical diagnostics.


To date, most efforts to image highly localized biochemical conditions such as abnormal pH and ion concentration – critical markers for many disorders – rely on various nanosensors that are probed using light at optical frequencies. But the sensitivity and resolution of the resulting optical signals decrease rapidly with increasing depth into the body. That has limited most applications to less obscured, more optically accessible regions. The new shape-shifting probe devices, described online in the journal Nature (16 March2015) are not subject to those limitations. They make it possible to detect and measure localized conditions on the molecular scale deep within tissues, and to observe how they change in real time. The design is based on completely different operating principles. Instead of optically based sensing, the shape-changing probes are designed to operate in the radio frequency (RF) spectrum, specifically to be detectable with standard nuclear magnetic resonance (NMR) or magnetic resonance imaging (MRI) equipment. In these RF ranges, signals are, for example, not appreciably weakened by intervening biological materials. As a result, they can get strong, distinctive signals from very small dimensions at substantial depths or in other locations impossible to probe with optically based sensors.


The novel devices, called geometrically encoded magnetic sensors (GEMs), are microengineered metal-gel sandwiches about 5 to 10 times smaller than a single red blood cell, one of the smallest human cells. Each consists of two separate magnetic disks that range from 0.5 to 2 micrometers (millionths of a meter) in diameter and are just tens of nanometers (billionths of a meter) thick. Between the disks is a spacer layer of a hydrogel. A hydrogel is a cross-linked network of polymers that can absorb various amounts of water depending on their chemical composition and structure as well as the environment around it. The hydrogels used in the NIST-NIH project were engineered to swell in neutral environments and to shrink in low-pH environments. Swelling or shrinking of the gel changes the distance (and hence, the magnetic field strength) between the two disks, and that, in turn, changes the frequency at which the protons in water molecules around and inside the gel resonate in response to radio-frequency radiation. Scanning the sample with a range of frequencies quickly identifies the current shape of the nanoprobes, effectively measuring the remote conditions through the changes in resonance frequencies caused by the shape-changing agents.


In the experiments reported in Nature, the authors tested the sensors in solutions of varying pH, in solutions with ion concentration gradients, and in a liquid growth medium containing living canine kidney cells as their metabolism went from normal to nonfunctional in the absence of oxygen. That phenomenon caused the growth medium to acidify, and the change over time was sensed by the GEMs and recorded through real-time shifting in resonant frequencies. Even for the un-optimized, first-generation probes used, the frequency shifts resulting from changes in pH were easily resolvable and orders of magnitude larger than any equivalent frequency shifting observed through traditional magnetic resonance spectroscopy approaches.


Tracking highly localized pH values in living organisms can be difficult. (A blood test cannot necessarily do it because the sample mixes blood from numerous locations.) Yet local pH changes can provide invaluable early signals of many pathologies. For example, the pH around a cancer cell is slightly lower than normal, and internal inflammation generally leads to local change in pH level. Detecting such changes might reveal, for example, the presence of an unseen tumor or show whether an infection has developed around a surgical implant.


The long-term goal is to improve techniques to the point at which GEMs can be employed for biomedical uses. However, that would require, among other things, further miniaturization. The 0.5 to 2 ?m diameter GEMs in the experiments are already small enough for many in vitro and other possible non-biological applications, as well as possibly for some in vivo cellular related applications. But preliminary estimates by the experimenters indicate that the sensors can be reduced substantially from their current size, and might conceivably be made smaller than 100 nanometers in diameter. That would open up many additional biomedical applications. One of the most significant features of GEMs is that they can be “tuned“ in fabrication to respond to different biochemical states and to resonate in different parts of the RF spectrum by altering the gel composition and the magnet shapes and materials, respectively. So placing two different populations of GEMs at the same site makes it possible to track changes in two different variables at the same time – a capability the authors demonstrated by placing GEMs with two different dimensions in the same location and detecting the signals from both simultaneously. NIST Tech Beat: 27 March 2015


FDA Approves New Treatment for Inhalation Anthrax Uses Animal Rule


Inhalational anthrax is a rare disease that can occur after exposure to infected animals or contaminated animal products, or as a result of an intentional release of anthrax spores. It is caused by breathing in the spores of the bacterium Bacillus anthracis. When inhaled, the anthrax bacteria replicate in the body and produce toxins that can cause massive and irreversible tissue injury and death.


To support the nation’s preparedness against a possible anthrax attack, the U.S. Department of Health and Human Services’ Biomedical Advanced Research and Development Authority (BARDA) purchased Anthrasil under Project BioShield in 2011 as an experimental drug for the U.S. Strategic National Stockpile. Because Anthrasil was not approved, its use prior to today’s approval would have required an emergency use authorization from the FDA.


