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April 19, 2021Target Healthy Eating
1 cauliflower (the larger the better), broken into bite-size florets.
1 teaspoon chili powder
3/4 cups cold water
Extra virgin olive oil or peanut oil (for frying) or canola oil
2 anchovy fillets + 2 garlic cloves mashed into a paste.
1/4 cup almond flour
1 and 1/2 corn starch
Different ingredients for sweet & sour sauce
1 onion, finely chopped
4 cloves garlic, finely chopped
2 anchovy fillets + 2 garlic cloves, mashed into a paste
2 teaspoons low sodium soy sauce
1 Tablespoon ketchup or tomato paste
2 Tablespoons honey
1/2 teaspoon corn starch
1/2 cup water (use 1/4 cup at a time)
1 teaspoon chili powder ( or slightly less spicy, add 2 big pinches chili flakes)
2 Tablespoons extra virgin olive oil or canola oil or peanut oil
Pinch black pepper (to your taste)
Bunch scallions, finely chopped (or chives finely chopped)
Directions for Frying Cauliflower
1. Cut cauliflower in half & then in quarters. Pull bite-size florets, apart and put into a large bowl.
2. In large bowl, put cauliflower florets and fill bowl with hot water to cover the florets. Cover the bowl and keep on counter for 15 minutes. Then using a colander, pour florets, so water drains out. Set aside colander with florets and pat dry before dipping them into batter.
3. While cauliflower sits in the bowl of water, chop the scallions well, then set aside.
4. If you haven't already made it, make a paste out of the anchovies and garlic cloves, in a mortar & pestle.
5. In a second wide bowl, add the almond flour, cornstarch and chili powder and stir to combine.
6. Next, to the dry ingredients, add the anchovy/garlic paste you made earlier. Stir to combine well. Now, add a little water at a time, to make the batter the right consistency. Be sure to add the water very slowly, so you have time to judge the thickness of the batter. You want it to be like pancake batter or cake batter.
7. Take out the pan you're using to fry the cauliflower and add the oil. Turn heat to medium high.
8. Now, dip the cauliflower florets, one by one, into the batter, cover all sides. Then fry in pan. Use tongs gingerly and be sure all sides of the floret are cooked and are crisp and golden. When done, remove and place on paper towel to drain the oil. You can fry many at one time, but only one layer at a time.
Directions for Sauce
1. In pan that can go from stove to table (from cookware to serve ware), heat the oil over medium high heat.
2. Add the anchovy/garlic paste you made earlier, then add the onion, the chopped garlic and combine with the paste.
3. Lower the heat and add either the chili powder or the pinches of chili flakes, black pepper and mix all together well.
4. Add the soy sauce, ketchup or tomato paste, and honey. Mix well. Keep heat on simmer and cover.
5. In a small bowl, add the cornstarch and 1/4 cup cold water. Mix well until this mixture (called a slurry) is smooth with no lumps.
6. Add your slurry plus the other 1/4 cup cold water to the sauce and turn the heat back up to medium high. Bring this mixture to a boil, then lower heat to a slow bubble for 5 minutes. The goal here is to reduce the liquid slightly and thicken the sauce.
7. Finally, slowly add the crispy cauliflower florets to the pan with sauce. Very slowly, coat the cauliflower. Go slow, in coating each floret. You don't want to mistakenly mash the cauliflower or chip off any of the golden crispy crust by mixing the sauce with the cauliflower too quickly. Mix, here, in slow motion.
8. Now, you're ready to bring this delicious cauliflower to the table, so sprinkle some finely chopped scallions (or chives) over the florets and serve while nice and hot.
We started our dinner with small slices of quiche. The entree was Sweet & Sour Cauliflower, over rice, with roast chicken and a crisp salad. Fresh fruit with a little cheese was dessert. We served Beaujolais and chilled Sauvignon Blanc.
