Persius/hicric huggingface dataset:
Valproic acid capsule delayed release overdosage

# Overdosage
Over dosage with valproate may result in somnolence, heart block, and deep coma. Fatalities have been reported; however patients have recovered from valproate levels as high as 2120 mcg/mL.
In overdose situations, the fraction of drug not bound to protein is high and hemodialysis or tandem hemodialysis plus hemoperfusion may result in significant removal of drug. The benefit of gastric lavage or emesis will vary with the time since ingestion. General supportive measures should be applied with particular attention to the maintenance of adequate urinary output.
Naloxone has been reported to reverse the CNS depressant effects of valproate over dosage. Because naloxone could theoretically also reverse the antiepileptic effects of valproate, it should be used with caution in patients with epilepsy.
WikiDoc scholar program letter of recommendation
- Contribution to WikiDoc will be awarded by a letter of recommendation.
- In order to request a letter of recommendation, a WikiDoc Scholar must meet the following criteria:
1.       Active participation in WikiDoc scholar program for a minimum of 3 months
2.       Completion of a minimum of 4 microchapters and or a minimum of 6 single pages in 3 months.
- 1.       Active participation in WikiDoc scholar program for a minimum of 3 months
- 2.       Completion of a minimum of 4 microchapters and or a minimum of 6 single pages in 3 months.
- Once the above outlined criteria is met, the scholar may request a letter of recommendation from the WikiDoc Program Director Meg Leitao (mleitao@bidmc.harvard.edu).
- The scholar will be provided with a list of all of the required documents upon submission of the request.
- At the completion of the WikiDoc scholar program, a certificate of completion may be requested.
A certificate of completion will only be sent if the scholar has participated for a minimum of 6 months and is no longer actively editing or has moved onto a residency program.
Certificates cannot be requested if the scholar is an active editor.
A certificate is only granted when the scholar's participation has ended.
- A certificate of completion will only be sent if the scholar has participated for a minimum of 6 months and is no longer actively editing or has moved onto a residency program.
- Certificates cannot be requested if the scholar is an active editor.
- A certificate is only granted when the scholar's participation has ended.
- Letter of recommendation will be addressed to any party nominated by the scholar.
- In order to highlight the validity and positive impact of the letter, the scholar will have to waive his/her right of reviewing the letter of recommendation.
- Letter of recommendation will not be given to the scholar; it will be submitted to the program directly.
Zinc finger and BTB domain-containing protein 16
Zinc finger and BTB domain-containing protein 16 is a protein that in humans is encoded by the ZBTB16 gene.

# Function
This gene is a member of the Krueppel C2H2-type zinc-finger protein family and encodes a zinc finger transcription factor that contains nine Kruppel-type zinc finger domains at the carboxyl terminus. This protein is located in the nucleus, is involved in cell cycle progression, and interacts with a histone deacetylase. Specific instances of aberrant gene rearrangement at this locus have been associated with acute promyelocytic leukemia (APL) and physiological roles have been identified in mouse Natural Killer T cells and gamma-delta T cells. Alternate transcriptional splice variants have been characterized in human.

# Interactions
Zinc finger and BTB domain-containing protein 16 has been shown to interact with:
- Angiotensin II receptor type 1,
- BCL6,
- BMI1,
- Calcitriol receptor,
- FHL2,
- GATA1,
- GATA2,
- HDAC1,
- HDAC4,
- HDAC6,
- Heparin-binding EGF-like growth factor,
- Histone deacetylase 5,
- Nuclear receptor co-repressor 2,
- Promyelocytic leukemia protein
- RUNX1T1,
- Retinoic acid receptor alpha,
- SIN3A,
- SIN3B,  and
- ZBTB32.
3-hydroxy-3-methylglutaryl-CoA lyase deficiency
3-hydroxy-3-methylglutaryl-CoA lyase deficiency also referred to as HMG-CoA lyase deficiency or Hydroxymethylglutaric aciduria, is an uncommon inherited disorder in which the body cannot properly process the amino acid leucine. Additionally, the disorder prevents the body from making ketones, which are used for energy during fasting.

# Presentation
This disorder usually appears within the first year of life. The signs and symptoms of HMG-CoA lyase deficiency include vomiting, dehydration, lethargy, convulsions, and coma. When episodes occur in an infant or child, blood sugar becomes extremely low (hypoglycemia), and harmful compounds can build up and cause the blood to become too acidic (metabolic acidosis). These episodes are often triggered by an infection, fasting, strenuous exercise, or sometimes other types of stress.

