Hair Loss Prevention in Breast Cancer Chemotherapy Presented at ASCO and NBC News

 

This hair loss project in cancer chemotherapy was presented at ASCO last week For this project Target Health performed all CRO services, including risk-based monitoring. From a technology perspective, all of the sites used the Target Health paperless clinical trial suite including Target e*CTR™ (eClinical Trial Record), fully integrated with Target e*CRF® to capture eSource records. The study was done at 5 major medical centers, and both Target Health and 3 of the medical centers were inspected by FDA. There were no Form FDA 483 findings issued to Target Health or any of the clinical sites related to Target e*CRF, Target e*CTR, Target Document® for the eTMF, and risk-based monitoring practices.

 

At ASCO, Saturday morning started with an opening session by the former ASCO president telling about individualized treatment including scalp cooling. Because Dignitana’s clinical trial was mentioned as one of the highlights in the ASCO daily news, there was a great interest and activity at the poster session. Later on in the afternoon, the poster discussion started with the following statement by Dr Charles Shapiro from Mount Sinai;“it’s about time“!! An hour later was the following video showed on NBC news; http://www.nbcnews.com/nightly-news/scalp-cooling-system-dignicap-helps-cancer-patient-keep-hair-during-n367106. Other media clips can be found on the Dignitana website.

 

NDA is planned for another program for Q4 2015.

 

Target Health Offices Opened Just 3 Days After the Crane Accident on Madison Avenue

 

As many of you know, the crane accident in NYC this past weekend resulted in our office in NYC being closed for 3 days. Thanks to our terrific staff and IT systems, we did not skip a beat and there was no impact on our business. This was the same experience we had when Hurricane Sandy hit a few years ago. While it may be tempting by some to push working from home, we all missed our face-to-face interactions so it is good to be back. We also want to thank our friend and colleague Ed Soh, Managing Director and Co-Founder of Excel Partners, who kindly let us use his conference room just a block from 261 Madison.

 

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Building Repairs Ongoing and Results of the Fire Department Needing to Enter Our Offices©Target Health Inc. 2015

 

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

 

QUIZ

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Your Viral Infection History in a Single Drop of Blood

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From a single drop of blood, researchers can now simultaneously test for more than 1,000 different strains of viruses that currently or have previously infected a person.

 

New technology developed by Howard Hughes Medical Institute (HHMI) researchers, makes it possible to test for current and past infections with any known human virus by analyzing a single drop of a person’s 1) ___. The method, called VirScan, is an efficient alternative to existing diagnostics that test for specific viruses one at a time. With VirScan, scientists can run a single test to determine which 2) ___ have infected an individual, rather than limiting their analysis to particular viruses. That unbiased approach could uncover unexpected factors affecting individual patients’ health, and also expands opportunities to analyze and compare viral infections in large populations. The comprehensive analysis can be performed for about $25 per blood sample.

 

Stephen Elledge, an HHMI investigator at Brigham and Women’s Hospital, led the development of VirScan. “We’ve developed a screening methodology to basically look back in time in people’s [blood] sera and see what viruses they have experienced,“ he says. “Instead of testing for 3) ___ individual virus at a time, which is labor intensive, we can assay all of these at once. It’s one-stop shopping.“ Elledge and his colleagues have already used VirScan to screen the blood of 569 people in the United States, South Africa, Thailand, and Peru. The scientists described the new technology and reported their findings in the June 5, 2015, issue of the journal Science. VirScan works by screening the blood for antibodies against any of the 206 species of viruses known to infect humans. The 4) ___ system ramps up production of pathogen-specific antibodies when it encounters a virus for the first time, and it can continue to produce those antibodies for years or decades after it clears an infection. That means VirScan not only identifies viral infections that the immune system is actively fighting, but also provides a history of an individual’s past infections.

 

To develop the new test, Elledge and his colleagues synthesized more than 93,000 short pieces of DNA, encoding different segments of viral proteins. They introduced those pieces of DNA into bacteria-infecting viruses called bacteriophage. Each bacteriophage manufactured one of the protein segments — known as a peptide — and displayed the peptide on its surface. As a group, the 5) ___ displayed all of the protein sequences found in the more than 1,000 known strains of human viruses. Antibodies in the blood find their viral targets by recognizing unique features known as epitopes that are embedded in proteins on the virus surface. To perform the VirScan analysis, all of the peptide-displaying bacteriophage are allowed to mingle with a blood sample. 6) ___ antibodies in the blood find and bind to their target epitopes within the displayed peptides. The scientists then retrieve the antibodies and washed away everything except for the few bacteriophage that cling to them.

