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January 21, 2019Target Healthy Eating
2 1/2 pounds red new potatoes (about 6 medium), unpeeled (DON'T PEEL) and cut into 1-inch cubes
25 fresh garlic cloves, sliced but not thin slices
3 heaping Tablespoons fresh (not dried) oregano, well chopped
Pinch salt (optional), I didn't use any salt
Pinch black pepper
Pinch chili flakes
1/2 cup extra virgin olive oil
1. Preheat oven to 425 degrees
2. Scrub potatoes, LEAVE THE SKINS ON, then cut into (approx) 1 inch cubes.
3. Wash the fresh oregano, then chop it well.
4. Peel the 25 garlic cloves, then cut them into thick slices
5. In a large roasting pan, combine potato cubes, garlic, oregano and extra virgin olive oil. Stir until potatoes are well-coated, and spread them evenly in pan.
6. Place in oven, and roast until golden brown and crispy, 40 minutes to an hour. (If the potatoes are crowded in the pan, they will take longer to crisp.) Give the potatoes a stir, every once in a while.
7. Remove potatoes and garlic from oven, and transfer to a serving dish. Sprinkle with salt (optional) to taste, and serve immediately.
This veggie side dish is good with beef, poultry, fish, seafood. If you want to go veggie only, serve the roasted potatoes with a Caesar salad, or your own favorite crispy salad, and warm grain bread and/or rolls that you dip in the garlic-y olive oil from the potatoes. You are going to have a fantastic treat with this recipe. Be prepared to want only this dish, until it's quickly disappeared.
We started with some chilled Pouilly-Fuisse and individual spinach pies, I've been experimenting with. Then fried chicken with these roasted potatoes and a crisp salad. For dessert some Brooklyn Blackout Cake, left over from a dinner party.
From Our Table to Yours
Have a Great Week Everyone!
January 21, 2019Regulatory
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive and rare disease of the bone marrow and blood that can affect multiple organs, including the lymph nodes and the skin. It often presents as leukemia or evolves into acute leukemia. The disease is more common in men than women and in patients 60 years and older.
The FDA has approved Elzonris (tagraxofusp-erzs) infusion for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and in pediatric patients, two years of age and older. Prior to this approval, there had been no FDA approved therapies for BPDCN. The standard of care has been intensive chemotherapy followed by bone marrow transplantation.
The efficacy of Elzonris was studied in two cohorts of patients in a single-arm clinical trial. The first trial cohort enrolled 13 patients with untreated BPDCN, and seven patients (54%) achieved complete remission (CR) or CR with a skin abnormality not indicative of active disease (CRc). The second cohort included 15 patients with relapsed or refractory BPDCN. One patient achieved CR and one patient achieved CRc.
Common side effects reported by patients in clinical trials were capillary leak syndrome (fluid and proteins leaking out of tiny blood vessels into surrounding tissues), nausea, fatigue, swelling of legs and hands (peripheral edema), fever (pyrexia), chills and weight increase. Most common laboratory abnormalities were decreases in lymphocytes, albumin, platelets, hemoglobin and calcium, and increases in glucose and liver enzymes (ALT and AST). Health care providers are advised to monitor liver enzyme levels and for signs of intolerance to the infusion. Women who are pregnant or breastfeeding should not take Elzonris because it may cause harm to a developing fetus or newborn baby. The labeling for Elzonris contains a Boxed Warning to alert health care professionals and patients about the increased risk of capillary leak syndrome which may be life-threatening or fatal to patients in treatment.
The FDA granted this application Breakthrough Therapy and Priority Review designation. Elzonris also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases. The FDA granted the approval of Elzonris to Stemline Therapeutics.
January 21, 2019Cardiology
A recent NIH-funded study showed that about 75% of African-American men and women are likely to develop high blood pressure by age 55, compared to 55% of white men and 40% of white women of the same age.
According to an article published in Circulation (10 December 2018), African-Americans with moderate or severe sleep apnea are twice as likely to have hard-to-control high blood pressure when their sleep apnea goes untreated. The findings, may partially explain why African-Americans suffer hypertension at rates higher than any other group, and can point to screening and treatment of sleep apnea as another important strategy for keeping uncontrolled high blood pressure at bay.
While sleep apnea, a common disorder that blocks the upper airways and causes people to stop breathing during sleep, has been linked to an increased risk of high blood pressure in whites, the association in blacks has been largely understudied. The study followed 664 African-Americans with hypertension who were participants in the Jackson Heart Study, the largest investigation of causes of cardiovascular disease in African-Americans. The authors tested the participants for obstructive sleep apnea (the most common kind) with a special device used overnight in the home. Sleep apnea was then classified as unaffected, mild, moderate, or severe based on the number of times a person either partially or completely stopped breathing during sleep. Results showed that more than a quarter of the participants had moderate or severe sleep apnea and that the condition had gone undiagnosed in almost all of them-i.e., 94% of the cases. The remaining participants had either no sleep apnea, or a milder form of it.