# Differential diagnosis
This condition is sometimes mistaken for Reye syndrome, a severe disorder that develops in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.

# Cause
Mutations in the HMGCL gene cause 3-hydroxy-3-methylglutaryl-CoA lyase deficiency. The enzyme made by the HMGCL gene plays an essential role in breaking down dietary proteins and fats for energy. Specifically, the enzyme is responsible for processing leucine, an amino acid that is part of many proteins. This enzyme also produces ketones during the breakdown of fats. If a mutation in the HMGCL gene reduces or eliminates the activity of this enzyme, the body is unable to process leucine or make ketones properly. A lack of ketones leads to hypoglycemia, and compounds called organic acids (which are formed as products of amino acid and fat breakdown) can cause the blood to become too acidic. Metabolic acidosis and hypoglycemia impair tissue function, especially in the central nervous system.

# Incidence
This is a rare condition that has been reported in fewer than 100 individuals throughout the world. This condition is inherited in an autosomal recessive pattern.
Guideline on the treatment of blood cholesterol

# 2018 AHA/ACC Guideline on the Management of Blood Cholesterol.

## Statin and adverse effects

# 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce ASCV Risk in Adults

## Statin Treatment
Intensity of Statin Therapy | LDL and Non-HDL Treatment Goals | Primary Prevention | Secondary Prevention | Heart Failure and Hemodialysis

## Safety
Statin | Nonstatin

## Managing Statin Therapy
Monitoring Statin Therapy | Optimizing statin therapy | Insufficient Response
CME Category::Cardiology
-  Jump up to: 1.0 1.1 1.2 Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS;  et al. (2019). "2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines". J Am Coll Cardiol. 73 (24): 31683209. doi:10.1016/j.jacc.2018.11.002. PMID 30423391.CS1 maint: Multiple names: authors list (link) .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
Amphotericin B cholesteryl sulfate microbiology

# Microbiology

### Mechanism of Action
The active ingredient of AMPHOTEC, amphotericin B, is a polyene antibiotic that acts by binding to sterols (primarily ergosterol) in cell membranes of sensitive fungi, with subsequent leakage of intracellular contents and cell death due to changes in membrane permeability. Amphotericin B also binds to the sterols (primarily cholesterol) in mammalian cell membranes, which is believed to account for its toxicity in animals and humans.

### Activity in vitro and in vivo
AMPHOTEC is active in vitro against Aspergillus and Candida species. One hundred and twelve clinical isolates of four different Aspergillusspecies and 88 clinical isolates of five different Candida species were tested, with a majority of minimum inhibitory concentrations (MICs) < 1 g/mL. AMPHOTEC is also active in vitro against other fungi. In vitro, AMPHOTEC is fungistatic or fungicidal, depending upon the concentration of the drug and the susceptibility of the fungal organism. However, standardized techniques for susceptibility testing for antifungal agents have not been established, and results of susceptibility studies do not necessarily correlate with clinical outcome.
AMPHOTEC is active in murine models against Aspergillus fumigatus, Candida albicans, Coccidioides immitis and Cryptococcusneoformans, and in an immunosuppressed rabbit model of aspergillosis in which endpoints were prolonged survival of infected animals and clearance of microorganisms from target organ(s). AMPHOTEC also was active in a hamster model of visceral leishmaniasis, a disease caused by infection of macrophages of the mononuclear phagocytic system by a protozoal parasite of the genus Leishmania. In this hamster model the endpoints were also prolonged survival of infected animals and clearance of microorganisms from target organ(s).

### Drug Resistance
Variants with reduced susceptibility to amphotericin B have been isolated from several fungal species after serial passage in cell culture media containing the drug and from some patients receiving prolonged therapy with amphotericin B deoxycholate. Although the relevance of drug resistance to clinical outcome has not been established, fungal organisms that are resistant to amphotericin B may also be resistant to AMPHOTEC.
Ampicillin Trihydrate dosage and administration

# Dosage and Administration

### Adults and children weighing over 20 kg
For genitourinary or gastrointestinal tract infections other than gonorrhea in men and women, the usual dose is 500 mg qid in equally spaced doses; severe or chronic infections may require larger doses. For the treatment of gonorrhea in both men and women, a single oral dose of 3.5 grams of ampicillin administered simultaneously with 1 gram of probenecid is recommended. Physicians are cautioned to use no less than the above recommended dosage for the treatment of gonorrhea. Follow-up cultures should be obtained from the original site(s) of infection 7 to 14 days after therapy. In women, it is also desirable to obtain culture test-of-cure from both the endocervical and anal canals. Prolonged intensive therapy is needed for complications such as prostatitis and epididymitis.
For respiratory tract infections, the usual dose is 250 mg qid in equally spaced doses.