 

By sequencing the DNA of those bacteriophage, they can identify which viral protein pieces were grabbed onto by antibodies in the blood sample. That tells the scientists which viruses a person’s immune system has previously encountered, either through infection or through 7) ___. Elledge estimates it would take about 2-3 days to process 100 samples, assuming sequencing is working optimally. He is optimistic the speed of the assay will increase with further development. To test the method, the team used it to analyze blood samples from patients known to be infected with particular viruses, including HIV and hepatitis C. “It turns out that it works really well,“ Elledge says. “We were in the sensitivity range of 95 to 100% for those, and the specificity was good — we didn’t falsely identify people who were negative. That gave us confidence that we could detect other viruses, and when we did see them we would know they were real.“

 

Elledge and his colleagues used VirScan to analyze the 8) ___ in 569 people from four countries, examining about 100 million potential antibody/epitope interactions. They found that on average, each person had antibodies to ten different species of viruses. As expected, antibodies against certain viruses were common among adults but not in 9) ___, suggesting that children had not yet been exposed to those viruses. Individuals residing South Africa, Peru, and Thailand, tended to have antibodies against more viruses than people in the United States. The researchers also found that people infected with HIV had antibodies against many more viruses than did people without HIV. Elledge says the team was surprised to find that antibody responses against specific viruses were surprisingly similar between individuals, with different people’s antibodies recognizing identical amino acids in the viral peptides. “In this paper alone we identified more antibody/peptide interactions to viral proteins than had been identified in the previous history of all viral exploration,“ he says. The surprising reproducibility of those interactions allowed the team to refine their analysis and improve the sensitivity of VirScan, and Elledge says the method will continue to improve as his team analyzes more samples. Their findings on viral epitopes may also have important implications for vaccine design. Elledge says the approach his team has developed is not limited to antiviral antibodies. His own lab is also using it to look for antibodies that attack a body’s own tissue in certain autoimmune 10) ___ that are associated with cancer. A similar approach could also be used to screen for antibodies against other types of pathogens. Sources: Howard Hughes Medical Institute (HHMI); G. J. Xu, T. Kula, Q. Xu, M. Z. Li, S. D. Vernon, T. Ndung’u, K. Ruxrungtham, J. Sanchez, C. Brander, R. T. Chung, K. C. O’Connor, B. Walker, H. B. Larman, S. J. Elledge: Comprehensive serological profiling of human populations using a synthetic human virome. Science, 2015; 348 (6239): aaa0698 DOI: 10.1126/science.aaa0698; ScienceDaily.com

 

ANSWERS: 1) blood; 2) viruses; 3) one; 4) immune; 5) bacteriophage; 6) Antiviral; 7) vaccination; 8) antibodies; 9) children; 10) diseases

 

Galen’s Documents Hidden in an Ancient Manuscript

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Credit: Courtesy of the Owner

 

The first time Grigory Kessel held the ancient manuscript, its animal-hide pages more than 1,000 years old, it seemed oddly familiar. A Syriac scholar at Philipps University in Marburg, Germany, Dr. Kessel was sitting in the library of the manuscript’s owner, a wealthy collector of rare scientific material in Baltimore. At that moment, Dr. Kessel realized that just three weeks earlier, in a library at Harvard University, he had seen a single orphaned page that was too similar to these pages to be coincidence. The manuscript he held contained a hidden translation of an ancient, influential medical text by Galen of Pergamon, a Greco-Roman physician and philosopher who died in 200 CE. It was missing pages and Dr. Kessel was suddenly convinced one of them was in Boston. Dr. Kessel’s realization in February 2013 marked the beginning of a global hunt for the other lost leaves, a search that culminated in May with the digitization of the final rediscovered page in Paris. Scholars are just beginning to pore over the text, the oldest known copy of Galen’s “On the Mixtures and Powers of Simple Drugs.“ It may well provide new insights into medicine’s roots and into the spread of this new science across the ancient world. “On so many levels it’s important,“ said Peter Pormann, a Graeco-Arabic expert at the University of Manchester who now leads a study of the text.

