Data Management and the Paperless Clinical Trial at Target Health Inc.

 

When developing a drug, biologic or device, it is all about the data. Data need to be accurate, precise, clean and validated so regulators and the public have confidence with what is reported by pharmaceutical and device companies. At Target Health, we have developed a 21CFR Part 11 compliant electronic data capture (EDC) system that allows for direct data entry of clinical trial data over the web. This patented system allows for the creation of source records, controlled by the clinical site, before the data hit our database. Target Health Inc. data management plans are created by the best team in the industry, which includes edit check and data transfer specifications, as well as data review plans to assure data consistency. Finally, Quality by Design meetings take place with our development team, including the sponsor and all relevant stakeholders, to do real-time data reviews. Consequently, we have the ability to respond rapidly to any data issues whether from specific sites, monitoring oversite, or the EDC system itself. As a result, we can lock databases within several weeks of the last patient, last visit (LPLV) monitored.

 

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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Glymphatic System of the Brain

Astrocytes stained for GFAP (green) and aquaporin-4 (purple)

Electron microscope photo credit: Jeffery J. Iliff – Sent personally from the owner, Public Domain, https://commons.wikimedia.org/w/index.php?curid=22858523

 

Editor’s note: This research is so exciting! In my next life, I would be a cell biologist/neuroscientist. At least now, I get to read all about it and share it with our intelligent curious readers.

 

The glymphatic system (or glymphatic clearance pathway) is a functional waste clearance pathway for the vertebrate central nervous system (CNS). The pathway consists of a para-arterial influx route for cerebrospinal fluid (CSF) to enter the brain parenchyma, coupled to a clearance mechanism for the removal of interstitial fluid (ISF) and extracellular solutes from the interstitial compartments of the brain and spinal 1) ___. Exchange of solutes between CSF and ISF is driven by arterial pulsation and regulated during sleep by the expansion and contraction of brain extracellular space. Clearance of soluble proteins, waste products, and excess extracellular fluid is accomplished through convective bulk flow of ISF, facilitated by astrocytic aquaporin 4 (AQP4) water channels.

 

The name “glymphatic system“ was coined by the Danish neuroscientist Maiken Nedergaard in recognition of its dependence upon glial cells and the similarity of its functions to those of the peripheral lymphatic system. Glymphatic flow was initially believed to be the complete answer to the long-standing question of how the sensitive neural tissue of the CNS functions in the perceived absence of a lymphatic drainage pathway for extracellular proteins, excess fluid, and metabolic waste products. However, two subsequent articles by Louveau et al. from the University of Virginia School of Medicine and Aspelund et al. from the University of Helsinki independently reported the discovery that the dural sinuses and meningeal arteries are in fact lined with conventional lymphatic vessels, and that this long-elusive vasculature forms a connecting pathway to the glymphatic 2) ___. In a study published in 2012, a group of researchers from the University of Rochester headed by M. Nedergaard used in-vivo two-photon imaging of small fluorescent tracers to monitor the flow of subarachnoid CSF into and through the brain parenchyma. The two-photon microscopy allowed for the visualization of the flux of CSF in living mice, in real time, without needing to puncture the CSF compartment (imaging was performed through a closed cranial window). According to findings of that study, subarachnoid CSF enters the brain rapidly, along the paravascular spaces surrounding the penetrating arteries, then exchanges with the surrounding interstitial fluid. Similarly, interstitial 3) ___ was cleared from the brain parenchyma via the paravascular spaces surrounding large draining veins. Paravascular spaces are CSF-filled channels formed between the brain blood vessels and leptomeningeal sheathes that surround cerebral surface vessels and proximal penetrating vessels. Around these penetrating vessels, paravascular spaces take the form of Virchow-Robin spaces. Where the Virchow-Robin spaces terminate within the brain parenchyma, paravascular CSF can continue traveling along the basement membranes surrounding arterial vascular smooth muscle, to reach the basal lamina surrounding brain capillaries. CSF movement along these paravascular pathways is rapid and arterial pulsation has long been suspected as an important driving force for paravascular fluid movement. In a study published in 2013, J. Iliff* and colleagues demonstrated this directly. Using in vivo 2-photon microscopy, the authors reported that when cerebral arterial pulsation was either increased or decreased, the rate of paravacular CSF flux in turn increased or 4) ___, respectively.

