184 results on '"Danino D"'
Search Results
2. Real-time genomic investigation underlying the public health response to a Shiga toxin-producing Escherichia coli O26 : H11 outbreak in a nursery
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MORAN-GILAD, J., ROKNEY, A., DANINO, D., FERDOUS, M., ALSANA, F., BAUM, M., DUKHAN, L., AGMON, V., ANUKA, E., VALINSKY, L., YISHAY, R., GROTTO, I., ROSSEN, J. W. A., and GDALEVICH, M.
- Published
- 2017
3. Microstructure and transitions in mixed micelles of cetyltrimethylammonium tosylate and bile salts
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Chavda, S., Danino, D., Aswal, V.K., Singh, K., Marangoni, D.G., and Bahadur, P.
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- 2017
- Full Text
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4. Rings and loops in perflurosurfactants viscoelastic solutions
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Ionita-Abutbul, I., Abezgauz, L., Danino, D., and Hoffmann, H.
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- 2015
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5. Self-assembly of multi-responsive poly(N-isopropylacrylamide)-b-poly(N,N-dimethylaminopropylacrylamide) in aqueous media
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Khimani, M., Yusa, S., Nagae, A., Enomoto, R., Aswal, V.K., Kesselman, E., Danino, D., and Bahadur, P.
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- 2015
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- View/download PDF
6. Synthesis of stimuli responsive PEG47–b-PAA126–b-PSt32 triblock copolymer and its self-assembly in aqueous solutions
- Author
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Chavda, S., Yusa, S., Inoue, M., Abezgauz, L., Kesselman, E., Danino, D., and Bahadur, P.
- Published
- 2013
- Full Text
- View/download PDF
7. Viscoelastic micellar water/CTAB/NaNO 3 solutions: Rheology, SANS and cryo-TEM analysis
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Kuperkar, K., Abezgauz, L., Danino, D., Verma, G., Hassan, P.A., Aswal, V.K., Varade, D., and Bahadur, P.
- Published
- 2008
- Full Text
- View/download PDF
8. Structural investigation of viscoelastic micellar water/CTAB/NaNO3 solutions
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Kuperkar, K., Abezgauz, L., Danino, D., Verma, G., Hassan, P. A., Aswal, V. K., Varade, D., and Bahadur, P.
- Published
- 2008
- Full Text
- View/download PDF
9. Microemulsions based on anionic gemini surfactant
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Magdassi, S, Ben Moshe, M, Talmon, Y, and Danino, D
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- 2003
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10. Digital cryogenic transmission electron microscopy: an advanced tool for direct imaging of complex fluids
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Danino, D, Bernheim-Groswasser, A, and Talmon, Y
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- 2001
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11. Mother-to-child transmission of extended-spectrum-beta-lactamase-producing Enterobacteriaceae.
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Danino, D., Melamed, R., Sterer, B., Porat, N., Hazan, G., Gushanski, A., Shany, E., Greenberg, D., Borer, A., Danino, Dana, Melamed, Rimma, Sterer, Batya, Porat, Nurith, Hazan, Guy, Gushanski, Alex, Shany, Eilon, Greenberg, David, and Borer, Avraham
- Abstract
Background: Preterm infants are at high risk for extended-spectrum-beta-lactamase-producing Enterobacteriaceae (ESBL-E) sepsis and neonatal intensive care unit (NICU) outbreaks. Maternal colonization with ESBL-E may be precursory to mother-to-child transmission. However, there is no consensus regarding surveillance of pregnant women for ESBL-E colonization.Aim: To identify pairs of mothers and infants harbouring same-strain ESBL-E colonization and to determine whether maternal transmission may play a role in increasing ESBL-E carriage in preterm infants.Methods: This was a one-year analysis from an ongoing, prospective ESBL-E surveillance of mothers of premature infants and their offspring. Mother-infant pairs colonized with the same bacteria underwent strain analysis using pulsed-field gel electrophoresis (PFGE). Clinical parameters were collected from the hospital computerized records.Findings: Between January 2015 and January 2016, 313/409 (76.5%) mothers and all 478 (100%) infants were screened for ESBL-E colonization; carriage rates were 21.5% and 14.8%, respectively. Four (5.6%) colonized infants developed late-onset sepsis and two (2.8%) died. Twenty-five mother-infant pairs colonized with the same bacterial strain were identified; a subgroup of 10 pairs of isolates underwent PFGE, and 70% displayed an identical PFGE fingerprint. No similarities were found between isolates recovered from unrelated neonates and mothers. ESBL-E colonization was found significantly earlier in infants of mothers colonized at birth (P<0.001) compared with infants of non-colonized mothers.Conclusions: ESBL-E carriage rates in mothers and NICU infants with non-negligible maternal-neonatal ESBL-E transmission in the study region indicate that maternal colonization surveillance and/or further infection control interventions should be considered. [ABSTRACT FROM AUTHOR]- Published
- 2018
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12. Real-time genomic investigation underlying the public health response to a Shiga toxin-producing Escherichia coli O26:H11 outbreak in a nursery.
- Author
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MORAN-GILAD, J., ROKNEY, A., DANINO, D., FERDOUS, M., ALSANA, F., BAUM, M., DUKHAN, L., AGMON, V., ANUKA, E., VALINSKY, L., YISHAY, R., GROTTO, I., ROSSEN, J. W. A., and GDALEVICH, M.
