text:
Q: DNS: migrating FROM Google Email + Google App hosted website TO Google Email + 3rd party hosting I inherited a DNS/website/email scenario I don't understand.
#
I need to modify DNS records so that email integrated with Google Apps is not altered, but so that web traffic goes to a 3rd party. Currently the web traffic goes to a Google App Engine account (under the previous developers personal account).
On the receiving end, I have a static IP address and the nameservers for the host the web account is on. I just need to know what to do with them.
I tried changing the A record, but that broke the Google Email integration. I tried specifying the current A record IP in the MX Host fields, and that was bad, too.
#
Current info:
#
A (Host)
@
216.239.32.21
CNAME (Alias)
e
email.secureserver.net
email
email.secureserver.net
ftp
@
imap
imap.secureserver.net
mail
pop.secureserver.net
mobilemail
mobilemail-v01.prod.mesa1.secureserver.net
pda
mobilemail-v01.prod.mesa1.secureserver.net
pop
pop.secureserver.net
smtp
smtp.secureserver.net
webmail
webmail.secureserver.net
www
ghs.google.com
MX (Mail Exchanger)
20
@
ALT1.ASPMX.L.GOOGLE.COM
30
@
ALT2.ASPMX.L.GOOGLE.COM
10
@
ASPMX.L.GOOGLE.COM
40
@
ASPMX2.GOOGLEMAIL.COM
50
@
ASPMX3.GOOGLEMAIL.COM
TXT (Text)
@
google-site-verification=REDACTED
#

A: When you changed the A record, that should not have broken the Google Apps email. Do you mean your users were unable to access the web interface? If so, tell them to use:
http://mail.google.com/a/YOUR_DOMAIN.COM
If you are using mail clients (like Outlook), test with the url above. The A record has no impact on the actual flow of email for Google Apps.
For your new host, you were right to change the A record for YOUR_DOMAIN.COM and www to the new static IP.
You want to leave all the MX records. These are what directs your mail to the Google mail servers.
NOTE: The records: email, imap, mail, mobilemail, pop, smtp, webmail and the CNAME e (possible pda as well) all appear to be legacy records from before you migrated to Google Apps. If you are not doing some mail redirection within Google Apps or some other fancy setup, these likely can be removed. My recommendation would be to remove one as a test if you are unsure -- once you have straightened out the other issues.
NOTE: Once you get this sorted out, I would strongly recommend a SPF record be added. See:
https://support.google.com/a/bin/answer.py?hl=en&answer=178723

redpajama_set_name: RedPajamaStackExchange


San óstán Hilton, Plás Charlemont, Baile Átha Cliath 2, a bhaileoidh pobal Gaeilge na tíre agus cairde na Gaeilge lena chéile ag Tóstal na Gaeilge chun plé a dhéanamh ar mhór nithe an lae i dtaobh na Gaeilge agus an tsochaí Gaelach.
Faoi chathaoirleacht an iriseora Gormfhlaith Ní Thuairisg de chuid RTÉ Raidió na Gaeltachta a bheidh an seisiún sin, agus orthu siúd a bheidh ag roinnt a dtuairimí ar an lá beidh: Feargal Ó Cuilinn, Ceannasaí Comhluadar; Dr Briain Ó Curnáin, saineolaí ar chanúineolaíocht agus socheolaíocht na Gaeilge le hInstitiúid Ard-Léinn Bhaile Átha Cliath; Aoife Ní Shéagha, Léachtóir sa Phleanáil Teanga le OÉ, Gaillimh; agus Sorcha Ní Chéilleachair, Cathaoirleach Thuismitheoirí na Gaeltachta – Conamara.
Tá clár an Tóstail ar fáil anseo: Tóstal na Gaeilge 2013 - Clár Oifigiúil.pdf. Beidh tuilleadh sonraí agus plé ar fáil ar na meáin shóisialta faoin haischlib #Tnag13.
€15 atá ar thicéad don Tóstal, agus cuirfear lón ar fáil. Is féidir ticéid a chur in áirithe trí theagmháil a dhéanamh le Máire Ní Phuirséil, Comhdháil Náisiúnta na Gaeilge, 01 6794780 nó maire@comhdhail.ie. Tá an tÓstán Hilton lonnaithe i lár chathair Bhaile Átha Cliath, le taobh stad Luas Plás Charlemont.


Looks Good from the Back: It's Better Than Cats!
M: Should we talk about handsome men?
M: OKAY. This is a bit outside of the norm but are you watching Sleepy Hollow?
A: I am not watching Sleepy Hollow. Should I be?
M: I think you should! It's great fun and the guy who plays Ichabod is fantastic. He's not bad to look at either.
A: Honey, he looks like Jesus. Not that there's anything wrong with that.
A: Better! Nice! Hello pretty man!
M: He manages to play a guy who wakes up 200 years in the future and make him funny. Plus, cheekbones.
But OMG why did THIS come up in my search?!
A: I used to love that show. LOVE.
A: It was the 80's. We didn't have much to pick from back then.
M: Okay, I've never seen it, but are we supposed to believe that Sarah Connor had the hots for Mr. Mistoffelees there?
A: They had an emotional bond! See, there was this secret Utopian society of outcasts and...never mind.
M: Yeah, I'm going to ask you to stop now.
A: Oh, I'm so sorry Future Ichabod Crane.
I'm watching Sleepy Hollow for the history. Yep, juuuuust the history.


Objective-C 2.0 Essentials Print and eBook (ePub/PDF/Kindle) editions contain 31 chapters.
The Objective-C 2.0 Essentials online book contains 34 chapters of detailed information intended to provide everything necessary to gain proficiency as an Objective-C programmer for both Mac OS X and iPhone development.
What is an Objective-C Constant?
This page was last modified on 18 November 2016, at 15:38.


text:
Afghanistan: Focus on mental health
KABUL, 12 February (IRIN) - Standing in a gated cell, Nurallah Herawi wants out. "Open the door. I want to go outside," the former police officer told IRIN. While his request is a simple one, staff members at Afghanistan's only mental hospital, a decrepit and ill-equipped facility in the capital, Kabul, are not so sure.
Brought in five days earlier by his wife, the 45-year-old suffers from acute schizophrenia and is known to lash out. As doctors ponder his treatment, Herawi is confined to room number three, a darkened cell reserved for patients deemed violent.
According to the World Health Organisation (WHO), about four million people, or some 20 percent of the population, suffer from mental health problems or some form of diminished capacity. Depression - particularly amongst women - remains widespread, while thousands of children demonstrate learning or behavioural problems, many the result of war-related trauma. In Afghanistan, devastated by decades of war, poverty and dislocation, cases like Herawi's are hardly uncommon.
What is new, however - over one year after the demise of the Taliban - is the continued lack of resources to meet this challenge. "There is an extreme shortage of expertise with regard to mental health," the WHO mental health officer, Dr Sayed Azimi, told IRIN. "We don't have trained qualified psychiatrists in the country, and the facilities to treat patients are inadequate," the Indian-trained physician - the only trained psychiatrist in the country - observed.
But inadequate is an understatement. Down the hall in a room permeated by the stench of urine, Javid Bydia, a 29-year-old former military officer from the western city of Herat, looks agitated. Brought in for reasons similar to Herawi's, he suffers from hallucinations and bouts of violence. "I have headaches all the time. Sometimes I hear voices," the father-of-three told IRIN.
Meanwhile, in the same room, another former soldier - his legs chained together to prevent escape - mumbles as he sits on his bed. "I'll be good. I promise," he says over and over again.
While conditions within this 40-bed unit are undeniably poor, strangely both of these men are considered lucky. Although there is a small outpatient mental health centre in Sherberghan, the provincial capital of northern Jawzjan Province, the Soviet-built former central clinic in Kabul remains the country's only facility remotely geared to helping those suffering from mental illness and trauma - a fact that baffles Afghan health workers.
"After two decades of war, 95 percent of the population were affected psychologically, and yet there is only one mental hospital for the entire nation," Dr Abdul Ahad Awarah, a former assistant at the hospital, told IRIN. "While we have thousands of regular hospitals, mental health has completely fallen to the wayside."
Deeply frustrated, the clinical psychiatrist maintained that no organisation - including the UN - had demonstrated a real willingness to help. "People aren't interested. It simply isn't a priority for them," he said.
Sadly his contention could be correct. Grossly under-resourced, the unit can barely provide the basics, much less treatment. "Conditions here are very poor," Dr Ahmad Shafi Zia, one of 21 attending doctors and 15 nurses working around the clock, told IRIN. "If any patient comes here, there is little we can do for them," he said. "We just try to keep them from hurting themselves."
To keep warm, patients routinely sleep in their soiled clothes for days on end, while the facility's antiquated heating system stands broken and unused. There are regular power cuts; the water supply remains sporadic and the water pump works for only one hour a day. "There is only one bathroom for 40 people and no hot water," Zia said, adding that food consisted of a meagre dish of rice, beans and water.
Drugs treatment at the centre is nonexistent, and patients are expected to purchase their own medicine on the open market. "Many of these people have no means to do this," Azimi conceded, recalling how until just recently families were given prescriptions for not just the medicine, but also a chain and lock to shackle the patient.
For 2003 alone, just US $100,000 has been allocated for mental health for the whole country. "This isn't enough to provide supplies for this one hospital, much less the whole country," Zia noted.
With limited resources, WHO aims to integrate mental health into primary health care services by providing training to general practitioners working in the various provinces. "So far, we have trained 40 practitioners on mental health," the WHO official said.
But lack of expertise on mental health starts at the top at the hospital. Dr Khetaab Kakar, the current director of the hospital, is actually a surgeon. Though he has received some training from WHO, he is not a trained psychiatrist.
For most of the staff, their training in the field of mental health is even more limited, with much of it conducted on an informal basis only. "We have to improve the knowledge and skills of doctors and nurses first," Azimi said. "The primary emphasis of our activity at the hospital is training," he added, noting that there was little motivation amongst staff to provide care. And with salaries often unpaid and averaging about $40 a month, it is not difficult to understand why.
Equally troubling, however, is the stigma attached to the issue of mental sickness. According to Azimi, it's a taboo subject not just in Afghan society, but also within the health ministry itself. After the ministry was awarded a recent donation of ambulances, it allegedly ignored a request by the mental health facility, leaving it the only hospital in Kabul without an ambulance.
"Their impression of mental health compared with other sectors is quite different," Azimi said, noting that in order to improve conditions at the hospital, they do not only need resources but also the will to do so. "Nobody is interested to work there," he remarked. "The ministry is now forcing some people," he asserted.
Following the overthrow of the Taliban, WHO issued an appeal for help. "Mental disease that one would see in any population has not been attended to for years in Afghanistan," Azimi observed, stressing the urgent need for mental health services to be established throughout Afghanistan.
"During the Taliban time, we never had people coming from rural areas - now we do," Awarah noted, adding that many new arrivals were simply being turned away.
Whereas WHO, given the limited resources, is rightfully addressing the issue of training, and efforts are under way to move patients to a new facility in the near future, it is clear that much more is needed. Reaffirming what he described as widespread neglect when it came to mental health in Afghanistan, Azimi said: "What we are doing is not enough. We can do so much more."
IRIN-Asia
Email: IrinAsia@irin.org.pk
Afghanistan: WASH Cluster Partners Activity Location Map (January to December 2020)
WASH Cluster

redpajama_set_name: RedPajamaCommonCrawl


text:
By wirk | April 1, 2020
Wimbledon has been canceled for the first time since World War II due to coronavirus pandemic
The 2020 Wimbledon has been canceled due to the coronavirus pandemic.
The All England Club announced after an emergency meeting that the oldest Grand Slam tournament in tennis would not be held in 2020. This is the first time the tournament has been canceled since WWII.
Wimbledon was scheduled to be played on the outskirts of London from June 29 to July 12. The club says they are currently developing a plan to help support those who rely on the tournament for financial support.
The club also said that all tickets will be refunded, and fans will be given the opportunity to purchase tickets for the same day and court during the 2021 tournament.
Gabby Barrett says she gets "so tired so quickly" during pregnancy


