The Talented Mr. Farley

James Farley, photographer extraordinaire, friend and colleague, sent us some recent photos. Hard to choose, but we all agreed that one below was exceptional.


Here are the specs:

The camera perspective (on a tall tripod) was above the head. That’s how high-up the flowers were. They were at the height of my eyes, as I stood.

RShot on Canon 5D Mark IV with Canon 17mm Tilt-shift lens using Lee Filters 0.6 standard filter.


Rhododendrons at Sunset on Roan Mountain, North Carolina, June 14, 2018. Jane Bald and Round Bald in view. © Copyright Advanced Fine Art 2018 / All Rights Reserved


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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Epithelial Cells

Illustration of the dividing epithelium cell surrounded by epithelium tissue. Spindle apparatus rotates inside the cell. The rotation is a result of astral microtubules pulling towards tri-cellular-junctions (TCJ), signaling centers localized at the regions where three cells meet. Graphic credit: Margo. raichman – Own work, CC BY-SA 4.0,



Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the outer surfaces of organs and blood vessels throughout the body, as well as the inner surfaces of cavities in many internal organs. An example is the epidermis, the outermost layer of the1) ___. There are three principal shapes of epithelial cell: squamous, columnar, and cuboidal. These can be arranged in a single layer of cells as simple epithelium, either squamous, columnar, cuboidal, pseudo-stratified columnar or in layers of two or more cells deep as stratified (layered), either squamous, columnar or cuboidal. All glands are made up of epithelial 2) ___. Functions of epithelial cells include secretion, selective absorption, protection, transcellular transport, and sensing.


Epithelial layers contain no blood 3) ___, so they must receive nourishment via diffusion of substances from the underlying connective tissue, through the basement membrane. Cell junctions are well-employed in epithelial tissues. Epithelial tissues have as their primary functions:


1. Protect the tissues that lie beneath from radiation, desiccation, toxins, invasion by pathogens, and physical trauma

2. Regulation and exchange of chemicals between the underlying tissues and a body cavity

3. Secretion of hormones into the circulatory system, as well as the secretion of sweat, mucus, enzymes, and other products that are delivered by ducts

4. Provide sensation


Cells of epithelial tissue are tightly packed and form a continuous sheet. They have almost no intercellular spaces. All epithelia is usually separated from underlying tissues by an extracellular fibrous basement membrane. The lining of the mouth, lung alveoli and kidney tubules all are made of epithelial 4) ___. The lining of the blood and lymphatic vessels are of a specialized form of epithelium called endothelium. Epithelium lines both the outside (skin) and the inside cavities and lumina of bodies. The outermost layer of human skin is composed of dead stratified squamous, keratinized epithelial cells. Tissues that line the inside of the mouth, the esophagus, the vagina, and part of the rectum are composed of nonkeratinized stratified squamous epithelium. Other surfaces that separate body cavities from the outside environment are lined by simple squamous, columnar, or pseudostratified epithelial cells. Other 5) ___ cells line the insides of the lungs, the gastrointestinal tract, the reproductive and urinary tracts, and make up the exocrine and endocrine glands. The outer surface of the cornea is covered with fast-growing, easily regenerated epithelial cells. A specialized form of epithelium – endothelium forms the inner lining of blood vessels and the heart, and is known as vascular endothelium, and lining lymphatic vessels as lymphatic endothelium. Another type, mesothelium, forms the walls of the pericardium, pleurae, and peritoneum.


In arthropods, the integument, or external “skin“, consists of a single layer of epithelial ectoderm from which arises the cuticle, an outer covering of chitin the rigidity of which varies as per its chemical composition.


Epithelial tissue rests on a basement membrane, which acts as a scaffolding on which epithelium can grow and regenerate after injuries. Epithelial tissue has a nerve supply, but no 6) ___ supply and must be nourished by substances diffusing from the blood vessels in the underlying tissue. The basement membrane acts as a selectively permeable membrane that determines which substances will be able to enter the epithelium. It is known that some corneal diseases and degenerations have a significant heritable background. Because the density of the corneal endothelial cells is strongly 7) ___, this knowledge should stimulate future genetic studies to identify genes and pathways that are involved in determining corneal endothelial cell density (ECD) which might in turn lead to future treatments to prevent epithelial cell (EC) loss.