- Abstract
Shiga toxin-producing Escherichia coli (STEC) is a significant cause of gastrointestinal infection and the haemolytic-uremic syndrome (HUS). STEC outbreaks are commonly associated with food but animal contact is increasingly being implicated in its transmission. We report an outbreak of STEC affecting young infants at a nursery in a rural community (three HUS cases, one definite case, one probable case, three possible cases and five carriers, based on the combination of clinical, epidemiological and laboratory data) identified using culture-based and molecular techniques. The investigation identified repeated animal contact (animal farming and petting) as a likely source of STEC introduction followed by horizontal transmission. Whole genome sequencing (WGS) was used for real-time investigation of the incident and revealed a unique strain of STEC O26:H11 carrying stx2a and intimin. Following a public health intervention, no additional cases have occurred. This is the first STEC outbreak reported from Israel. WGS proved as a useful tool for rapid laboratory characterization and typing of the outbreak strain and informed the public health response at an early stage of this unusual outbreak. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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13. Microstructures in the aqueous solutions of a hybrid anionic fluorocarbon/ hydrocarbon surfactant
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Danino, D., Weihs, D., Zana, R., OrÄdd, G., Lindblom, G., Abe, M., Talmon, Y., Institut Charles Sadron (ICS), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), and Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
[PHYS.COND.CM-SCM]Physics [physics]/Condensed Matter [cond-mat]/Soft Condensed Matter [cond-mat.soft] - Published
- 2003
14. WITHDRAWN: Application of cryo-TEM techniques in the colloidal sciences
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Danino, D.
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- 2008
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15. Poly(glycoamidoamine) brush nanomaterials for systemic siRNA delivery in vivo.
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Luo, X., Wang, W., Dorkin, J. R., Veiseh, O., Chang, P. H., Abutbul-Ionita, I., Danino, D., Langer, R., Anderson, D. G., and Dong, Y.
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- 2017
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16. Nurse-Led Anemia Clinic in Pre-Dialysis Patients: Quality and Safety Initiative
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Mersch, S., Danino, D., Brothers, R., and Thakar, C.V.
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- 2013
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17. Structural investigation of viscoelastic micellar water/CTAB/NaNO3 solutions.
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Kuperkar, K., Abezgauz, L., Danino, D., Verma, G., Hassan, P. A., Aswal, V. K., Varade, D., and Bahadur, P.
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VISCOELASTIC materials ,BROMIDES ,MICELLES ,VISCOSITY ,NEUTRON scattering ,CONSTITUTION of matter ,PHYSICS - Abstract
A highly viscoelastic worm-like micellar solution is formed in hexadecyltrimethylammonium bromide (CTAB) in the presence of sodium nitrate (NaNO
3 ). A gradual increase in micellar length with increasing NaNO3 was assumed from the rheological measurements where the zero-shear viscosity (η0) versus NaNO3 concentration curve exhibits a maximum. However, upon increase in temperature, the viscosity decreases. Changes in the structural parameters of the micelles with addition of NaNO3 were inferred from small angle neutron scattering measurements (SANS). The intensity of scattered neutrons in the low q region was found to increase with increasing NaNO3 concentration. This suggests an increase in the size of the micelles and/or decrease of intermicellar interaction with increasing salt concentration. Analysis of the SANS data using prolate ellipsoidal structure and Yukawa form of interaction potential between micelles indicate that addition of NaNO3 leads to a decrease in the surface charge of the ellipsoidal micelles which induces micellar growth. Cryo-TEM measurements support the presence of thread-like micelles in CTAB and NaNO3 . [ABSTRACT FROM AUTHOR]- Published
- 2008
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18. E. coli high-cell-density-culture for the production of Zymomonas mobilis levansucrase
- Author
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Goldman, D., Lavid, N., Shoham, G., Danino, D., and Shoham, Y.
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- 2010
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19. Structural Characterization of the Interactions between Amphiphilic Block-Copolymers and Nonionic Surfactants.
- Author
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Shimoni, Karin and Danino, D.
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- 2004
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20. Controlling the Size Distribution of Spontaneous Vesicles by Incorporating Tethered Polymers.
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van Zanten, R. M., Coldren, B. A., Danino, D., and Zasadzinski, J. A.
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- 2004
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21. Viscoelastic micellar water/CTAB/NaNO3 solutions: Rheology, SANS and cryo-TEM analysis
- Author
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Kuperkar, K., Abezgauz, L., Danino, D., Verma, G., Hassan, P.A., Aswal, V.K., Varade, D., and Bahadur, P.
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VISCOELASTIC materials , *PARTICLES (Nuclear physics) , *NANOPARTICLES , *NANOTECHNOLOGY - Abstract
Abstract: Aqueous micellar solutions of the cationic surfactant hexadecyltrimethylammonium bromide (CTAB) and sodium nitrate (NaNO3) were examined using steady and dynamic rheology, small-angle neutron scattering (SANS) and cryogenic-transmission electron microscopy (cryo-TEM). Upon addition of NaNO3, the CTAB spherical micelles transform into long, flexible wormlike micelles, conveying viscoelastic properties to the solutions. The zero-shear viscosity () versus NaNO3 concentration curve exhibits a well-defined maximum. Likewise, upon increase in temperature, the viscosity decreases. Dynamic rheological data of the entangled micellar solutions can be well described by the Maxwell model. Changes in the structural parameters of the micelles with addition of NaNO3 were inferred from SANS measurements. The intensity of scattered neutrons at the low q region was found to increase with increasing NaNO3 concentration. This suggests an increase in size of the micelles and/or decrease of intermicellar interactions with increasing salt concentration. Analysis of the SANS data using prolate ellipsoidal structure and Yukawa form of interaction potential between micelles indicates that addition of NaNO3 leads to a decrease in the surface charge of the ellipsoidal micelles and consequently an increase in their length. The structural transition from spherical to entangled threadlike micelles, induced by the addition of NaNO3 to CTAB micelles is further confirmed by cryo-TEM. [Copyright &y& Elsevier]
- Published
- 2008
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22. Synthesis of stimuli responsive PEG47–b-PAA126–b-PSt32 triblock copolymer and its self-assembly in aqueous solutions
- Author
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Chavda, S., Yusa, S., Inoue, M., Abezgauz, L., Kesselman, E., Danino, D., and Bahadur, P.