I have 4 beautiful Chihuahua's ready to go to their new homes. Puppies will not come with. Lillington, North Carolina » Chihuahua ». $400 .
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. Yorkshire Terrier. Raleigh, NC 27601 change. Jake Chihuahua Puppy for Sale 9.52 miles. Breed: Chihuahua. . Location: Durham, NC. We have two male .
Category. Cars & Trucks (6074). Community (4). Items for Sale (21). Jobs. Real Estate (8). Rentals (2). Services (18). Yard Sales (12) .


Daily and severe weather and global climate. Topics: structure and composition of the atmosphere, fog and cloud formation, rainfall, local winds, wind energy, global circulation, jet streams, high and low pressure systems, inversions, el Niño, la Niña, atmosphere/ocean interactions, fronts, cyclones, thunderstorms, lightning, tornadoes, hurricanes, pollutant transport, global climate and atmospheric optics.
Infrastructure is critical to the economy, global competitiveness and quality of life. Topics include energy, transportation, water, public facilities, and communications sectors. Analysis of the condition of the nation's infrastructure and how projects are planned and financed. Focus is on public works in the U.S. The role of public and private sectors through a step-by-step study of the project development process. Case studies of real infrastructure projects. Industry guest speakers. Student teams prepare project environmental impact statements.
Infrastructure is critical to the economy, global competitiveness and quality of life. Topics include energy, transportation, water, public facilities ,and communications sectors. Analysis of how projects are designed, constructed, operated, and maintained. Focus is on public works projects in the U.S. Alternative project delivery approaches and organizational strategies. Case studies of real infrastructure projects. Industry guest speakers. Student teams prepare finance/design/build/operate/maintain project proposals.
Nine current global infrastructure projects presented by top project executives or company leaders from industry. Water, transportation, energy and communication projects are featured. Course provides comparisons of project development, win and delivery approaches for mega-projects around the world. Alternative project delivery methods, the role of public and private sector, different project management and construction strategies, and lessons learned. The course also includes field trips to local mega-projects. Grade (one unit) is based on attending all 9 lectures and at least 2 field trips.


Twice a day, like clockwork, diehard trivia fans pull out their phones to play a live game of HQ Trivia with the hope of earning a piece of the jackpot.
The free trivia app has become an overnight sensation, thanks in part to its marriage between trivia, live streaming and the allure of earning a cash prize for answering all 12 questions correctly. The game runs twice a day during the week, at 3 p.m. and 9 p.m. ET, and only at 9 p.m. on weekends.
"HQ is a fun game that I can play for just 10 to 15 minutes a couple of times a day," said Sam Houston, a San Francisco HQ player who has been participating in games for the past few weeks. "I like that it's live, that I can play it with my friends or coworkers around, and we're all part of this shared experience."
The questions get progressively harder. If a player makes it through all 12, they'll be entitled to a piece of the jackpot, which is usually around $1,000. Some days that may mean each winner walks away with a few dollars, while on harder days, fewer winners means each person gets a bigger piece of the pie.
Host and comedian Scott Rogowsky, nicknamed the "Quiz Daddy," has already become a celebrity in the past three months.
"Its all been very flattering and fun. It's a thrill to be recognized," Rogowsky told the New York Post. "I don't know, if it gets to the point like Tom Cruise, who can't walk down the street. I don't ever want to get to that point. It doesn't seem fun when you can't function in society ... when you can't go to Sweetgreen. I'm very comfortable with the level of fame right now. I would say let's try to keep it at that."
Rus Yusupov and Colin Kroll, the two co-founders, launched the app with funding from Lightspeed Venture Partners. The app's founders haven't monetized HQ, but they could have a huge moneymaker on their hands.
The app's founders are said to be raising a new funding round that could value HQ at $100 million, according to Recode.
But their biggest issue right now may be their overnight success. With more than 200,000 people tuning in for every game, HQ has at times suffered from a video lag.
"When there are over 100,000 people playing, especially as you get closer to 200,000 plus, the video gets very choppy. I'm hoping they can fix that soon," Houston told NBC News.
As of Friday afternoon, HQ Trivia was the No. 55 free app in Apple's App Store. It's coming to Android later this month, which is sure to bring a slew of new players.
If you haven't gotten on the bandwagon just yet, here's a pro tip: Ask a friend for their referral code. When you sign up, they'll get an extra life, which will let them stay in the game if they get knocked out on a question. You'll then be able to give the uninitiated your referral code, earning an extra life for every friend you turn on to HQ Trivia.
Watch tonight's NBC Nightly News with Lester Holt for a look behind the scenes of the app taking the country by storm.


text:
Governor's decision to step back from TMT conflict gets mixed reviews
By Rick Daysog
Updated: Jul. 24, 2019 at 6:05 PM HST
HONOLULU, Hawaii (HawaiiNewsNow) - Gov. David Ige's decision to hand over negotiations with protesters on Mauna Kea to Big Island Mayor Harry Kim is getting mixed reviews.
Hawaiian activist and attorney Mililani Trask worries that the talks are set up to fail because Mauna Kea is not under Hawaii County control and the mayor can't truly speak for the state.
She believes that when talks do fall apart, the governor will call in the National Guard.
"I think it will be a failure and when that occurs, my guess is that the governor will then try use it as his second excuse to bring up heavy weapons," said Trask, who was among those arrested on Mauna Kea last week.
"The governor's bungling and his inability to address the problems that he's been unable to resolve in the past has caused him to lose face."
Ken Lawson of the University of Hawaii Law School is a veteran of civil rights protests on the mainland. He agrees that the governor's strategy is to make protesters look unreasonable.
"In order to save face, Gov. Ige comes in and lets him negotiate, knowing full well that those protectors aren't going to give up that land ― give up that position ― unless TMT tells them we're not going to build this telescope," he said.
"Then Gov. Ige can stand back and say look we tried everything we could and even Mayor Kim ... couldn't get these people to be reasonable."
But University of Hawaii Political Science Professor Colin Moore thinks those theories are far-fetched. He believes Ige is making the right move.
Moore said many on the Big Island trust Kim and that Ige squandered a lot of his goodwill there by arresting elders while allowing the protest to swell.
"I think there is tremendous anger from the protectors of Mauna Kea about how Gov. Ige had handled this so far," he said.
"I think he has been wise to recognize he's not the right person to negotiate this."


University and Georgia State University's campuses.
in music, especially hip-hop. Born in Shiraz, Iran and growing up in both Germany and the U.S., he was influenced by middle-eastern folk music and western genres such as jazz, soul, and rap. Self-taught, he has been producing since 2002 and began deejaying in 2012.
bring the freestyle rap culture of Atlanta to the forefront.
in improvised rhyming, beatmaking and cartooning.


Portsmouth Used Car Superstore loves to receive comments, suggestions and questions from our valued customers! We encourage you to submit feedback in the form below. Upon receipt, someone from our dealership will get back to you as soon as possible.
To contact us with any concerns or feedback just dial 800-611-7845.


text:
La ferme Peyronnet est une ferme située à Sagnes-et-Goudoulet, en France.

Description

Localisation
La ferme est située sur la commune de Sagnes-et-Goudoulet, dans le département français de l'Ardèche.

Historique

L'édifice est inscrit au titre des monuments historiques en 1985.

Annexes

Articles connexes
 Liste des monuments historiques de l'Ardèche

Liens externes

Références

Peyronnet
Peyronnet
Monument historique en Ardèche
Monument historique inscrit en 1985

redpajama_set_name: RedPajamaWikipedia


text:
Home Upcoming Center for Asian Studies Events Exhibition as an Art Historical Space: The 1933 Chinese Art Exhibition in Paris. 2021.01.28
Exhibition as an Art Historical Space: The 1933 Chinese Art Exhibition in Paris. 2021.01.28
Non-CAS Event
Thursday, January 28 at 4pm PST
The 1933 Chinese Art Exhibition in Paris played a crucial role in establishing the category of "modern Chinese painting" in Europe. Opened at the Musée Jeu de Paume in May 1933, the Exposition de la Peinture Chinoise was the first large-scale exhibition of Chinese art in France. It attracted unprecedented numbers of viewers, and afterwards the museum founded a Chinese art gallery. Motivated by the success of earlier Japanese art exhibitions in Paris, the curator Xu Beihong (1895-1953) collaborated with French art museums, private collectors and Chinese artists to organize this show. By analyzing its visual and textual narratives, I argue that this exhibition was shaped by three factors: the international politics between France, Japan, and China; the complex social network among Chinese artists; and the personal vision of the curator. It was through the interaction and competition among various agents and institutions that the category of "modern Chinese painting" was created in the early 20th century.
Stephanie Su is an Assistant Professor of Asian Art at the University of Colorado, Boulder. Her research interests include global modernism, historiography, the history of display and collecting, and cultures of color. Her book manuscript, Entangled Modernities: Constructing East Asian Classicism in Early Twentieth Century Chinese and Japanese Art, examines how regional identity and historical connections across East Asia led to the formation of modern nations and arts. Her second project, Colors of Modernity: Changing Aesthetics in Meiji Japanese Prints, explores the impact of the global trade network on the late 19th century Japanese prints. Her articles have appeared on the Frontier of Literary Studies in China, The Art Bulletin (forthcoming), Kimono in Print: 300 Years of Japanese Design, and among others.