The authors also took blood pressure measurements and found that 48% of the participants had uncontrolled high blood pressure, meaning they had the condition even though they took one or two antihypertensive medications. About 14% had resistant hypertension, meaning they had the condition while on three or more antihypertensive medications. Resistant hypertension is more severe than uncontrolled and carries a higher risk for heart disease and death. The authors then compared measures of sleep apnea to categories of blood pressure control. Results showed that study participants with moderate or severe sleep apnea were twice as likely to have resistant hypertension when compared to participants without sleep apnea. Those with severe sleep apnea were 3.5 times as likely to have resistant hypertension compared to participants without sleep apnea. Somewhat unexpectedly, the authors found no association between milder forms of sleep apnea and uncontrolled or resistant hypertension. The results suggest that African-Americans with more severe forms of sleep apnea are at higher risk of having hard-to-treat hypertension. The current study did not explore what proportion of resistant hypertension is attributable to sleep apnea.
The study did not examine the mechanisms by which sleep apnea increases blood pressure, but the authors noted that earlier studies indicated that untreated sleep apnea can cause blood pressure to surge during sleep and remain high during the day when a patient is awake.
January 21, 2019Psychiatry
According to the NIH, it is one thing to detect sites in the genome associated with mental disorders, but it is quite another to discover the biological mechanisms by which these changes in DNA work in the human brain to boost risk. In the first concerted effort to tackle the latter, 15 collaborating research teams of the National Institutes of Health-funded PsychENCODE Consortium leveraged statistical power gained from a large sample of about 2,000 postmortem human brains. The teams published their findings in seven research articles, spotlighted on the cover of a psychiatric genomics special issue of Science - along with two in Translational Medicine and one in Science Advances - on Dec. 14, 2018. In addition, the consortium is sharing their data with the research community via the online PsychENCODE Knowledge Portal.
Applying newly uncovered secrets of the brain's molecular architecture, the authors developed an artificial intelligence model that's six times better than previous ones at predicting risk for mental disorders. They also pinpointed several hundred previously unknown risk genes for mental illnesses and linked many known risk variants to specific genes. According to the authors, for the first time, there is a beginning of an understanding of the biology, the molecular pathophysiology, of schizophrenia, bipolar disorder and autism spectrum disorder (ASD).
For the study, both in brain tissue and in single cells, the authors examined patterns of gene expression (transcriptome), marks of gene regulation (epigenome), as well as genetic variants linked to mental illnesses in genome-wide association studies. The goals of the study included elucidating the mechanisms by which cellular diversity and patterns of gene expression change throughout development, as well as to reveal how neuropsychiatric risk genes are concentrated into distinct co-expression modules and cell types. The implicated variants are mostly small-effect genetic variations that fall within regions of the genome that don't code for proteins, but instead are thought to regulate gene expression and other aspects of gene function. PsychENCODE sought to uncover the specific roles played by these elusive actors at particular time points and places in the developing brain.
The authors examined brain tissue and molecules from prenatal development as well as from people with schizophrenia, bipolar disorder, ASD and typical development - and compared findings with parallel data from non-human primates. They also incorporated data from related NIH initiatives in humans, including ENCODE and GTEx, which enhanced the statistical power of the analysis.
Among the key findings:
-- Gene variants linked to mental illnesses exert more effects when they collectively form modules - groups of co-expressed, communicating genes with related functions - in specific cell types and brain areas, and at specific developmental time points that seem to coincide with the course of illness. For example, ASD-linked modules were seen early in prenatal development - possibly related to the early onset of symptoms - while schizophrenia-linked modules formed later, plausibly accounting for the onset of symptoms in late adolescence or early adulthood.
-- One suspect module (ME37) in particular showed rapid change in a late prenatal transition period. It harbored genes and transcription factors linked to multiple neurodevelopmental disorders, including ASD and schizophrenia, to traits such as neuroticism and IQ - and to key processes, such as the birth of new neurons and epigenetic regulation of gene expression and behaviors including learning and memory.
-- Variability in risk gene expression and cell types peaked during formative stages in early prenatal development and again during the teen years - a pattern also seen in non-human primates.
-- Mental illness risk genes are among genes found to be unique to humans.
-- An artificial intelligence computational learning model that integrated postmortem brain-derived data increased researchers' ability to retrospectively predict a person's risk for developing a mental illness to about 25% better than chance, compared to only about 4% with previous models based on genetic data alone. This multi-omic model integrates postmortem data across the transcriptome, epigenome, and proteome -- in addition to genome data.
