Sulphonamides, MOA, SAR, History of development, Nomenclature of the Sulfonamides, Classification, Spectrum of Action of the Sulfonamides,Structure Activity Relationship, Reducing Toxicity, Cotrimoxazole
THIS PRESENTATION ABOUT ANTIMALARIAL DRUGS DETAILING THE COMPLETE INFORMATION ABOUT THE DRUGS USED WITH ITS MECHANISM OF ACTION, STRUCTURAL ACTIVITY AND DOSES.
Quinolones are synthetic antimicrobials having a quinolone
structure.
Active against gram-ve bacteria, newer fluorinated compounds also inhibit gram +ve bacteria.
First member was nalidixic acid introduced in 1960’s
Their usefulness is limited to urinary and GI tract infections because of
Low potency
Modest blood and tissue levels
Limited spectrum
High frequency of bacterial resistance
In gram negative bacteria –
Inhibition of DNA gyrase enzyme (Inhibit negative super coiling)
In gram positive bacteria –
Inhibition of Topoisomerase IV – Inhibition of nicking and separation of daughter DNA strands after DNA replication
The malformed DNA is digested by Exoneucleases
Malignancy is most familiar as a characterization of cancer.Chemotherapy is a category of cancer treatment that uses one or more anti-cancer drugs as part of a standardized chemotherapy regimen
The all the content in this profile is completed by the teachers, students as well as other health care peoples.
thank you, all the respected peoples, for giving the information to complete this presentation.
this information is free to use by anyone.
Aminoglycosides(medicinal chemistry by p.ravisankar)Dr. Ravi Sankar
Aminoglycosides,Aminocyclitols,Source,Structures of streptomycin,Dihydrostreptomycin,A mention of other aminoglycoside antibiotics,Acid hydrolysis,Mechanism of action,SAR,Dihydrostreptomycin and its importance,therapeutic uses, toxicity.
Sulphonamides, MOA, SAR, History of development, Nomenclature of the Sulfonamides, Classification, Spectrum of Action of the Sulfonamides,Structure Activity Relationship, Reducing Toxicity, Cotrimoxazole
THIS PRESENTATION ABOUT ANTIMALARIAL DRUGS DETAILING THE COMPLETE INFORMATION ABOUT THE DRUGS USED WITH ITS MECHANISM OF ACTION, STRUCTURAL ACTIVITY AND DOSES.
Quinolones are synthetic antimicrobials having a quinolone
structure.
Active against gram-ve bacteria, newer fluorinated compounds also inhibit gram +ve bacteria.
First member was nalidixic acid introduced in 1960’s
Their usefulness is limited to urinary and GI tract infections because of
Low potency
Modest blood and tissue levels
Limited spectrum
High frequency of bacterial resistance
In gram negative bacteria –
Inhibition of DNA gyrase enzyme (Inhibit negative super coiling)
In gram positive bacteria –
Inhibition of Topoisomerase IV – Inhibition of nicking and separation of daughter DNA strands after DNA replication
The malformed DNA is digested by Exoneucleases
Malignancy is most familiar as a characterization of cancer.Chemotherapy is a category of cancer treatment that uses one or more anti-cancer drugs as part of a standardized chemotherapy regimen
The all the content in this profile is completed by the teachers, students as well as other health care peoples.
thank you, all the respected peoples, for giving the information to complete this presentation.
this information is free to use by anyone.
Aminoglycosides(medicinal chemistry by p.ravisankar)Dr. Ravi Sankar
Aminoglycosides,Aminocyclitols,Source,Structures of streptomycin,Dihydrostreptomycin,A mention of other aminoglycoside antibiotics,Acid hydrolysis,Mechanism of action,SAR,Dihydrostreptomycin and its importance,therapeutic uses, toxicity.
sulfonamides are the antimicrobial agents.It's act by folic acid synthesis inhibitors.It is PABA analogue competitive antagonist. first synthesised drug is prontosil.
In this slide contents history, mechanism of action, SAR, classification of drugs, some structure of important drugs, choice of drugs in different purpose, side effect, adverse effect.