text:
Christopher Gibson
Born: 12/27/1992 Age: 27 yrs Nationality: FIN
Goalie Ratings
2014-15 Wilkes-Barre/Scranton Penguins 12 9 3 5 2 37 317 3.60 0.883 0 0 616:30
2015-16 Wilkes-Barre/Scranton Penguins 44 43 19 19 5 129 1328 2.96 0.903 0 1 2614:38
2018-19 Penguins 5 5 2 2 0 17 132 3.94 0.871 0 1 259:38
2019-20 Wilkes-Barre/Scranton Penguins 12 12 7 4 1 28 385 2.32 0.927 0 1 724:36
NHL TOTALS 5 5 2 2 0 17 132 3.94 0.871 0 1 259:38
AHL TOTALS 253 247 114 107 26 708 7,646 2.83 0.907 6 6 14992:19
2014-15 Wilkes-Barre/Scranton Penguins 12 9 0 0 0 0 0 0
2015-16 Wilkes-Barre/Scranton Penguins 44 43 0 4 2 1 2 3
2018-19 Penguins 5 5 0 0 0 1 0 0
NHL TOTALS 5 5 0 0 0 1 0 0
AHL TOTALS 253 247 0 14 16 19 14 7
PS%
2014-15 Wilkes-Barre/Scranton Penguins 12 5 7 0.286
2015-16 Wilkes-Barre/Scranton Penguins 44 4 24 0.833
2018-19 Penguins 5 0 0 0
AHL TOTALS 253 29 122 0.762
$700,000 - - - -
[12/7/2019] - Christopher Gibson of Penguins cleared waivers and cleared waivers and was sent down to farm.
[12/5/2019] - Penguins placed Christopher Gibson on waivers.
[12/29/2018] - Christopher Gibson of Penguins was sent to farm.
[4/8/2018] - Christopher Gibson [W-Penguins] was injured (Fatigue) and is out for up to 1 week.
[2/12/2018] - Christopher Gibson [W-Penguins] has been selected to the East for the 2018 AHL All-Star Classic!
[11/5/2017] - Christopher Gibson of Penguins was sent to farm.
[10/6/2017] - Christopher Gibson re-signed as a restricted free agent by the Penguins to a 3-year contract ($700,000 per season).
[10/11/2016] - Christopher Gibson of Penguins was sent down to farm.
[4/1/2016] - Christopher Gibson [Penguins] was injured (Fatigue) and is out for up to 1 week.
[2/9/2015] - Christopher Gibson signed by the Penguins to a 3-year contract ($575,000 per season).
[1/13/2015] - Christopher Gibson was selected by the Pittsburgh Penguins as the 937th overall pick of the EHE Inaugural Draft.
NHL.com hockeyDB