-- A module with many genes coding for brain immune cells showed a pattern of dysregulated gene expression linked to mental illnesses - excess expression in ASD and weak expression in schizophrenia and bipolar disorder. This, and other signs, added to evidence linking the disorders to inflammation in the brain.
-- In postmortem brains of people with a mental illness, thousands of RNAs, which are molecules of gene expression, were found to have anomalies.
-- ASD risk gene variants and the regulators they disrupt were highly expressed in organoids, brain-like tissue from human cells growing in a dish, that mimic the cortex during early prenatal development, when modules linked to ASD are active.
January 21, 2019History of Medicine
Daniel Hale Williams (January 18, 1856 - August 4, 1931) was an African-American general surgeon, who in 1893 performed the first documented, successful pericardium surgery in the US. Dr. Williams also founded Chicago's Provident Hospital, the first non-segregated hospital in the US. The heart surgery at Provident, which his patient survived for the next twenty years, is referred to as the first successful heart surgery by Encyclopedia Britannica. In 1913, Dr. Williams was elected as the only African-American charter member of the American College of Surgeons.
At the time that Williams graduated from what is today Northwestern University Medical School, he opened a private practice where his patients were white and black. Black doctors, however, were not allowed to work in American hospitals. As a result, in 1891, Williams founded the Provident Hospital and training school for nurses in Chicago. This was established mostly for the benefit of African-American residents, to increase their accessibility to health care but its staff and patients were integrated from the start. In 1893, Dr. Williams became the first African American on record to have successfully performed pericardium surgery to repair a wound. On July 10, 1893, Williams repaired the torn pericardium of a knife wound patient, James Cornish. Cornish, who was stabbed directly through the left fifth costal cartilage, had been admitted the previous night. Williams decided to operate the next morning in response to continued bleeding, cough and pronounced symptoms of shock. He performed this surgery, without the benefit of penicillin or blood transfusion. He undertook a second procedure to drain fluid. About fifty days after the initial procedure, Cornish left the hospital.
In 1893, during the administration of President Grover Cleveland, Williams was appointed surgeon-in-chief of Freedman's Hospital in Washington, D.C., a post he held until 1898. That year he married Alice Johnson, who was born in the city and graduated from Howard University, and moved back to Chicago. In 1897, he was appointed to the Illinois Department of Public Health, where he worked to raise medical and hospital standards. Williams was a Professor of Clinical Surgery at Meharry Medical College in Nashville, Tennessee and was an attending surgeon at Cook County Hospital in Chicago. He worked to create more hospitals that admitted African Americans. In 1895 he co-founded the National Medical Association for African American doctors,.
Daniel Hale Williams was born in 1856 and raised in the city of Hollidaysburg, Pennsylvania. His father, Daniel Hale Williams Jr. was the son of a Scots-Irish woman and a black barber. His mother was African-American and likely also mixed race. The fifth child born, Williams lived with his parents, a brother and five sisters. His family eventually moved to Annapolis, Maryland. Shortly after when Williams was nine, his father died of tuberculosis. Williams' mother realized she could not manage the entire family and sent some of the children to live with relatives. Williams was apprenticed to a shoemaker in Baltimore, Maryland but ran away to join his mother, who had moved to Rockford, Illinois. He later moved to Edgerton, Wisconsin, where he joined his sister and opened his own barber shop. After moving to nearby Janesville, Wisconsin, Williams became fascinated by the work of a local physician and decided to follow his path. He began working as an apprentice to Dr. Henry W. Palmer, studying with him for two years. In 1880, Williams entered Chicago Medical College. After graduation from Northwestern in 1883, he opened his own medical office in Chicago.
In the 1890s several attempts were made to improve cardiac surgery. On September 6, 1891 the first successful pericardial sac repair operation in the United States of America was performed by Henry C. Dalton of Saint Louis, Missouri. The first successful surgery on the heart itself was performed by Norwegian surgeon Axel Cappelen on September 4, 1895 at Rikshospitalet in Kristiania, now Oslo. The first successful surgery of the heart, performed without any complications, was by Dr. Ludwig Rehn of Frankfurt, Germany, who repaired a stab wound to the right ventricle on September 7, 1896. Despite these improvements, heart-related surgery was not widely accepted in the field of medical science until during World War II. Surgeons were forced to improve their methods of surgery in order to repair severe war wounds. Although they did not receive early recognition for their pioneering work, Dalton and Williams were later recognized for their roles in cardiac surgery. Williams received honorary degrees from Howard and Wilberforce Universities, was named a charter member of the American College of Surgeons, and was a member of the Chicago Surgical Society.