 

Astrocytes extend long processes that interface with neuronal synapses, as well as projections referred to as ‘end-feet’ that completely ensheathe the brain’s entire vasculature. Although the exact mechanism is not completely understood, astrocytes are known to facilitate changes in blood flow and have long been thought to play a role in waste 5) ___ in the brain. It has long been known that astrocytes express water channels called aquaporins. Until recently, however, no physiological function has been identified that explains their presence in the astrocytes of the mammalian CNS. Aquaporins are membrane-bound channels that play critical roles in regulating the flux of water into and out of 6) ___. Relative to simple diffusion, the presence of aquaporins in biological membranes facilitates a 3-10-fold increase in water permeability. Two types of aquaporins are expressed in the CNS: aquaporin-1, which is expressed by specialized epithelial cells of the choroid plexus, and aquaporin-4 (AQP4), which is expressed by astrocytes. Aquaporin-4 expression in astrocytes is highly polarized to the endfoot processes ensheathing the cerebral vasculature. Up to 50% of the vessel-facing endfoot surface that faces the vasculature is occupied by orthogonal arrays of AQP4. In 2012, it was shown that AQP4 is essential for paravascular CSF-ISF exchange. Analysis of genetically modified mice that lacked the AQP4 gene revealed that the bulk flow-dependent clearance of interstitial solutes decreases by 70% in the absence of AQP4. Based upon this role of AQP4-dependent glial water transport in the process of paravascular interstitial solute clearance, Iliff and Nedergaard termed this brain-wide glio-vascular pathway the ?glymphatic system’. A publication by L. Xie and colleagues in 2013 explored the efficiency of the 7) ___ system during slow wave sleep and provided the first direct evidence that the clearance of interstitial waste products increases during the resting state. Using a combination of diffusion ionophoresis techniques pioneered by Nicholson and colleagues, in vivo 2-photon imaging, and electroencephalography to confirm the wake and sleep states, Xia and Nedergaard demonstrated that the changes in efficiency of CSF-ISF exchange between the awake and sleeping brain were caused by expansion and contraction of the extracellular space, which increased by ~60% in the sleeping brain to promote clearance of interstitial wastes such as amyloid beta. On the basis of these findings, they hypothesized that the restorative properties of 8) ___ may be linked to increased glymphatic clearance of metabolic waste products produced by neural activity in the awake brain.

 

Another key function of the glymphatic system was documented by Thrane et al., who in 2013 demonstrated that the brain’s system of paravascular pathways plays an important role in transporting small lipophilic molecules. Led by M. Nedergaard, Thrane and colleagues also showed that the paravascular transport of lipids through the glymphatic pathway activated glial calcium signaling and the depressurization of the cranial cavity, and thus impairment of the glymphatic circulation, led to unselective lipid diffusion, intracellular lipid accumulation and pathological signaling among astrocytes. Although further experiments are needed to parse out the physiological significance of the connection between the glymphatic circulation, calcium signaling and paravascular lipid transport in the brain, the findings point to the adoption of a function in the CNS similar to the capacity of the intestinal lymph vessels (lacteals) to carry 9) ___ to the liver.

 

Pathologically, neurodegenerative diseases such as amyotrophic lateral sclerosis, Alzheimer’s disease, Parkinson’s disease and Huntington’s disease are all characterized by the progressive loss of neurons, cognitive decline, motor impairments, and sensory loss. Collectively these diseases fall within a broad category referred to as proteinopathies, due to the common assemblage of misfolded or aggregated intracellular or extracellular proteins. According to the prevailing amyloid hypothesis of Alzheimer’s disease, the aggregation of amyloid-beta (a peptide normally produced in and cleared from the healthy young brain) into extracellular plaques drives the neuronal loss and brain atrophy that is the hallmark of Alzheimer’s dementia. Although the full extent of the glymphatic system’s involvement in 10) ___ disease and other neurodegenerative disorders remains unclear, researchers have demonstrated through experiments with genetically modified mice that the proper function of the glymphatic clearance system was necessary to remove soluble amyloid-beta from the brain interstitium. In mice, that lack the AQP4 gene, amyloid-beta clearance is reduced by approximately 55%.

 

The glymphatic system may also be impaired after acute brain injuries such as ischemic stroke, intracranial hemorrhage or subarachnoid hemorrhage. In 2014, a group of researchers from the French Institute of Health and Medical Research (INSERM) demonstrated by MRI that the glymphatic system was impaired after subarachnoid hemorrhage, because of the presence of coagulated blood in the paravascular spaces. Interestingly, injection of tissue plasminogen activator (a fibrinolytic drug) in the CSF improved glymphatic functioning. In a parallel study, they also demonstrated that the glymphatic system was impaired after ischemic stroke in the ischemic hemisphere, although the pathophysiological basis of this phenomenon remains unclear. Notably, recanalization of the occluded artery also reestablished the glymphatic flow.