 

The manuscript held by Dr. Kessel that day was a palimpsest: older text covered up by newer writing. It was a common practice centuries ago, a medieval form of recycling. In this case, 11th-century Syrian scribes had scraped away Galen’s medical text and had overwritten hymns on the parchment. The hymn book itself is of interest, but for now it is the original text, all but invisible to the naked eye and known as the undertext, that has captured the imagination of scholars.

 

For centuries, Galen’s “Simple Drugs“ was required reading for aspiring physicians, the summation of ancient knowledge about medicine, patient care and pharmaceutical plants. Galen described a root that cures “roughness of the throat“ and recommended hemp as an earache remedy that “does not produce flatulence“ (though it “dries out the semen“). Much of “Simple Drugs“ was eventually translated into Syriac, a form of Aramaic used by Middle Eastern Christian communities. The undertext of the manuscript in Baltimore, most likely from the ninth century CE, is a copy of the first Syriac translation, itself painstakingly completed in the sixth century CE by Sergius of Reshaina, a Syriac physician and priest. “Today, it doesn’t look to be special when somebody translates one language to another, but in those days, it was indeed a great achievement,“ Dr. Kessel said. “He had to create vocabulary, to find Syriac words to correspond to this Greek medical vocabulary.“ By the sixth century, Syriac-speaking Christians were spreading east from Turkey through Syria, Iraq and Iran. They needed translations of Greek scholarly work, partly to support missionary work like running hospitals.

 

 

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One leaf of the Syriac Galen Palimpsest remains at St. Catherine’s Monastery in the Sinai Desert in Egypt.  Here is the world’s oldest continuously operating library.  The monastery library preserves the second largest collection of early codices and manuscripts in the world, outnumbered only by the Vatican Library. It contains Greek, Arabic, Armenian, Coptic, Hebrew, Georgian, and Aramaic texts.  Built between 548 and 565, the monastery is one of the oldest working Christian monasteries in the world.

Credit: Wikipedia

 

“Simple Drugs“ was a large work, an 11-book treatise. Sergius’s translations of Galen’s text were copied and recopied for centuries, and eventually became a bridge for moving the medical expertise of the ancient Greeks to Islamic societies. Syriac texts were much easier than Greek ones to translate into Arabic. As Muslim influence grew in the Near and Middle East, Christian populations dwindled, and so did Syriac. “These great Christian cultures that used it suffered so much,“ said Columba Stewart, the executive director of the Hill Museum and Manuscript Library in Collegeville, Minn. “By the time you have modern scholarship, these ancient Syriac cultures are just a vestige of their former selves – often quite isolated from Western culture, so there’s not a lot of awareness.“ Little is known of the history of the manuscript in Baltimore, formally known as the Syriac Galen Palimpsest, from its recycling in the 11th century until the 1920s, when it was sold to a private collector in Germany. After that, the manuscript fell again from public view until 2002, when it was purchased by a collector in a private sale. He has not been publicly identified. In 2009, the Galen Palimpsest was lent to the Walters Art Museum for spectral imaging of its leaves by an independent group of specialists, which would reveal the erased Galen undertext. Each page is photographed digitally at extremely high resolution with varying colors and configurations of light, which in various ways illuminate the inks, grooves from writing and parchment itself. Computer algorithms exploit these variations to maximize the visibility of the undertext. The resulting images went online under a “creative commons“ license, meaning that anyone can use the material free for any noncommercial purpose. Once the images were online, William Noel, who was the curator of manuscripts and rare books at the museum, began organizing members of the tiny community of scholars who study Syriac scientific texts to study the new material. One of them was Dr. Kessel, who was on a fellowship at Harvard’s Dumbarton Oaks Research Library in Washington. Eventually, Michael B. Toth, a systems engineer who managed the imaging work arranged for him to see the Galen Palimpsest for himself. “I couldn’t even imagine how it looked,“ Dr. Kessel said. “Then when I saw the manuscript, I had the kind of deja vu impression that I had already seen it. And then I recalled the single folio in the Harvard library.“ By analyzing the page size, handwriting and other features, as well as the visible text, Dr. Kessel was able to determine that the Harvard leaf did indeed fill one of the gaps in the Galen Palimpsest. But six more were apparently missing. Dr. Kessel set out to find them. He began with a list of 10 libraries known to have ancient Syriac material, combing through online catalogs when available to look for clues such as the right dimensions or vague references to undertext. Sometimes, he traveled to the libraries himself.