### Children weighing 20 kg or less
For genitourinary or gastrointestinal tract infections, the usual dose is 100 mg/kg/day total, qid in equally divided and spaced doses. For respiratory infections, the usual dose is 50 mg/kg/day total, in equally divided and spaced doses three to four times daily. Doses for children should not exceed doses recommended for adults.

### All patients, irrespective of age and weight
Larger doses may be required for severe or chronic infections. Although ampicillin is resistant to degradation by gastric acid, it should be administered at least one-half hour before or two hours after meals for maximal absorption. Except for the single dose regimen for gonorrhea referred to above, therapy should be continued for a minimum of 48 to 72 hours after the patient becomes asymptomatic or evidence of bacterial eradication has been obtained. In infections caused by hemolytic strains of streptococci, a minimum of 10 days treatment is recommended to guard against the risk of rheumatic fever of glomerulonephritis (see PRECAUTIONSLaboratory Tests). In the treatment of chronic urinary or gastrointestinal infections, frequent bacteriologic and clinical appraisal is necessary during therapy and may be necessary for several months afterwards. Stubborn infections may require treatment for several weeks. Smaller doses than those indicated above should not be used.
Aortic insufficiency classification of severity

# Overview
The results of a variety of diagnostic studies can be integrated to assess or classify the severity of aortic insufficiency as shown in the table below.

# ACC/AHA Guidelines- Classification of the Severity of Aortic Regurgitation in Adults (DO NOT EDIT) 
AR = aortic regurgitation; cath = catheterization; echo = echocardiography; LVOT = left ventricular outflow tract.
Archael Richmond Mine Acidophilic Nanoorganisms
Nanoarchaeum equitans is a species of tiny microbe, discovered in 2002 in a hydrothermal vent off the coast of Iceland by Karl Stetter.  Since it grows in temperatures approaching boiling, it is considered to be a thermophile.  Nanoarchaeum appears to be an obligatory symbiont on the archaeon Ignicoccus; it must be in contact with the host organism to survive.  Its cells are only 400 nm in diameter, making it the next smallest known living organism, excepting possibly nanobacteria and nanobes, whose status as living organisms are controversial.  Its genome is only 490,885 nucleotides long; the smallest non-viral genome ever sequenced next to C. ruddii's in 2006.
Genetically, Nanoarchaeum is peculiar in that its 16S rRNA sequence is undetectable by the most common methods.  Initial examination of single-stranded ribosomal RNA indicated that the organism most likely belonged to the Archaea domain. However, its difference from the existing phyla, Euryarchaeota and Crenarchaeota, was as great as the difference between the phyla.  Therefore, it was given its own phylum, called Nanoarchaeota.  However, another group (see References) compared all of the open reading frames to the other Archaea.  They argue that the initial sample, ribosomal RNA only, was biased and Nanoarchaeum actually belongs to the Euryarchaeota phylum.
The sequencing of the Nanoarchaeum genome has revealed a wealth of information about the organism's biology.  The genes for several vital metabolic pathways appear to be missing.  Nanoarchaeum cannot synthesize most nucleotides, amino acids, lipids, and cofactors.  The cell most likely obtains these biomolecules from Ignicoccus.  However, unlike many parasitic microbes, Nanoarchaeum has many DNA repair enzymes, as well as everything necessary to carry out DNA replication, transcription, and translation.  This may explain why the genome lacks the large stretches of non-coding DNA characteristic of other parasites. The organism's ability to produce its own ATP is also in question.  Nanoarchaeum lacks the ability to metabolize hydrogen and sulfur for energy, as many thermophiles do.  It does have five subunits of an ATP synthase as well as pathways for oxidative deamination.  Whether it obtains energy from biological molecules imported from Ignicoccus, or whether it receives ATP directly is currently unknown. The genome and proteome composition of N. equitans are marked with the signatures of dual adaptation  one to high temperature and the other to obligatory parasitism (or symbiosis).
Azithromycin (ophthalmic) clinical pharmacology

# Clinical Pharmacology

### Mechanism of Action
Azithromycin is a macrolide antibiotic .

### Pharmacokinetics
The plasma concentration of azithromycin following ocular administration of AzaSite (azithromycin ophthalmic solution) in humans is unknown. Based on the proposed dose of one drop to each eye (total dose of 100 mcL or 1 mg) and exposure information from systemic administration, the systemic concentration of azithromycin following ocular administration is estimated to be below quantifiable limits (10 ng/mL) at steady-state in humans, assuming 100% systemic availability.