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BLOCK copolymers , *CHEMICAL synthesis , *POLYETHYLENE glycol , *MOLECULAR self-assembly , *AQUEOUS solutions , *POLYMERIZATION , *GEL permeation chromatography - Abstract
Abstract: An ABC type amphiphilic triblock copolymer poly(ethylene glycol)–b-poly(acrylic acid)–b-poly(styrene), PEG47–b-PAA126–b-PSt32, was successfully synthesized by reversible addition–fragmentation chain transfer (RAFT) controlled radical polymerization, and was characterized by 1H NMR and gel permeation chromatography (GPC). The pH and salt responsive micellization of the copolymer in aqueous solution was studied using dynamic light scattering (DLS) and cryogenic-transmission electron microscopy (Cryo-TEM). The micelle is composed of a hydrophobic PSt core, PAA shell and PEG corona with hydrodynamic size (D h) of ∼80nm independent of the copolymer concentration at 30°C and pH=3.5. The complexation results from collapse of the polymer chains, which is induced by the contraction of PAA chains and the enhanced association between PAA and PEG chains. The changes in the D h of micelles at different pH and in the presence of two salts, sodium sulfate (Na2SO4) and calcium chloride (CaCl2) are reported. Both salts increase D h; CaCl2 interacts with PAA and Na2SO4 with PEG, making the respective polymer block less hydrophilic. We further find that in presence of the cationic surfactant dodecyltrimethylammonium bromide (DTAB), micelle size decreased. Such stimuli-responsive block copolymers may be attractive candidates as “smart” pH- and salt-responsive drug delivery systems. [Copyright &y& Elsevier]
- Published
- 2013
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23. Inhibition of cholesterol transport into skin cells in cultures by phytosterol-loaded microemulsion
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Rozner, S., Verkhovski, L., Nissimov, Y., Aserin, A., Vilensky, R., Danino, D., Zouboulis, C.C., Milner, Y., and Garti, N.
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ISOPENTENOIDS , *CHOLESTEROL , *NANOSTRUCTURES , *KERATINOCYTES - Abstract
Abstract: Cholesterol and plant phytosterols are lipophilic compounds solubilized by intestinal micelles in a competitive manner. In this work, we used radioactive cholesterol- and phytosterol-loaded oil-in-water microemulsions to follow their incorporation and mutual competition in HaCaT keratinocytes, SZ95 sebocytes, and skin pieces in cultures. Dynamic light scattering showed homogenous nanostructures of 10.5±1.5nm diameter and cryo-transmission electron microscopy confirmed the presence of uniform spherical droplets of 7.0±1.0nm diameter. Up to 320nmol/ml of cholesterol can be solubilized and transported into cells with minimal toxic effect by 0.5wt% nanodroplets in a cell medium. Phytosterols inhibit incorporation of cholesterol into cells, in vitro, at molar ratios (phytosterols/cholesterol) of 4 and above. The loaded nanodroplets accumulate in intracellular vesicles (presumably endosomes). No metabolic conversion of cholesterol or phytosterols was found in these cells, in vitro, after 24h, at 37°C. [Copyright &y& Elsevier]
- Published
- 2008
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24. Diurnal rhythms in varicella vaccine effectiveness.
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Danino D, Kalron Y, Haspel JA, and Hazan G
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- Humans, Female, Male, Child, Preschool, Infant, Vaccination, Child, Herpesvirus 3, Human immunology, Cohort Studies, Immunization Schedule, Proportional Hazards Models, Chickenpox Vaccine immunology, Chickenpox Vaccine administration & dosage, Circadian Rhythm physiology, Chickenpox prevention & control, Chickenpox immunology, Chickenpox epidemiology, Vaccine Efficacy
- Abstract
BACKGROUNDImmune processes are influenced by circadian rhythms. We evaluate the association between varicella vaccine administration time of day and vaccine effectiveness.METHODSA national cohort, children younger than 6 years, were enrolled between January 2002 and December 2023. We compared children vaccinated during morning (7:00-10:59), late morning to afternoon (11:00-15:59), or evening hours (16:00-19:59). A Cox proportional hazards regression model was used to adjust for ethnicity, sex, and comorbidities. The first varicella infection occurring at least 14 days after vaccination and a second dose administration were treated as terminal events.RESULTSOf 251,141 vaccinated children, 4,501 (1.8%) experienced breakthrough infections. Infection rates differed based on vaccination time, with the lowest rates associated with late morning to afternoon (11:00-15:59), HR 0.88, 95% CI 0.82-0.95, P < 0.001, and the highest rates with evening vaccination (16:00-19:59), HR 1.41, 95% CI 1.32-1.52, P < 0.001. Vaccination timing remained significant after adjustment for ethnicity, sex, and comorbidities. The association between immunization time and infection risk followed a sinusoidal pattern, consistent with a diurnal rhythm in vaccine effectiveness.CONCLUSIONWe report a significant association between the time of varicella vaccination and its clinical effectiveness. Similar association was observed with the COVID-19 vaccine, providing proof of concept consistent with a diurnal rhythm in vaccine effectiveness.