 

It was not long before Dr. Kessel had good news. He found one missing page in a catalog from the Sacred and Imperial Monastery of the God-Trodden Mount of Sinai. It is known more commonly as St. Catherine’s in the Sinai Desert in Egypt, which has the world’s oldest continuously operating library. Another leaf turned up at the National Library of France in Paris. And at the Vatican’s vast library in Rome, he was able to identify the other three missing leaves, bringing the total to six. The seventh missing page is believed to have been blank and was probably discarded. No one knew how much of “Simple Drugs“ might be hidden in the Galen Palimpsest. The only other known Syriac copy resides at the British Library in London and includes only Books 6 to 8. Translations of these later books in the series are the most common, because they contain more specific medicinal information and details about the properties of plants. But as their preliminary studies progressed, Dr. Kessel and his colleagues spotted words from Books 2 and 4 in one of the loose leaves. The full text of “Simple Drugs“ is known to scholars, but only from more recent translations in languages other than Syriac. “This was something absolutely unexpected,“ he said.

 

Siam Bhayro, a specialist in early Jewish studies at the University of Exeter in England, had believed that Sergius must have translated the earlier books, but there had been no proof. When he heard that Dr. Kessel might have found pages from the early translations, “I was almost dancing up and down,“ he said. Another of Dr. Kessel’s intriguing discoveries was a note in Arabic on the first leaf, indicating that the manuscript – by then a hymn book concealing Galen’s text – had been donated to the brothers of the Sinai monastery, a reference to St. Catherine’s Monastery in Mt. Sinai, Egypt.

 

 

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The bound Syriac Galen Palimpsest.  Credit: Courtesy of the Owner

 

How it left the monastery is unclear: Particularly in the early 20th century, some of the library’s holdings were borrowed legitimately, while others were stolen by visitors hoping to make private sales. The independent imaging team is now finishing the work necessary to add the rediscovered leaves to the digital collection. But translating and studying the Syriac text revealed in the images will take much longer, perhaps five years or more. That work is now underway because of a recent $1.5 million grant from the United Kingdom’s Arts and Humanities Research Council. Scholars are eager to compare the Syriac material to existing copies of “Simple Drugs“ written in Greek, all of which appear to be centuries younger than the Galen Palimpsest and much further removed from the original. As texts went through multiple rounds of copying, they underwent significant changes. A scribe might remove parts that seemed unimportant or add material based on new knowledge. Comparing the Galen Palimpsest and the British Syriac copy, for instance, could offer telling insights into how the ancient Greeks treated the ill and how these remedies spread across the Middle East. “Some of the stuff is not entirely scientific by our standards,“ even if it enabled progress, Dr. Petit said. Indeed, little of Galen’s advice would stand up to modern scrutiny. Like other ancient physicians, he believed health was controlled by the balance of four “humors“ in the body and recommended certain stones for their cleansing powers. “The Galenic system is completely bonkers,“ Dr. Bhayro said. Still, it was the best thinking available in an era in which the very idea of medical science was relatively new. “It’s likely to be a central text once it’s fully deciphered,“ said Dr. Pormann of the University of Manchester. “We might discover things we really can’t dream of yet.“ Sources: Mark Schrope for the New York Times; Wikipedia; YouTube; The Guardian

 

 

Read more about the lack of security in the Middle East, causing St. Catherine’s Monastery to close.

 

Video: St. Catherine’s Monastery in Mt. Sinai, Egypt

 

Video: St. Catherine’s Monastery

 

NCI-Match Trial Will Link Targeted Cancer Drugs to Gene Abnormalities

 

Investigators for the nationwide trial, NCI-MATCH: Molecular Analysis for Therapy Choice, announced at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago that the precision medicine trial will open to patient enrollment in July. The trial seeks to determine whether targeted therapies for people whose tumors have specific gene mutations will be effective regardless of their cancer type.

 

NCI-MATCH will incorporate more than 20 different study drugs or drug combinations, each targeting a specific gene mutation, in order to match each patient in the trial with a therapy that targets a molecular abnormality in their tumor. The study was co-developed by the National Cancer Institute (NCI), part of the National Institutes of Health, and the ECOG-ACRIN Cancer Research Group, part of the NCI-sponsored National Clinical Trials Network (NCTN). It is being led by ECOG-ACRIN.

