micro final review 2

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micro final review 2
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  1. Important things about anaerobic bacterial pathogens
    • Most human anaerobic bacterial pathogens are RELATIVELY aerotolerant
    • identification: Commercial packaged microsystems
  2. What are the pathogenic Clostridia mechanisms?
    • Anaerobiosis
    • Spore formation
    • Toxin production
  3. Important things about Clostridium perfringens
    • Gram-positive, anaerobic
    • spore forming rod
    • producing gas (gas gangrene)
    • Found in soil, and as a significant component of the normal flora of the colon of humans and animals

    • disease:
    • food poisoning
    • epigastric pain and watery diarrhea, 8-12 hours following consumption of contaminated food (usually meats)

    • pathogenesis:
    • organisms survive initial cooking by sporulation
    • spores germinate on cooling or reheating of food
    • toxin released by sporulating organisms in small intestine
    • meat products, common cause of diarrheal illness, high attack rate
    • **myonecrosis** (gas gangrene) --> Shock, renal failure, coma, death

    • dx:
    • high numbers of C. perfringens in food

    • tx:
    • maintain hydration, antibiotics not indicated
  4. Important things about Clostridium tetani
    Anaerobic, gram-positive, spore forming rods, found in soil, feces

    • disease:
    • tetanus – spastic paralysis
    • Incubation period days to weeks after introduction of spores by puncture wound, cut or burn
    • Trismus (spasms of jaw muscle) initial sign of generalized form of disease, progresses
    • Mortality: untreated disease - >50%
    • Most deaths occur in first week, from pulmonary infection, aspiration.
    • With proper treatment, mortality <20%
    • Deaths from autonomic dysfunction resulting in hypo/hypertension. tachy/bradycardia, cardiac arrest
    • Adult survivors show complete recovery

    Neonatal tetanus: Entry of spores at umbilical stump

    • pathogenicity:
    • Spores introduced by trauma, germinate in necrotic tissue
    • Toxin produced, transmitted to CNS via motor neuron
    • Tetanus toxin inhibits release of inhibitory neurotransmitter (glycine, GABA) into synaptic cleft
    • Toxin is a protease specific for synaptic vesicle protein required for fusion with cytoplasmic membrane.

    • tx:
    • antitoxin
    • supportive
    • Immunization: primary in infancy (DPT), booster every ten years (Tetanus toxoid) for life
  5. Important things about Clostridium botulinum
    Anaerobic, motile, Gram-positive, spore-forming rod

    • disease: botulism
    • Flaccid paralysis
    • ingestion of toxin
    • Neurologic symptoms: cranial nerves affected first, descending symmetrical weakness, respiratory muscle weakness

    • pathogenesis:
    • Spores survive improper food preparation, germinate in food – toxin produced
    • Toxin absorbed in stomach, small intestine, slowly in colon, circulated in bloodstream
    • Toxin binds to peripheral neuromuscular junctions
    • Toxin acts by blocking neurotransmitter (acetylcholine) release at peripheral cholinergic synapses.
    • Toxin is a protease specific for synaptic vesicle proteins required for fusion with cytoplasmic membrane.
    • Heat labile

    tx: antitoxin
  6. Tetanus vs. Botulism
    • both Clostridia toxin-producers
    • Different effects of the toxins presumably due to differences in binding domains
    • Active domain transported into neuron, specifically cleaves membrane protein of synaptic vesicle, preventing fusion with cell membrane

    • botulism: stays at NMJ
    • tetanus: transported to CNS via retrograde axonal transport --> crosses synapse to inhibitory neurons
  7. Important things about Clostridium difficile
    • Gram-positive, spore-forming, anaerobic rod
    • Occasional member of normal intestinal flora

    • diseases:
    • Antibiotic-associated diarrhea (AAD) (30%)
    • Antibiotic-associated colitis (70%)
    • Pseudomembranous colitis (100%)

    • pathogenesis:
    • Alteration of normal flora by antibiotic therapy
    • Production of toxin in lumen, no invasion
    • Toxins A and B: Glycosylation of Rho - family GTPases
    • Binary toxin

    tx: antibiotics (metronidazole)