### NONCLINICAL TOXICOLOGY
Long-term studies in animals have not been performed to evaluate carcinogenic potential. Azithromycin has shown no mutagenic potential in standard laboratory tests: mouse lymphoma assay, human lymphocyte clastogenic assay, and mouse bone marrow clastogenic assay. No evidence of impaired fertility due to azithromycin was found in mice or rats that received oral doses of up to 200 mg/kg/day.
Phospholipidosis (intracellular phospholipid accumulation) has been observed in some tissues of mice, rats, and dogs given multiple systemic doses of azithromycin. Cytoplasmic microvacuolation, which is likely a manifestation of phospholipidosis, has been observed in the corneas of rabbits given multiple ocular doses of AzaSite. This effect was reversible upon cessation of AzaSite treatment. The significance of this toxicological finding for animals and for humans is unknown.
Bundle branch reentrant ventricular tachycardia

# Overview
Bundle branch reentry ventricular tachycardia usually occurs either in patients with structural heart disease or in patients with conduction disturbances with a structurally normal heart. Bundle branch reentry is a macro-reentrant tachycardia that incorporates the His-Purkinje system, the bundle branches, and transseptal myocardial conduction in the circuit. Typical Bundle Branch reentry tachycardia uses the right bundle as the anterograde limb and the left bundle as the retrograde limb. Atypical Bundle Branch reentry uses the left bundle (anterior fascicle, posterior fascicle or both) as the antegrade limb and the right bundle as the retrograde limb. The tachycardia appears as a typical Left Bundle Branch Block or Right Bundle Branch Block.

# Diagnosis
- Each ventricular activation is preceeded by His bundle activation (see Figure)
- Changes in the HH Interval precede changes in the VV interval
- Tachycardia induction is associated with critical delay in the HPS Initiation or a V-H increment (V-H jump) (see Figure)
- A longer H-V interval during tachycardia as compared with sinus rhythm. This is paradoxical because one would expect it to be analogous to the situation with fascicular tachycardia, the wavefront in Bundle Branch Reentry Ventricular Tachycardia usually proceeds retrogradely through the left bundle branch system. It then divides with a portion continuing retrogradely to the site of the His bundle recording, and another portion turning anterogradely along the right bundle branch to the ventricle. Since this impulse enters the distal His bundle, and then proceeds retrogradely to the His bundle recording site and simultaneously anterogradely down the right bundle branch, one might expect the ventricle to be depolarized with an HV interval shorter than during sinus rhythm. This does not occur and the longer HV interval typically seen in BBRT is probably due to a combination of some effects of relative refractoriness of the right bundle and a predominant role of anisotropic conduction.
- Tachycardia is terminated by block in the HPS
- Tachycardia is abolished by ablation of the RBBB

# Helpful Maneuvers
- Single PVC advances His
- Entrainment from Left bundle. The interval from the stimulus to QRS approximates that from the LBB potential to onset of QRS. PPI and TCL are the same.
Leukoencephalopathy with vanishing white matter
Synonyms and keywords: CACH; childhood ataxia with central nervous system hypomyelinization; vanishing white matter leukodystrophy; cree leukoencephalopathy; CLE; vanishing white matter leukodystrophy with ovarian failure, included; ovarioleukodystrophy, included

# Overview
Leukoencephalopathy with vanishing white matter (VWM disease) is an autosomal recessive neurological disease. The cause of the disease are mutations in any of the 5 genes encoding subunits of the translation initiation factor EIF2B: EIF2B1, EIF2B2, EIF2B3, EIF2B4, or EIF2B5.
Adult-onset VWM disease can present with psychosis and may be hard to differentiate from schizophrenia.