 

NCI-MATCH is a phase II trial with numerous small sub-studies (arms) for each treatment being investigated. It will open with approximately 10 sub-studies, moving to 20 or more within months. The study parameters for the first 10 arms are being sent to 2,400 participating sites in the NCTN for review in preparation for patient enrollment beginning in July. The exact date for the opening of patient enrollment will be decided shortly after the ASCO meeting. Additional sub-studies are in development and will be added over time as the trial progresses. The NCI-MATCH trial has two enrollment steps. Each patient will initially enroll for screening in which samples of their tumor will be removed (biopsied). The samples will undergo DNA sequencing to detect genetic abnormalities that may be driving tumor growth and might be targeted by one of a wide range of drugs being studied. If a molecular abnormality is detected for which there is a specific sub-study available, to be accepted in NCI-MATCH patients will be further evaluated to determine if they meet the specific eligibility requirements within that arm. Once enrolled, patients will be treated with the targeted drug regimen for as long as their tumor shrinks or remains stable. Overall, trial investigators plan to screen about 3,000 patients during the full course of the NCI-MATCH trial to enroll about 1,000 patients in the various treatment arms. Adults 18 years of age and older with solid tumors or lymphomas that have advanced following at least one line of standard systemic therapy, or with tumors for which there is no standard treatment, will be eligible. Each arm of the trial will enroll up to 35 patients. The trial’s design calls for at least a quarter of the 1,000-patients enrolled to involve people with rare types of cancer.

 

Since many gene mutations in tumors are infrequent or unique, screening for individual mutations is not cost-effective or efficient in clinical trials. Instead, NCI-MATCH will use advanced gene sequencing techniques to screen for many molecular abnormalities at once. Large numbers of patient tumors will need to be screened because most gene mutations occur in 10% or less of cancer patients. Most patients are expected to have one, or at most two, treatable mutations in their tumors. By having multiple treatments available for these genetic abnormalities in a single clinical trial, several different study drugs or drug combinations can be evaluated simultaneously.

 

NCI-MATCH will use a single DNA sequencing test to identify gene mutations in patients’ tumors. The NCI Molecular Characterization Laboratory at the NCI Frederick National Laboratory for Cancer Research in Frederick, Maryland, has developed the test which looks for 143 genes associated with cancer that can be targeted by drugs in the trial. To ensure quality control, biopsy specimens from all 3,000 screened patients will be sent to a single location for processing: the ECOG-ACRIN Central Biorepository and Pathology Facility at the University of Texas MD Anderson Cancer Center in Houston. The DNA sequencing analysis will be done at one of four facilities using a standardized process.

 

The cancer treatment drugs being used in NCI-MATCH include both U.S. Food and Drug Administration approved drugs as well as investigational agents that are being contributed by a number of pharmaceutical companies. Most of the arms in the trial will incorporate single-agent drugs that are either commercially available or are still being tested in clinical trials. However, a few arms will contain combinations of drugs for which there are enough safety data and evidence that they might be active against a particular genetic abnormality. Since NCI-MATCH is designed to explore whether drugs are effective against specific molecular abnormalities, patients who have tumors that can be treated with a drug already approved by the FDA for their molecular abnormality will not be eligible to use the same drug in NCI-MATCH. They could be considered for other drugs within NCI-MATCH if they have already received an approved therapy and have a different genetic abnormality that could be targeted with a new drug.

 

There are two main clinical endpoints in the NCI-MATCH trial. The primary endpoint is the overall response rate, which is the proportion of patients in the trial whose tumors shrink by a predefined amount over a specific time period. The secondary endpoint is 6-month progression-free survival, which is a measure of whether a patient’s disease remains stable. For this study, a response rate of 5% or less in a molecularly-defined population will not be considered promising, whereas a response rate of 16% to 25% will be encouraging. After starting treatment in NCI-MATCH, a 6-month progression-free survival of 15% will not be considered promising, whereas a progression-free survival at six months of 35% will indicate that the treatment should be explored further..

 

Enrollment in NCI-MATCH will be available across the country through NCTN sites. In addition, the trial will be available through sites nationwide that participate in the NCI Community Oncology Research Program. All of the approximately 2,400 sites that participate in the trial will use the NCI Central Institutional Review Board as the institutional review board of record. Sites will access the trial under the protocol identification EAY131 via the NCI Cancer Trials Support Unit. The principal investigators who will lead the sub-studies are situated throughout the NCTN and its participating network groups: ECOG-ACRIN, the Alliance for Clinical Trials in Oncology, NRG Oncology and SWOG. All of these investigators have expertise in molecular studies, and many are junior researchers involved with, and being mentored by, experienced senior investigators. Patient advocates were engaged in the development of the trial and will help oversee the protocol and other aspects of the study.