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- 2024
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25. Viral load in hospitalized infants with respiratory syncytial virus bronchiolitis: a three-way comparative analysis.
- Author
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Golan-Tripto I, Danino D, De Waal L, Akel K, Dizitzer-Hillel Y, Tal A, Langman Y, and Goldbart A
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- Humans, Infant, Male, Prospective Studies, Female, Specimen Handling methods, Hospitalization, Viral Load, Respiratory Syncytial Virus Infections diagnosis, Respiratory Syncytial Virus Infections virology, Bronchiolitis, Viral virology, Bronchiolitis, Viral diagnosis, Respiratory Syncytial Virus, Human isolation & purification, Real-Time Polymerase Chain Reaction
- Abstract
Viral load measurement of Respiratory syncytial virus (RSV) in acute bronchiolitis depends on specimen collection, viral load quantification, and transport media. The aim of this study was to investigate viral load in three-way-comparative analyses; nasal swab versus nasal wash, quantitative real-time polymerase chain reaction (RT-PCR) versus cell tissue culture, and various transport media. A prospective cohort study of infants aged < 12 months, admitted to the Soroka Medical Center, due to acute bronchiolitis, was conducted. Two nasal swabs and two nasal wash samples (in UTM and VCM) were collected from each infant upon admission and after 48 h. Samples were immediately stored at -80 °C and tested at Viroclinics DDL (Rotterdam, Netherlands). Quantitative RT-PCR and quantitative virus culture were performed using tissue culture infective dose (TCID50). Spearman's correlation coefficient test assessed the correlation between the different methods, viral load, and clinical severity score. One hundred samples were collected from 13 infants (mean age 5.7 ± 3.8 months, 46% males). Twelve patients were RSV-A positive, and one was RSV-B positive. A high correlation was found between transport media- UTM and VCM (0.92, P < 0.001) and between nasal swabs and nasal wash samples (0.62, P = 0.02). RSV signals were higher in nasal wash than in swabs. PCR signals were lower in the second collection compared to the first. No correlation was found between viral load and clinical severity. Conclusion: RSV viral load is comparable across nasal wash, nasal swabs, and various transport media. However, it did not correlate with clinical severity, probably due to the limited sample size. Broader analyses are warranted. What is Known: • Viral load measurement in Respiratory Syncytial Virus (RSV) bronchiolitis depends on specimen collection, viral load quantification, and transport media. • The COVID-19 pandemic underscored the paramount significance of proper specimen collection, notably through nasal swabs. What is New: • RSV viral load was investigated in three-way-comparative analyses. • RSV viral load correlated well across PCR and tissue culture, nasal wash and swabs, and various transport media. RSV viral load did not correlate with clinical severity., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2024
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26. Candida lusitaniae Fungemia in Children: A multicenter case series of emerging pathogen.
- Author
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Snapiri O, Danziger CR, Sachs N, Krause I, Zvi HB, Danino D, Kriger O, Shachor-Meyouhas Y, Averbuch D, and Bilavsky E
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- Child, Preschool, Female, Humans, Male, Candidemia microbiology, Candidemia epidemiology, Fungemia microbiology, Fungemia mortality, Microbial Sensitivity Tests, Retrospective Studies, Risk Factors, Tertiary Care Centers statistics & numerical data, Antifungal Agents therapeutic use, Antifungal Agents pharmacology, Candida drug effects, Candida genetics, Candida isolation & purification, Candida pathogenicity
- Abstract
Candida lusitaniae fungemia is a serious infection that is rarely reported in children. The aim of this study is to describe a case series of C. lusitaniae fungemia and review previous publications regarding this rare pathogen. This is a multicenter case series of children diagnosed with C. lusitaniae fungemia. A total of 18 cases that occurred over a 15-year period in five tertiary hospitals were included. Additionally, a review of the literature regarding C. lusitaniae fungemia in children was performed. A total of 18 cases were enrolled; 11/18 (61%) were males, with a mean age of 2.3 years. All patients had severe underlying diseases and risk factors for opportunistic infection, most commonly prematurity and malignancies. More than one-third of cases occurred during the last 2 years of the study period. All isolates were susceptible to all tested antifungals. The survival rate following the acute infection was 94%, whereas the survival rate of 14 previously published cases was 71%, with the most common underlying diseases being CGD and malignancies. Candida lusitaniae fungemia is not a common event in the pediatric population, occurring exclusively in children with severe underlying diseases and significant risk factors. This cohort revealed better clinical outcomes than previously reported. All tested isolates were susceptible to all antifungal agents; variability in susceptibility as previously reported was not found in this study. The allegedly higher rate of infection in recent years is in need of further investigation in larger prospective studies in order to conclude if a real trend is at play., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)
- Published
- 2024
- Full Text
- View/download PDF
27. Comparative analysis of granular starch hydrolysis and multi-structural changes by diverse α-amylases sources: Insights from waxy rice starch.
- Author
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Chen R, Zhao J, Sui Z, Danino D, and Corke H
- Subjects
- Amylopectin chemistry, alpha-Amylases metabolism, Hydrolysis, Starch chemistry, Oryza chemistry
- Abstract
Three cultivars of waxy rice starch with different multi-scale structures were subjected to α-amylase hydrolysis to determine amylopectin fine structure, production of oligosaccharides, morphology, and crystallinity of the partially hydrolyzed starch granules. α-amylases hydrolyzed the amylopectin B2 chain during the initial stage of hydrolysis, suggesting that it is primarily located in the outer shell of the granules. For waxy rice starch with loose structure, α-amylases attacked the crystalline and amorphous regions simultaneously in the initial stage, while for starch granules with compact structure, the outer shell blocklet (crystalline structure) can be a hurdle for α-amylases to proceed to hydrolysis of the internal granule structure. The ability of α-amylases from porcine pancreatic α-amylases to attack the outer shell crystalline structure was lower than that of α-amylases from Bacillus amyloliquefaciens and Aspergillus oryzae. These results show that α-amylase source and rice cultivar combinations can be used to generate diverse structures in degraded waxy rice starch., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)
- Published
- 2024
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28. Comparing single versus multiple virus detection in pediatric acute gastroenteritis postimplementation of routine multiplex RT-PCR diagnostic testing.