Here's some music that was in the background (from one of many playlists, I have compiled). This is wonderful music for relaxation and meditation. Try, listening, if you have trouble going to sleep. For my dear husband and me, music has helped us get through the Covid-19 pandemic, in one (relatively sane) piece.
Lang Lang playing Frederick Chopin, Piano Concerto #1 (Larghetto only)
You can carry on, the torch of peace and brotherhood and simply live by the Golden Rule!
From Our Table to Yours
Have a Great Week Everyone!
April 19, 2021Regulatory
Multiple myeloma is an uncommon type of blood cancer in which abnormal plasma cells build up in the bone marrow and form tumors in many bones of the body. This disease keeps the bone marrow from making enough healthy blood cells, which can result in low blood counts. Myeloma can also damage the bones and the kidneys and weaken the immune system. The exact cause of multiple myeloma is unknown. According to the National Cancer Institute, myeloma accounted for approximately 1.8% (32,000) of all new cancer cases in the United States in 2020.
The FDA has approved Abecma (idecabtagene vicleucel), a cell-based gene therapy to treat adult patients with multiple myeloma who have not responded to, or whose disease has returned after, at least four prior lines (different types) of therapy. Abecma is the first cell-based gene therapy approved by the FDA for the treatment of multiple myeloma.
Abecma is a B-cell maturation antigen (BCMA)-directed genetically modified autologous chimeric antigen receptor (CAR) T-cell therapy. Each dose of Abecma is a customized treatment created by using a patient's own T-cells, which are a type of white blood cell, to help fight the myeloma. The patient's T-cells are collected and genetically modified to include a new gene that facilitates targeting and killing myeloma cells. Once the cells are modified, they are infused back into the patient.
The safety and efficacy of Abecma were established in a multicenter study of 127 patients with relapsed myeloma (myeloma that returns after completion of treatment) and refractory myeloma (myeloma that does not respond to treatment), who received at least three prior antimyeloma lines of therapy. About 88% of patients in the study group had received four or more prior lines of antimyeloma therapy. Overall, 72% of patients partially or completely responded to the treatment. Of those studied, 28% of patients showed complete response - or disappearance of all signs of multiple myeloma, and 65% of this group remained in complete response to the treatment for at least 12 months.
In terms of safety, the label carries a boxed warning for, cytokine release syndrome (CRS), hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS), neurologic toxicity, and prolonged cytopenia, all of which can be fatal or life-threatening. CRS and HLH/MAS are systemic responses to the activation and proliferation of CAR-T cells causing high fever and flu-like symptoms, and prolonged cytopenia is a drop in the number of a certain blood cell type for an extended period of time. The most common side effects of Abecma include CRS, infections, fatigue, musculoskeletal pain, and a weakened immune system. Side effects from treatment usually appear within the first one to two weeks after treatment, but some side effects may occur later. Patients with multiple myeloma should consult with their health care professionals to determine whether Abecma is an appropriate treatment for them.
Because of the risk of CRS and neurologic toxicities, Abecma is being approved with a risk evaluation and mitigation strategy which includes elements to assure safe use. The FDA is requiring that hospitals and their associated clinics that dispense Abecma be specially certified and staff involved in the prescribing, dispensing or administering of Abecma are trained to recognize and manage CRS and nervous system toxicities and other side effects of Abecma. Also, patients must be informed of the potential serious side effects and of the importance of promptly returning to the treatment site if side effects develop after receiving Abecma. To further evaluate the long-term safety, the FDA is also requiring the manufacturer to conduct a post-marketing observational study involving patients treated with Abecma.
Abecma was granted Orphan Drug and Breakthrough Therapy designations by the FDA. Orphan Drug designation provides incentives to assist and encourage the development of drugs for rare diseases. Breakthrough Therapy designation is a process designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s). Breakthrough Therapy designation was granted based on sustained responses observed in patients with relapsed and refractory myeloma. Drugs approved under expedited programs, such as Breakthrough Therapy designation, are held to the same approval standards as all other FDA approvals.