text:
contact@gavinpublishers.org
Pharmaceutial
Basic-Sciences
Case Report Articles
MANUSCRIPT GUIDELINES
Gavin Conferences
Journal of Diabetes and Treatment	(ISSN: 2574-7568)
Journal Menu About Journal Board Members Article In Press Current Issues Archive APC Special Issues
Review of Formulations and Methods for Prevention and Treatment of COVID-19 and other Viral Infections
Leon Margolin*, Jeremy Luchins, Daniel Margolin, Michelle Margolin, Sanford Lefkowitz
Comprehensive Pain Management Institute, LLC (www.cpmiohio.com), Columbus, Ohio, USA
*Corresponding author: Leon Margolin, Comprehensive Pain Management Institute, LLC, Columbus, Ohio 43213, USA
Received Date: 25 May, 2020; Accepted Date: 11 June, 2020; Published Date: 16 June, 2020
Show Citation
Citation: Margolin L, Luchins J, Margolin D, Margolin M, Lefkowitz S (2020) Review of Formulations and Methods for Prevention and Treatment of COVID-19 and other Viral Infections. J Diabetes Treat 5: 1079. DOI: 10.29011/2574-7568.001079
While the number of COVID-19 cases keeps increasing with more and more data suggesting spread by asymptomatic carriers (especially as quarantine is lifted or eased in many locations), there is an urgent need for prophylactic formulations and methods that can be easily available to the public. The goal of the prophylactic formulations and methods is to reduce disease rate among the exposed population and severity of symptoms among the symptomatic cases and to facilitate development of community herd immunity, without overloading hospital systems and depleting medications, ICU beds and other resources.
This is an extensive case review analysis of use of over the counter formulations and methods for prevention and treatment of COVID-19. The analysis shows a strong statistical significance in favor of the use of the formulations and methods in a large patient sample even with the assumption that only 10% percent of the exposed patients get infected, which is an extremely conservative underestimate in light of the current virus spread pattern. The conservative infection rate and exposure model compensates for the lack of complete randomization of the sample.
Diabetic Medicine, Diabetic Nutrition, Diabetology
From early March to mid-May 2020, I took the call for about 600 patients in the Columbus and Cleveland areas, Ohio regions most heavily affected by COVID-19, and did consults for several friends and colleagues in the NYC area. Over that period, we dealt with dozens of clinical and/or confirmed cases of COVID-19.
Since accurate testing and effective medications were at best scarce, we developed and implemented over-the-counter formulations and methods for prevention and treatment of the potentially deadly viral pandemic. Even prior to confirmation through our quantitative analyses presented herein of data of about 100 patients and their contacts on results of using the formulations and methods, the qualitative outcomes were overwhelmingly positive as to the effectiveness of the over-the-counter formulations and methods for prevention and treatment of early-stage COVID-19.
Our approach provides an economical and safe over-the-counter option for prevention and treatment, freeing such prescribed medications as hydroxychloroquine and remdesivir for treatment of moderate to severe COVID-19 cases. Our approach to prevention and treatment of early-stage COVID-19 may also decrease the number of cases with moderate to severe symptoms requiring powerful drugs and/or hospitalization. In addition, the formulations and methods may prevent virus spread from asymptomatic carriers and address "second wave infection" threats.
We review below the background for the formulations and methods used:
Role of Cinchona bark, quinine and similar products
Native to the Andes, Quina (Cinchona calisaya) is a Peruvian evergreen shrub with large glossy leaves and fragrant yellow/green or red flowers. Quina is the source for the malaria treatment quinine, of which the highest concentration exists primarily in the bark of the shrub.
For example, Nutramedix, the U.S. manufacturer of Quina™, utilizes a proprietary extraction and enhancement process that claims as features:
• Efficient full spectrum extract
• Clinically appears to cross the blood/brain barrier within 2 min.
• Water/Alcohol extract that does not damage protein
• Easy to use for all ages
Practitioners are now using Quina to treat Lyme borrelisosis. Lyme borreliosis has been linked to hundreds of medical conditions; many researchers and physicians believe that Lyme borreliosis may be a factor in many prevalent chronic conditions. Quina's antibiotic affect can help to prevent secondary infection.
For centuries, Cinchona bark alkaloids (Cinchona calisaya) were the primary treatment of malaria [1]. Quinine, one of the components of the extract and the prototype of hydroxychloroquine, has been shown to have an independent anti-viral activity [2].
Since the limited availability of hydroxychloroquine (which cannot be easily obtained even by prescription in numerous locations and, even if prescribed, can be used for usually 5 days only (see link in Table 1)), the Quina extracts and other quinine-preparations given below (under Formulations) as components of our formulations provide an economical and safe prophylaxis modality. Since the quinine and other components of the extract may have a shorter pharmacokinetic half-life than hydroxychloroquine, we suggest daily use of the formulations for prevention and treatment.
In addition, on many occasions hydroxychloroquine is not well tolerated (in contrast to the formulations disclosed herein) and can cause serious side effects, especially in older patient.
Role of Quercetin as Zn Ionophore
Quercetin is a bioflavonoid supplement that has been shown [3] to act as a zinc ionophore, enhancing entrance of zinc into cells to inhibit virus replication (e.g., [4]). Increasing the intracellular Zn2+ concentration with zinc-ionophores like pyrithione (PT) can efficiently impair the intracellular replication of a variety of RNA viruses, including poliovirus and influenza virus [4]. Quercetin is similar in this respect to hydroxychloroquine which also is a zinc ionophore [4]. It is also believed to block viruses from entering cells in the first place, lowering the 'viral load'. A study published by the University of Tennessee and Oak Ridge National Labs used the most powerful IBM supercomputer to model which FDA-approved compounds or supplements might interfere with the COVID-19-causing coronavirus binding to cells. Quercetin was listed as fifth most effective of almost twenty (Table 3 herein, from [5]). This study has also suggested Quercetin's beneficial effect on the ACE2 receptors used by the COVID-19 virus to bind to the outside of potential host cells as an essential step before entering those cells. Additionally, a study [6] showed that Quercetin has anti-inflammatory properties, which could help limit the inflammatory response of the cytokine storm caused by COVID-19.
Dr. Michel Chrétien and Dr. Qiu are well known Canadian researchers who have been researching the effects of Quercetin for decades and have found it to inhibit various bacteria and viruses. They have seen positive results in mice with its use against Ebola and Zika [7]. It has also been tested against influenza [8] and SARS [9]. As reported March 2020, they are in the process of testing it against COVID-19 [10, 11].
There is evidence of the anti-TNF alpha effect of quinine [12] that contributes to the assumed protective effect for COVID-19 patients. For example, research on IBD patients shows possible protective effects of anti-TNF alpha antibodies and other treatments in Crohn's patients [13]. Interestingly, Quercetin also shows a significant anti-TNF alpha activity in vitro [14, 15] and in animal models [16].
Use of Ivermectin for COVID-19
Ivermectin has been researched in Australia for use for COVID-19 prophylaxis and treatment.
Ivermectin has been used as an anti-parasitic in more than 6 million people globally for a variety of indications which includes treatment and sometimes elimination of scabies, river blindness, a variety of worm infections, and filariasis. It can be used orally, with well-established dose schedules effective for those common conditions, at modest costs, and with minimal toxicity.
Ivermectin also has some effects on a variety of RNA and DNA viruses, and is being evaluated for malaria. A manuscript published in Antiviral Therapy on April 3, 2020, by Caly, Druce, Catton, Jans and Wagstaff from the Monash BioMedicine Discovery Institute and the Doherty Institute in Melbourne, Australia, describes complete destruction of COVID-19-causing virus in cell culture after incubation for 48 hours with Ivermectin [17].
With research proceeding on optimal doses for efficacy and likely safety, the WHO is directing additional focus to Ivermectin, and the Bill and Melinda Gates Foundation is supporting redirection of US$19 million of its grant funds to repurposing Ivermectin for COVID-19 management [18].
Trials with Ivermectin are not yet listed among the COVID-19 clinical trials dashboard [19]. We advocate that Ivermectin be evaluated for management of COVID-19 in three contexts: treatment of hospitalized patients with serious manifestations of COVID-19; management of COVID-19 positive symptomatic patients at home or in other forms of social isolation; and prophylaxis for close contacts of people symptomatic with, or diagnosed to have, COVID-19.
Controlled trials could be implemented immediately of oral Invermectin at current therapeutic doses (often two single doses a week apart), generally deemed safe, to assess its efficacy in both treatment and prophylaxis of COVID-19 infections.
Case report series analysis. Since the availability of testing and treatment was limited in Ohio, we monitored clinical cases of COVID-19, patients with documented exposure to COVID-19 (essential workers, family members and other patients exposed to documented cases of COVID-19) and documented cases in those areas where testing was available. Many of the documented patients started on a regimen of our formulations and methods after having had a course of hydroxychloroquine and Zithromax or as an alternative in cases of poor tolerance of hydroxychloroquine. Results of administration of the recommended core formulations (below) were followed as described in the statistical analysis sections below. In addition to the core formulations according to their recommended administration protocols, patients were encouraged to implement one or more additional/ancillary methods herein described. The additional/ancillary components and methods are suggested based on the available literature analysis.
The formulations consist of the following components and substances that have been demonstrated to have beneficial effect both outside of and within clinical settings in the prevention of COVID-19 and other viral infections and also in the treatment of early stages of such diseases:
A mixture of Quercetin together with drops of Quina (NutraMedix Cinchona Calisaya extract; all similar plant extracts including, but not limited, to Quina Raja, Cinchona extracts, Quinine tinctures, extracts or other preparations, teas or powders can be used) with Zn.
The mixture, additionally, contains Vitamin C, Vitamin E, L-Lysine and Vitamin D3.
These components and substances been demonstrated to have beneficial effect (see Background and References).
Additional components and substances that these formulations for prevention and treatment of viral disease may comprise:
Parts, extracts and/or derivatives of one or more of the following: Amla fruit, Lianhuaqingwenjiaonang, Ginger, Lemon, Licorice (Glycyrrhiza glabra), Red Reishi mushroom, Oregano oil, Garlic, Olive leaf, Guduchi (Tinospora cordifolia), other such natural products.
Representative other natural products that may be ancillary components and substances that these formulations for prevention and treatment of viral disease may comprise:
Parts, extracts and/or derivatives of one or more of the following: Bee propolis (Apismellifica; e.g., extract 5:1), Red Marine Algae (whole plant; e.g., extract 10:1), Self-Heal (Prunella vulgaris fruit; e.g., extract 10:1), Lomatium dissectum (including Lomatium "Immune support" tincture), Holy Basil (Ocimum sanctum), Terminalia bellerica, Adhatoda vasica, Piper nigrum (fruit), Zingiber officinale (rhizome), Piper longum (fruit) (e.g., "Trikatu," a blend of equal parts of the last three listed items).
Copper (e.g., copper orotate) may also be an ancillary component that these formulations for treatment of viral disease may comprise.
Methods of administration
Oral administration (self-administration and/or as supervised by caregiver) of the formulations via capsule, powder, softgel, tablet, mixture in such liquids as water or juice, or other forms of administration.
For prevention of disease (implemented and monitored in the group of 54 individuals discussed below in the statistical analysis):
One dose/day (as, for example, one capsule), the dose containing: 400 mg of Quercetin together with 10 drops of Quina (we used NutraMedix Cinchona Calisaya extract to good effect, but all similar plant extracts including, but not limited to, Quina Raja, Cinchona extracts, Quinine tinctures extracts or other preparations, teas or powders may be used) with 25 mg of Zn, 1000 mg of Vitamin C, 400 IU of Vitamin E, 500 mg of L-Lysine, and 1000 units of Vitamin D3. Other amounts and proportions of these substances and components may be used. None, one or more than one of the additional/ancillary substances and components presented above have been used.
Prevention-dosing may be continued prophylactically over any period of concern of contracting COVID-19 or other viral diseases.
For treatment of mild to moderate symptoms in early-stage disease:
Multiples of the prevention-dose daily. We have used two prevention-doses per day, administered separately or together; on the second day of administration, with an additional 50 mg of Zn (titrated up to 200 mg of Zn for 5 days over 2-3 days as tolerated). Patient and/or caregiver may consider adding 500 mg daily Azithromycin (Zithromax) for 5 days (as prescribed by a treating physician), as well as none, one or more of the additional/ancillary components and substances.
Treatment dosing can be administered for 1, 2, 3, 4 or 5 days or until symptoms are alleviated. After symptoms are alleviated, prevention-dosing may be maintained.
We suggest a daily dose of 400mg of Quercetin together with 10 drops of Quina (Cinchona Calisaya extract) with 25 mg of Zn for prevention; and 800 mg of Quercetin together with 20 drops of Quina plus 50 mg of Zn for symptomatic patients. (Zn can be titrated up to 200 mg for 5 days.)