 

TED talk by researcher, J. Iliff, on special role of sleep in cleansing the brain

 

ANSWERS: 1) cord; 2) system; 3) fluid; 4) decreased; 5) removal; 6) cells; 7) glymphatic; 8) sleep; 9) lipids; 10) Alzheimer’s

 

Emanuel Swedenborg (1688 – 1772)

Graphic credit: By Carl Frederik von Breda – http://www.newchurchhistory.org/articles/ceg2006b/ceg2006b.php, Public Domain, https://commons.wikimedia.org/w/index.php?curid=15230429

 

 

Emanuel Swedenborg, born on 29 January 1688 and died 29 March 1772, was a Swedish scientist, philosopher, theologian, revelator, mystic and founder of Swedenborgianism. Swedenborg had a prolific career as an inventor and scientist. During the 1730s, Swedenborg undertook many studies of anatomy and physiology. He had the first known anticipation of the neuron concept. It was not until a century later that science recognized the full significance of the nerve cell. He also had prescient ideas about the cerebral cortex, the hierarchical organization of the nervous system, the localization of the cerebrospinal fluid, the functions of the pituitary gland, the perivascular spaces, the foramen of Magendie, the idea of somatotopic organization, and the association of frontal brain regions with the intellect. In some cases, his conclusions have been experimentally verified in modern times.

 

In the 1730s, Swedenborg became increasingly interested in spiritual matters and was determined to find a theory to explain how matter relates to spirit. Swedenborg’s desire to understand the order and the purpose of creation first led him to investigate the structure of matter and the process of creation itself. In the Principia, he outlined his philosophical method, which incorporated experience, geometry (the means by which the inner order of the world can be known) and the power of reason. He also outlined his cosmology, which included the first presentation of his nebular hypothesis. There is evidence that Swedenborg may have preceded Kant by as much as 20 years in the development of that hypothesis. Although the first known observations of the CSF (cerebrospinal fluid) date back to Hippocrates (460-375 BCE) and later Galen (130-200 CE), its discovery is credited to Emanuel Swedenborg (1688-1772 CE), who, being a devoutly religious man, identified the CSF during his search for the seat of the soul. The 16 centuries of anatomists that came after Hippocrates and Galen may have missed identifying the CSF due to the time period’s prevailing autopsy technique, which included severing the head and draining the blood before dissecting the brain. Although Swedenborg’s work (in translation) was not published until 1887, due in part to his lack of medical credentials, he may have also made the first connection between the CSF and the lymphatic system. His description of the CSF was of a “spirituous lymph.“

 

In the peripheral organs, the lymphatic system performs important immune functions, and runs parallel to the blood circulatory system to provide a secondary circulation that transports excess interstitial fluid, proteins and metabolic waste products from the systemic tissues back into the blood. The efficient removal of soluble proteins from the interstitial fluid is critical to the regulation of both colloidal osmotic pressure and homeostatic regulation of the body’s fluid volume. The importance of lymphatic flow is especially evident when the lymphatic system becomes obstructed. In lymphatic associated diseases such as elephantiasis (where parasites occupying the lymphatic vessels block the flow of lymph), the impact of such an obstruction can be dramatic. The resulting chronic edema is due to the breakdown of lymphatic clearance and the accumulation of interstitial solutes. In 2015, about 300 years after Emanuel Swedenborg, the presence of a meningeal lymphatic system was first identified. For over a century the prevailing hypothesis was that the flow of cerebrospinal fluid (CSF), which surrounds but does not come in direct contact with the parenchyma of the CNS, could replace peripheral lymphatic functions and play an important role in the clearance of extracellular solutes.