 

A New Role For Zebrafish: Larger Scale Gene Function Studies

 

Dr. Mitchel’s PhD Sponsor at NYU was Dr. Al Perlmutter who was a zebrafish expert. Dr. Perlmutter had a passion for his research and guided Dr. Mitchel’s research in aging of the Killifish, Nothobranchius guentheri. Dr. Mitchel met his wife, Joyce Hays, now CEO of Target Health, when he was looking for a partner in his first venture known as “Instant Fish.“

 

Researchers often try to determine the role of a gene by knocking it out — turning it off or removing it — and watching the potential effects on an organism lacking it.

 

The zebrafish and the mouse are the most commonly studied vertebrate laboratory animals whose genomes have been completely sequenced. The zebrafish is better suited to larger scale gene editing because about 70% of zebrafish genes appear to have human counterparts and the fish are far less costly to maintain than are mice. They multiply astonishingly quickly; a female may produce as many as 200 eggs at one time. And the embryos are fertilized externally and are transparent, making them readily accessible to researchers.

 

According to a study posted online on June 5, 2015, and to be published in the July 2015 issue of Genome Research, a relatively new method of targeting specific DNA sequences in zebrafish could dramatically accelerate the discovery of gene function and the identification of disease genes in humans. Results showed that the gene-editing technology known as CRISPR/Cas9, is six times more effective than other techniques at homing in on target genes and inserting or deleting specific sequences. The study also demonstrated that the CRISPR/Cas9 method can be used in a “multiplexed” fashion — that is, targeting and mutating multiple genes at the same time to determine their functions. According to the authors, it was shown about a year ago that CRISPR can knock out a gene quickly and it has been possible to establish an entire pipeline for knocking out many genes and testing their function quickly in a vertebrate model.

 

Such larger scale — termed high-throughput — gene targeting in an animal model could be particularly useful for human genomic research. Only 10 to 20% of recognized human genes have been subjected to such rigorous testing. The functions of many other genes have been inferred based on analyzing proteins or have been identified as possible disease genes, but the functions of those genes have not been confirmed by knocking them out in animal models and seeing what happens. The zebra fish model is a way to do that on a more cost-efficient and large scale.

 

The CRISPR/Cas9 method of gene editing is one of the two essential components in the team’s high-throughput method. Modeled on a defense mechanism evolved by bacteria against viruses, CRISPR/Cas9 activity was first described in 2012. Since then, its use has spread quickly in genomic research labs in the United States and abroad. The acronym CRISPR stands for “clustered, regularly interspaced, short palindromic repeat,” referring to a pattern of DNA sequences that appears frequently in bacterial DNA. It is believed the CRISPR sequences reflect evolutionary responses to past viral attacks. The Cas9 protein is a nuclease, an enzyme that snips a stretch of DNA in two places, in effect cutting out a piece. Bound together, CRISPR/Cas9 becomes a powerful research tool that permits researchers to target and delete a particular sequence or to insert a new sequence into the DNA of animal-model embryos. The CRISPR/Cas9 methodology works in mice, too, but it is more costly and takes far longer. Although mice actually reach sexual maturity earlier than zebrafish, they produce far fewer offspring.

 

To demonstrate the feasibility of high throughput editing, the authors targeted 162 locations in 83 zebrafish genes — about 50 of which are similar to human genes involved in deafness. This produced mutations in 82 of the 83 genes. In screening embryos by fluorescent polymerase chain reaction (a technology that allows researchers to produce millions of copies of a specific DNA sequence) and high-throughput DNA sequencing, the authors determined that overall, mutations were passed on to the next generation in 28 percent of cases.  The transmission rate was higher for some genes than for others, but in most cases, screening offspring from parent fish should be enough to spot most mutations. The results demonstrated that using the CRISPR/Cas9 technique in zebrafish will make it possible to both generate mutants for all genes in the zebrafish genome and carry out large-scale phenotyping.

 

Ultimately, the authors will use the new method to knock out about 10% of the zebrafish’s roughly 25,000 genes, and would like to see an even broader effort.