The FDA granted approval of Abecma to Celgene Corporation, a Bristol Myers Squibb company.
April 19, 2021COVID-19
When variants of SARS-CoV-2 (the virus that causes COVID-19) emerged in late 2020, concern arose that they might elude protective immune responses generated by prior infection or vaccination, potentially making re-infection more likely or vaccination less effective. To investigate this possibility, researchers from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and colleagues analyzed blood cell samples from 30 people who had contracted and recovered from COVID-19 prior to the emergence of virus variants. The study, published in Open Forum Infectious Diseases (30 March 2021) found that one key player in the immune response to SARS-CoV-2 -- the CD8+ T cell -- remained active against the virus. The research team was led by NIAID's Andrew Redd, Ph.D., and included scientists from Johns Hopkins University School of Medicine, Johns Hopkins Bloomberg School of Public Health and the Immunomics-focused company, ImmunoScape.
The authors asked the question whether CD8+ T cells in the blood of recovered COVID-19 patients, infected with the initial virus, could still recognize three SARS-CoV-2 variants: B.1.1.7, which was first detected in the United Kingdom; B.1.351, originally found in the Republic of South Africa; and B.1.1.248, first seen in Brazil. Each variant has mutations throughout the virus, and, in particular, in the region of the virus' spike protein that it uses to attach to and enter cells. Mutations in this spike protein region could make it less recognizable to T cells and neutralizing antibodies, which are made by the immune system's B cells following infection or vaccination. Although details about the exact levels and composition of antibody and T-cell responses needed to achieve immunity to SARS-CoV-2 are still unknown, researchers have assumed that strong and broad responses from both antibodies and T cells are required to mount an effective immune response. CD8+ T cells limit infection by recognizing parts of the virus protein presented on the surface of infected cells and killing those cells.
In the study of recovered COVID-19 patients, it was determined that SARS-CoV-2-specific CD8+ T-cell responses remained largely intact and could recognize virtually all mutations in the variants studied. While larger studies are needed, the authors noted that their findings suggest that the T cell response in convalescent individuals, and most likely in vaccinees, are largely not affected by the mutations found in these three variants, and should offer protection against emerging variants.
The authors stressed that optimal immunity to SARS-CoV-2 likely requires strong multivalent T-cell responses in addition to neutralizing antibodies and other responses to protect against current SARS-CoV-2 strains and emerging variants. They stressed the importance of monitoring the breadth, magnitude and durability of the anti-SARS-CoV-2 T-cell responses in recovered and vaccinated individuals as part of any assessment to determine if booster vaccinations are needed.
April 19, 2021Ophthalmology
An estimated 30 million Americans have diabetes, which can cause blood vessel abnormalities, including the growth of new blood vessels in the eye. In the early stages of diabetic retinopathy, called non-proliferative diabetic retinopathy, changes in the eye's blood vessels are visible to clinicians but generally do not affect sight. In the advanced stages, people can develop proliferative diabetic retinopathy, where retinal blood vessels grow abnormally, and/or diabetic macular edema, where fluid leaks out of the retinal blood vessels. Both can lead to vision loss and blindness. Treatment, such as with anti-VEGF drugs, can slow or prevent vision loss in people with proliferative diabetic retinopathy or diabetic macular edema, if treatment occurs promptly.
According to an article published in JAMA Ophthalmology (30 March 2021), a clinical trial from the Network has demonstrated that early treatment with anti-vascular endothelial growth factor (VEGF) injections slowed diabetic retinopathy. However, two years into the four-year study, the early treatment's effect on vision - including changes in visual acuity and vision loss - was similar to standard treatment, which usually begins only after the onset of late disease.