- Author
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Hazan G, Goldstein Y, Greenberg D, Khalde F, Mahajna R, Keren-Naos A, Hershkovitz E, Faingelernt Y, Givon-Lavi N, and Danino D
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- Child, Humans, Infant, Child, Preschool, Reverse Transcriptase Polymerase Chain Reaction, Multiplex Polymerase Chain Reaction, Diagnostic Techniques and Procedures, Feces, Gastroenteritis diagnosis, Gastroenteritis epidemiology, Rotavirus genetics, Rotavirus Infections diagnosis, Rotavirus Infections epidemiology, Viruses genetics, Norovirus genetics
- Abstract
Utilizing multiplex real time polymerase chain reaction (RT-PCR) for rapid diagnosis of gastroenteritis, enables simultaneous detection of multiple pathogens. A comparative analysis of disease characteristics was conducted between cases with single and multiple viruses. Rotavirus vaccine was introduced in 2010, reaching a 70% coverage in 2 years. All rectal swabs collected from diarrheic children (<5 years) between December 2017 and March 2022 were included. Detection of the same viruses within 2 months was considered a single episode. Episodes with positive stool bacterial PCR were excluded. A total of 5879 samples were collected, revealing 86.9% (1509) with single virus detection and 13.1% (227) with multiple viruses. The most frequent combination was rotavirus and norovirus (27.8%), these infections followed a winter-spring seasonality akin to rotavirus. Children with multivirus infections exhibited higher immunodeficiency (OR 2.06) rates, but lower food allergy (OR 0.45) and prematurity rates (OR 0.55) compared to single infections. Greater disease severity, evaluated by the Vesikari score, was observed in multivirus episodes (p < 0.001, OR 1.12). Multivirus infections accounted for 13.1% of symptomatic cases in hospitalized young children. Despite vaccination efforts, rotavirus remained prominent, frequently in co-infections with norovirus. Overall, multivirus infections were linked to more severe diseases than single virus cases., (© 2023 Wiley Periodicals LLC.)
- Published
- 2024
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29. Dynamics of Pediatric Antibiotic Use Differ between High- and Low-Prescribing Clinics after Pneumococcal Conjugate Vaccines.
- Author
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Danino D, van der Beek BA, Givon-Lavi N, Ben-Shimol S, Greenberg D, and Dagan R
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- Child, Humans, Infant, Child, Preschool, Pneumococcal Vaccines therapeutic use, Anti-Bacterial Agents therapeutic use, Vaccines, Conjugate, Amoxicillin-Potassium Clavulanate Combination, Streptococcus pneumoniae, Pneumococcal Infections drug therapy, Pneumococcal Infections epidemiology, Pneumococcal Infections prevention & control
- Abstract
Objective: To compare dispensed oral antibiotic prescription rates (DAPRs) after implementation of pneumococcal conjugate vaccine (PCV) in high antibiotic-prescribing clinics (HPC) with low antibiotic-prescribing clinics (LPC) in 2 distinct ethnic groups of children (Jewish and Bedouin children) <5 years of age., Methods: Clinics with ≥50 insured children, active both pre-PCV (2005-2009) and post-PCV (2010-2018) implementation, were included. HPC and LPC were defined by DAPRs above or below the median in each age and ethnic group. Monthly dispensed antibiotic prescription rate (DAPR) trends (adjusted for age and ethnicity) were calculated using interrupted time series. Mean yearly incidence rate-ratios (late PCV13 vs pre-PCV) were calculated., Results: Bedouin HPC had the highest pre-PCV overall-DAPR per 1000 child-years ± SD (2520.4 ± 121.2), followed by Jewish HPC (1885.5 ± 47.6), Bedouin LPC (1314.8 ± 81.6), and Jewish LPC (996.0 ± 19.6). Shortly after PCV implementation, all DAPRs and amoxicillin/amoxicillin-clavulanate DAPRs declined in all groups except Jewish LPC, stabilizing within 4-5 years post-PCV. The rates and magnitudes of declines were directly proportional to the pre-PCV DAPR magnitudes, achieving near-complete closure of the pre-PCV DAPR gaps between the 4 groups (rates during late-PCV13 ranging from 1649.4 ± 23.5 [Bedouin HPC] to 1200.3 ± 72.4 [Jewish LPC])., Conclusions: PCVs are a powerful tool in reducing outpatient antibiotic consumption among young children, especially in HPC, resulting in partial closure of DAPR gap between HPC and LPC. The higher impact on HPC suggests that PCV-associated declines of respiratory disease may strongly contribute to a judicious antibiotic approach in clinics with high antibiotic consumption., Competing Interests: Declaration of Competing Interest R.D. reports grants from Pfizer, MSD, and MedImmune/AstraZeneca; scientific consultant to Pfizer and MSD; review board membership for Pfizer and MSD; speakers' bureau membership for of Pfizer, MSD, Sanofi Pasteur, and GSK. D.G. reports grants from MSD; scientific consultant to Pfizer, MSD, and GSK; speakers' bureau membership for Pfizer, MSD, and GSK. S.B.-S. reports grants from Pfizer; scientific consultant to Pfizer and MSD; review board membership for Pfizer and MSD; speakers' bureau membership for Pfizer, MSD, and GSK. D.D. reports grants from Pfizer. The other authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2023
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30. The impact of pneumococcal conjugate vaccine on ceftriaxone consumption in the community among young children.