There is evidence that a major pressure driving evolution of CNS blood-tissue barriers was the selective advantage given by fine control (homeostasis) of the brain ionic microenvironment. The blood-brain barrier (BBB) is a diffusion barrier, which impedes influx of most compounds from blood to brain. Three cellular elements of the brain microvasculature compose the BBB-endothelial cells, astrocyte end-feet, and pericytes (PCs). Tight junctions (TJs), present between the cerebral endothelial cells, form a diffusion barrier, which selectively excludes most blood-borne substances from entering the 8) ___. At the blood brain 9) ___, the endothelial cells do not act alone, but function within a well organized ‘neurovascular unit’ (NVU), a modular structure integrating the local neuronal population and its associated astrocytic glia with the cells forming the microvascular tube providing blood flow, the endothelium and pericytes, and in arterioles also smooth muscle. Microglia, the resident immune cells of the CNS, are associated with the NVU, in quiescent state in normal physiology, but becoming activated in pathology.


When researchers today refer to HERS, they are including the studies, done over a century ago, of Oskar Hertwig. HERS stands for: Hertwig’s Epithelial Root Sheath. Today, NIH clinical reports in tandem with developmental and evolutionary studies re-introduce HERS as the ultimate governor of the periodontal ligament, the regulator of its width and homeostasis and the shield against resorption and ankylosis. From an evolutionary 10) ___ perspective, HERS appears to have evolved first to provide elastic anchorage for and mediate eruption of amphibian teeth and then may have evolved to facilitate the formation of a non-mineralized periodontal ligament in crocodiles and mammals and maintain its functional integrity. During development, HERS fenestration allows mesenchymal cells from the dental follicle to penetrate the epithelial barrier and deposit cementum. A part of this function may be related to the induction of acellular cementogenesis, and future studies will provide definitive answers to address this important issue.


ANSWERS: 1) skin; 2) cells; 3) vessels; 4) tissue; 5) epithelial; 6) blood; 7) heritable; 8) brain; 9) barrier; 10) biology


Sources:; /; Wikipedia


Oskar Hertwig, Developmental Biologist

Oskar Hertwig: Photo credit: Erik Nordenskiold, The history of biology: a survey. Knopf, New York, 1935, S. 594. Online:, Public Domain,


Oscar Hertwig (21 April 1849 – 25 October 1922) was a German zoologist and professor, who also wrote about the theory of evolution circa 1916, over 55 years after Charles Darwin’s book The Origin of Species. He was the elder brother of zoologist-professor Richard Hertwig (1850-1937). The Hertwig brothers were the most eminent scholars of Ernst Haeckel (and Carl Gegenbaur) from the University of Jena. They were independent of Haeckel’s philosophical speculations but took his ideas in a positive way to widen their concepts in zoology. Initially, between 1879-1883, they performed embryological studies, especially on the theory of the coelom (1881), the fluid-filled body cavity. These problems were based on the phylogenetic theorems of Haeckel, i.e. the biogenic theory (German = biogenetisches Grundgesetz), and the “gastraea theory”.


Within 10 years, the two brothers moved apart to the north and south of Germany. Oscar Hertwig later became a professor of anatomy in 1888 in Berlin; however, Richard Hertwig had moved 3 years prior, becoming a professor of zoology in Munich from 1885-1925, at Ludwig Maximilians Universitat, where he served the last 40 years of his 50-year career as a professor at 4 universities. Richard’s research focused on protists (the relationship between the nucleus and the plasm = “Kern-Plasma-Relation”), as well as on developmental physiological studies on sea urchins and frogs. He also wrote a leading Zoology textbook. He also discovered mitosis and meiosis.