    • Risk factors:
    • Old age , hospitalization, antibiotics, proton pump inhibitors
    • Nosocomial outbreaks may occur
    • Increasing incidence, recent series of severe hospital outbreaks
  8. Important things about Bacterioides fragilis
    • Gram-negative bacillus, obligate anaerobe
    • Minor component of normal fecal flora

    • disease:
    • Intra-abdominal abscesses
    • Skin and soft tissue infections
    • surgical wound infections: necrotizing fascitis

    • Pathogenesis:
    • Zwitterionic capsular polysaccharides - Induce abscess formation by direct interaction with T cells

    • dx:
    • Gram stain, culture

    • tx:
    • Drainage of abscess
    • antibiotics
  9. Important things about Bacillus cereus
    Facultative Gram-positive spore-forming bacilli Widespread in environment

    • disease:
    • mild food poisoning – wide variety of food types
    • 2 distinct forms: vomiting without diarrhea type (emetic toxin); diarrhea type (enterotoxin)
    • clinically similar to C. perfringens

    • pathogenesis:
    • production of emetic toxin (vomiting)
    • production of enterotoxins (diarrhea)

    • dx:
    • culture of organisms in large numbers from implicated food
    • culture from blood, wound, CSF

    • tx:
    • diarrhea: antibiotics not indicated
    • invasive infections: antibiotics (vancomycin + clindamycin)
  10. Important things about Actinomyces
    • Gram-positive filamentous bacilli
    • microaerophilic or strictly anaerobic
    • normal flora
    • A. israelii most common species associated with invasive disease

    • disease:
    • Indolent inflammatory lesion: masses consisting of purulent center surrounded by dense fibrosis
    • extensive sinus tract formation
    • sulfur granules
    • Oral-cervicofacial disease most common manifestation
    • thoracic disease
    • pelvic disease: associated with IUD

    • dx:
    • gram stain
    • sulfur granule

    • tx:
    • antibiotics
    • long course of therapy
    • drainage of abscesses
  11. Important things about Nocardia
    • Filamentous Gram-positive bacilli
    • Weakly acid-fast staining
    • Obligate aerobes
    • Ubiquitous in environment, particularly soil
    • N. asteroides complex (former designation): invasive disease
    • N. braziliensis: progressive lymphocutaneous diseasemycetoma

    • invasive disease: pulmonary (masses, pneumonia) and CNS (brain abscesses); in immunocompromised; slowly progressive
    • N. brasiliensis: cutaneous lessions, cellulitis, progressive lymphocutaneous disease

    • dx:
    • Gram stain and culture of sputum
    • acid fast-staining

    • therapy:
    • antibiotics
    • long course
    • surgical
  12. What type of bacteria is the family Chlamydiaceae? What are its most common pathogenic species?
    • Family of obligate intracellular bacteria
    • forms: elementary body; reticulate body

    • Chlamydia trachomatis: urogenital infections, ocular infections
    • Chlamydophila (Chlamydia) pneumoniae: respiratory tract infections
    • Chlamydophila (Chlamydia) psittaci: pneumonia and systemic infections usually acquired through exposure to birds
  13. Important things about Chlamydia trachomatis
    • Most commonly reported infectious disease in U.S.
    • Highest incidence in sexually active 15-19 y.o. women

    • diseases:
    • Urethritis/Cervicitis: most asymptomatic; mucopurulent discharge
    • epididymitis
    • Neonatal infections: Inclusion conjunctivitis; pneumonia
    • Perinatal infections
    • Ocular infections: inclusion conjunctivitis
    • Lymphogranuloma venereum
    • Trachoma : Severity due to repeated reinfections; Chronic follicular conjunctivitis --> trichiasis causes corneal scratching
    • inguinal lymphadenopathy
    • PID --> tubal infertility, ectopic pregnancy

    • pathogenesis:
    • EB induces epithelial cell internalization
    • Inclusion associates with Golgi secretion apparatus
    • RBs obtain host nucleotides, amino acids, and lipids from host cell
    • Inflammatory response induced in infected epithelial cells
    • Tissue damage associated with inflammation

    • dx:
    • nucleic acid amplification techniques (NAAT)

    screen all women under 25 y.o.

    tx: antibiotics
  14. Important things about Chlamydophila (Chlamydia) pneumoniae
    Common cause of community acquired pneumonia