Sulphonamindes and Cotrimoxazole Chemotherapy.pdfsudhaunmesh
Chapter 50 of the K. D. Tripathi textbook has information on sulphonamide and cotrimaxazole. In short, I'v used his insights to explore the specifics of sulphonamide and cotrimaxazole in antimicrobial therapy, including their historical background, mechanism of action, clinical applications and more, in using this simple to grasp poerpoint presentation.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
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- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
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Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
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These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
2. INTRODUCTION
The sulphonamides were the first effective
chemotherapeutic agents to be employed systematically
for the treatment and prevention of bacterial infections in
humans.
It is found to be metabolic product of protonsil which is
rensponsible for antibacterial activity.
This has given initiation to develop sulphonamides as a
antibacterial agents.
December 7, 2020 2
4. MODE OF ACTION
Folinic acid (N5 -formyl tetrahydrofolic acid, N5 , N10 -
methylene-tetrahydrofolic acid and N10 -
formyltetrahydrofolic acid) are the important co-enzyme
required for several biosynthetic pathways in human,
bacteria, animals and plants.
In absence of these folate coenzymes, for e.g thymidine
monophosphate (TMP) will not be available to form
nucleic acid hence result in stoppage of cell division.
December 7, 2020 4
5. December 7, 2020 5
Sulfonamide and Trimethoprim acts as inhibitor of folinic acid
pathway and acts as bacteriostatic. They inhibit tetrahydrofolate
synthesis by inhibiting dihydro-pteroate synthase and folate
reductase respectively.
6. SAR OF
SULPHONAMIDES
December 7, 2020 6
The major features of SAR of sulphonamides include the
following:
Sulphanilamide skeleton is the
minimum structural requirement for
antibacterial activity.
7. December 7, 2020 7
The amino- and sulphonyl-groups on the benzene ring
are essential and should be in 1 and 4 position.
The N-4 amino group could be modified to be prodrugs,
which are converted to free amino function in vivo.
8. December 7, 2020 8
Sulphur atom should be directly linked to the benzene ring.
Replacement of benzene ring by other ring systems or the
introduction of additional substituents on it decreases or abolishes its
activity.
Exchange of the –SO2NH group by –CONH reduces the activity.
On N-1-substituted sulphonamides, activity varies with the nature of
the substituent at the amino group. With substituents imparting
electron-rich characters to SO2 group, bacteriostatic activity increases.
9. December 7, 2020 9
Heterocyclic substituents lead to highly potent derivatives, while
sulphonamides, which contain a single benzene ring at N-1 position,
are considerably more toxic than heterocyclic ring analogues.
The free aromatic amino groups should reside para to the
sulphonamide group. Its replacement at ortho or meta position results
in compounds devoid of antibacterial activity.
The active form of sulphonamide is the ionized, maximum activity that
is observed between the pKa values 6.6–7.4.
10. December 7, 2020 10
Substitutions in the benzene ring of sulphonamides produced
inactive compounds.
Substitution of free sulphonic acid (–SO3 H) group for
sulphonamido function destroys the activity, but replacement by a
sulphinic acid group (–SO2 H) and acetylation of N-4 position retains
back the activity.
The lipid solubility influences the pharmacokinetic and antibacterial
activity, and so increases the half-life and antibacterial activity in
vitro
11. CLASSIFICATION
Sulphonamides can be classified in various ways:
On the basis of the site of action
Sulphonamides for general infection: Sulphanilamide,
Sulphapyridine, Sulphadiazine, Sulphamethoxacine,
Sulphamethoxazole.
Sulphonamides for urinary tract infections:
Sulphaisoxazole, Sulphathiazole.
Sulphonamides for intestinal infections:
Phthalylsulphathiazole, Succinyl sulphathiazole,
Sulphasalazine.
December 7, 2020 11
12. December 7, 2020 12
Sulphonamides for local infections: Sulpahacetamide,
Mafenamide, Silver sulphadiazine.
Sulphonamides for dermatitis: Dapsone, Solapsone.
Sulphonamides in combination: Trimethoprim with
Sulphamethoxazole
13. December 7, 2020 13
On the basis of the pharmacokinetic properties
Poorly absorbed sulphonamides (locally acting
sulphonamides)—Sulphasalazine, Phthalylsulphathiazole,
Sulphaguanidine, Salicylazo sulphapyridine, Succinyl sulpha
thiazole.
Rapidly absorbed and rapidly excreted (systemic sulphanamides):
Sulphamethoxazole, Sulphaisoxazole, Sulphadiazine,
Sulphadimidine, Sulphafurazole, Sulphasomidine,
Sulphamethiazole, Sulphacetamide Sulphachlorpyridazine.