 

Veterinary Feed Directive (VFD) Final Rule

 

The FDA has announced the Veterinary Feed Directive (VFD) final rule, an important piece of the agency’s overall strategy to promote the judicious use of antimicrobials in food-producing animals. This strategy will bring the use of these drugs under veterinary supervision so that they are used only when necessary for assuring animal health. The VFD final rule outlines the process for authorizing use of VFD drugs (animal drugs intended for use in or on animal feed that require the supervision of a licensed veterinarian) and provides veterinarians in all states with a framework for authorizing the use of medically important antimicrobials in feed when needed for specific animal health purposes.

 

The VFD final rule continues to require veterinarians to issue all VFDs within the context of a veterinarian-client-patient relationship (VCPR) and specifies the key elements that define a VCPR. These key elements include that the veterinarian engage with the client (i.e., animal producer or caretaker) to assume responsibility for making clinical judgments about patient (i.e., animal) health, have sufficient knowledge of the animal by conducting examinations and/or visits to the facility where the animal is managed, and provide for any necessary follow-up evaluation or care. The final rule will require veterinarians to follow state-defined VCPR requirements; in states where the FDA determines that no applicable or appropriate state VCPR requirements exist, veterinarians will need to issue VFDs in compliance with federally defined VCPR requirements. All veterinarians will need to adhere to a VCPR that includes the key elements in the final rule.

 

In December 2013, the FDA published a guidance document, which calls on animal drug manufacturers of approved medically important antimicrobials that are put into water or feed of food-producing animals to voluntarily stop labeling them as drugs that can be used to promote animal growth and change the labeling of their products for the remaining uses to require veterinary oversight of these drugs when they are used for therapeutic purposes. All of the affected makers of these drugs have committed in writing to participate in the strategy.

 

Warm Mushroom Chickpea Pancakes with Baby Arugula and Toasted Pine Nuts

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A different kind of warm and tasty meal, with chilled white wine. ©Joyce Hays, Target Health Inc.

 

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These fresh herbs smell wonderful! So do the sun dried tomatoes! ©Joyce Hays, Target Health Inc.

 

Ingredients For the following 3 parts of this recipe:

 

1) Roasted Mushrooms

 

3 cups Shitake or Cremini or baby Portobello mushrooms

4 Tablespoons red wine vinegar (pinot noir)

3 fresh garlic clove, minced

3 fresh shallot, minced

5 Tablespoons extra virgin olive oil

Pinch black pepper

Pinch pink Himalayan salt (or grind to your taste)

Pinch chili flakes

 

2) Chickpea Batter for the Pancake

 

4 cups dry, ground chickpea flour

4 cups water

1 egg

2 teaspoon shallot, minced

2 Tablespoon Extra Virgin Olive Oil

1 Tablespoon fresh thyme, minced

1 Tablespoon fresh parsley, minced

Pinch black pepper

Pinch pink Himalayan salt (or grind to your taste)

Mushrooms from above

 

3) Sun Dried Tomato Vinaigrette Dressing

 

2 cups sun dried tomatoes, chopped

2 teaspoons minced shallots

1 garlic clove, minced

1 teaspoon minced fresh thyme

4 teaspoon minced fresh basil

2 teaspoon minced fresh parsley

1 cup toasted pine nuts

2 cups Extra Virgin Olive Oil

1 cup aged balsamic vinegar

Pinch black pepper

Pinch pink Himalayan salt (or grind to your taste)

1 or 2 Bunches of fresh arugula

 

Simple salad: Enough fresh arugula for 4 people

 

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Aroma of saut?ed mushrooms  Mmmm ©Joyce Hays, Target Health Inc.

 

Directions For 4 Parts of this Recipe

1)    Make the Mushrooms

 

Preheat oven to 350?F

Clean mushrooms with a damp cloth. Slice the mushrooms and toss all the ingredients (in part one) together to season the mushrooms. Spread out the seasoned mushrooms on a sheet pan and roast on a middle rack of the oven for 15 minutes.

Set aside to cool to room temperature.

 

 

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Chickpea Batter ©Joyce Hays, Target Health Inc.

 

2) Make the Chickpea Pancake Batter

 

Heat a small saute pan over medium heat, then add the oil and the shallots. Cook the shallots until they are translucent, but be careful not to burn them.

 

In large mixing bowl, combine the chickpea flour with the water, whisking well to incorporate and make a smooth batter with no lumps. Add the egg and mix it in well. Add all the herbs for part two. Also, add the shallots from the saut? pan, and mix well. Season with salt & pepper to taste.