    • disease:
    • Pneumonia, URI

    dx: Problematic, lack of agreement between methods
  15. Important things about Chlamydophila (Chlamydia) psittaci
    • Systemic febrile disease and pneumonia acquired from birds
    • fever, pneumonia, hepatoslenomegaly
    • Untreated disease can become protracted and severe
  16. Important things about Histoplasma capsulatum
    • Consider the diagnosis in persons with a history of exposure and compatible illness.
    • Order cultures, obtain biopsy for histology if feasible, and send histo antigen from urine and serum for Dx.
    • Treatment depends on severity of illness, with no treatment for mild infections.
    • where you find histo you also find blasto geographically
    • Histo: oHio and Mississippi river valleys
  17. Important things about Penicilliosis
    • Agent: Penicillium marneffei
    • Penicilliosis in AIDS patients in Asia can mimic disseminated histoplasmosis
  18. Important things about Blastomyces dermatitidis‚Ä® (North American Blastomycosis)
    • Dimorphic fungus
    • where you find histo you also find blasto geographically
    • BlastoW: Big, Broad Based Budding yeast, Wet Wisconsin and mid-West
  19. Important things about Coccidioides
    • Endemic to desert areas: lower Sonoran life-zone of Southwestern US, Mexico, Central and South America
    • Hot, arid, alkaline soil
    • Cocci is one of few fungal diseases where Ab detection useful
    • Endemic mycosis of desert southwest can produce pneumonia and meningitis (spherule), diagnosed with serology, treat more severe dz
    • Cocci: Large Cocciod yeasts from Crispy California (dry desert) and TuCson
  20. Important things about Paracoccidioidomycosis
    • Agent: Paracoccidioides brasiliensis
    • Granulomatous lesions: GI, skin, oral mucosa, lymph nodes, liver, spleen
    • pilot’s wheel yeasts
  21. Important things about Lobomycosis
    • Agent: Lazazia loboi (aka Loboa loboi)
    • Chronic subcutaneous infection
    • Treatment: surgery
  22. Important things about Rhinosporidiosis
    • Agent: Rhinosporidium seeberi
    • Not a true fungus, but traditionally considered such

    • Disease:
    • tumor-like lesions of mucous membranes
    • Nose: nasal polyps, bleeding, obstruction
    • Eye: conjunctival growths
    • Granulation tissue: acute and chronic inflammation
  23. Which endemic mycoses is an encapsulated yeast with a narrow bud?
    Cryptococcosis
  24. Which mycoses is a variably shaped yeast with a cigar form?
    Sporotrichosis
  25. Important things about endemic mycoses
    • The endemic mycoses are caused be dimorphic fungi
    • Asymptomatic infections are the rule; common
    • Pneumonia is most frequent clinical presentation
    • Immunocompromised have higher risk of disease
    • Exposure helps define risk: travel history
    • Know the geographic distribution of endemic fungi
    • Common pathogenesis: cell mediated immunity
    • Diagnosis: Know the different diagnostic approaches
    • Treatment: Itraconazole has antifungal activity for most of the endemic mycoses, though fluconazole is the treatment of choice for cocci meningitis.
    • For severe disease use an amphotericin B compound.
  26. Mycoses: opportunistic vs. primary pathogen
    • opportunistic:
    • Aspergillus
    • Non-Aspergillus mould (Zygomycetes, Fusarium, Scedosporium, Alternaria, etc.)
    • Candida
    • Pneumocystis
    • Cryptococcus

    • primary pathogens:
    • Histoplasma
    • Coccidioides
    • Blastomyces
    • Sporothrix
    • Paracoccidioides
    • Cryptococcus
  27. Important things about mycoses (fungi: yeasts; molds; dimorphic) in general
    • Cellular immunity is critical for fungal infections!
    • fungal cell wall: glucan
    • Antifungal medications: Topical; Systemic