 

The majority of the CSF is formed in the choroid plexus and flows through the brain along a distinct pathway: moving through the cerebral ventricular system, into the subarachnoid space surrounding the brain, then draining into the systemic blood column via arachnoid granulations of the dural sinuses or to peripheral lymphatics along cranial nerve sheathes. Many researchers have suggested that the CSF compartment constitutes a sink for interstitial solute and fluid clearance from the brain parenchyma. However, the distances between the interstitial fluid and the CSF in the ventricles and subarachnoid space are too great for the efficient removal of interstitial macromolecules and wastes by simple diffusion alone. Helen Cserr at Brown University calculated that mean diffusion times for large molecules such as albumin would exceed 100 hrs to traverse 1 cm of brain tissue, a rate that is not compatible with the intense metabolic demands of brain tissue. A clearance system based on simple diffusion would additionally lack the sensitivity to respond rapidly to deviations from homeostatic conditions. Key determinants of diffusion through the brain interstitial spaces are the dimensions and composition of the extracellular compartment. In a series of elegantly designed experiments in the 1980s and 1990s, C. Nicholson and colleagues from New York University explored the microenvironment of the extracellular space using ion-selective micropipettes and ionophoretic point sources. Using these techniques Nicholson showed that solute and water movement through the brain parenchyma slows as the extracellular volume fraction decreases and becomes more tortuous.

 

As an alternative explanation to diffusion, Cserr and colleagues proposed that convective bulk flow of interstitial fluid from the brain parenchyma to the CSF was responsible for efficient waste clearance. Experiments conducted at the University of Maryland in the 1980s by Patricia Grady and colleagues postulated the existence of solute exchange between the interstitial fluid of the brain parenchyma and the CSF via paravascular spaces. In 1985, Grady and colleagues suggested that cerebrospinal fluid and interstitial fluid exchange along specific anatomical pathways within the brain, with CSF moving into the brain along the outside of blood vessels. Grady’s group suggested that these ?paravascular channels’ were functionally analogous to peripheral lymph vessels, facilitating the clearance of interstitial wastes from the brain. Other labs at the time, however, did not observe such widespread paravascular CSF-ISF exchange. The continuity between the brain interstitial fluid and the CSF was confirmed by H. Cserr and colleagues from Brown University and Kings College London. The same group postulated that interstitial solutes in the brain parenchyma exchange with CSF via a bulk flow mechanism, rather than diffusion. However other work from this same lab indicated that the exchange of CSF with interstitial fluid was inconsistent and minor, contradicting the findings of Grady and colleagues.

 

Cigarette Smoking Behavior Identifies Genes That Regulate Blood Pressure

 

High blood pressure is a leading cause of illness and death worldwide, and managing it is a major public health priority. According to the Centers for Disease Control and Prevention, about 75 million American adults have high blood pressure.

 

According to an article published in The American Journal of Human Genetics (1 March 2018), using a technique that is opening the door to more complex analyses of the human genome, dozens of new genetic variations have been identified that affect blood pressure. The new genetic regions-have confirmed the role of many previously known ones-by looking specifically at cigarette smoking behavior, one of many lifestyle factors that impact blood pressure. According to the authors, the findings could eventually lead to the development of individually targeted treatments to manage hypertension.

 

By using the technique known as gene-environment interaction analysis, the authors used cigarette smoking as an environmental marker to zero in on areas of the genome associated with blood pressure. Since it is well-established that cigarette smoking raises blood pressure, the authors tested different points of the genome of more than 610,000 individuals to find where there were interactions between cigarette smoking and blood pressure. These would be the areas where genes regulate blood pressure. Results confirmed 56 known genetic regions and identified 83 novel ones associated with blood pressure. The discovery was possible because the effects of some genes on blood pressure only show up under certain environmental factors, such as cigarette smoking. Absent those conditions, those genes’ connection to hypertension could have gone unnoticed. The same is true for the more detailed insights related to cigarette smoking that the authors were able to glean. Ten of the newly discovered genes appeared to have a much larger impact on the blood pressure levels of smokers than of nonsmokers-in some cases as much as eight times higher. The analysis of the large samples was possible through the work of researchers in the Gene-Lifestyle Interactions Working Group of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Also funded by NHLBI, CHARGE was formed to facilitate genome-wide association meta-analyses, using several large longitudinal studies.

 

In future studies, the authors will use even larger sample sizes and investigate the influence of other lifestyle factors on blood pressure and lipids.

 

NIAID Unveils Strategic Plan to Develop a Universal Flu Vaccine

 

Good news, hopefully, for those of us who know what it is like to get the flu.

 

Developing a universal influenza vaccine — a vaccine that can provide durable protection for all age groups against multiple influenza strains, including those that might cause a pandemic — is a priority for the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

 

According to an article published in Journal of Infectious Diseases (28 February 2018), NIAID officials detail the Institute’s new strategic plan for addressing the research areas essential to creating a safe and effective universal influenza vaccine. They describe the scientific goals that will be supported to advance influenza vaccine development. The strategic plan builds upon a workshop NIAID convened in June 2017 that gathered scientists from academia, industry and government who developed criteria for defining a universal influenza vaccine, identified knowledge gaps, and delineated research strategies for addressing those gaps.