With the exception of the readily available Azithromycin to be considered in treating mild to moderate symptoms of early-stage disease, none of the components and substances of the formulations used in these methods of administration requires prescription by physician. Thus, these formulations and methods provide options that are economical and almost completely Over-The-Counter (OTC; completely OTC for prevention, and mostly OTC even for the treatment outlined above for relieving early-stage symptoms). Through use of our formulations and methods, prescribed medications such as hydroxychloroquine can be reserved for moderate to severe cases. We note that use of these formulations and methods can also decrease the number of moderate or severe cases that require such prescribed medications and/or hospitalization. In addition, use of these formulations and methods may prevent virus spread from asymptomatic carriers and, thus, help address threats of "second wave infections."
Methods specification, route of administration
Oral administration, when possible, of the formulations via capsule, powder, soft gel, tablet, mixture in such liquids as water or juice, or other forms of administration.
Formulation ingredients may be divided among various modes of administration, such as: IV or other parenteral routes for vitamins C and E, extracts containing quinine-analogs/derivatives, and/or zinc; and PEG administration for vitamin D3, L-Lysine, and/or other components and substances of the formulations.
For treatment of moderate to severe disease, administration of two doses per day, each dose containing:
400 mg of Quercetin together 10 drops of Quina (we used NutraMedix Cinchona Calisaya extract to good effect. However, all similar plant extracts including, but not limited to Quina Raja, Cinchona extracts, Quinine tinctures, extracts or other preparations, teas or powders may be used) with 25 mg of Zn, 1000 mg of Vitamin C, 400 IU of Vitamin E, 500 mg of L- Lysine, and 1000 units of Vitamin D3.
Other amounts and proportions of these substances and components may be used.
After the first day of administration of the formulations, we recommend, in addition to the two doses/day indicated above, also another 50 mg of Zn the second day, titrated up to 200 mg of Zn over 2-3 days for 5 days as tolerated.
We anticipate and advocate use of none, one or more than one of the additional/ancillary substances and components (For instance, if copper orotate is used, we recommend 1 mg/dose). Patient condition may indicate yet additional/ancillary treatment components. For instance, for patients with pulmonary symptoms with contraindications and drug interactions, we anticipate and advocate as useful Bupleurum extract, with possible dosing of 1 gm daily (via tablet, tincture or other means or preparations/administration).
We anticipate and advocate considering supplementing the above regimen with one or more antibiotics and/or anti-parasitic agents (each by prescription by the treating physician), for instance: Azithromycin (Zithromax) 500 mg daily for 5 days; Ivermectin [17], with possible dosing being 3 mg, typically orally or by PEG, if possible titrating to up 15 mg (or as indicated and as tolerated) for a single dose, with a single dose repeat in 7 days (or as indicated and as tolerated); Isoniazide, Nitrofurantoin, Doxycycline and/or Levaquin (for secondary infection prevention) or other medications (dosing per PDR).
We note that the formulations without prescription-necessary supplementation (i.e., entirely OTC), have been demonstrated effective in preventing COVID-19 at 1 dose/day; and, at 2 doses/day with no or only minimal prescription-necessary supplementation (e.g., only Azithromycin, Doxycycline or other medications, as above), are considered effective in treating the mild to moderate symptoms of early-stage COVID-19. Thus, prophylactic use of our OTC formulations and early use of the OTC formulations plus minimal antibiotic supplementation may significantly reduce the incidence of the moderate to severe symptoms of later-stage COVID-19 that may require expensive, scarce or potentially risk-bearing prescribed medications and/or in-hospital procedures. As noted, use of our OTC formulations and methods may prevent virus spread from asymptomatic carriers and, thus, help address threats of "second wave infections."
In addition, our formulations and methods may have beneficial effects on weight reduction, blood pressure control [20], diabetes [21], cardiovascular health [22], mood and memory [23].
Additional methods
Combination of the formulations and methods with anti-TNF and interleukin-modulating substances; with antibiotic and anti-viral substances
We anticipate and advocate for treatment of COVID-19 any combinations of the above formulations and methods with use of existing medications, both chemical compounds and or antibodies with known anti-TNF alpha activity (e.g., Remicade (infliximab) and other compounds), substances known and/or that become accepted as effective modulators of interleukins such as IL-6 and of other cytokines (e.g., Acterma (tocilizumab) [24] and other compounds).
We anticipate and advocate any combinations of the above formulations and methods with use of macrolide and other antibiotics, including but not limited to the aforementioned Zithromax, Isoniazide, Nitrofurantoin, Doxycycline and/or Levaquin, and/or with retroviral therapy (ribavirine, leronlimab, remdesivir or any other retroviral medication; see Tables 1 and 2). In a hospital setting, the above formulations and methods can also be combined with use of dipyridamole and/or steroids. Such enhanced formulations (i.e., the formulations and methods presented above in the Formulations and Methods sections, plus any of the additional chemical and/or biological components of this section and/or following sections of the disclosure) can generally be used even in circumstances of mechanical ventilation if administered via PEG or other feeding tube or, with adjustments addressing solution state, by IV.
Combination of the formulations and methods with ultraviolet light (UVC and/or UVA) disinfection
A factor contributing to infection by the pathogens that cause COVID-19, other viral diseases and other microbial illnesses, is contact with surfaces upon which the pathogens have been deposited and remain infectious, invisible to the eye. Even freshly washed or gloved hands can readily pick up infectious agents from such surfaces, and then spread the agents.
Current evidence suggests that novel coronavirus may remain viable for hours to days on surfaces of a variety of materials. Cleaning of visibly dirty surfaces followed by disinfection of the cleaned surfaces is a best practice measure for prevention of COVID-19 and other viral respiratory illnesses in households and community settings.
Ultraviolet light (UVC and/or UVA) has been shown to be effective in disinfection of surfaces against coronavirus and other viruses and bacteria [25-27]. As an important step in prevention of infection by such pathogens, household surfaces and the outer packaging of products and groceries should be made free of infectious agents. This is certainly true of surfaces that are used as preparation areas for the formulations and of products that are components of the formulations.
We anticipate and advocate any combinations of the above formulations and methods with ultraviolet light (UVC/UVA) surface disinfection using standard LED, fluorescent lamps or other light emitting devices, and even a simple timer (see below) set for times people are not in the room being treated (e.g. 3-4 am). We anticipate and advocate use of our device system of light source and timer. As illustrated in Figures 1, 1a, 2, 2a, 2b and 2c, the lamps of this additional system and method can be installed in ceiling fixtures or on mounts and used to disinfect surfaces, purchases and groceries. Extrapolating from sterilization times under lab conditions of the studies [25-27], we suggest using our system of lamps with timers (or of lamps without timers in vacant and preferably closed rooms or other enclosures such as closets) for a one hour time period. With adequate precautions and eye-protection, the same lamps can be used hand-held to disinfect surfaces, purchases and groceries.
Combination of the formulations and methods with chemical surface disinfection
We anticipate and advocate any combinations of the above formulations and methods with surface disinfection using germicidal disinfectants, such as Mediclean germicidal cleaner concentrate or spray, alcohol-based (e.g., 70% or higher alcohol) cleaners, 70% isopropyl alcohol.
Combination of the formulations and methods with local heat for patients with pulmonary symptoms
Local heating of the throat, chest, sides and back of the thorax can be achieved with local wet wraps (based on Zalmanov techniques or methods [28]), heating patches (e.g., mustard patch (Sinapis charta, or "gorchichnik"), capsicum patch or any type of heating patch), by applying vessels to the skin filled with hot air ("banki"), or any other local heating method. Such heating has been used to good effect to alleviate symptoms. We anticipate and advocate any combinations of the above formulations and methods with such local heating.
Combination of the formulations and methods with probiotics
Probiotics have been shown to modulate and enhance the mammalian immune system [29]. We anticipate and advocate any combinations of the above formulations and methods with probiotic treatments (e.g., Florastor Saccharomyces boulardii CNCM I-745 (S. boulardii) or other yeast or bacteria species and/or other probiotic and prebiotic substances).
Combination of the formulations and methods with hot fluid hydration
We anticipate and advocate any combinations of the above formulations and methods with use of hot fluid hydration to prevent or alleviate dehydration, which can compound a patient's discomfort. While plain hot water suffices to this end, tastier brews increase compliance with a hydration regimen. Addition of some of the above mentioned ancillary components may enhance therapeutic effect. Thus, a suggested recipe: Cut fresh, preferably organic ginger and lemon into an empty pot, kettle or thermos cup. Pour freshly fully boiled water, steep for 5-10 min; serve with honey and optionally add one or more the following (as plant piece extract and/or derivative): Licorice, LianhuaQingwenJiaoNang, Weeping Forsythia Capsule, Japanese or other brands of Honeysuckle Flower, Ephedra Herb (honey-fried), Bitter Apricot Seed (stir-baked), Isatis Root, Male Fern Rhizome, Heartleaf Houttuynia Herb, Cablin Patchouli Herb, Rhubarb, Big flower Rhodiola Root or other herbs.
Combination of the formulations and methods with modalities for stress control and reduction
We anticipate and advocate any combinations of the above formulations and methods with modalities for stress control and reduction. Patients and others (e.g., patient's relatives, neighbors, coworkers, caregivers, etc.) often experience high stress during the course of a potentially life-threatening medical condition. This is true all the more so in the case of COVID-19, with its characteristics of global pandemic, high infection rate and demonstrated fatality, all exacerbated by endless media coverage, lengthy societal lockdown and the uncertainties generated by the suddenness, novelty and unknowns of the disease.
Studies have established long-term high stress as a suppressor of the immune response, rendering patients and others more susceptible to disease effects, with negative health outcomes ensuing. Additionally, distressed patients and others are often less likely to properly follow through on hygiene and medicament protocols that may be key elements of prevention and treatment of disease.
A modality for patient's and other's stress control and reduction includes adding to our dosing formulations (presented above in the Formulations and Methods sections) (or for a patient or other taking in conjunction with our dosing formulations) one or more of extracts, compounds, parts or derivatives: Valerian Root (e.g., 0.8% Varleric acid), Ashwagandha (e.g., root extract, 1.5% Withanolides), Chamomile (Matricarcia recutita flower), Lemon Balm Leaf (Melissa officinalis), Passion Fruit (Passiflora edulis), L-Tryptophan, Gamma-Aminobutyric acid (GABA) (e.g., 200 mg), Jujube Seed Extract (e.g., 2% Jujubosides), Inositol (e.g., 600 mg), Niacin (e.g., 10 mg), Calcium (e.g., 200 mg), Magnesium (e.g., 200 mg), Vitamin B-6 (e.g. pyridoxine hydrochloride, 20 mg), Taurine (e.g., free form, 600 mg), Glycine (e.g., free form, 400 mg).
Another modality for patient's and other's stress control and reduction includes hot fluid relaxation therapy. In this modality for stress control and reduction, use is made of hot tea infusions based on any of Valerian Root, Ashwagandha, Chamomile (Matricarcia recutita flower), Lemon Balm Leaf (Melissa officinalis), Passion Fruit (Passiflora edulis) or other herbs.
Combination of the formulations and methods with isometric exercise
Isometric exercise, in which static positions are maintained without movement for specific time periods, has shown to decrease stress and boost immune response. Such exercise can be readily performed even under COVID-19 quarantine conditions without special equipment or accommodations even by individuals with deconditioning, medical problems or disability. We anticipate and advocate any combinations of the above formulations and methods with isometric exercise.
Exemplary isometric exercises are illustrated in Figure 3. Recommendations often include starting with exercises number 1, 5 and 7 illustrated below, beginning with one minute for each exercise, twice a day, and then increasing as tolerated to at least 20 minutes a day total of those and other exercises.
Combination of the formulations and methods with low sugar anti-inflammatory diet
We anticipate and advocate any combinations of the above formulations and methods with low sugar anti-inflammatory diets. Such diets generally call for elimination from one's diet of junk food and most commercial carbonated drinks (exceptions: seltzer and similar drinks); for decrease or elimination of processed carbohydrates; and for increase of complex, slowly digested carbohydrates, of organic vegetables (including green leafy vegetables) and of fruits and nuts. Such diets may replace the minimized sugar with zero calorie or low calorie substitutes such as those derived from the Stevia leaf or from Monk fruit or with tolerated sugar-alcohols. Such diets often allow a once-weekly serving of red meat, with a strong recommendation for organic or free-range meat. Additional recommendations include a daily input of fish oil and/or turmeric (2-4 gm daily).