William Harvey (1578-1657) is recognized as the man who discovered and published the first accurate description of the human circulatory system, based on his many years of experiments and observations as a scientist and physician. Harvey had accumulated a mass of irrefutable experimental evidence in support of his dramatic new view, knowing that a tremendous amount of criticism and disbelief would be mounted against his groundbreaking, revolutionary theory of the physiology of blood circulation. Although the majority of the physicians and scientists of his day refused to accept his research, Harvey's discovery and written description of the true functioning of the heart and circulatory system remains as one of the landmark medical textbooks and the foundation of modern physiology.
Most physicians, scientists, and philosophers of 17th century Europe were adherents of Galen's doctrine, which contained several significant errors regarding the movement of blood and the workings of the heart. These were actually quite ancient ideas and notions, still accepted more than 1,400 years after first being postulated by Galen, the Greek physician of Rome. Over time, the dogma of Galen became sacrosanct, even though most of his anatomical knowledge and physiological investigations were based on his studies of monkeys and pigs, because dissections of human bodies were typically not permitted. Galen recognized the usefulness of comparative anatomy for gaining understanding of the human body, and he studied the workings of animal bodies and various structures in some detail. He was a prolific writer and dedicated scientist, venerated for centuries, and long considered to be the authority on medicine and health. Galen and his proponents believed that the circulation of blood began in the gastric and intestinal blood vessels, and was carried to the liver, where it was elaborated by the liver. This venous blood then entered the hepatic vein, which he believed to be the origin of the vena cava, and the descending vena cava transported blood to the lower body, while the ascending branch sent blood to the upper body. As blood entered the right side of the heart, it was thought to pass through invisible pores in the septum that divided the heart, forced into the left ventricle, mixed with air brought in from the lungs by the pulmonary veins, and transformed into the arterial blood. The heart was seen as a type of bellows, expanding when a small volume of blood in the left ventricle was greatly heated by the addition of vital spirits, forcing the heart to expand and draw blood inside. In a similar fashion, the arteries carried this boiled up blood away from the heart to the body, but the blood did not return to the heart. According to Galenic doctrine, the liver was seen as the continual source of new blood, replenishing the blood that was vaporized and converted into waste material, and released from the lungs as soot. As the personal physician of King Charles I and the recipient of the best medical education possible, Harvey was perhaps the preeminent physician in England and perhaps all Europe, and he long doubted the accuracy of many of the facts that the medical profession espoused. Harvey finally published the results of his research in his text Exercitatio anatomica de motu cordis sanguinis in animalius (On the movement of the heart and blood in animals) in 1628. Harvey only accepted as facts those ideas that were supported with repeated experimental evidence, and, as was his nature, he methodically and forcefully exposed the errors of the long held misconceptions about the heart and blood circulation. His new system completely altered the Galenic concept of blood circulation, proving that the heart is a hollow muscle that contracts regularly to provide the single motive force of the blood's movement. He patiently exposed the other unacceptable aspects of Galen's erroneous system, using well-designed experiments that attempted to dispel various falsehoods.
Harvey was able to fully illustrate the actions of the heart, its chambers and valves, as well as clarify the long misunderstood pattern of pulmonary circulation. Harvey concluded that blood moved from the right ventricle into the lungs via the renamed pulmonary artery (correctly changed from pulmonary vein), which Galen thought carried only air and soot back and forth between the lungs and heart. Harvey properly stated that the blood then returned to the left side of the heart via the pulmonary veins. Harvey would not attempt to answer why the blood traveled to the lungs and back, as he did not have any knowledge about gas exchange during pulmonary respiration. Harvey also fully detailed the systematic circulatory system, tracing the flow of blood through the arteries coursing within the body, returning to the heart via the network of veins. He also artfully illustrated the workings of the valves in veins, proving the one-way circulation of venous blood towards the heart, and refuting the notion that the valves were actually reinforcement structures that prevented the over expansion of the veins as blood was forced through, as his university mentor Girolamo Fabrici (1537-1619) had taught. When Harvey found that his experimental evidence could not provide an answer to a question, he did not attempt to evoke rational mysticism by way of explanation, as in the case of how and why blood in the arteries eventually passed into the veins and traveled back to the heart. Harvey could not see the capillaries found in tissues and had no way of addressing blood's metabolic function, but he did anticipate the presence of the anastomoses between arteries and veins and the possibility of blood providing nourishment or some other function. These blood-carrying structures were too small to be seen with the naked eye, but Harvey strongly believed that their existence would be detected eventually. Later, in the seventeenth century, both Marcello Malpighi (1628-1694) and Anton van Leeuwenhoek (1632-1723) would use the improved microscope to describe the presence of capillaries and blood cells in a wide variety of animals, including humans.