Oscar Hertwig was a leader in the field of comparative and causal animal-developmental history. He also wrote a leading textbook. By studying sea urchins he proved that fertilization occurs due to the fusion of a sperm and egg cell. He recognized the role of the cell nucleus during inheritance and chromosome reduction during meiosis: in 1876, he published his findings that fertilization includes the penetration of a spermatozoon into an egg cell. Oscar Hertwig experiments with frog eggs revealed the ‘long axis rule’, or Hertwig rule. According to this rule cell divides along its long axis (1884). In 1885 Oscar wrote that nuclein (later called nucleic acid) is the substance responsible not only for fertilization but also for the transmission of hereditary characteristics. This early suggestion was proven correct much later in 1944 by the Avery – MacLeod – McCarty experiment which showed that this is indeed the role of the nucleic acid DNA. While Oscar was interested in developmental biology, he was opposed to chance as assumed in Charles Darwin?s theory. His most important theoretical book was: “Das Werden der Organismen, eine Widerlegung der Darwinschen Zufallslehre” (Jena, 1916) (translation: “The Origin of Organisms – a Refutation of Darwin’s Theory of Chance”).


Hertwig was elected a member of the Royal Swedish Academy of Sciences in 1903. Oscar Hertwig is known as Oscar Hedwig in the book “Who discovered what when” by David Ellyard. A history of the discovery of fertilization for mammals including scientists like Hertwig and other workers is given by the book “The Mammalian Egg” by Austin.

New Evidence that Viruses May Play a Role in Alzheimer’s Disease


Alzheimer’s disease (AD) is an irreversible, progressive brain disorder that slowly destroys memory and thinking skills and, eventually, the ability to carry out simple tasks. More evidence is accumulating to indicate that this loss of cognitive functioning is a mix of many different disease processes in the brain, rather than just one, such as buildup of amyloid or tau proteins. Identifying links to viruses may help researchers learn more about the complicated biological interactions involved in AD, and potentially lead to new treatment strategies.


National Institute on Aging (NIA) study finds new evidence that viruses may play a role in AD.


According to an article published online in the journal Neuron Analysis (21 June 2018), large data sets from post-mortem brain samples of people with and without AD has revealed new evidence that viral species, particularly herpesviruses, may have a role in AD biology. The study harnessed data from brain banks and cohort studies participating in the Accelerating Medicines Partnership – Alzheimer’s Disease (AMP-AD) consortium. The authors emphasized that while their findings do not prove that the viruses cause the onset or progression of AD, the findings do show that viral DNA sequences and activation of biological networks — the interrelated systems of DNA, RNA, proteins and metabolites — may interact with molecular, genetic and clinical aspects of AD.


The authors originally set out to find whether drugs used to treat other diseases can be repurposed for treating AD, and designed the study to map and compare biological networks underlying AD. What they found is that AD biology is likely impacted by a complex constellation of viral and host genetic factors, adding that there are specific testable pathways and biological networks. The authors used multiple layers of genomic and proteomic data from several NIA-supported brain banks and cohort studies. They began their direct investigation of viral sequences using data from the Mount Sinai Brain Bank and were able to verify their initial observations using datasets from the Religious Orders Study, the Memory and Aging Project and the Mayo Clinic Brain Bank. They were then able to incorporate additional data from the Emory Alzheimer’s Disease Research Center to understand viral impacts on protein abundance. Through the application of sophisticated computational modeling the authors made several key findings, including:

Human herpesvirus 6A and 7 were more abundant in Alzheimer’s disease samples than non-Alzheimer’s.


There are multiple points of overlap between virus-host interactions and genes associated with Alzheimer’s risk.


Multiple viruses impact the biology of Alzheimer’s disease across domains such as DNA, RNA and proteins.

Important roles for microbes and viruses in Alzheimer’s disease have been suggested and studied for decades. Since the 1980s, hundreds of reports have associated AD with bacteria and viruses. These studies combined suggest a viral contribution but have not explained how the connection works. While the current findings are more specific, they do not provide evidence to change how risk and susceptibility are assessed, nor the diagnosis and treatment of AD. Rather, the research gives scientists reason to revisit the old pathogen hypothesis and will be the basis for further work that will test whether herpes virus activity is one of the causes of AD.


More on this research is available in announcements from the Icahn School of Medicine at Mount SinaiArizona State University and Cell Press, the publisher of Neuron.