Combination of the formulations and methods with immune-response boosting supplementation:
We anticipate and advocate any combinations of the above formulations and methods with products, substances and/or extracts clinically accepted as enhancing the human immune response, such as the extracts/derivatives of the above-mentioned Amla fruit and Red Reishi mushrooms. These also include low-concentration coffee bean supplements, and extracts and/or derivatives of Maitake mushroom (Grifola frondosa) and Turkey Tail mushroom (Trametes versicolor). Echinacea (purpurea, angustifolia and pallida) may be recommended, particularly for early and short-term use. (Until clarifying research is available, Elderberry would not be recommended.)
Combination of the formulations and methods with essential oil use
We anticipate and advocate any combinations of the above formulations and methods with essential oil use, for both external and internal use of any type of essential oil (e.g., formulas branded "Thieves", "Immune Boost", and others).
Combination of the formulations and methods with mindful meditation
We anticipate and advocate any combinations of the above formulations and methods with mindful meditation. Mindful meditation is widely thought to reduce stress and anxiety, and to boost immune system performance. We have used the protocol available in the link below to good effect. We recommend starting with track 1 daily for one week, then track 2 for one week, etc. In addition, on each day, track 5 and/or track 6 and/or track 7 can be added:
https://www.penguinrandomhouse.com/mindfulness-meditation-downloads/
Combination of the formulations and methods with pulmonary hygiene exercises
We anticipate and advocate any combinations of the above formulations and methods with exercises for maintenance of pulmonary hygiene.
Exemplary breathing exercises for pulmonary hygiene, instructions for which are presented in stages addressed to the patient (preferably, all the following three stages should be included in a personal regimen cycle of pulmonary hygiene breathing exercises):
• RELAXATION: Inhale through your nose for a count of four; then hold your breath for a count of seven; and then exhale through your mouth for a count of eight. (Repeat RELAXATION stage 2-3 times.)
• FOCUS: Inhale through your nose for a count of five; then hold your breath for a count of five; then exhale through your mouth for a count of five; then pause for a count of five. (Repeat FOCUS stage 2-3 times.)
• PULMONARY CAPACITY: (Requires equipment: "Blow-bottle" as supplied by hospital; or, an upright water bottle ~2/3 full, with narrow plastic tubing inserted fully into the water to the bottle bottom and secured to the bottle's exterior, with the tube length such that the free end is readily available to the patient; see Figure 4, below. Both the tubing diameter and the bottle size may be chosen based on availability and, as the patient will be exhaling against the water, also the patient's tolerance/capacity.) Take 6 deep breaths; then cough (covering mouth/face); then, lying down on your belly, take shallow breaths for 5-10 minutes; then, remaining on your belly, breath for another 5-10 minutes, but now exhaling by mouth into the tubing connected with the bottle, raising the ball or bellows within the hospital-supplied blow-bottle or, in a DIY device as given in Figure 4, causing bubbles to rise through the water of the open bottle.
We recommend repeating the personal regimen cycle of breathing exercises 2-3 times a day. (In a hospital setting, typically only the PULMONARY CAPACITY stage's blow-bottle activities are conducted. We recommend a full personal regimen including all stages.)
Combination of the formulations and methods with anticoagulation medication
We anticipate and advocate any combinations of the above formulations and methods with oral (or other route) regimens of anti-coagulant medication, both in the clinical setting and on an out-patient basis. It has become increasingly clear that a large percentage of COVID-19 patients, particularly those that become critically ill, develop a pro-thrombotic state which places them at a significantly increased risk of thrombosis. Thrombotic events include autopsy-proven microvascular thrombosis in a variety of vascular beds (pulmonary, hepatic, renal), likely contributory to end-organ-function deterioration. Also clinically established is the increased risk of large vessel thrombosis such as extensive DVTs, as well as life- and/or limb-threatening arterial thromboses, even in otherwise low risk patients [30, 31].
We recommend oral (or other route) anticoagulant regimens that may include physician-recommended selection from ASA (aspirin) and Plavix, as well as Lovenox (low molecular weight heparin), warfarin, rivaroxaban, apixaban, dabixaban or other anti-coagulation medicines. A diet or supplementation regimen rich in Omega-3 fish oils and/or Vitamin E may also or alternatively be beneficial for its blood thinning effect.
Combination of the formulations and methods with use of angiotensin receptor blockers
We anticipate and advocate any combinations of the above formulations and methods with use of angiotensin receptor blockers (ACE receptor blockers) and of other medicaments that interfere with viral binding. As a first step in mounting its viral attack, the coronavirus that causes COVID-19 binds to ACE2 receptor molecules on the exterior of lung lining cells. Thus, blocking the receptors with specific medicinal molecules may render the receptors completely or partly inaccessible to virus binding, preventing or at least partly inhibiting the COVID-19 virus from latching onto and then entering the potential host cells. Preparations that include such medicinal molecules would include Moexipril HCl or other medications and agents with ACE inhibitory actions.
The virus binds to the ACE2 receptor by means of a spike (S) protein of the viral coat. To bind, the S protein needs to first be primed by an enzyme. Inhibiting that enzyme prevents priming and, thus, prevents binding. There are specific medicinal molecules that inhibit the enzyme. Preparations that include such medicinal molecules would include Camostat mesilate or other medications and agents with such selective protease action.
Combination of the formulations and methods with other medications/agents
We anticipate and advocate any combinations of the above formulations and methods with other medications or agents (such as antibodies) that contribute to the prevention of COVID-19, to alleviation of its symptoms and/or to cure of the disease. Such medications and agents include those presented in Tables 1 and 2.
Patient groups monitoring
Since our office was open for essential procedures and treatments, 94 patients were followed for up to an 8 week period during the COVID-19 pandemic in Ohio, with all CDC and state rules and guidelines carefully observed. The same 94 patients usually had to follow up with other medical facilities and had other potential exposures to the virus.
Since testing and the conventional medications were not readily available and access to personal protective equipment was limited, we suggested to participants to voluntarily use our over-the-counter formulations and methods for prevention and treatment. 54 participants (Group 1) implemented the over-the-counter regimen (mostly the core formulations and some or all the methods), while 60 (Group 2) chose to decline the regimen of formulations and methods out of concerns ranging from cost, education and socio-economic barriers or other reasons. Patients typically reported use of the recommended Vitamin C, Zinc and Vitamin E, as described above, over the observation time, with some use of Quercetin as above (based on the availability and cost) and of Quina, and implementation of methods described above (usually life style modifications, exercises and relaxation). All individuals in a high exposure group (exposed 6 times or more) were sure to use Quercetin. The individuals in this group included members of our staff who were in close contact with the high risk patients providing them our office's essential procedures and treatments.
Six patients out of 60 (of Group 2) who refused the formulations and methods described above developed clinical COVID-19 infection and were quarantined (but, prior to development of symptoms, they were seen in our office, creating exposure for other participants). Only three out of six had access to testing and, upon being tested, were positive for COVID-19.
Since the exact infection rate after an exposure to COVID-19 is not known, we assumed two models of 30% infection and of 10% infection after an exposure. Lack of complete randomization (some of the 54 patients implemented most of the core formulations and only part of the methods; compliance was based on patient self-reporting), is compensated by the very conservative assumptions about the rate of infection (30% and 10%) and exposure rate (for six symptomatic patients, we can assume four times more asymptomatic carriers than six symptomatic patients based on the CDC model, according to which 80% of infected individuals remain asymptomatic and 20% develop symptoms).
30% of patients who are exposed get infected
Probability of getting sick once exposed =20% (after each exposure; this is constant for each exposure)
54 patients in group that used the formulations and methods.
Expected number of patients getting infected =16.2 (30% of 54)
To simplify the model, round this number and assume 16 patients are infected.
8 exposed 6 times;
Apply binomial model
Probability any individual stays well after 1 exposure =.8
Probability any individual stays well after 6 exposures =.8^6 =.2621
Probability all 8 patients stay well = .2612^8 =.00002.
8 exposed 3 times
Probability any individual stays well after 3 exposures = .8^3 =.512
Probability all 8 patients stay well = .512^8 =.0047
Probability all individuals in both groups stay well =product of above probabilities = .0000001
This is statistically significant at the .05 level (also well below .01).
Probability that all individuals stay well is .0000001
This would be considered statistically significant at the .05 level (also well below the .01 level)
This model is statistically significant even with the assumption that only 10% percent of the exposed patients get infected (an extremely conservative underestimate in light of the current virus spread pattern):
54 patients in experiment
Expected number of patients getting infected =5.4 (10% of 54)
To simplify the model, round this number and assume 5 patients are infected
(To gauge the effect of rounding to 5, we separately, below, run a case where we round to 6.)
Probability any individual stays well after 6 exposures = .8^6 =.2621
Probability all 4 patients stay well = .2621^4 =.0047
Probability any individual stays well = 0.8^3 =.512
Probability all individuals in both groups stay well =product of above probabilities = .0024
Case where we round to 6:
Probability any individual stays well after 6 exposures= .8^6 =.2621
Probability any individual stays well after 3 exposures= .8^3 =.512
Result: Probability that all individuals stay well is between .0012 and .0024
Group 1 vs. Group 2 analysis
54 patients take supplements; 0 of these develop symptoms.
60 patients do not take supplements; 7 of these develop symptoms. Using this information to estimate the probability
of an individual developing symptoms, we conclude that:
The probability of an individual developing symptoms = 7/60 = .1167
Binomial probability calculation
The probability of an individual not developing symptoms = 1- .1167=.8833
Result: Probability that none of the 54 patients develop symptoms = .8833^54 = .0012. This is statistically significant at the .05 level (also significant at the .01 level).
This is an extensive case review analysis of use of over the counter formulations and methods for prevention and treatment of COVID-19. The analysis shows a strong statistical significance in favor of the use of the formulations and methods in a large patient sample even with the assumption that only 10% percent of the exposed patients get infected (which is an extremely conservative underestimate in light of the current virus spread pattern). The conservative infection rate and exposure model compensates for the lack of complete randomization of the sample described above.
While the pandemic is unfolding and disrupting lives of hundreds of millions of people and causing millions of infected cases and hundreds of thousands of death, the scientific debate is still continuing as to whether COVID-19 will follow the pattern of the 2003 SARS outbreak or the 2012 MERS outbreak (which is still developing in waxing and waning fashion over 8 years). Some epidemiologists expect "COVID-19 activity" over the next 18-24 months [32]. While the studies are ongoing, there is still a dearth of clear data on the effectiveness of the prescribed medications and also substantial uncertainty regarding schedules of vaccine production and availability (Tables 1 and 2).
Debate is ongoing over efficacy of testing protocols and over efficacy and duration of antibody immunity. In this environment, the over-the-counter formulations and methods described above can provide an economical and effective alternative available to the public and healthcare workers.
Formulations and Methods are US patent pending to Leon Margolin, with foreign filing license granted.
Figure 1: Portable ultraviolet light (UVC/UVA) lamp mounted on stand and set via appliance timer for surface disinfection. Timer below kitchen counter is illustrative of the type shown here.
Figures 1a and 1b: UVC/UVA (black light) stand for office waiting room after-hours disinfection.
Figure 2: Use of existing fixture of mudroom (or any other closed room) for ultraviolet light disinfection.
Figure 2a: Mail, clothes, mask, utensils and food set for ultraviolet light disinfection in UVC/UVA-equipped room.
Figures 2b and 2c: Using closeable clothing closet for UVC/UVA disinfection of personal items and clothing (for emergency/essential workers and general public).
Figure 3: Exemplary isometric exercises.
Figure 4: A person wishing to incorporate PULMONARY CAPACITY with a device such as that depicted, would inhale through the nose and exhale by mouth into the free end of the tube, forcing bubbles through the water. The duration of the exercise can be set based on the patient's tolerance/capacity and may be increased accordingly. Our recommendation for duration is at least 15 minutes daily.
MEDICAMENT NAME
Studies/Comments
Hydroxychloroquine Sulfate