14. December 7, 2020 14
Topically used sulphonamides: Sulphacetamide,
Mafenide, Sulphathiazole, Silver sulphadiazine.
On the basis of the pharamacological activity
Antibacterial agents: Sulphadiazine, Sulfi soxazole.
Drugs used in dermatitis: Dapsone.
15. December 7, 2020 15
On the basis of the duration of action
Extra long-acting sulphonamides (half-life greater than
50 h): Sulphasalazine, Sulphaclomide, Sulphalene.
Long-acting sulphonamides (half-life greater than 24
h):Sulphadoxine, Sulphadimethoxine, Sulphamethoxy
pyridazine, Sulphamethoxydiazine, Sulphaphenazole,
Sulphamethoxine.
Intermediate-acting sulphonamides (half-life between
10–24 h): Sulphasomizole, Sulphamethoxazole.
16. December 7, 2020 16
Short-acting sulphonamides (half-life less than 20 h):
Sulphamethiazole, sulphaisoxazole.
Injectables (soluble sulpha drugs): Sulphafurazole,
Sulphadiazine, Sulphamethoxine.
17. December 7, 2020 17
On the basis of the chemical structure
N-substituted sulphonamide:Sulphadiazine,
Sulphacetamide, Sulphadimidine.
N-4 substituted sulphonamides (prodrugs): Prontosil.
Both N-1 and N-4 substituted sulphonamides: Succinyl
sulphathiazole, Phthalylsulphathiazole.
Miscellaneous: Mefenide sodium.
24. SULPHONAMIDE FOR TOPICAL
APPLICATION
Sulphacetamide
It is White in color.
Highly soluble in water.
Highly soluble at biological pH 7.4
Used in the treatment of bacterial infections of urinary
tract.
DOSE :Dose for eyes, as drops 10%, 15%, 20%, and 30%;
in ointments 2.5% and 6% of Sulphacetamide
December 7, 2020 24
25. December 7, 2020 25
SYNTHESIS
When sulphanilamide is treated with acetic anhydride
and subsequent selective,reductive deacylation of the
resulting acetamide gives sulphacetamide.
26. MODE OF ACTION
Sulfacetamide is a synthetic sulfanylacetamide derivative
with bacteriostatic activity.
Sulfacetamide inhibits bacterial folic acid synthesis by
competing with para amino benzoic acid with a broad
spectrum of action.
December 7, 2020 26
27. SULPHONAMIDE FOR BURN
THERAPY
December 7, 2020 27
Silver sulfadiazine
The silver salt of sulfadiazine applied in a
water miscible cream base has proven to
be an
effective topical antimicrobial agent,
especially against Pseudomonas species.
Salt form is slightly soluble and does not
penetrate the cell wall but acts on the
external cell
surface.
Effective than Silver nitrate and mefenide.
28. MODE OF ACTION
Silver sulfadiazine may act through a combination of the
activity of silver and sulfadiazine.
When this agent interacts with sodium chloride-containing
body fluids, silver ions are released slowly and sustainably
into wounded areas.
Ionized silver atoms catalyze the formation of disulfide bonds
leading to protein structural changes and inactivating thiol-
containing enzymes; silver ions may also intercalate DNA
thereby interfering with replication and transcription of
bacteria.
As a competitive inhibitor of para- aminobenzoic acid (PABA),
sulfadiazine inhibits bacterial dihydropteroate synthase,
thereby resulting in disruption of folic acid metabolism and
ultimately DNA synthesis
USES ; Indicated for the prevention and treatment of wound
sepsis in patients with second and third degree burns.December 7, 2020 28
29. SULFASALAZINE
December 7, 2020 29
Sulphasalazine is a bright
yellow or brownish-yellow fine
powder.
It is very slightly soluble in
alcohol, practically insoluble in
methylene chloride.
It dissolves in dilute solutions
of alkali hydroxides.
It is used in the treatment of
ulcerative colitis.
31. SULFADOXINE
December 7, 2020 31
Sulfadoxine is a sulfonamide
consisting of pyrimidine
having methoxy substituents
at the 5- and 6-positions and
a aminobenzenesulfonamido
group at the 4-position.
In combination with the
antiprotozoal pyrimethamine.