PCIT-ED Shows Promise for Treating Depression in Preschool-Aged Children


Children as young as 3-years-old can be diagnosed with clinical depression, and although preschool-aged children are sometimes prescribed antidepressants, a psychotherapeutic intervention is greatly needed. According to a study published online in the American Journal of Psychiatry (20 June 208), it was shown that a therapy-based treatment for disruptive behavioral disorders can be adapted and used as an effective treatment option for early childhood depression. The authors adapted Parent-Child Interaction Therapy (PCIT), which has been shown to be an effective way to treat disruptive behavioral disorders in young children. In standard PCIT treatment, parents are taught techniques for successfully interacting with their children. They then practice these techniques in controlled situations while being coached by a clinician.


In order to target the therapy for childhood depression, the authors adapted this standard intervention by adding a new emotional development (ED) module to the treatment. This extra material used the basic techniques of PCIT to train parents to be more effective at helping their children regulate emotions and to be better emotion coaches for their children. The training was designed to help enhance the children’s emotional competence and emotion regulation abilities. For the study, children ages 3-6 who met criteria for early childhood depression and their parents were randomly assigned to PCIT-ED treatment or a waitlist group. Children in the PCIT-ED group completed standard PCIT modules for a maximum of 12 treatment sessions, followed by an emotional development module lasting eight sessions. There are currently no empirically tested treatments that are widely used to treat early childhood depression; therefore, children in the waitlist group were monitored but received no active intervention. Children and their parents in the waitlist group were offered PCIT-ED treatment after completion of the study. The authors assessed before and after treatment or the waiting period (depending on group assignment), children’s psychiatric symptoms, their emotional self-regulation abilities, their level of impairment and functioning, and their tendency to experience guilt. Parents were assessed for depression severity, coping styles, and strategies they used in response to their child’s negative emotions, and for stress within the parent-child relationship.


Results showed that at the completion of treatment, children in the PCIT-ED group were less likely to meet criteria for depression, more likely to have achieved remission, and were more likely to score lower on depression severity than children in the waitlist group. Children in the PCIT-ED treatment group had improved functioning, fewer comorbid disorders, and were rated as having greater emotional regulation skills and greater “guilt reparation“ (e.g., spontaneously saying ”sorry” after having done something wrong, appropriate empathy with others, etc.) compared with children in the waitlist group. Parents in the PCIT-ED group also benefited. They were found to have decreased symptoms of depression, lower levels of parenting stress, and reported employing more parenting techniques that focused on emotion reflection and processing than parents in the waitlist group. Parents also overwhelmingly reported positive impressions of the therapeutic program.


According to the authors, the study provides very promising evidence that an early and brief psychotherapeutic intervention that focuses on the parent-child relationship and on enhancing emotion development may be a powerful and low-risk approach to the treatment of depression,“ and that it will be very important to determine if gains made in this early treatment are sustained over time and whether early intervention can change the course of the disorder.


FDA Approves Automated Insulin Delivery and Monitoring System for Use in Younger Pediatric Patients


The human pancreas naturally supplies a low, continuous rate of insulin, known as basal or background insulin. In patients with diabetes, the body’s ability to produce or respond to insulin is impaired. Because the pancreas does not make insulin in people with type 1 diabetes, patients must consistently monitor their glucose levels throughout the day and inject insulin with a syringe, pen or pump to avoid becoming hyperglycemic (high glucose levels). In addition, management of type 1 diabetes includes following a healthy eating plan and physical activity. Type 1 diabetes, also known as juvenile diabetes, is typically diagnosed in children and young adults.


The FDA has expanded the approval of the MiniMed 670G hybrid closed looped system, a diabetes management device that is intended to automatically monitor glucose (sugar) and provide appropriate basal insulin doses with little or no input from the user, to include individuals aged 7 to 13 with type 1 diabetes. The FDA originally approved this device in September 2017 for use in patients 14 years of age and older with type 1 diabetes.


The MiniMed 670G hybrid closed looped system works by measuring glucose levels in the body every five minutes and automatically adjusting insulin delivery by either administering or withholding insulin. The system includes: a sensor that attaches to the body to measure glucose levels under the skin; an insulin pump strapped to the body; and an infusion patch connected to the pump with a catheter that delivers insulin. While the device automatically adjusts insulin levels, users need to manually request insulin doses to counter carbohydrate consumption at mealtime.