Harvey worked long and hard to create what became the starting point for modern mammalian physiology. His still impressive research is also seen as the first milestone of modern experimental science, and can be used as an example of how to perform experimental scientific research. Being the person to inaugurate two new scientific systems that condemned long-held beliefs, Galen's doctrine and the school of rationalism, Harvey must have recognized the likelihood of dire consequences. The derision and attack of the medical community was inevitable, and accusations and charges made by the Church and legal authority would not be without common precedence. New ideas that change entire systems of knowledge were always viewed with skepticism and apprehension, often evoking harsh criticisms and accusations of quackery. Harvey risked being rejected as foolishly misled or even acquiring the stigma of being labeled a quack. After his publication, his private practice suffered a great decline as a result of the intense controversy he created, but Harvey steadfastly maintained himself and his convictions during the controversy.
As a professor and physician, Harvey advocated the use of comparative techniques to study anatomy and physiology, recognizing the advantages and practicality of using the animals that were available for study. Harvey worked with fish, amphibians and reptiles, birds, mammals, and humans, experimenting and comparing where ever possible, building his theory methodically and with great care. In the case of the action of the heart, he found that in many lower animals, the heart's movement was slower and could be seen more readily, and he used the slower heart rate of chilled fish and amphibians for analysis and comparison to the faster mammalian heart. Many of Harvey's experiments would later be described as direct, artfully simple, and beautifully designed. Throughout his career, Harvey emphasized the experimental method of scientific research, which would become a basic tenet of modern science. Harvey would not accept any rationalism or mysticism as evidence for determining how or why something occurred in the body. Only experimental evidence that was repeated many times, using as many different animal examples as possible, could be considered in reaching any conclusions. Harvey avoided having any preconceived ideas about his experiments, rather, he gathered his evidence, analyzed the data, and then created a scientific hypothesis that he knew he could further test directly with more experiments. He built his new theory of blood circulation in a straightforward analysis of each step in the process, gathering extensive experimental data to confirm every aspect. He anticipated potential criticisms and designed more experiments to refute future controversies. His reliance on the experimental method was in contrast to many scientists and philosophers of his time, who instead employed rationalism or dialectics to essentially think their way through a question or problem, often following anecdotal or casual observational information, and using little to no experimental evidence. This type of analysis typically evoked the presence of unseen forces or principles, usually a supernatural or divine phenomenon. Harvey tended to avoid this kind of philosophical reasoning, referred to as ratiocination.
The adherents of the Galenic doctrine did not surrender to the new physiology quietly, but rather a great controversy raged for many years and long after Harvey's death. Harvey, humble and dignified as a person and in his work, was patient and understanding when dealing with his critics and doubting contemporaries. Occasionally he would answer his critics with a direct letter or a publication that would add to or reiterate the existence of the relevant experimental evidence that confirmed his conclusions. Nevertheless, recognition of the truths that he illuminated did not come in his lifetime. Eventual acceptance came much later, when scientists developed new tools of investigation and better understanding of modern science. Harvey is remembered and revered both as the founder of modern physiology and a champion of modern experimental science.
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January 21, 2019Quiz
Blood vessels are the part of the circulatory system, and microcirculation, that transports blood throughout the human 1) ___. These vessels are designed to transport nutrients and oxygen to the tissues of the body. They also take waste and carbon dioxide and carry them away from the tissues and back to the heart. Blood vessels are needed to sustain life as all of the body's tissues rely on their functionality. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and the tissues; and the 2) ___, which carry blood from the capillaries back toward the heart. The word vascular, meaning relating to the blood vessels, is derived from the Latin vas, meaning vessel. A few structures (such as cartilage and the lens of the eye) do not contain blood vessels.
Blood vessels function to transport 3) ___. In general, arteries and arterioles transport oxygenated blood from the lungs to the body and its organs, and veins and venules transport deoxygenated blood from the body to the lungs. Blood vessels also circulate blood throughout the circulatory system. Oxygen (bound to hemoglobin in red blood cells) is the most critical nutrient carried by the blood. In all arteries apart from the pulmonary artery, hemoglobin is highly saturated (95-100%) with oxygen. In all veins apart from the pulmonary vein, the saturation of hemoglobin is about 75%. (The values are reversed in the pulmonary circulation.) In addition to carrying 4) ___, blood also carries hormones, waste products and nutrients for cells of the body.