In this study, subjects with non-proliferative diabetic retinopathy were randomly assigned at baseline to receive either injections of Eylea (aflibercept) or a sham injection. They were examined at one, two, and four months, and then every four months for two years, receiving Eylea or sham injection at each visit. The authors tracked the subject's visual acuity and the severity of their diabetic retinopathy. If disease progressed, regardless of whether they were in the treatment or sham group, participants were given Eylea more frequently as is given in standard practice. If their condition did not improve with additional anti-VEGF treatment, participants could be given treatments such as laser photocoagulation or surgery if necessary.
The study included 328 participants (399 eyes). Results showed that after two years of treatment, the rate of proliferative diabetic retinopathy development was 33% in the control group, compared with 14% in the treatment group. Likewise, the rate of development of diabetic macular edema affecting vision was 15% in the control group, compared with 4% in the treatment group. However, loss of visual acuity was essentially the same between the two groups at two years, suggesting that standard treatment at the appearance of proliferative diabetic retinopathy or diabetic macular edema affecting vision is sufficient to prevent further vision loss at this time point.
April 19, 2021History of Medicine
Michael Thomas Osterholm (born March 10, 1953) is an American epidemiologist, regents professor, and director of the Center for Infectious Disease Research and Policy at the University of Minnesota. On November 9 he was named a member of President-elect Joe Biden's COVID-19 Advisory Board.
Michael Osterholm was born in Waukon, Iowa, the son of a newspaper photographer. He graduated from Luther College in 1975 with a B.A. in biology and political science and received his M.S. and Ph.D. in environmental health and his M.P.H. in epidemiology from the University of Minnesota.
From 1975 to 1999, Osterholm served in various roles at the Minnesota Department of Health (MDH), including as state epidemiologist and Chief of the Acute Disease Epidemiology Section from 1984 to 1999. At the MDH, Osterholm strengthened the department's role in infectious disease epidemiology, notably including numerous foodborne disease outbreaks, the association between tampons and toxic shock syndrome, and the transmission of hepatitis B and human immunodeficiency virus (HIV) in healthcare workers. Other work included studies regarding the epidemiology of infectious diseases in child-care settings, vaccine-preventable diseases (particularly Haemophilus influenzae type b and hepatitis B), Lyme disease, and other emerging and reemerging infections.
From 2001 to early 2005, Osterholm served as a Special Advisor to then - Department of Health and Human Services (HSS) Secretary Tommy G. Thompson on issues related to bioterrorism and public health preparedness. In April 2002, he was appointed to the interim management team to lead the Centers for Disease Control and Prevention (CDC), until the appointment of Julie Gerberding as director in July 2002.
Osterholm was the principal investigator and director of the National Institutes of Health (NIH)-supported Minnesota Center of Excellence for Influenza Research and Surveillance (2007-2014) and chaired the Executive Committee of the Centers of Excellence Influenza Research and Surveillance network. He is a past president of the Council of State and Territorial Epidemiologists and served on the CDC's National Center for Infectious Diseases Board of Scientific Counselors from 1992 to 1997. Osterholm also served on the Institute of Medicine (IOM) Forum on Microbial Threats from 1994 to 2011 and has served on the IOM Committee on Emerging Microbial Threats to Health in the 21st Century and the IOM Committee on Food Safety, Production to Consumption. Finally, he was a reviewer for the IOM Report on Chemical and Biological Terrorism.
In March 2017, Osterholm and Mark Olshaker published the critically acclaimed Deadliest Enemy: Our War Against Killer Germs (Little, Brown and Company). The book explores public health emergencies including antimicrobial resistance, emerging infectious disease, and the threat of an influenza pandemic. It proposes a nine-point "battle plan for survival" for dealing with these threats, including solutions to antimicrobial drug resistance. The book also focuses on the epidemiology of HIV/AIDS, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), toxic shock syndrome, Zika, Ebola, bioterrorism, influenza research, and the antivaccine movement. Osterholm describes his book as "part history, part current affairs, and part blueprint for the future". Top of his concerns are influenza pandemics, antibiotic resistance and bioterrorism, combined with "no clear international governance structure for how we are going to deal with these issues". Focusing on major infectious diseases, he highlights the world's vulnerability to their emerging threats. His concerns include the effects of major outbreaks on medicine and vaccine production, should countries where these are produced be affected.