The FDA evaluated data from a clinical trial of the MiniMed 670G hybrid closed looped system that included 105 individuals aged 7 to 11 years old. Study participants wore the device for approximately 3.5 months and participated in three phases of the study to evaluate both at-home use as well as remote use. The study found no serious adverse events associated with use of the MiniMed 670G and that the device is safe for use in people age 7 to 13 years with type 1 diabetes. Risks associated with use of the system may include hypoglycemia, hyperglycemia, as well as skin irritation or redness around the device’s infusion patch. As part of this approval, the FDA is requiring the product developer to conduct a post-market study to evaluate device performance in real-world settings in children between the ages of 7 and 13. This device is not approved for use in children 6 years of age or younger and in individuals who require less than eight units of insulin per day.


The expanded approval of MiniMed 670G hybrid closed looped system was granted to Medtronic.


Jackson Pollack Salad

This week. ©Joyce Hays, Target Health Inc.


Two weeks ago. ©Joyce Hays, Target Health Inc.


Three weeks ago. ©Joyce Hays, Target Health Inc. 


Four weeks ago. ©Joyce Hays, Target Health Inc. 


Yummy salad; we ate this all weekend. ©Joyce Hays, Target Health Inc.



1/2 head red cabbage, shredded with mandolin

1/4 head green cabbage, shredded with mandolin

1 and 1/2 carrots, grated

2 heaping Tablespoons parsley, chopped

3 heaping Tablespoons dill, chopped

1 large shallot, chopped

3 large garlic cloves, pressed

1 pinch salt

1 pinch black pepper

1 pinch chili flakes (optional)

1/2 teaspoon agave

1/4 teaspoon Dijon mustard

4 Tablespoons apple cider vinegar

1/2 cup buttermilk

2 Tablespoons sour cream

4 Tablespoons Kraft mayonnaise


This salad has been evolving for ten years and will continue. The next time I make it, I will add 3 mashed anchovy fillets (mashed with the garlic cloves), instead of any salt. As well as being salty, the anchovies add that umami flavor. However, I promise you, that this iteration of the Jackson Pollock salad, will be filled with awesome flavors. ©Joyce Hays, Target Health Inc.



1. Do all cutting, shredding, slicing, chopping so everything is ready to add when needed.


Chopping the dill, parsley and shallot, at the same time. ©Joyce Hays, Target Health Inc.


I wouldn’t have the patience to do this salad without the mandolin, which I got at Williams-Sonoma. The cutting board under the mandolin is specially tempered clear glass. ©Joyce Hays, Target Health Inc.


I graduated from art school, before I went to Columbia Univ (grad & undergrad) and always wondered how I would combine my psychology credentials with the art degree. As the founder of THI and also of the ON TARGET newsletter, I guess that’s the combo. Anyway, I digress. I really love color, so when I had the chance to paint with veggies, as in this salad, I couldn’t resist the homage to Jackson Pollock, a wild genius, if there ever was one. I know he would’ve liked the idea and loved this salad.

©Joyce Hays, Target Health Inc.


2. Put the first five ingredients in a large salad serving bowl and toss well.






3. Put the next eleven ingredients in a smaller bowl, starting with the chopped shallot, and mix well


I added all the dressing ingredients to my large measuring cup. ©Joyce Hays, Target Health Inc.


Added the dressing and ready for 3 minutes of tossing all ingredients so well combined. ©Joyce Hays, Target Health Inc.


4. Having tossed well, refrigerate this salad for about 2 hours before serving, so all of the diverse flavors have a chance to mingle.


Oh, how good this combo was: very fresh shrimp (Whole Foods) sauteed in a little oil and garlic, with the Jackson Pollock salad; Yum! ©Joyce Hays, Target Health Inc.


This chardonnay was perfect for the seafood and JP salad at lunch and another meal of saut?ed chicken thighs & pears, with JP Salad. ©Joyce Hays, Target Health Inc.


Have a great week everyone!

Bon Appetit!