Blood vessels do not actively engage in the transport of blood (they have no appreciable peristalsis). Blood is propelled through arteries and arterioles through pressure generated by the 5) ___. Blood vessels also transport red blood cells which contain the oxygen necessary for daily activities. The amount of red blood cells present in your vessels has an effect on your health. Hematocrit tests can be performed to calculate the proportion of red blood cells in your blood. Higher proportions result in conditions such as dehydration or heart disease while lower proportions could lead to anemia and long-term blood loss. Permeability of the endothelium is pivotal in the release of nutrients to the tissue. It is also increased in inflammation in response to histamine, prostaglandins and interleukins, which leads to most of the symptoms of inflammation (swelling, redness, warmth and pain).
Blood vessels play a huge role in virtually every medical condition. Cancer, for example, cannot progress unless the tumor causes formation of new blood vessels, which is called 6) ___, to supply the malignant cells' metabolic demand. Atherosclerosis, the formation of lipid lumps (atheromas) in the blood vessel wall, is the most common cardiovascular disease, the main cause of death in the Western world.
Blood vessel permeability is increased in inflammation. Damage, due to trauma or spontaneously, may lead to hemorrhage due to mechanical damage to the vessel endothelium. In contrast, occlusion of the blood vessel by atherosclerotic plaque, by an embolized blood clot or a foreign body leads to downstream ischemia (insufficient blood supply) and possibly necrosis. Vessel occlusion tends to be a positive feedback system; an occluded vessel creates eddies in the normally laminar flow or plug flow blood currents. These eddies create abnormal fluid velocity gradients which push blood elements such as cholesterol or chylomicron bodies to the endothelium. These deposit onto the arterial walls which are already partially occluded and build upon the blockage. The most common disease of the blood vessels is hypertension or high blood pressure. This is caused by an increase in the 7) ___ of the blood flowing through the vessels. Hypertension can lead to more serious conditions such as heart failure and stroke. To prevent these diseases, the most common treatment option is medication as opposed to surgery. Aspirin helps prevent blood clots and can also help limit inflammation.
Scientists have managed to grow perfect human blood vessels as organoids in a petri dish for the first time. The breakthrough engineering technology dramatically advances research of vascular diseases like diabetes, identifying a key pathway to potentially prevent changes to blood vessels -- a major cause of death and morbidity among those with diabetes. The breakthrough engineering technology, outlined in a new study published this week in Nature, dramatically advances research of vascular diseases like diabetes, identifying a key pathway to potentially prevent changes to blood vessels -- a major cause of death and morbidity among those with diabetes. An organoid is a three-dimensional structure grown from stem 8) ___ that mimics an organ and can be used to study aspects of that organ in a petri dish. Being able to build human blood vessels as organoids from stem cells is a game changer.
Every single organ in our body is linked with the circulatory system. This could potentially allow researchers to unravel the causes and treatments for a variety of vascular diseases, from Alzheimer's disease, cardiovascular diseases, wound healing problems, stroke, cancer and, of course, diabetes. Diabetes affects an estimated 420 million people worldwide. Many diabetic symptoms are the result of changes in blood vessels that result in impaired blood circulation and oxygen supply to tissues. Despite its prevalence, very little is known about the vascular changes arising from diabetes. This limitation has slowed the development of much-needed treatment. To tackle this problem, a scientific team developed a groundbreaking model: three-dimensional human blood vessel organoids grown in a petri dish. These so-called vascular organoids can be cultivated using stem cells in the lab, strikingly mimicking the structure and function of real human blood vessels. When researchers transplanted the blood vessel organoids into mice, they found that they developed into perfectly functional human blood vessels including arteries and capillaries. The discovery illustrates that it is possible not only to engineer blood vessel organoids from human stem cells in a dish, but also to grow a functional human vascular system in another species. What is so exciting about this research, is that there was success in making real human blood vessels out of stem cells. The resulting organoids resemble human capillaries to a great extent, even on a molecular level, which can now be used to study blood vessel diseases directly on human tissue. One feature of 9) ___ is that blood vessels show an abnormal thickening of the basement membrane. As a result, the delivery of oxygen and nutrients to cells and tissues is strongly impaired, causing a multitude of health problems, such as kidney failure, heart attacks, strokes, blindness and peripheral artery disease, leading to amputations. When the authors exposed the blood vessel organoids to a diabetic environment in a petri dish, a massive expansion of the basement membrane in the vascular organoids was observed. This typical thickening of the basement membrane is strikingly similar to the vascular damage seen in diabetic patients. The authors searched for chemical compounds that could block thickening of the blood vessel 10) ___. They found none of the current anti-diabetic medications had any positive effects on these blood vessel defects. However, they did discover that a secretase inhibitor, a type of enzyme in the body, prevented the thickening of the blood vessel walls, suggesting, at least in animal models, that blocking secretase could be helpful in treating diabetes. This research could enable the identification of underlying causes of vascular disease, and has the potential to develop and test new treatments for patients with diabetes. Sources: Nature, 2019 DOI: 10.1038/s41586-018-0858-8; ScienceDaily.com; Wikipedia
ANSWERS: 1) body; 2) veins; 3) blood; 4) oxygen; 5) heartbeat; 6) angiogenesis; 7) pressure; 8) cells; 9) diabetes; 10) walls
January 21, 2019What's New
Target Health, Champions of the Paperless Clinical Trial™, is committed to effective and efficient 21st century clinical trials, where digital records replace the paper records of the past. And yes, we always do what we say.