    • Chromoblastomycosis, phaeohyphomycosis, and mycetoma are rare in the United States, but consider in immigrants or immunocompromised hosts (phaeohyphomycosis)
    • The subcutaneous mycoses are more common in the tropics with the exception of sporotrichosis which is widespread and which tends to be more acute
    • Diagnosis by tissue biopsy and culture
    • Treatment depends on syndrome and fungus
  28. What are the major antifungal drugs?
    • Polyenes: amphotericin B
    • Azoles: voriconazole
    • Echinocandins: micafungin
    • Nucleoside analogue: 5-FC
    • Microtubule inhibitor: Griseofulvin
    • Squalene epoxidase inhibitors: Terbinafine
    • Other agents which are topicals
  29. What is the mechanism of action for the main antifungals?
    • Ampho B (polyene): perforation of cell membrane
    • Azoles: inhibit ergosterol synthesis
    • Echinocandins: inhibit cell wall synthesis (glucan)
    • Flucystosine: inhibits DNA and RNA synthesis
  30. Important things about Aspergillus
    • mycoses: mould; Ubiquitous moulds in the environment
    • Aspergillus fumigatus most common isolate

    • disease: opportunistic
    • invasive asperillosis: pneumonia, sinusitis, angioinvasion --> common cause of death and morbidity in immunocompromised patients such as recipients of transplants

    dx: cannot rule in by histology; similar appearance of other fungi

    • tx: Don’t use fluconazole, it has no activity!
    • Voriconazole is the treatment of choice for IA
  31. Important things about non-Aspergillus moulds
    for septated, acute angle hyphae, voriconazole as intitial therapy
  32. Important thing about mucorales
    • Zygomycetes‚Ä®(agents of mucormycosis)
    • Free iron promotes the growth of the mucorales

    disease: mucormycosis (eye infection)

    • Suspect mucormycosis in patients who are immunosuppressed or have diabetes (DKA), particularly with organ appropriate disease (rhinocerebral; sino-orbital)
    • Radiographic changes lag behind clinical disease; initiate empirical treatment, obtain tissue via early surgical consultation and intervention, and use lipid based amphotericin for empiric and directed therapy
  33. Important things about Neisseria family
    • Gram-negative aerobic diplococci
    • Pathogens: N. meningitidis, N. gonorrhoeae

    • pathogenesis:
    • Adhesive fimbriae
    • Porins
    • Opa outer membrane proteinsm multiple, variable
    • IgA protease
    • Lipo-oligosaccharide (LOS): endotoxin secreted by bacteria
  34. Important things about Neisseria meningitidis
    • Gram-negative diplococcus, microaerophilic
    • Transient component of nasopharyngeal flora
    • Highest incidence in 6 months - 2 year age group
    • 14-20 year old age group at risk – higher mortality
    • Epidemics occur

    • Diseases:
    • Meningococcemia: Acute onset of fever, rash,
    • Fulminant meningococcemia: Rapid progression, shock; Purpuric, hemorrhagic lesions
    • meningococcal sepsis
    • Meningitis: same as other bacterial meningitis
    • Overall mortality: 5 –15% despite antibiotic therapy

    • pathogenesis:
    • Antiphagocytic polysaccharide capsuleL Serotypes A,B,C,W-135,Y (B identical to E. coli K1 – non immunogenic)
    • Endotoxin-mediated effects - sepsis
    • Endotoxin released from bacterial cell surface

    • dx:
    • Gram stain of CSF
    • Culture of organism from blood or CSF

    treatment: antibiotics

    • prevention:
    • vaccine: Conjugate vaccine against type all serotypes except B
    • antibiotic prophylaxis
  35. Important things about Neisseria gonorrhoeae
    • Gram-negative diplococcus, microaerophilic
    • Gonorrhea is frequently transmitted by asymptomatic women
    • Highest incidence in urban, black heterosexuals

    • disease:
    • Urethritis, cervicitis, with discharge
    • Complications: Male - epididymitis; Female - PID (10-20% of untreated women)
    • Neonatal gonorrhea: Acute conjunctivitis
    • Disseminated gonococcal infection: Acute arthritis, skin lesions

    • Pathogenesis:
    • Invasion of epithelial cells
    • Survival in neutrophils
    • Antigenic variation during course of infection
    • Colonization of epithelial cells mediated by adhesive fimbriae
    • Antigenic variation of fimbriae associated with DNA rearrangement

    • dx:
    • Gram-stain, culture from exudate
    • Nucleic acid-based detection

    • tx:
    • Combination therapy to cover Chlamydia
  36. Etiologies of bacterial meningitis
    • Neonate:
    • E. coli (K1 serotype)
    • Group B Streptococcus
    • Listeria monocytogenes