 

 

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Cooking the first chickpea pancake. ©Joyce Hays, Target Health Inc.

 

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Sauteed Mushrooms added to the chickpea batter, in the frying pan. ©Joyce Hays, Target Health Inc.

 

3) Now Cook the 4 Chickpea Pancakes-

 

If you have it, use a cast iron skillet or griddle; otherwise, use what you have.

 

Pre-heat the pan over medium-high heat. Spray pan with olive oil or canola spray.

 

Make 4 separate pancakes.

Using a 2 ounce ladle, pour 1/4 of the batter onto the hot pan.

Sprinkle 1/4 of the roasted mushrooms onto the batter when it’s in the pan.

Cook pancake until batter bubbles, and bottom turns golden brown. Flip the pancake over and continue to cook until it is golden brown. Remove and keep warm while you make the next three pancakes, the same way.

 

 

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My dressing came out a little too thick, so I thinned it down with some chicken stock (or broth). ©Joyce Hays, Target Health Inc.

 

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To the chopped arugula, add some of the vinaigrette dressing and toss, just before you serve the chickpea pancake. ©Joyce Hays, Target Health Inc.

 

4) Make the Vinaigrette Dressing

 

Combine all the ingredients except the vinegar in the bowl of a food processor and pulse to combine until it resembles a paste. Scrape the sides of the bowl. Then while food processor is running, slowly drizzle in the vinegar. Add salt & pepper as needed to taste.

 

 

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Next, toss the arugula with the dressing. ©Joyce Hays, Target Health Inc.

 

After the dressing is done, toss it in a bowl, onto 3 cups of chopped arugula (washed and dried first). Set this salad aside.

 

 

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Here’s the first nice and warm pancake done and waiting, for the arugula salad to be added on top, before serving. ©Joyce Hays, Target Health Inc.

 

To Serve: Place the chickpea pancake on an individual plate. Top each pancake with one cup of the arugula salad. Garnish with some extra toasted pine nuts and serve immediately.

 

 

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One serving ©Joyce Hays, Target Health Inc.

 

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Appetizer of olives, roasted red peppers and parmesan cheese cubes ©Joyce Hays, Target Health Inc.

 

We started our meal with icy sauvignon blanc (Cervantes) and some nibbles of olives, cheese and roasted red peppers. Then came my (vegetarian heaven) new recipe. It took a very long time to come up with this dish. I had been experimenting with making one entr?e out of small circles of pita bread and an interesting topping. I have also been using almond flour instead of regular starchy flour for many years. And I love to create meatless yet delicious meals. Somehow, everything came together in this delicious mushroom pancake, using chickpea flour (for a change) instead of almond flour and including salad as a topping for the pancake. I must say, I held my breath, as we raised our forks, and took the first bite. Joyous success! It was delicious! The garlic-y arugula added to the overall medley of flavors in this recipe. I would even go so far as to say, this was consumed like a comfort food. The good news is that comfort foods are usually high in calories; however this dish contains (except for the 1 egg) 99.9% veggies, so that the following morning, I weighed one pound less, attributed to this meal from vegetarian heaven. Jules weighed less also. (I will never resort to pita bread again. I will serve my warm chickpea pancake with hummus and not pita).

 

We were so pleased with this wonderful veggie pancake, that we plan to have it for one meal each week. It’s delicious, very filling, wonderful with wine, and low calorie.

 

This week we saw a play called Airline Highway, at one of the theater clubs we support, Manhattan Theater Club. Our theater club owns the Broadway theater, Samuel J. Friedman Theater and it happens to be my favorite Broadway theater. Excellent ensemble acting in this play – we stayed for a talk-back afterwards, always very stimulating. Several actors from this play are up for Tony Awards, which will be announced Sunday night at the Tony Award Ceremony. Airline Highway happens to be a real highway outside of New Orleans. This play is based on real people living in a rundown motel outside the famous city. We talked to the playwrights’ brother who is also in the play. We had a great time.

 

Aside from the terrible accident, damaging one of our office buildings, (but our company didn’t miss a beat) we had a wonderful week and weekend.Hope you did too!

 

 

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We tried a new Italian white wine – Cervantes. We know we like the Cervantes reds. ©Joyce Hays, Target Health Inc.

 

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When we put the Cervantes in a wine cooler with ice water, the label fell off. You can see we polished off, every last drop. A lovely white with a strong personality.

 

From Our Table to Yours!

 

Bon Appetit!