April 19, 2021Quiz
Washing one's hands, is an effective way to prevent the spread of infectious disease.
Primary pathogens cause disease as a result of their presence or activity within the normal, healthy host, and their intrinsic virulence is, in part, a necessary consequence of their need to reproduce and spread. Many of the most common primary pathogens of humans only infect humans. However, many serious diseases are caused by organisms acquired from the environment or that infect non-human hosts.
An 1) _____ is the invasion of an organism's body tissues by disease-causing agents. Infections can be caused by a wide range of pathogens, most prominently bacteria and viruses but also more unusual types. Hosts can fight infections using their immune system. Mammalian hosts react to infections with an innate response, involving inflammation, followed by an adaptive response.
Specific medications used to treat infections include antibiotics, antivirals, antifungals, antiprotozoals, and antihelminthics AKA (2) _____). Infections are caused by infectious agents including:
1. Bacteria (Mycobacterium tuberculosis, Staphylococcus aureus, Escherichia coli, Clostridium botulinum, and Salmonella spp.)
2. Viruses and related agents such as viroids (HIV, Rhinovirus, Lyssaviruses such as Rabies virus, Ebolavirus and SARS-CoV-2)
3. Fungi, further subclassified into: Ascomycota, including 3) _____ such as Candida, filamentous fungi such as Aspergillus, Pneumocystis species, and dermatophytes.
4. Basidiomycota, including the human-pathogenic genus Cryptococcus.
6. Parasites, which are usually divided into:
a. Unicellular organisms (e.g. malaria, Toxoplasma, Babesia)
b. Macroparasites (worms or helminths) including nematodes such as parasitic roundworms and pinworms, tapeworms (cestodes), and flukes (trematodes, such as schistosomiasis)
c. Arthropods such as 4) _____, mites, fleas, and lice.
Symptomatic infections are apparent and clinical, whereas an infection that is active but does not produce noticeable 5) _____ may be called inapparent, silent, subclinical, or occult. An infection that is inactive or dormant is called a latent infection. An example of a latent bacterial infection is latent tuberculosis. Some viral infections can also be latent, examples of latent viral infections are any of those from the Herpesviridae family.
Different terms are used to describe infections. The first is an acute infection in which symptoms develop rapidly and its course can either be rapid or protracted. The next is a chronic infection. A chronic infection is when symptoms develop gradually, over weeks or months, and are slow to resolve. A subacute infection is one in which symptoms take longer to develop than in an acute infection but arise more quickly than a chronic infection. A latent infection is a type of infection that may occur after an acute episode when the organism is present but symptoms are not and after time, the disease can reappear. A focal infection is defined as the initial site of infection from which organisms travel via the 6) _____ to another area of the body.
Opportunistic pathogens can cause an infectious disease in a host with depressed resistance (7) _____) or if they have unusual access to the inside of the body (for example, via trauma). Opportunistic infections may be caused by microbes ordinarily in contact with the host, such as pathogenic bacteria or fungi in the gastrointestinal or the upper respiratory tract, and they may also result from (otherwise innocuous) microbes acquired from other hosts (as in Clostridium difficile colitis) or from the environment as a result of traumatic introduction (as in surgical wound infections or compound fractures). An opportunistic disease requires impairment of host defenses, which may also occur as a result of genetic defects (such as Chronic granulomatous disease), exposure to antimicrobial drugs or immunosuppressive agents (as might occur following poisoning or cancer chemotherapy), exposure to ionizing radiation, or as a result of an infectious disease with immunosuppressive activity (such as with measles, malaria or HIV disease).