    • Infants (6 months – 2 years):
    • Neisseria meningitidis
    • Streptococcus pneumoniae
    • Haemophilus influenzae (essentially eliminated in U.S. by vaccine)

    • Young adults:
    • Neisseria meningitidis (epidemics)

    Vaccines: H. influenzae, N. meningitidis, S. pneumoniae
  37. Important things about Pneumocystis jirovecii
    • opportunistic fungal pathogen
    • most commonly causes interstitial pneumonia and is a common AIDS defining condition
    • Cultivation is not useful
    • Diagnosis by histology/cytology
    • Treatment uses agents that are outside the usual antifungal spectrum
    • Steroids used for severe hypoxia
    • Prophylaxis for at risk populations
  38. Important things about the order Rickettsiales
    • Obligate intracellular Gram-negative bacteria
    • Transmission by arthropod vectors
    • sx: Fever, rash
    • Patients remain latently infected after recovery, and reactivation disease may occur years later
  39. Important things about Rickettsia rickettsii
    • Gram-negative
    • transmitted by bites from ticks
    • Highest incidence in South Atlantic and South Central States
    • G6PD deficiency (10% of black males) at risk for fulminant, fatal infection
    • Transmission takes about 24 hours

    • disease:
    • Rocky Mountain Spotted Fever: Fever, myalgia, severe headache; Maculopapular rash
    • Severe disease involves multiple organ systems

    • pathogenesis:
    • vascular endothelial cells
    • actin-based motility
  40. What causes human monocytic ehrlichiosis (HME)?
    • Ehrlichia chaffeensis (order Rickettsiales)
    • Transmitted by Amblyomma americanum (Lone Star Tick)
    • Survival in monocytes/macrophages
  41. What causes human granulocytic anaplasmosis (HGA)?
    • Anaplasma phagocytophilum (order Rickettsiales)
    • Transmitted by Ixodes scapularis (Deer Tick)
    • Survival in neutrophils
  42. Important things about Coxiella burnetti
    • Obligate intracellular Gram-negative coccobacillus
    • Most infections associated with exposure to sheep, goats, cattle

    • Disease:
    • Q fever – most cases mild and self-limiting
    • Acquired by inhalation of contaminated aerosols associated with animal exposure
    • Intracellular survival in monocytes/macrophages
  43. Important about Bartonella spp.
    • Cat-scratch Disease – B. henselae
    • cutaneous papule or pustule at site of cat scratch or bite
    • cat-flea vector
    • regional lymphadenitis
  44. Important about Spirochetes
    • Spiral shaped, poorly staining
    • Periplasmic flagella
    • Variability, multiple stages
    • Cytokine induction
    • Immune mediated pathology
    • Tropism for CSF

    • disease:
    • recurring/relapsing fevers (louse form more severe than tick form)
    • Jarisch-Herxheimer reaction associated with antibiotic treatment of all spirochaetal infections
  45. Important things about Leptospira interrogans
    • spirochete
    • Slow growth (6-8 weeks) on primary isolation using specialized media
    • Persists in renal tubules of animals
    • Most human disease occurs in tropical and subtropical developing countries
    • Most important sources of infection in U.S.dogs, cattle, rodents (inner city cases)
    • most cases unrecognized

    • disease:
    • Anicteric leptospirosis (>90% of cases)
    • Icteric leptospirosis (Weil's disease): high mortality rate

    • pathogenesis:
    • Entry into circulation through skin abrasions, mucous membranes
    • Tubular damage in kidneys

    • tx:
    • Early antibiotic therapy most effective
    • Antibiotics associated with Jarisch-Herxheimer reaction (Doxycycline, penicillin, ceftriaxone)
  46. Important things about Borrelia burgdorferi
    • spirochete
    • slow growth
    • Most common vector-borne infection in U.S.
    • Transmitted by ticks (Ixodes scapularis)
    • Highest incidence in NE U.S.