 

The cornerstone of both seasonal and pandemic influenza prevention and control is the development of vaccines against specific influenza strains that pose a potentially significant risk to the public. Seasonal influenza vaccines are made anew each year to best match the strains projected to circulate in the upcoming season. However, this approach has limitations and difficulties. To reduce the public health consequences of both seasonal and pandemic influenza, vaccines must be more broadly and durably protective. Advances in influenza virology, immunology and vaccinology make the development of a universal influenza vaccine more feasible than a decade ago, according to the authors. To develop a universal influenza vaccine, NIAID will focus resources on three key areas of influenza research: improving the understanding of the transmission, natural history and pathogenesis of influenza infection; precisely characterizing how protective influenza immunity occurs and how to tailor vaccination responses to achieve it; and supporting the rational design of universal influenza vaccines, including designing new immunogens and adjuvants to boost immunity and extend the duration of protection.

 

FDA Warns of Fraudulent and Unapproved Flu Products

 

As part of the FDA’s ongoing efforts to protect consumers from health fraud, the agency is reminding consumers to be wary of unapproved products claiming to prevent, treat or cure influenza, or flu. This year’s severe flu season raises new concerns about the potential for consumers to be lured into buying unproven flu treatments, and even worse, buying counterfeit antivirals online from websites that appear to be legitimate online pharmacies. As the flu continues to make people sick – and even cause deaths – unscrupulous actors may also be taking advantage of unsuspecting consumers by promoting their fraudulent products that have not been reviewed by the FDA to be safe and effective. The FDA is warning consumers to be alert, and try and steer clear of fraudulent flu products, which may be found online or in retail stores. FDA is advising consumers on some of the telltale signs to look for when trying to spot flu products that may be fraudulent. People who are sick with flu-like symptoms and those who are at high risk of serious flu complications should see a health care professional as soon as possible to see if they should be treated with antiviral drugs.

 

Consumers should be aware that there are no legally marketed over-the-counter (OTC) drugs to prevent or cure the flu. However, there are legal OTC products to reduce fever and to relieve muscle aches, congestion and other symptoms typically associated with the flu. Products sold online are fraudulent if they claim to prevent, treat or cure the flu, and have not been evaluated by the FDA for that intended use. These flu claims may indicate that an OTC product is fraudulent:

 

– reduces severity and length of the flu;

– boosts your immunity naturally without a flu shot;

– safe and effective alternative to the flu vaccine;

– prevents catching the flu;

– effective treatment for the flu;

– faster recovery from the flu; or

– supports your body’s natural immune defenses to fight off the flu.

 

Health fraud scams waste money, lead to delays in getting a proper diagnosis and treatment, and may even lead to more serious injuries or death. The FDA routinely warns the public about health scams and has recently taken action against companies promoting and selling unproven treatments for cancer, opioid addiction and other illnesses. However, there are numerous unapproved and potentially unsafe products that continue to be sold directly to consumers in part because companies or individuals can move their marketing operations to new websites. Online pharmacies present another opportunity for scammers to take advantage of unsuspecting consumers. Online pharmacies may claim to sell prescription antiviral drugs, such as Tamiflu, at reduced prices or without a prescription. The FDA advises consumers to avoid purchasing products making such claims. Beware of online pharmacies that:

 

– allow you to buy prescription medicine without a prescription from your health care provider;

– do not have a U.S. state-licensed pharmacist available to answer your questions;

– offer very low prices that seem too good to be true; or

– are located outside of the U.S. or ship worldwide.

 

These pharmacies often sell medicines that can be dangerous because they may:

 

– have too much or too little of the active ingredient you need to treat your disease or condition;

– not contain the right active ingredient; or

– contain wrong or other harmful ingredients.

 

Legitimate online pharmacies exist, but so do many websites that look like professional and legitimate pharmacies, but are actually fraudulent. The FDA recommends consumers buy prescription drugs from their local pharmacy or only through an online pharmacy that requires a valid prescription from a doctor or other authorized health care professional and is licensed by the state board of pharmacy (or equivalent state agency) where the patient is located.

 

Kale and Cheese Stuffed Potatoes

This is a delicious recipe and easy to make. ©Joyce Hays, Target Health Inc.