A 8) _____ infection is a sequela or complication of that root cause. For example, an infection due to a burn or penetrating trauma as the root cause. Primary pathogens often cause primary infection and often cause secondary infection. Usually, opportunistic infections are viewed as secondary infections since immunodeficiency or injury was the predisposing factor.
Other types of infection consist of mixed, iatrogenic, nosocomial, and community-acquired infection. A mixed infection is an infection that is caused by two or more pathogens. An example of this is Appendicitis, which is caused by Bacteroides fragilis and Escherichia coli. The second is an iatrogenic infection. This type of infection is one that is transmitted from a health care worker to a patient. Nosocomial infections are those that are acquired during a hospital stay. Lastly, a community-acquired infection is one in which the infection is acquired from a whole community.
Infections can be classified by the anatomic location or organ system infected, including:
? 9) _____ tract infection
? Skin infection
? Respiratory tract infection
? Odontogenic infection (an infection that originates within a tooth or in the closely surrounding tissues)
? Reproductive organ infections
? Intra-amniotic infection
Diagnosis of infectious disease is nearly always initiated by medical history and physical examination. More detailed identification techniques involve the culture of infectious agents isolated from a patient. 10) _____ allows identification of infectious organisms by examining their microscopic features, by detecting the presence of substances produced by pathogens, and by directly identifying an organism by its genotype. Other techniques (such as X-rays, CAT scans, PET scans or NMR) are used to produce images of internal abnormalities resulting from the growth of an infectious agent. The images are useful in detection of, for example, a bone abscess or a spongiform encephalopathy produced by a prion.
ANSWERS: 1) infection; 2) worms; 3) yeasts; 4) ticks; 5) symptoms; 6) bloodstream; 7) immunodeficiency; 8) secondary; 9) Urinary; 10) Culture
April 19, 2021What's New
While COVID-19 has created a difficult time for many of us both at home and around the world, had the world at large only followed the experiences of the 1918 pandemic, much pain and suffering would have been mitigated. We have all been homebound but have not skipped a beat and fortunately we are weathering the storm.
In terms of some accomplishments so far this year, a major neurology clinical trial program is underway for Big Pharma which is being managed remotely using our paperless clinical trial software suite, starting with eInformed consent. Two INDs have been opened from our colleagues in China and we continue to expand in the orphan drug space. On a senior level, we want to welcome Bill Duval who has joined Target Health as Chief Operating Officer, and Luis Rojas, PhD as Executive Director, Head of Biostatistics. It is a very exciting time at Target Health as our extraordinary staff, some who have been with us for over 20 years, transition to be part of a global company.
Target Health's staff are dedicated to all aspects of Drug, Biologics, Device and Diagnostic Development, including: Strategic Planning, Regulatory Affairs, Toxicology, Clinical Research, Biostatistics, Data Management and Medical Writing. In addition, Target Health has developed innovative web-based software tools supporting the paperless clinical trial that provides our clients with a significant productivity edge. For more information about Target Health, contact Kathleen Kane Tremmel, Vice President, Business Development. For those who have been working with Warren Pearlson, Director, New Business Development, please continue to do so. Also visit the Target Healthy Eating Website, created by Joyce Hays, founder of Target Health, to see all of the fantastic recipes since 2012.
Joyce Hays, Founder and Editor in Chief of On Target
Dr. Jules T. Mitchel, Editor
January 19, 2021Target Healthy Eating
1 onion, well-chopped
2 Tablespoons fresh parsley, well-chopped
1/2 cup freshly grated parmesan
2 cups almond flour
2 Tablespoons extra virgin olive oil
3 cloves garlic, ground with 3 anchovy fillets = paste
10 more fresh garlic cloves, sliced very thin
1 teaspoon turmeric
1 teaspoon curry
2 pinches chili flakes
1 pinch pepper
1 or 2 large cauliflower heads, cleaned, then broken into florets
1/2 teaspoon baking power
1/2 teaspoon baking soda
2 Tablespoons ricotta
6 or 7 fresh figs, run under cold water, dry with paper towel. Cut in half. Bake in a tin, next to the cauliflower cake
Bunch green grapes, wash, pat dry, drain. Pick off the stems and bake with the figs.