A new paper, entitled Query Effectiveness in Light of Risk-based Monitoring (RBM), was just published in Data Basics (Winter 2018). The co-authors are Imogene McCanless Dunn (vTv Therapeutics); Michelle Nusser-Meany (Mutare Lifesciences) and Vadim Tantsyura, Yong Joong Kim, Timothy Cho and Jules Mitchel (Target Health Inc.). The publication uses data derived from a study where direct data entry at the time of the patient encounter occurred. And as icing on the cake, the product was recently approved by FDA.
The following is abstracted from the paper:
Query management within a clinical trial is a standardized process utilized by data management and clinical operations. The resources and costs associated with query management are not trivial, as querying is a long, multi-step process that involves many individuals and sites. Unfortunately, multitudes of queries that have no impact on the study performance or conclusion, which then inflates the overall cost of studies, is commonplace. In order to reduce costs and improve efficiencies, the question can be asked as to whether an effective query be differentiated from a noneffective query? The Query Effectiveness Ratio (QER), defined as the ratio of the number of queries leading to change divided by the total number of queries issued may be such a solution.
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.
Joyce Hays, Founder and Editor in Chief of On Target
Jules Mitchel, Editor
January 14, 2019Target Healthy Eating
Visit the Target Health Eating Website to see all of the fantastic recipes since 2012
One 8-ounce container tofutti (soybean cream cheese)
Pinch black pepper, (grind to your taste)
Pinch salt (optional)
2 garlic cloves, juiced
1 teaspoon lemon zest
1 Tablespoon sherry (optional)
1/2 cup extra virgin olive oil (best olive oil)
1 teaspoon agar
2 Tablespoons chopped onion
1.5 to 2 lbs. shrimp, shelled, deveined, and cooked
Parsley, chopped for garnish only
Add all ingredients except shrimp to a large food processor. Process until well mixed. Drop in shrimp and process until either pureed or chopped to desired consistency. This recipe can be pureed to the consistency of butter or left with chunky pieces of shrimp. Garnish with a few little flakes of chopped parsley. Serve on crackers as an appetizer or on baguettes or on circles of cucumber, or fill pieces of celery (from celery hearts) with the shrimp butter. You could also make pumpernickel circles with a cookie cutter, and top with this dip. Or consider filling tomatoes with the shrimp salad.
As the photo below shows, this past Wednesday, I bought 2 large ugli tomatoes (or 2 large beefsteak tomatoes). Wash the tomatoes well, and then scoop out the insides of the tomatoes and fill them with the shrimp mixture (save the tomato for marinara sauce or soup). Make a salad plate for each shrimp/tomato and serve them on one lettuce leaf (romaine lettuce), along with quartered Italian bread, which I toasted with one quick swipe of a pastry brush dipped in our best extra virgin oil. Chop fresh parsley for garnish. We each had one tomato filled, as a beginning appetizer or salad course.
I removed the peppers from the oven, let them cool for 30+ minutes, then stuffed them with the shrimp salad. If you wanted smaller servings, do the following: just before putting in oven, cut each pepper in half. Roast for 30+ minutes, remove, cool and fill each pepper section with the shrimp salad. Arrange each section on a plate with a lettuce leaf and crackers. Garnish with chopped parsley.
From Our Table to Yours
Have a Great Week Everyone!
January 14, 2019Regulatory
The FDA has approved Ultomiris (ravulizumab) injection for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH), a rare and life-threatening blood disease. Ultomiris is a long-acting complement inhibitor that prevents hemolysis, and uses a novel formulation so patients only need treatment every eight weeks, without compromising efficacy.
PNH is a rare acquired disorder that leads to the rupture or destruction of red blood cells (hemolysis). Patients with PNH are missing a certain protein that normally protects red blood cells from being destroyed by the patient's immune system. Patients with PNH have sudden, recurring episodes where red blood cells are prematurely destroyed which may be triggered by stresses on the body, such as infections or physical exertion. During these episodes, the following symptoms may occur: severe anemia, profound fatigue, shortness of breath, intermittent episodes of dark colored urine, kidney disease or recurrent pain. PNH can occur at any age, although it is most often diagnosed in young adulthood.