Hydroxychloroquine Sulfate is an antimalarial agent used for the treatment of systemic lupus erythematosus, rheumatoid arthritis and other autoimmune, inflammatory and dermatologic conditions. Also acts as an inhibitor of autophagy and toll-like receptor (TLR) 7/9.
Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial
Carfilzomib (PR-171)
Carfilzomib (PR-171) is an irreversible proteasome inhibitor with IC50 of <5 nM in ANBL-6 cells, displayed preferential in vitro inhibitory potency against the ChT-L activity in the β5 subunit, but little or no effect on the PGPH and T-L activities.
Fast Identification of Possible Drug Treatment of Coronavirus Disease -19 (COVID-19) Through Computational Drug Repurposing Study
Favipiravir (T-705)
Favipiravir (T-705) is a potent and selective RNA-dependent RNA polymerase inhibitor, used to treat influenza virus infections.
Discovering drugs to treat coronavirus disease 2019 (COVID-19)
Azithromycin is an antibiotic by inhibiting protein synthesis, used for the treatment of bacterial infections.
Darunavir Ethanolate
DarunavirEthanolate (DRV) is a nonpeptidic HIV protease inhibitor, used to treat HIV infection.
Many drugs already approved by FDA may have promise against COVID-19
Ciclesonide
Ciclesonide is a glucocorticoid used to treat obstructive airway diseases.
Therapeutic potential of ciclesonide inhalation for COVID-19 pneumonia: Report of three cases
Daunorubicin HCl
Daunorubicin HCl inhibits both DNA and RNA synthesis and inhibits DNA synthesis with Ki of 0.02 μM in a cell-free assay.
Chloroquine diphosphate
Chloroquine diphosphate is a 4-aminoquinoline anti-malarial and anti-rheumatoid agent, also acting as an ATM activator.
Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro
Tideglusib
Tideglusib is an irreversible, non ATP-competitive GSK-3β inhibitor with IC50 of 60 nM in a cell-free assay; fails to inhibit kinases with a Cys homologous to Cys-199 located in the active site. Phase 2.
Structure of M pro From COVID-19 Virus and Discovery of Its Inhibitors
Camostat is a trypsin-like protease inhibitor, inhibits airway epithelial sodium channel (ENaC) function with IC50 of 50 nM, less potent to trypsin, prostasin and matriptase.
The Impact of Camostat Mesilate on COVID-19 Infection (CamoCO-19)
Remdesivir (GS-5734)
Remdesivir,amonophosphoramidate prodrug of an adenosine analog, is an investigational broad-spectrum antiviral agent with in vitro activity against multiple RNA viruses, including Ebola and CoV.
Bictegravir is a novel, potent, once-daily, unboosted inhibitor of HIV-1 integrase.
Potential COVID-2019 3C-like Protease Inhibitors Designed Using Generative Deep Learning Approaches
Pitavastatin Calcium
Pitavastatin calcium, a novel member of the medication class of statins, is a calcium salt formulation of pitavastatin which is a highly effective HMG-CoA reductase inhibitor.
Disulfiram is a specific inhibitor of aldehyde-dehydrogenase (ALDH1), used for the treatment of chronic alcoholism by producing an acute sensitivity to alcohol.
Nafamostat mesilate is a synthetic serine protease inhibitor, used as an anticoagulant during hemodialysis.
Nafamostat inhibits SARS-CoV-2 infection, preventing COVID-19 transmission
Lamivudine is a potent nucleoside analog reverse transcriptase inhibitor, used for treatment of chronic HBV and HIV/AIDS. It works by blocking the HIV reverse transcriptase and hepatitis B virus polymerase.
Shikonin
Shikonin, a potent and specific Pyruvate kinase M2 (PKM2) inhibitor, is a major component of zicao (purple gromwell, the dried root of Lithospermum erythrorhizon), a Chinese herbal medicine with various biological activities. It is also an inhibitor of TMEM16A chloride channel activity using cell-based fluorescent-quenching assay.
Lopinavir
Lopinavir is a potent HIV protease inhibitor with Ki of 1.3 pM in a cell-free assay.
Clinical characteristics and therapeutic procedure for four cases with 2019 novel coronavirus pneumonia receiving combined Chinese and Western medicine
Mitoxantrone 2HCl
Mitoxantrone is a type II topoisomerase inhibitor with IC50 of 2.0 μM, 0.42 mM for HepG2 and MCF-7/wt cells, respectively.
Nelfinavir Mesylate
Nelfinavir Mesylate is a potent HIV protease inhibitor with Ki of 2 nM.
Ritonavir
Ritonavir is a Cytochrome P450 3A and Protease Inhibitor; Also inhibits Cytochrome P450 2D6, P-Glycoprotein and induces Cytochrome P450 2C19, Cytochrome P450 1A2, Cytochrome P450 2C9, Cytochrome P450 2B6 and UDP Glucuronosyltransferases.
Ivermectin is a glutamate-gated chloride channel (GluCls) activator, used as a broad-spectrum antiparasitic drug.
Tenofovir blocks reverse transcriptase and hepatitis B virus infections.
Rosuvastatin is an inhibitor of HMG-CoA reductase, an enzyme that catalyzes the rate-limiting step in cholesterol biosynthesis, with Ki value (inhibition constant) of approximately 0.1 nM.
Darunavir is a nonpeptidic HIV protease inhibitor, used to treat HIV infection.
Ledipasvir (GS5885)
Ledipasvir (GS5885) is a HCV NS5A polymerase inhibitor, used for the treatment of hepatitis C virus infection.
Prediction of the SARS-CoV-2 (2019-nCoV) 3C-like protease (3CL pro) structure: virtual screening reveals velpatasvir, ledipasvir, and other drug repurposing candidates
Telaprevir (VX-950)
Telaprevir (VX-950) is an HCV NS3-4A serine protease inhibitor with IC50 of 0.35 μM.
α-Ketoamides as Broad-Spectrum Inhibitors of Coronavirus and Enterovirus Replication: Structure-Based Design, Synthesis, and Activity Assessment
Danoprevir (ITMN-191)
Danoprevir(ITMN-191) is a peptidomimetic inhibitor of the NS3/4A protease of hepatitis C virus (HCV) with IC50 of 0.2-3.5 nM, inhibition effect for HCV genotypes 1A/1B/4/5/6 is ~10-fold higher than 2B/3A. Phase 2.
First Clinical Study Using HCV Protease Inhibitor Danoprevir to Treat Naive and Experienced COVID-19 Patients
Rosuvastatin Calcium
Rosuvastatin Calcium is a competitive inhibitor of HMG-CoA reductase with IC50 of 11 nM in a cell-free assay.
Carmofur
Carmofur is a highly potent acid ceramidase inhibitor, used in the treatment of breast and colorectal cancer.
PX-12
PX-12 is a potent thioredoxin-1 (Trx-1) inhibitor by irreversibly thioalkylation of Cys73 of Trx-1. Phase 2.
Atovaquone
Atovaquone is a medication used to treat or prevent for pneumocystis pneumonia, toxoplasmosis, malaria, and babesia.
TDZD-8
TDZD-8 is a non-ATP competitive GSK-3β inhibitor with IC50 of 2 μM; minimal inhibitory effect observed on CDK1, casein kinase II, PKA and PKC.
Praziquantel is an anthelmintic effective against flatworms.
Boceprevir
Boceprevir is an oral, direct acting hepatitis C virus (HCV) protease inhibitor with Ki value of 14 nM for NS3. It is used in combination with other antiviral agents in the treatment of chronic hepatitis C, genotype 1.
Velpatasvir
Velpatasvir is a second-generation NS5A inhibitor that inhibits hepatitis C viral replication through acting on the crucial "membranous web" that facilitates RNA replication.
Prulifloxacin (NM441)
Prulifloxacin, the prodrug of ulifloxacin, is a broad-spectrum oral fluoroquinolone antibacterial agent.
Indinavir Sulfate
Indinavir sulfate is a specific and potent inhibitor of HIV-1 protease and is widely used in the treatment of AIDS.
Potential Therapeutic Agents for COVID-19 Based on the Analysis of Protease and RNA Polymerase Docking
Moexipril HCl
MoexiprilHCl is a potent orally active nonsulfhydryl angiotensin converting enzyme (ACE) inhibitor, used for the treatment of hypertension and congestive heart failure.
Bepotastine Besilate
Bepotastine is a non-sedating, selective antagonist of histamine 1 (H1) receptor with pIC50 of 5.7.
Bepotastine is a non-sedating, selective antagonist of the histamine 1 (H1) receptor that is indicated in allergic rhinitis, urticaria, and pruritus associated with skin disease.
Ebselen
Ebselen is a small-molecule capsid inhibitor of HIV-1 Replication with IC50 of 46.1 nM in TR-FRET assay.
Table 1: List of additional agents; description, with suggested mechanism of action; studies/comments.
Tocilizumab (anti-IL-6R)
Tocilizumab (anti-IL-6R) is a humanized monoclonal antibody that binds to the interleukin-6 receptor, MW: 148 KD.
Tocilizumab treatment in COVID-19: A single center experience
Serum antibody, with or without modifications, for conferring passive immunity
Harvested through plasmapheresis from convalesced COVID-19 patients presenting sufficiently high antibody titers
Numerous programs underway worldwide for titer testing, harvesting, therapeutic use
Table 2: COVID-19 Related Antibodies.
Table 3: Top scoring ligands for S-protein: ACE2 receptor interface that have undergone regulatory review in the USA or elsewhere [5].
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Li X, Zhang C, Liu L, Gu M (2020) Existing bitter medicines for fighting 2019-nCoV-associated infectious diseases. FASEB J: 34.
Dabbagh-Bazarbachi H, Clergeaud G, Quesada IM, Ortiz M, O'Sullivan CK, Fernández-Larrea JB (2014) Zinc Ionophore Activity of Quercetin and Epigallocatechin-Gallate: From Hepa 1-6 Cells to a Liposome Model. J Agric Food Chem 13: 8085-8093.
te Velthuis AJW, van den Worm SHE, Sims AMC, Baric RS, Snijder EJ, et al. (2010) Inbihibits Coronavirus and Arterivirus RNA polymerase Activity In Vitro and Zn ionophore Block the Replication of These Viruses in Cell Culture. PLoS Pathog 6: e1001176.Zn.
Smith M, Smith JC (2020) Repurposing Therapeutics for COVID-19: Supercomputer-Based Docking to the SARS-CoV-2 Viral Spike Protein and Viral Spike Protein-Human ACE2 Interface.
Kim YJ, Park W (2016) Anti-Inflammatory Effect of Quercetin on RAW 264.7 Mouse Macrophages Induced with Polyinosinic-Polycytidylic Acid. Molecules 21: 450.
Qiu X, Kroeker A, He S, Kozak R, Audet J, et al. (2016) Prophylactic Efficacy of Quercetin 3-β-O-d-Glucoside Against Ebola Virus Infection. Antimicrob Agents Chemother 60: 5182-5188.
Wu W, Li R, He J, Jiang S, Liu S, et al. (2016) Quercetin as an Antiviral Agent Inhibits Influenza A Virus (IAV) Entry. Viruses: 8.
Yi L, Li Z, Yuan K, Qu X, Chen J, et al. (2004) Small Molecules Blocking the Entry of Severe Acute Respiratory Syndrome Coronavirus into Host Cell. J Virol 78: 11334-11339.
McGill Tribune, SBT (Student Society of McGill University). Montreal researchers propose a treatment for COVID-19: Written by Abbas Mehrabian and Sepideh Mikaeeli on March 17, 2020.
Montreal Clinical Research Institute: The Lazaridis Family Foundation contributes $1 million to the IRCM to support its research on the COVID-19: March 4 2020.
Liu W, Qi Y, Liu L, Tang Y, Wei J, et al. (2016) Suppression of Tumor Cell Proliferation by Quinine via the Inhibition of the Tumor Necrosis Factor Receptor‑associated Factor 6‑AKT Interaction. Mol Med Rep 14: 2171-2179.
Higgins PDR, Ng S, Danese S, Rao K (2020) The Risk of SARS-CoV-2 in Immunosuppressed IBD Patients. Crohn's & Colitis: 2.
Cheng SC, Wu YH, Huang WC, Pang JHS, Huang TH, Cheng CY (2019) Anti-inflammatory Property of Quercetin Through Downregulation of ICAM-1 and MMP-9 in TNF-α-activated Retinal Pigment Epithelial Cells. Cytokine: 48-60.
Liu Y, Yu C, Ji K, Wang X, Li X, et al. (2019) Quercetin Reduces TNF-α-induced Mesangial Cell Proliferation and Inhibits PTX3 Production: Involvement of NF-κB Signaling Pathway. Phytother Res 33: 2401-2408.
Haleagrahara N, Miranda-Hernandez C, Alim A, Hayes L, Bird G, et al. (2017) Therapeutic Effect of Quercetin in Collagen-Induced Arthritis. Biomed Pharmacother 90: 38-46.
Caly J, Druce JD, Catton MG, Jans DA, Wagstaffb KM (2020) The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Therapy 178: 104787.
Gates Foundation funded French Research Group commences Clinical Trial targeting COVID-19. April 26, 2020.
Thorlund K, Dron L, Park J, Hsu G, Forrest JI, et al. (2020) A real-time dashboard of clinical trials for COVID-19. Lancet Digital Health.
Marunaka Y, Marunaka R, Sun H, Yamamoto T, Kanamura N, et al. (2017) Actions of Quercetin, a Polyphenol, on Blood Pressure. Molecules 22: 209.
Eid HM, Haddad PS (2017) The Antidiabetic Potential of Quercetin: Underlying Mechanisms. Curr Med Chem 24: 355-364.
Patel RV, Mistry BM, Shinde SK, Syed R, Singh V, et al. (2018) Therapeutic Potential of Quercetin as a Cardiovascular Agent. Eur J Med Chem 155: 889-904.
Babaei F, Mirzababaei M, Nassiri-Asl M (2018) Quercetin in Food: Possible Mechanisms of Its Effect on Memory. J Food Sci: 2280-2287.
Alattar R, Ibrahim TBH, Shaar SH, Abdalla S, Shukri K, et al. (2020) Tocilizumab for the Treatment of Severe COVID-19 J Med Virol.
Eickmann M, Gravemann U, Handke W, Tolksdorf F, Reichenberg S, et al. (2020) Inactivation of three emerging viruses - severe acute respiratory syndrome coronavirus, Crimean-Congo haemorrhagic fever virus and Nipah virus - in platelet concentrates by ultraviolet C light and in plasma by methylene blue plus visible light. Vox Sang 115: 146-151.
Eickmann M, Gravemann U, Handke W, Tolksdorf F, Reichenberg S, et al. (2018) Inactivation of Ebola virus and Middle East respiratory syndrome coronavirus in platelet concentrates and plasma by ultraviolet C light and methylene blue plus visible light, respectively. Transfusion 58: 2202-2207.
Szeto W, Yam WC, Huang H, Leung DYC (2020) The efficacy of vacuum-ultraviolet light disinfection of some common environmental pathogens. BMC Infect Dis 20: 127.
Eremin MS, Shevchenko LI, Korgun ZF, Eremin SM, Pegova LA, et al. (1969) Hydrotherapy according to the method of I. Gillershtein and A.S. Zalmanov] (Russian). VoprKurortolFizioter Lech FizKult 34: 467-468.
Yousefi B, Eslami M, Ghasemian A, Kokhaei P, SalekFarrokhi A, et al. (2019) Probiotics importance and their immunomodulatory properties. J Cell Physiol: 8008-8018.
Lippi G, Favaloro EJ (2020) D-dimer is Associated with Severity of Coronavirus Disease 2019: A Pooled Analysis. Thrombosis and Haemostasis.
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At Limoneto the day starts with a good breakfast.
Milk and coffee or tea, bread , butter and jam or marmelade, yogurt,cheese and ham or sliced sausages , fresh fruit and fruit juice, and more are available on our morning buffet. We serve our own homemade lemon and orange marmalade .
At night we prepare dinner for our guests.
Limoneto offers typical Sicilian cooking with home–made pasta . Most of the vegetables served are grown organically on the farm. Fish and meat are bought locally to help our local economy grow .
Francesco , the chef ,cooks from fresh and will try to comply with your tastes. Guests can choose from a choice of bottled Sicilian wines.
On Saturday night we suggest a special evening meal. On a long buffet table there are lots of different preparation and guests can help themselves of whatever they like as many times as they want! Local people enjoy coming to our place in parties to spend an evening out.
We have recently improved our offer of food with a delicious Italian pizza served on some days during the week .
In summer dinner is served on our open terrace, surrounded by lemon trees.