 

Kale and Cheese Stuffed Potatoes

(Kale for Brunch, Lunch or Dinner)

3 russet potatoes about 10 oz. each (long and flat)

1 bunch Tuscan kale

Coarse salt

1 Tablespoon olive oil

1 Tablespoon butter

1 large leek

1 cup coarsely grated cheddar, gruyere or comte

3/4 cup sour cream

Pinch black pepper

Pinch cayenne

3 fresh garlic cloves, minced

 

Get all ingredients together ©Joyce Hays, Target Health Inc.

 

Directions 

Heat oven to 400oF.

 

1. Cook potatoes the first time: Gently scrub potatoes but do not peel. Pierce all over with a fork so that steam escapes. If you don’t poke some holes, you could have a potato explosion followed by a mess. Bake 1 hour to 1 hour 15 minutes or until potatoes are tender when pierced in center. Leave oven on.

 

2. While potatoes cook, prepare stuffing: Tear kale leaves off the stems, and wash leaves in cold water to remove any dirt. Don’t dry. Tear leaves into large pieces. Heat a pan over medium-high and add the kale and a pinch of salt. Cook in the pan with just the water clinging to the leaves until they wilt down. Remove from pan and transfer to a colander and when cool enough to handle, wring out any extra moisture. I use either paper toweling or a clean kitchen towel. On a cutting board, finely chop greens. There should be about a cup of well-chopped greens; more or less.

 

3. Trim leek down to the yellow and pale green part. Halve lengthwise and wash in cold water to remove any dirt, then pat dry. Cut leek halves the long way, again, so they’re in quarter-stalks, and thinly slice.

 

In a bowl, mixing the cooked kale, garlic and leeks ©Joyce Hays, Target Health Inc.

 

4. Heat a large skillet over medium heat; add butter and oil. When both are warm, add leek and reduce heat to medium-low. Cook until mostly tender and sweet, about 10 to 15 minutes, stirring. Avoid letting it brown. Add the minced garlic and chopped kale back to pan and warm up with leeks, for about 1 minute. Transfer mixture to a bowl.

 

Potatoes, leeks, kale have been mashed, sour cream and 3/4 grated cheese have been stirred in. Mixture is ready to heap into the baked shells of the potato. ©Joyce Hays, Target Health Inc.

 

5. Prepare potatoes: When potatoes are cool enough to handle, halve lengthwise and scoop out all but the last 1/4-inch thickness of skin and potato (you want the potato shell to remain strong enough to hold all the stuffing). Now add the potato insides, to bowl with leeks and greens. Arrange the potato shells on a baking sheet. Mash potatoes, leeks and kale together until smooth. Stir in the sour cream, 3/4 of cheese and more salt and pepper (optional). Now, heap the kale/potato mixture into the potato skins. Sprinkle with remaining 1/4 of cheese.

 

Going in oven for second time ©Joyce Hays, Target Health Inc.

 

6. Bake potatoes a second time, 20 to 30 minutes, until golden brown and crispy. Serve while still nice and warm

 

We opened some of this bottled red satin, which we were saving for a special occasion. This is a well-known vineyard putting forth, year after year, only excellent wines. You can’t go wrong drinking it now or investing in futures. ©Joyce Hays, Target Health Inc.

 

Friday night, we started by toasting with this delicious (from start to finish), full bodied cab, and a salad with fresh ripe tomatoes, cut up avocados, green olives, mini thin-skinned cucumbers, endive and a fresh lemon juice/olive oil dressing. Then came the unbelievably tender center-cut fillet mignon with marsala/mushroom sauce, the (recipe above) kale/cheese stuffed potatoes, some cauliflower fritters with pomegranate arils (will post my recipe soon), some sweet potato/date patties with chopped pistachios (will post another of my recipes soon) and more wine.

 

Our house guests for a while from LA:  our son and his friend.  We went to the MetOpera to see the gorgeous Anthony Minghella production of Puccini’s Madam Butterfly and enjoyed it immensely. A wonderful weekend was had by all. Here we are dining out at Sardi’s. We look forward to many more visits like the stimulating one we’re in the midst of now.  ©Joyce Hays, Target Health Inc.

 

Here are two favorite moments from an extraordinary production of Puccini’s Madame Butterfly:

 

The beautiful Humming Chorus, as the curtain falls on Act 2

 

Madama Butterfly: “Un bel di” – Maria Callas

 

 

Have a great week everyone!

 

From Our Table to Yours

Bon Appetit!