    • disease:
    • Lyme disease: Disease occurs in three stages: Localized infection; Disseminated infection; Persistent infection
    • Erythema migrans = stage 1
    • disseminated infection = stage 2 (Headache, stiff neck, fever, myalgias, arthralgias, malaise and fatigue; secondary EM lesions)
    • persistent infection = stage 3 (recurring arthritis; Acrodermatitis chronica atrophicans)

    • pathogenesis:
    • Antigenic variation of major surface lipoprotein

    • prevention:
    • early detection
    • antibiotic prophylaxis
    • avoid ticks
    • vaccine removed from market
  47. Important things about Triponema pallidum
    Spirochete, cannot be cultured in vitro

    • Disease: syphilis
    • Sexually transmitted disease characterized by 4 stages
    • 1. (Genital) ulceration: chancre
    • 2. Disseminated disease - rashes, fever, mylagias, meningitis
    • 3. Latent syphilis - silent; Infection of fetus in utero can occur
    • 4. Late syphilis - neurological, cardiovascular, granulomatous manifestations

    • pathogenesis:
    • Entry via minor skin lesions
    • Large numbers of spirochetes in blood, CSF, and tissues
    • Progressive inflammatory disease

    • dx:
    • non-specific and specific (remains positive after therapy) tests
  48. Important things about Haemophilus ducreyi
    • Small, fastidious, Gram-negative coccobacillus
    • Important agent of genitial ulceration in AfricaContributes to transmission of HIV
    • sporadic outbreaks

    • Disease:
    • chancroid
    • Genital ulceration
    • inguinal lymphadenopathy

    dx: Culture difficult, insensitive

    tx: macrolides
  49. What are some common pathogenic yeasts? superficial mycocses?
    • Yeasts:
    • Candida species
    • Cryptococcus neoformans
    • Cryptococcus gattii

    • Superficial mycoses (usually caused by moulds):
    • Dermatophytes
    • Malassezia species
    • Trichosporon species
    • Others
  50. Important things about Candida
    • Don’t use fluconazole for C. krusei or glabrata
    • Candida is most common fungal opportunist
    • Candida species are the 4th most common cause of bloodstream infection in the U.S.
    • Candida albicans is a common cause of superficial and deep/disseminated disease
    • Candida krusei and C. glabrata are increasing in frequency as pathogens related to the increased use of fluconazole
    • Echinocandins are the newest class of antifungals with excellent activity against most Candida species (Candida parapsilosis is less susceptible)

    • disease:
    • Oropharyngeal Candidiasis (OPC)
    • Vulvovaginal Candidiasis (VVC)
    • Urinary Candidiasis


    Risk factors: AIDS, diabetes, surgery, catheters, antibiotics, neutropenia, burns, dialysis, chemotherapy, radiation therapy, prolonged ICU stay, liver transplant
  51. Important things about Candida Vulvovaginitis
    • disease:
    • Vulvovaginal Candidiasis (VVC)
  52. What are the major Candida species?
    • C. albicans --> most common cause of human infection
    • C. tropicalis
    • C. glabrata
    • C. krusei
    • C. lusitaniae and guilliermondii
    • C. parapsilosis
  53. Important things about Candida albicans
    • Candida albicans is a common cause of superficial and deep/disseminated disease
    • opportunistic pathogen producing a wide diversity of infections at different sites
    • Candida albicans is germ tube positive
    • Pneumonia is uncommon
  54. Important things about Cryptococcus
    • environmental yeast with thick capsule
    • Narrow budding, capsule is antiphagocytic
    • Common pathogen in AIDS: meningitis with elevated intracranial pressure
    • Outbreak of C. gattii in Pacific Northwest
    • Both a primary pathogen (normal host) and an opportunist (AIDS, Transplant)

    • disease:
    • lung
    • CNS

    • Pathogenesis: Primary pulmonary infection after inhalation of yeasts with self-limited disease in most patients.
    • Pneumonia, meningitis, or disseminated disease (skin) possible.

    Risk factors for disease: AIDS, hematological malignancy, steroids
  55. Important things about superficial mycoses
    • Variety of fungal pathogens implicated
    • Very common infections
    • Remember the dermatophytes (3 genera): Geophilic, Zoophilic, Anthropophilic (person to person)
    • Diagnosis is usually clinical, with empiric use of OTC topical or prescription oral antifungals
    • Can do scraping for KOH microscopy, culture
    • Tinea capitis usually treated with oral agents such as terbinafine or griseofulvin
    • Onychomycosis: difficult to eradicate, topicals don’t work, need months of oral therapy: itraconazole, terbinafine

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