- Author
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Danino D, van der Beek BA, Greenberg D, Ben-Shimol S, and Dagan R
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- Child, Humans, Infant, Child, Preschool, Pneumococcal Vaccines, Ceftriaxone therapeutic use, Vaccines, Conjugate, Anti-Bacterial Agents therapeutic use, Arabs, Respiratory Tract Infections, Pneumococcal Infections drug therapy, Pneumococcal Infections epidemiology, Pneumococcal Infections prevention & control
- Abstract
Objectives: Following pneumococcal conjugate vaccine (PCV) introduction, community pediatric dispensed prescription rates (DPR) of oral antibiotics declined, in parallel to respiratory tract infection (RTI). We assessed the dynamics of outpatient parenteral ceftriaxone DPR., Methods: Computerized data for children <5 years were examined during 13 years (including 4 pre-PCV years). DPR from clinics with ≥50 insured children, active both before and after PCV implementation were included. Interrupted time series with segmented regression stratified by age and ethnicity, and adjusted for seasonality was applied to show monthly DPR trends., Results: A total of 29,226 prescriptions were dispensed. No significant trends in ceftriaxone DPR were seen pre-PCV. Shortly after PCV implementation, DPR abruptly and significantly declined, stabilizing in late-PCV period (5 years postimplementation). The dynamics were compared between the two ethnic groups in the region, Jewish and Bedouin children (the latter with higher crowding and respiratory disease rates). Among Jewish children, ceftriaxone was mainly dispensed during winter vs no seasonality among Bedouin children., Conclusions: In southern Israel, outpatient ceftriaxone DPR declined post-PCV in young children, similar to the trends of RTIs and oral antibiotic prescriptions, suggesting a causative role of PCVs. The differences between the two ethnic groups suggest possible involvement of additional factors., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2023
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31. Implementing a multiplex-PCR test for the diagnosis of acute gastroenteritis in hospitalized children: Are all enteric viruses the same?
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Danino D, Hazan G, Mahajna R, Khalde F, Farraj L, Avni YS, Greenberg D, Hershkovitz E, Faingelernt Y, and Givon-Lavi N
- Subjects
- Child, Humans, Child, Hospitalized, Pandemics, Multiplex Polymerase Chain Reaction, Antigens, Viral, COVID-19 Testing, COVID-19, Enterovirus Infections, Gastroenteritis diagnosis, Gastroenteritis epidemiology, Rotavirus genetics, Astroviridae
- Abstract
Background: Multiplex-PCR is a valuable tool for diagnosing viral acute gastroenteritis (AGE), enabling the detection of multiple pathogens. However, distinguishing between active disease and shedding poses challenges. This study aimed to evaluate viral AGE epidemiology and compare clinical characteristics among the five most common viruses., Methods: Rotavirus vaccine was introduced in 2010, with 70% coverage achieved in southern Israel in two years. All rectal swabs for multiplex-PCR targeting rotavirus, norovirus, adenovirus, astrovirus and sapovirus from hospitalized diarrheic children <5 years were included, from December 2017 through March 2022. Detection of the same virus within two months was considered a single episode. Clinical analysis included episodes with single-virus detection and negative bacterial PCR., Results: Among 5,879 rectal swabs, 2,662 (45.3%) tested positive for at least one virus, with 245 (9.2%) showing multiple virus detection. Rotavirus was the most prevalent. While rotavirus exhibited typical winter-spring seasonality in 2018-19, an unusual off-season surge was observed during the second year of the COVID-19 pandemic. Among negative bacterial PCR episodes, 34.6% had mucus stool, 5.9% had bloody stool, and 29.3% received antibiotics. Astrovirus or sapovirus infections were associated with higher rates of hospital-acquired AGE and immunodeficiency (P<0.05), whereas rotavirus infections had higher rates of dehydration severity and acute kidney injury (P<0.05)., Discussion: Enteric viruses were detected in 45.3% of rectal swabs from hospitalized children with diarrhea. Despite vaccination efforts, rotavirus remained prevalent and caused more severe disease. Continuous surveillance using multiplex-PCR is crucial for accurate management and future prevention strategies for viral AGE., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)
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- 2023
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32. Challenging diagnosis of Mycolicibacterium cosmeticum/canariasense infection: A case report and literature review.
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Grupel D, Sagi O, Nissan I, Grossman R, Yair M, Moran-Gilad J, and Danino D
- Abstract
We present the case of an immunocompromised child with Mycolicibacterium cosmeticum/ canariasense infection. Our case highlights the difficulty in adequate speciation. Most isolates described in the literature were identified using 16 s- rRNA PCR, which if performed on our sample would at best be inconclusive. Misidentifications could have a real impact on the body of evidence collected on these isolates thus far., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)
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- 2023
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33. Comparison Between Peripheral and Central Blood Cultures in Pediatric Oncology Patients With Blood Stream Infections.