It is used as an antimalaria
32. FOLATE REDUCTASE
INHIBITORS
December 7, 2020 32
Trimethoprim
Trimethoprim is a white or yellowish-
white powder.
It very slightly soluble in water and
slightly soluble in ethanol.
It is used as dihydrofolate reductase
inhibitor, effective against chloroquine
and pyrimethamine resistant strains of
Plasmodium falsiparum.
33. MODE OF ACTION
It works by blocking folate metabolism in some bacteria
which results in their death.
Trimethoprim binds to dihydrofolate reductase and
inhibits the reduction of dihydrofolic acid (DHF) to
tetrahydrofolic acid (THF).
Uses; is used in the treatment of bladder infections,
middle ear infections and travelers' diarrhea.
Originally introduced in combination with
sulfamethoxazole, it is now available as single agents.
December 7, 2020 33
34. SULFAMETHOXAZOLE
December 7, 2020 MEDICINAL CHEMISTRY 34
Properties
It is crystal white or off-white powder.
It is practically odourless.
It has half life 10hrs and may increased
in patient with renal failure.
It is practically insoluble in water, ether
and chloroform.
It is sparingly soluble in
ethanol,dissolves in dilute solution of
NaoH and in dilute acids.
It is bacteriostatic sulfonamide
antibiotic that interferes with folic acid
synthesis in susceptible bacteria.
It is generally given in combination
with trimethoprim that inhibits the
sequential step in bacterial folic acid
synthesis.
It is used for urinary tract’s
35. MODE OF ACTION
December 7, 2020 35
Sulfamethoxazole is a structural analog of para-aminobenzoic acid (PABA).
They inhibit the conversion of PABA to folic acid which interferes with normal
bacterial synthesis of folic acid.
Hence, blockage of folate production inhibits the folate-dependent metabolic
processes for bacterial growth.
36. December 7, 2020 36
The carbamic acid , when lose the carbondioxide gives
5-methylisoxazol-3-amine.
When 5-methylisoxazol3-amine is reacted with p-
acetamido benzene sulphonyl chloride (PABS) gives
sulphamethoxazole.
37. SYNERGISM OF
SULFONAMIDES AND FOLATE
REDUCTASE INHIBITORS
Blocking the biosynthesis of folate co-enzymes at
more than one point in the biosynthetic pathway of
bacteria will results in a synergistic antimicrobial
effect. It shows less chances of drug resistance.
Sulphonamides show synergistic action with
diaminopyrimidines such as trimethoprim.
Trimethoprim is a potent and selective competitive
inhibitor of dihydrofolate reductase enzyme in
susceptible microorganisms, the enzyme required to
reduce dihydrofolate to tetrahydrofolate.
Combination of sulphonamide and trimethoprim
produces sequential blocks in the synthesis of
tetrahydrofolate, the reduced form of folic acid that is
required for one carbon transfer reactions.December 7, 2020 37
39. SULFAMETHOXAZOLE AND
TRIMETHOPRIM COMBINATION
The fixed dose combination of sulfamethoxazole and
trimethoprim in the dose ratio of 5:1 is called as
cotrimoxazole.
Sulfamethoxazole was selected for combining with
trimethoprim because both have nearly half life (~10hrs).
December 7, 2020 39
40. December 7, 2020 40
Both trimethoprim and sulfamethoxazole works
sequentially in inhibition of enzyme systems in bacterial
synthesis of tetrahydrofolic acid.
Trimethoprim binds to bacterial dihydrofolate reductase
(in preference to human dihydrofolate reductase), also
preventing the formation of THF.
41. December 7, 2020 41
Uses;
It is used for urinary tract infections, MRSA skin infections, travelers'
diarrhea, respiratory tract infections, and cholera, among others.
It may be used both to treat and prevent pneumocystis pneumonia in
people with HIV/AIDS. It can be given by mouth or intravenously. It is used
to prevent or treat Pneumocystis jiroveci pneumonia or Pneumocystis
carinii pneumonia (PCP), a very serious kind of pneumonia
42. DAPSONE
Properties
1. It is white or slightly yellow white-crystalline powder.
1. It is very slightly soluble in water.
2. It is soluble in acetone and dilute mineral
acids,sparingly soluble in alcohol.
3. It is used as folic acid synthesis inhibitor in the
treatment of leprosy and nocardiosis.
December 7, 2020 42