The FDA approved Anthrasil, Anthrax Immune Globulin Intravenous (Human), to treat patients with inhalational anthrax in combination with appropriate antibacterial drugs. Anthrasil is manufactured from the plasma of individuals vaccinated against anthrax which contains antibodies that neutralize toxins produced by the anthrax bacteria. The efficacy of Anthrasil was studied in animals because it was not feasible or ethical to conduct adequately controlled efficacy studies in humans. Rabbits and monkeys were exposed to a lethal aerosolized dose of B. anthracis spores, then treated with Anthrasil or a placebo, and evaluated for survival. Survival in anthrax-infected monkeys treated with Anthrasil ranged from 36 to 70% compared to 0% survival in the placebo group with a trend toward increased survival at higher doses of Anthrasil. Rabbits treated with a moderate dose of Anthrasil after infection exhibited 26% survival compared to 2% survival in the placebo group. Another study in rabbits showed that a combination of Anthrasil and antibiotics resulted in 71% survival compared to 25% survival in animals treated with antibiotics alone. The results of studies in research animals provided sufficient evidence that Anthrasil is reasonably likely to benefit humans with inhalational anthrax. The FDA’s Animal Rule allows efficacy findings from adequate and well-controlled animal studies to support FDA approval when it is not feasible or ethical to conduct trials in humans. The safety of the product was tested in 74 healthy human volunteers. The most commonly observed side effects were headache, back pain, nausea and infusion site pain and swelling.


The product is manufactured by Cangene Corporation, based in Winnipeg, Canada and was developed with support from BARDA within HHS’ Office of the Assistant Secretary for Preparedness and Response.


Fresh Garden Vegetables Baked with Cashews and Orange Sauce


A recipe as beautiful as it is flavorful ©Joyce Hays, Target Health Inc.





1 head of broccoli, washed, cut into florets

1 red pepper, washed, seeds removed, diced

1 yellow pepper, washed, seeds removed, diced

Olive oil to cook the onions, garlic and chives, etc.

Chicken stock or broth on hand, if needed.

2/3 cup fresh cilantro, chopped

1 cup fresh chives, chopped or chopped fresh scallions

3 fresh garlic cloves, sliced

1 onion, chopped or sliced

1/2 cup walnuts or cashews, toasted, then chop coarsely

1 teaspoon cumin

3 Tablespoons low-sodium soy sauce

1/2 cup freshly squeezed orange juice

1 Tablespoon honey or agave

1 teaspoon turmeric (already mixed with black pepper)

Pinch salt (or to your taste)

Pinch black pepper (or grind to your taste)

Pinch chili flakes (or to your taste)




Gather all the ingredients ©Joyce Hays, Target Health Inc.




Preheat the oven to 350 degrees.

In the oven or on top of the stove, quickly toast your nuts (about 3 minutes). Allow them to cool, then chop them coarsely so you have big pieces. Set aside

In a casserole baking dish, put the broccoli florets

In a large fry pan add one or two glugs of olive oil over a medium flame. When the oil is hot add the sliced onions and sliced garlic. Stir until they start to become transparent.

Now, add the last 8 ingredients (above) of the recipe, to the onion/garlic mixture and stir to make the orange sauce.

To the orange sauce, add the chives, cilantro, red and yellow peppers and stir for about 3 minutes, until the peppers get softer. If you feel the sauce is not liquid enough, add a little of the chicken stock, slowly and stir until you get the consistency you want.

Finally, add the nuts and stir for 1 minute, just to combine all the ingredients, well.

Next, using a spatula to scrape down the sides of the pan, pour this sauce over the broccoli, stir to coat the broccoli completely with the sauce,

then cover the casserole dish and put into the oven for about 15 minutes. For the last 5 minutes, bake uncovered, then serve




Still experimenting with cabs. This is one of the Stag’s Leap Vineyards many cabs. There’s one for every budget. This is called Artemis; however, there’s even more than one Artemis. ©Joyce Hays, Target Health Inc.


This was a cool but lovely Spring weekend in the Big Apple. Happiness reigned!


We’re trying to be more vegan. Saturday, the meal with the broccoli casserole, began by toasting with red wine and my new recipe for chopped chicken livers, not vegan of course, but very successful. The secret might have been using an aged Maderia wine in my recipe.


Then, I served some crispy baked zucchini circles, which is in the experimental stage, and almost ready to share with friends and colleagues in a future newsletter. Finally, the casserole which was yummy with all of those delicious flavors exploding in your mouth.


For dessert, we had unbelievably juicy and sweet, fresh Cara Cara orange segments and rainbow cookies, a treat, only at this time of year.


If you feel you want more protein in the broccoli casserole, you can always sprinkle over the top of it, in the last 5 or so minutes, your favorite cheese freshly grated, and wait for it to melt before you serve. Another idea, which I am keen to try, is in the last 5 minutes of baking, break 2 or more eggs into a separate small bowl (to be sure the yolks aren’t broken before you add them), then carefully pour these eggs over the top of the casserole and bake them until the yolks are the way you like them. I would say, for slightly runny, bake for 3 minutes. For slightly harder, bake for 5 minutes, then serve each person a portion with an egg on top. When you add more protein, this casserole can be a meal in itself.


Recently, in restaurants, I have been ordering an egg on top of lots of dishes. All restaurants oblige because they like the adventure of trying this. I love veal chop parmesan with eggs on top (runny is my preference). Wild mushroom risotto is wonderful with eggs on top and even salmon tartare is more delicious with eggs on top (If the salmon tartare sauce is made correctly, with seaweed, and sesame oil).


De gustibus non est disputandum !


Hope your weekend was as relaxing and lovely as ours was.



From Our Table to Yours!


Bon Appetit!