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Asleh M, Khalaila A, Yousef R, Leibovitz E, and Danino D
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- Child, Humans, Blood Culture, Prospective Studies, Catheterization, Central Venous adverse effects, Bacteremia diagnosis, Bacteremia drug therapy, Bacteremia complications, Catheter-Related Infections, Sepsis complications, Neoplasms complications
- Abstract
Background: Current guidelines for fever in children with cancer recommend obtaining blood cultures from all lumens of the central venous catheter (CVC) and to consider a concurrent peripheral blood culture. We assessed the characteristics of blood stream infections (BSI) in oncology children and compared central and peripheral pathogen growth., Methods: A prospective, computerized surveillance of BSI in children treated at the oncology unit between May 2014 and July 2020. The growth of the same organism within a month was considered a single episode, ≥2 organisms in the same culture were defined as different episodes. Only children with concomitant cultures, drawn at presentation before initiation of antibiotics were included in the comparison between CVC and peripheral cultures., Results: A total of 139 episodes in 81 children (with implanted Port-A-catheters) were considered true BSI. Of the 94/139 (67.6%) cases where a central and peripheral culture were concomitantly obtained, 52/94 (55.3%) had positive central/peripheral cultures that grew the same organism, 31/94 (33.0%) had positive central cultures only, and 11/94 (11.7%) had positive peripheral cultures only. In 3/94 cases, the organisms that grew from the CVC were not identical to those from the peripheral site. Four of 52 (7.7%) of the same positive central/peripheral pathogens had different susceptibility testing results. Higher CVC removal rates were observed when both peripheral and CVC cultures were positive ( P =0.044)., Conclusions: Overall, 11.7% of BSI episodes were identified only by peripheral culture and 7.7% of paired organisms did not share the same susceptibility test results which emphasizes the importance of a peripheral culture in managing fever in oncology children., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2023
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34. The COVID-19 pandemic as an opportunity for unravelling the causative association between respiratory viruses and pneumococcus-associated disease in young children: a prospective study.
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Dagan R, van der Beek BA, Ben-Shimol S, Greenberg D, Shemer-Avni Y, Weinberger DM, and Danino D
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- Infant, Humans, Child, Child, Preschool, Streptococcus pneumoniae, Prospective Studies, Pandemics, Adenoviridae, Rhinovirus, COVID-19 epidemiology, Respiratory Tract Infections epidemiology, Influenza, Human, Metapneumovirus, Pneumonia, Viral, Respiratory Syncytial Virus, Human, Pneumonia, Pneumococcal epidemiology, Pneumococcal Infections epidemiology
- Abstract
Background: In young children, rates of lower respiratory infections (LRI) and invasive pneumococcal disease (IPD) have been associated with respiratory syncytial virus (RSV), human metapneumovirus (hMPV), influenza (flu), and parainfluenza (PIV) (collectively termed here as pneumonia and pneumococcal disease-associated viruses [PDA-viruses]). However, their contribution to the pathogenesis of these disease endpoints has not yet been elucidated. The COVID-19 pandemic provided a unique opportunity to examine the question., Methods: This prospective study comprised all children <5 years, living in southern Israel, during 2016 through 2021. The data were previously collected in multiple ongoing prospective surveillance programs and include: hospital visits for community-acquired alveolar pneumonia (CAAP), non-CAAP LRI; nasopharyngeal pneumococcal carriage (<3 years of age); respiratory virus activity; and nationwide, all-ages COVID-19 episodes and IPD in children <5 years. A hierarchical statistical model was developed to estimate the proportion of the different clinical endpoints attributable to each virus from monthly time series data, stratified by age and ethnicity. A separate model was fit for each endpoint, with covariates that included a linear time trend, 12-month harmonic variables to capture unexplained seasonal variations, and the proportion of tests positive for each virus in that month., Findings: During 2016 through 2021, 3,204, 26,695, 257, and 619 episodes of CAAP, non-CAAP LRI, pneumococcal bacteremic pneumonia and non-pneumonia IPD, respectively, were reported. Compared to 2016-2019, broad declines in the disease endpoints were observed shortly after the pandemic surge, coincident with a complete disappearance of all PDA-viruses and continued circulation of rhinovirus (RhV) and adenovirus (AdV). From April 2021, off-season and abrupt surges of all disease endpoints occurred, associated with similar dynamics among the PDA-viruses, which re-emerged sequentially. Using our model fit to the entire 2016-2021 period, 82% (95% CI, 75-88%) of CAAP episodes in 2021 were attributable to the common respiratory viruses, as were 22%-31% of the other disease endpoints. Virus-specific contributions to CAAP were: RSV, 49% (95% CI, 43-55%); hMPV, 13% (10-17%); PIV, 11% (7-15%); flu, 7% (1-13%). RhV and AdV did not contribute. RSV was the main contributor in all endpoints, especially in infants. Pneumococcal carriage prevalence remained largely stable throughout the study., Interpretation: RSV and hMPV play a critical role in the burden of CAAP and pneumococcal disease in children. Interventions targeting these viruses could have a secondary effect on the burden of disease typically attributed to bacteria., Funding: There was no funding for this study., Competing Interests: Declaration of interests RD has received grants from Pfizer, MSD, MedImmune/AstraZenaca. He serves as a scientific consultant and on the advisory board of Pfizer and MSD. He also is part of the speakers' bureau of Pfizer, MSD, Sanofi Pasteur, and GSK. SB-S has received grants from Pfizer and serves as a scientific consultant and on the advisory board of Pfizer and MSD. He also is part of the speakers' bureau of Pfizer, MSD, and GSK. DG has received grants from MSD, and he serves as scientific consultant for Pfizer, MSD, and GSK where he is also part of the speakers' bureau. DMW has received consulting fees from Pfizer, Merck, Affinivax, Matrivax, and GSK and is principal investigator on grants from Pfizer and Merck to Yale University. DD has received grants from Pfizer., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2023
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35. Effectiveness of BNT162b2 Vaccination During Pregnancy in Preventing Hospitalization for Severe Acute Respiratory Syndrome Coronavirus 2 in Infants.