# Related Chapters
- CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy)
- Progressive multifocal leukoencephalopathy
- Metachromatic leukodystrophy
Cardiovascular magnetic resonance imaging (CMR)

# Overview
- CMR-Related Definitions
- ACCF/ACR/SCCT/SCMR/ASNC/NASCI/SCAI/SIR 2006 Appropriateness Criteria for Cardiac Magnetic Resonance Imaging
- ACR Practice Guideline for the Performance and Interpretation of Cardiac Magnetic Resonance Imaging (MRI)
- Basic MRI Physics
- CMR Image Acquisition Protocols
- Standard Image Orientation
- Normal Cardiac Anatomy as Viewed by CMR
- Contrast CMR
- Cine CMR
- Myocardial Tagging
- Flow Quantification by CMR
- CMR in Valvular Heart Disease

## ACC/AHA Guidelines- ACCF/ACR/AHA/NASCI/SCMR 2010 Expert Consensus Document on Cardiovascular Magnetic Resonance (DO NOT EDIT)
- CMR in Dilated Cardiomyopathy, Hypertrophic cardiomyopathy, myocarditis, amyloidosis, other infiltrative heart diseases and arrhythmogenic right ventricular dysplasia

## ACC/AHA Guidelines- ACCF/ACR/AHA/NASCI/SCMR 2010 Expert Consensus Document on Cardiovascular Magnetic Resonance (DO NOT EDIT)
- CMR in Cardiac Masses

## ACC/AHA Guidelines- ACCF/ACR/AHA/NASCI/SCMR 2010 Expert Consensus Document on Cardiovascular Magnetic Resonance (DO NOT EDIT)
- CMR in Pericardial Disease

## ACC/AHA Guidelines- ACCF/ACR/AHA/NASCI/SCMR 2010 Expert Consensus Document on Cardiovascular Magnetic Resonance (DO NOT EDIT)
- CMR in Congenital heart Disease

## ACC/AHA Guidelines- ACCF/ACR/AHA/NASCI/SCMR 2010 Expert Consensus Document on Cardiovascular Magnetic Resonance (DO NOT EDIT)
- CMR in Athlete's Heart
- Coronary MRI
- Peripheral Vascular MRA
- Atherosclerosis/Plaque Imaging with CMR
- CMR Risk Factors: NSF
- CMR in Heart failure

## ACC/AHA Guidelines- ACCF/ACR/AHA/NASCI/SCMR 2010 Expert Consensus Document on Cardiovascular Magnetic Resonance (DO NOT EDIT)
- CMR in Coronary artery disease

## ACC/AHA Guidelines- ACCF/ACR/AHA/NASCI/SCMR 2010 Expert Consensus Document on Cardiovascular Magnetic Resonance (DO NOT EDIT)
- CMR in Ischemic heart disease

## ACC/AHA Guidelines- ACCF/ACR/AHA/NASCI/SCMR 2010 Expert Consensus Document on Cardiovascular Magnetic Resonance (DO NOT EDIT)
- CMR in Myocardial infarction

## ACC/AHA Guidelines- ACCF/ACR/AHA/NASCI/SCMR 2010 Expert Consensus Document on Cardiovascular Magnetic Resonance (DO NOT EDIT)
- CMR in Pulmonary angiography

## ACC/AHA Guidelines- ACCF/ACR/AHA/NASCI/SCMR 2010 Expert Consensus Document on Cardiovascular Magnetic Resonance (DO NOT EDIT)
- CMR in atrial fibrillation

## ACC/AHA Guidelines- ACCF/ACR/AHA/NASCI/SCMR 2010 Expert Consensus Document on Cardiovascular Magnetic Resonance (DO NOT EDIT)
- CMR in peripheral arterial disease

## ACC/AHA Guidelines- ACCF/ACR/AHA/NASCI/SCMR 2010 Expert Consensus Document on Cardiovascular Magnetic Resonance (DO NOT EDIT)
- CMR in Carotid artery disease

## ACC/AHA Guidelines- ACCF/ACR/AHA/NASCI/SCMR 2010 Expert Consensus Document on Cardiovascular Magnetic Resonance (DO NOT EDIT)
- CMR in thoracic aortic disease

## ACC/AHA Guidelines- ACCF/ACR/AHA/NASCI/SCMR 2010 Expert Consensus Document on Cardiovascular Magnetic Resonance (DO NOT EDIT)
- CMR in renal artery disease

## ACC/AHA Guidelines- ACCF/ACR/AHA/NASCI/SCMR 2010 Expert Consensus Document on Cardiovascular Magnetic Resonance (DO NOT EDIT)