1. Preheat oven to 350-370 degrees, depending on your oven.
2. Do all chopping, slicing, grating etc. now.
3. Boil or steam the cauliflower for 20 minutes, or until soft. Drain well, dry with paper towel and set aside.
4. In a skillet, add extra virgin olive oil and cook the garlic/anchovy paste, onions and extra garlic. Let it cool down and set aside.
5. Get out a medium mixing bowl and add the eggs. Beat the eggs and add the spices. Then, beat in the ricotta.
6. Using a medium or large sieve, held over the mixing bowl, add the flour, baking powder and baking soda. Slowly sift, into the egg mixture, stirring all the time.
7. Add the parmesan into the dough and combine well.
8. Add contents of the skillet, into the dough and combine well.
9. Add the cooked cauliflower into the dough and combine well.
10. Add the chopped parsley into the dough and combine well.
11. Butter a spring-form baking pan.
12. With a spatula, scrape out all the dough from the mixing bowl, into the baking pan.
13. Place pan into a 350 degree oven and bake for 45 minutes.
14. Put the figs and green grapes into a buttered tin and bake along with the cauliflower cake. Serve as garnish with the cake.
Easy Wild Mushroom Sauce
1 pound mixture of 4 different mushrooms (i.e.: white button, baby bella, shitake, cremini), cleaned with damp paper towel then, thinly sliced & chopped a little
1 Tablespoon butter
1 Tablespoon extra-virgin olive oil
1 teaspoon, low sodium soy sauce
1 Onion, very well-chopped
2 garlic cloves, ground with 2 anchovy fillets = paste
6 to 10 more garlic cloves, sliced.
1 Tablespoon flour (any flour you have. I used almond flour)
1 cup broth (chicken, beef, veggie - I used chicken broth. For a deeper flavor, use beef broth)
1/4 cup sour cream
1 teaspoon Worcestershire sauce
1/2 teaspoon Dijon mustard
2 pinches chili flakes
1/2 cup white wine or sherry or brandy (I used sherry)
3/4 cup heavy cream
Garnish: small handful fresh chives, well chopped
1. Get all cleaning, chopping, slicing, measuring, done, so that all you need to do next, is the cooking.
2. In a large skillet, melt the butter and add the soy sauce. Mix the two together. An interesting chemical reaction takes place and a new umami flavor is the result.
3. Add the anchovy/garlic paste to the skillet and cook for a few minutes. You can also just add the anchovies and the sliced garlic to the skillet and mash them in the skillet. Make the paste right there in the skillet. When possible, I like to use anchovies instead of salt. Stir this paste into the butter.
4. Add the olive oil, all the onions and garlic to the skillet. Stir and cook for a few minutes.
5. Add all the chopped and sliced mushrooms. Stir into the mixture and continue cooking.
You can carry on, the torch of peace and brotherhood and simply live by the Golden Rule!
From Our Table to Yours
Have a Great Week Everyone!
January 19, 2021Regulatory
The following is based on an FDA press release.
Advances in scientific knowledge and drug development technology have provided an opportunity for new approaches to drug development, which have contributed to an increase in development and approval of drugs for the treatment of rare/orphan diseases. In the past eight years, the FDA has approved more than twice as many drugs for rare/orphan diseases as in the previous eight years. For genetic diseases, recent approaches to testing and molecular diagnosis have allowed the pinpointing, in some cases, to the exact cause of a patient's disease. Thus, for a patient with a very rare genetic disease, development of a drug product that is tailored to that patient's specific genetic variant may be possible.