The efficacy of Ultomiris was studied in a clinical trial of 246 patients who previously had not been treated for PNH (treatment naive), who were randomized to be treated with Ultomiris or eculizumab, the current standard of care for PNH. The results of the trial demonstrated that Ultomiris had similar results to eculizumab (non-inferior) - patients did not receive a transfusion and had similar incidence of hemolysis measured by the normalization of LDH levels in patients' blood (lactate dehydrogenase, or LDH, is an enzyme required during the process of turning sugar into energy in the body's cells). In addition, Ultomiris was studied in a second clinical trial of 195 patients with PNH who were clinically stable after having been treated with eculizumab for at least the past six months. These patients were randomly selected to be treated with Ultomiris or to continue eculizumab. Ultomiris again demonstrated similar effects to eculizumab (non-inferior) based on several clinical measures including hemolysis and avoiding transfusion.
Common side effects reported by patients in clinical trials were headache and upper respiratory infection. Health care providers are advised to use caution when administering Ultomiris to patients with any other systemic infection.
The prescribing information for Ultomiris includes a Boxed Warning to advise health care professionals and patients about the risk of life-threatening meningococcal infections and sepsis. Health care providers are advised to comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients with complement deficiencies. Patients should be immunized with meningococcal vaccines at least two weeks prior to administering the first dose of Ultomiris, unless the risks of delaying treatment outweigh the risks of developing a meningococcal infection. Patients and health care providers are also advised that vaccination reduces, but does not eliminate, the risk of meningococcal infection. Patients should be monitored for early signs of meningococcal infections and evaluated immediately if infection is suspected. Ultomiris is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Ultomiris must be dispensed with a patient Medication Guide that describes important information about the drug's uses and risks.
The FDA granted this application Priority Review designation. Ultomiris also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.
The FDA granted the approval of Ultomiris to Alexion Pharmaceuticals.
January 14, 2019Psychiatry
According to the Centers for Disease Control and Prevention, in 2016 alone, sadly more than 6,000 youth in the United States under the age of 25 died by suicide. Studies have found that a majority of youth who died by suicide visited a health care provider or medical setting in the month prior to killing themselves. Thus, the interactions of these youth with the health care system make medical settings an ideal place for positioning suicide intervention efforts.
According to an article published online in Psychosomatics (22 September 2018), a new report provides guidance on how to implement universal suicide risk screening of youth in medical settings. The report describes a way for hospitals to address the rising suicide rate in a way that is flexible and mindful of limited resources.
In 2007, The Joint Commission (TJC) released a National Patient Safety Goal requiring that all behavioral health patients who present to psychiatric and general hospitals be screened for suicide risk. However, upon examining the data, it was discovered that over a quarter of hospital suicides occur on non-behavioral health units, and at-risk patients were passing through emergency departments, inpatient medical units, and outpatient clinics undetected. This realization led TJC, in 2016, to recommend that all patients presenting to medical settings be screened for suicide risk.
While good practice, universal screening can present a strain on the resources of hospitals and other health care facilities the report presents a new three-tiered clinical pathway system as a flexible and resource-conscious way to implement universal suicide risk screening within pediatric health care settings. The system was created by an international subcommittee of the Pathways in Clinical Care workgroup from within the Physically Ill Child committee of the American Academy of Child and Adolescent Psychiatry.
The clinical pathway model consists of three main components, the first of which is an initial screen of all youth using the NIMH IRP-created Ask Suicide-Screening Questions (ASQ) tool. The ASQ is the first screening tool developed specifically to detect suicide risk in pediatric medical patients, is available in 14 languages, and takes about 20 seconds to administer. The second tier of screening is the most critical step and calls for a brief suicide safety assessment (BSSA), which takes about 10-15 minutes to administer. This measure is used to classify a person's risk of suicide (low risk, high risk, or imminent risk) based on survey responses and clinical judgment, guiding the clinician's decision for next steps. The third tier of screening, if deemed necessary during the BSSA, involves a full comprehensive safety evaluation by a licensed mental health provider. The goal of this assessment is to address safety issues and establish an intervention plan.
Decisions about patient care are made at each of the three assessment stages and are dependent on clinical insight in combination with responses to the surveys.
The clinical pathway model presented in this report is accompanied by a variety of resources to help health care settings implement the outlined model (e.g. the ASQ Toolkit). It is hoped that the clinical pathways model described in this report can be used in health care settings to implement universal screening for youth in an effective manner-a manner that will help identify youth at risk for suicide and save lives.