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Q: how to power up a subtractor using a window comparator? I'm making a circuit that will detect whether a voltage(V1)is in between the range 1-2 V. If so I want to switch ON a subtractor and output V1 - 1 V.
I initially thought of connecting the output of the window comparator to power up the subtractor. What i thought was if V1 is in the correct range, the window comparator's output will be around +7V so I connected it to the supply of the subtractor(created using an opamp).
However what i noticed is that the output voltage drops significantly when powering up the subtractor. Is there any better recommended way which I can use?


In Wave Planning customer is releasing waves using scheduled concurrent request.
It is possible to schedule the request directly from the Wave Workbench (as shown on attached screenshots) and It is very important for the business to set not only exact day, but also hour – for example 15-MAY-2018 13:00:00.
The concurrent request is being scheduled, but the information about the desired hour is lost. According to previous example the request will be scheduled to 15-MAY-2018 00:00:00.
Desired behavior is to have concurrent request scheduled on exactly the same date/time that was selected by user on Wave Workbench.
Go to Release Concurrently and schedule the release for specific date and time.


Robert has directed the Central Ohio Youth Ballet for 23 years. For the company, he has restaged a number of full length story ballets including La Fille Mal Gardée, A Midsummer Night's Dream, Giselle and The Nutracker and he has set dozens of shorter original ballets. Robert's solid background in classical ballet gives him a solid foundation upon which to draw his ideas and to engage his skill in adapting these works to his young cast of dancers, while maintaining much of the character, story and movement of the traditional works.
Robert danced for five years with the National Ballet of Canada, considered one of the world's top tier ballet companies. While there, he was fortunate to have worked under the direction of Alexander Grant and Eric Bruhn. While with the company, he toured throughout Canada, Europe and the United States performing numerous character and soloist roles. A few that he particularly enjoyed were Puck in A Midsummer Night's Dream, Alain in La Fille Mal Gardée and The Short Guy (hamming it up) in Elite Syncopations.
Robert's early training was in response to an ankle injury he sustained as a high school athlete. Upon the advice of his physical therapist, he began classes at Mary Lynn's Ballet Arts (now California's Riverside Ballet Arts), where he studied alongside noted dancers Darci Kistler and Kip Houston. Robert was a passionate student, finding that his athleticism and ability to perform blended into a field of study where he excelled. From his California base, he went on to train at the National Ballet School on a full scholarship and subsequently as a corps member of National Ballet of Canada.
Following his five years with the National Ballet of Canada, Bob turned his attention to develop his artistic skills as a photographer, as his foster father taught photography at the college level and was thrilled to mentor him. Robert worked professionally in photography for a few years, but was not quite finished with ballet and chose to go to New York to take a take a position with Dennis Wayne's Dancers for a three month tour in Italy. Additionally, Robert has been a guest dancer with many regional companies and from 1994-2004, he taught ballet and choreographed numerous works for the Denison dance department.
Robert also founded The Ballet Academy in Newark, Ohio, a dance school that shares its home with the Central Ohio Youth Ballet, both emphasizing solid technique in primarily ballet and modern dance. He has continued his connection with the National Ballet School by periodically attending their summer teacher training sessions, working with neuromuscular specialist, Irene Dowd as well as the faculty at The NBS. Robert's students have been accepted, many with scholarships, for further training at such schools as The National Ballet School, Julliard, Pacific Northwest Ballet, American Ballet Theatre, New York City Ballet, Boston Ballet, Pittsburgh Ballet Theatre, The Rock School, The Joffrey Ballet, The Kirov Academy, North Carolina School of the Arts, Alvin Ailey American Dance Theatre, the Gelsey Kirkland Academy and with David Howard. His students have also gone on to train, apprentice or dance professionally with companies including Munich Ballet, San Francisco Ballet, BalletMet, The Joffrey Ballet, Grand Rapids Ballet, Rochester City Ballet, Light of the World Ballet, and others.
In partnership with Robert Cole, Lisa Cole created the modern dance branch of the Central Ohio Youth Ballet. The intention was to create and offer a platform of solid training for dancers with specific interests; as a result, they could grow, develop, and thrive. With Lisa's background in ballet and her breadth of training in Cunningham technique, Lewitzky technique and ballet, her vision for concert level work from the COYB dancers blended seamlessly with Robert's.
Like Robert, Lisa's ballet training base was mostly in California at Riverside Ballet Arts, with Bella Lewitzky Dance Company member Fred Strickler, and with UC Riverside faculty member Stephanie Gilliland. Like Robert, having come to dance late in life (her first dance class was at the age of 19), Lisa's path in the field was unconventional. After training solidly in ballet and in modern dance, Lisa was accepted into the university based regional company Groundwork, directed by Stephanie Gilliland, where she danced for two years. From there, she began pursuing an MFA at Ohio State where she was thrilled to work with former Merce Cunningham Dance Company members Ellen Cornfield and Louise Burns. Lisa was encouraged to go to New York and pursue training at the Cunningham Studio, where she accepted a yearlong scholarship, and where she loved the intricacies and technicality of the work. Lisa's path then led to teaching and choreographing for young dancers . She has choreographed dozens of modern pieces for The Central Ohio Youth Ballet which have been showcased in its spring productions. Other pieces were created for the Northeast Ohio Dance Festival and for the Ohio Dance Young Artists Showcase at The Capitol Theatre in Columbus. In addition to her dance training, Lisa holds a BS in Business Administration from the University of California Riverside where she graduated Phi Beta Kappa. Lisa also maintains full certification in Stott Pilates and maintains a studio in Newark, Ohio.
Brittany first danced with Central Ohio Youth Ballet, in the role of Sugar Plum Fairy, as a student at Denison while pursuing a degree in biochemistry. She previously trained with Connecticut Concert Ballet under the direction of former American Ballet Theater dancer, Brian Adams in Manchester, CT . While at the Connecticut Concert Ballet, she also trained with Wendy Fish and David Lawrence. Additionally, as a teen, she pursued intensive training during the summers at the Walnut Hill School. At Denison, Brittany studied both modern dance and ballet to achieve a minor in dance. Brittany also holds an MS in chemistry from The University of Utah and a PharmD from The Ohio State University. She currently works as a pharmacist in Newark and she teaches at The Ballet Academy.
Vanessa began her dance training at Cynthia Kniffin Dance Academy in Norwalk, Ohio where she focused on ballet and pointe. She continued her studies at The University of Akron where she majored in Dance Performance. Vanessa got a taste of the professional ballet world as an intern with the Ohio Ballet, a contemporary ballet company then under the direction of Heinz Poll. Vanessa has performed in COYB's The Nutcracker and she has choreographed for COYB's Bravo!. Vanessa is currently teaching at The Ballet Academy and at Shining Star Dance Studio in Loudonville. Vanessa lives in Mount Vernon with her husband, Terry, and their daughters, Madeline and Gabrielle.


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Home / Attorneys / Amy D. Mitchell
Amy D. Mitchell
200 E. Saint Julian Street
Savannah, GA	31412
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More about this attorney
University of Mississippi School of Law: J.D., 2016
University of Georgia: B.A., International Affairs, 2012
Licensed to Practice
(Not licensed in Georgia)
U.S. District Court: District of Colorado, The Honorable Kathleen Tafoya
U.S. District Court: Northern District of Mississippi, The Honorable Sharion Aycock
Girls on the Run of Coastal Georgia and Lowcountry: Board of Directors
Amy works as an associate in the Firm's employment practice group. Before joining HunterMaclean, Amy served as a clerk for the Honorable Kathleen Tafoya, the U.S. Magistrate Judge for the District of Colorado. Amy also spent two years clerking for the Honorable Sharion Aycock, Chief Judge of the U.S. District Court for the Northern District of Mississippi.
Amy earned her bachelor's degree in international affairs from the University of Georgia in 2012 and her J.D., cum laude, from the University of Mississippi in 2016. During law school, she served as a student advocate for the University of Mississippi Low-Income Housing Clinic. Amy also completed a volunteer legal internship with the Georgia Legal Services Program in Athens, Georgia, in the summer of 2015.