Developing these products - also referred to as n of 1 therapies by some because they are designed for a patient population of one person - brings a set of challenges and considerations not seen with the typical drug development process. First, the disease is often rapidly progressing, requiring prompt medical intervention. Therefore, development needs to proceed very quickly to have a chance at helping the individual. Second, drug discovery and development for these drug products may be carried out by academic investigators, rather than by biopharmaceutical or pharmaceutical companies. These investigators may be less familiar with FDA's regulations, policies and practices, and less experienced in interacting with the FDA.
At this time, development of individualized genetic drug products is most advanced for antisense oligonucleotide (ASO) products. Therefore, the FDA has taken the first steps in bringing clarity to this emerging area of individualized drug development by releasing a new draft guidance on investigational new drug (IND) submissions for individualized ASO drug products. The guidance was developed to advise those developing ASO products on an approach to interacting with, and making regulatory submissions to, the FDA. The guidance addresses the following points:
As also discussed in a New England Journal of Medicine editorial in October 2019, FDA is fully aware that this new drug-discovery paradigm raises many ethical and societal issues that will need to be addressed throughout the process. For example, in these situations, the individuals and their families often function more like drug development collaborators than traditional trial participants. Therefore, it is important to discuss with the individual and family members how effectiveness will be measured. It is also important to ensure that the individual and family members understand the parameters for continuing administration of the investigational drug product before emotions influence decisions, and to recognize that some investigational drug products may fail, or worse, lead to unforeseen side effects.
The FDA understands that it will need to work together with the developers of these drug products to bring them safely to patients, and we are willing to engage as needed to address the challenges. For example, for those developing these drug products, it will be important to further understand the required data and information that must be submitted to the FDA so that clinical testing can begin. The FDA is continuing to consider and further develop policy to address some of these issues.
FDA stated that they are optimistic that development of these individualized drug products may spur gene sequencing that leads to the development of additional individualized drug products for the same disease. For this approach to drug development, all of those involved need to determine, collectively, how to effectively bring these drug products to all who need them. If there is the scientific ability to develop drug products for these rare/orphan diseases, there is a need to find ways to bring them to patients while ensuring there is the right balance of risk to benefit. This draft guidance provides clarity on the early development and IND submission process, is the FDA's first step in working with those who are developing these individualized drug products.
January 19, 2021Neurology
Several neurological disorders have been linked to repeat expansions, a type of mutation that results in abnormal repetition of certain DNA building blocks. For example, Huntington's disease occurs when a sequence of three DNA building blocks that make up the gene for a protein called huntingtin repeats many more times than normal. These repeats can be used to predict whether someone will develop the illness and even when their symptoms are likely to appear, because the more repeats in the gene, the earlier the onset of disease. On 4 December 2020, the NIH released results of a study that has made a surprising connection between frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), which opens a potentially new avenue for diagnosing and treating some individuals with FTD or ALS.
For the study, the authors, taking advantage of technology available at the NIH, screened the entire genomes from large cohorts of FTD/ALS patients and compared them to those of age-matched healthy individuals. While several patients had a well-established genetic marker for FTD/ALS, a small subset surprisingly had the same huntingtin mutation normally associated with Huntington's disease. Remarkably, these individuals did not show the classical symptoms of Huntington's but rather those of ALS or FTD. According to the authors, none of these patients' symptoms would have clued their physicians into thinking that the underlying genetic cause was related to the repeat expansion seen in Huntington's disease. The authors stated that whole genome sequencing is changing how neurological patients can be diagnosed, and that traditionally this has been based on which disease best fit the overall symptoms with treatment aimed at managing those symptoms as best as possible. The authors added that clinicians can now generate genetically defined diagnoses for individual patients, and these do not always align with established symptom-based neurological conditions.
One implication of these findings is that, if successful, these therapies could be applied to the small subset of FTD and ALS patients with that mutation as well. The authors noted that, while the number of FTD/ALS patients seen with the Huntington's-linked mutation is small (roughly 0.12-0.14%), adding genetic screening for the mutation to the standard diagnostic procedure for patients showing symptoms of FTD or ALS should be considered.