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Danino D, Ashkenazi-Hoffnung L, Diaz A, Erps AD, Eliakim-Raz N, Avni YS, Greenberg D, Givon-Lavi N, and Youngster I
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- Female, Pregnancy, Infant, Humans, BNT162 Vaccine, Retrospective Studies, Vaccination, Hospitalization, SARS-CoV-2, COVID-19 epidemiology, COVID-19 prevention & control
- Abstract
Objective: To assess the clinical effectiveness of the BNT162b2 vaccine during pregnancy in preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hospitalizations of infants., Study Design: A retrospective, multicenter, 1:3 case-control (test-negative) study. Symptomatic hospitalized infants less than 6 months of age, with a positive SARS-CoV-2 polymerase chain reaction test between January 3, 2021, and March 11, 2021, were matched by age and time to negative controls, hospitalized with symptoms compatible with SARS-CoV-2 infection. Mothers were defined as fully vaccinated who received 2 doses of BNT162b2 with the second given 2 weeks to 6 months before delivery; or partially vaccinated, if they received only 1 dose or 2 doses with the second given more than 6 months or less than 2 weeks before delivery. Severe SARS-CoV-2 was defined as a need for assisted ventilation., Results: We matched 116 SARS-CoV-2 positive infants with 348 negative controls with symptoms compatible with SARS-CoV-2 infection. The effectiveness of fully vaccinated mothers was 61.6% (95% CI, 31.9-78.4) and the effectiveness of partially vaccinated mothers was not significant. Effectiveness was higher in infants 0-2 vs 3-6 months of age. The effectiveness (57.1%; 95% CI, 22.8-76.4) was similar when excluding mothers who were infected with SARS-CoV-2 during pregnancy. The OR of severe infection in infants born to unvaccinated vs fully vaccinated mothers was 5.8., Conclusions: At least 2 doses of BNT162b2 vaccine administered during the second or third trimester of pregnancy had an effectiveness of 61.6% in decreasing hospitalization for SARS-CoV-2 infection in infants less than 6 months of age., (Copyright © 2022 Elsevier Inc. All rights reserved.)
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- 2023
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36. Implementing a screening algorithm for early recognition of sepsis in hospitalized children: a quality improvement project.
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Feinstein Y, Kogan S, Dreiher J, Noham A, Harosh S, Lecht J, Sror T, Cohen N, Bar-Yosef E, Hershkowitz E, Lazar I, Schonmann Y, Greenberg D, and Danino D
- Subjects
- Child, Humans, Child, Hospitalized, Intensive Care Units, Pediatric, Algorithms, Quality Improvement, Sepsis diagnosis
- Abstract
Sepsis is a leading cause of mortality in children. Utilizing a screening tool for early recognition of sepsis is recommended. Our centre had no screening tool for sepsis nor a standardized protocol for sepsis management. In December 2020, a screening algorithm for sepsis was implemented. The algorithm consisted of vital signs measurements in children with an abnormal body temperature, a pop-up alert, nurse's and physician's evaluation, and activation of a workup protocol. The project's primary aim was to increase vital signs measurement rates in hospitalized children with abnormal body temperature from 40% to >90% within 6 months, by 1 June 2021, and sustain until 31 December 2021. Adherence to the algorithm and performance were monitored during 2021, and the outcomes were compared to the preceding 5 years and a control ward. The alert identified 324 children and 596 febrile episodes. Vital signs measurement adherence increased from 42.7% to >90% in 2 months. A nurse evaluated 86.4% of episodes, and a physician evaluated 83.0% of these. Paediatric intensive care unit (PICU) admission rates were lower in the intervention period vs. the pre-intervention period vs. the control ward (4.6% vs. 5.6% vs. 6.0%, respectively); the median PICU length of stay was shorter in the intervention vs. the control ward [2.0 (IQR 1, 4) vs. 5.5 (IQR 2, 7), respectively]. These differences were not statistically significant. During the intervention period, the adherence to vital signs measurements reached the goal of >90%. The alert system prompted an evaluation by caregivers and management according to the protocol. Further monitoring is needed to improve outcomes., (© The Author(s) 2023. Published by Oxford University Press on behalf of International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2023
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37. Protecting infants through covid-19 vaccination during pregnancy.
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Danino D and Youngster I
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- Pregnancy, Female, Infant, Humans, COVID-19 Vaccines, Vaccination, COVID-19 prevention & control, Pregnancy Complications, Infectious prevention & control
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- 2023
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38. Infant Botulism, Israel, 2007-2021.
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Goldberg B, Danino D, Levinsky Y, Levy I, Straussberg R, Dabaja-Younis H, Guri A, Almagor Y, Tasher D, Elad D, Baider Z, Blum S, and Scheuerman O
- Subjects
- Infant, Humans, Retrospective Studies, Israel epidemiology, Incidence, Multicenter Studies as Topic, Botulism diagnosis, Botulism epidemiology, Botulism etiology, Clostridium botulinum
- Abstract
Infant botulism (IB) is an intestinal toxemia that manifests as descending paralysis, constipation, and, in some cases, respiratory failure. Laboratory-confirmed IB cases are rare, and recent data in Israel are lacking. We conducted a national multicenter retrospective study of laboratory-confirmed IB cases reported in Israel during 2007-2021. A total of 8 cases were reported during the study period. During 2019-2021, incidence may have increased because of a cluster of 5 cases. Infant median age for diagnosis was 6.5 months, older than previously reported (3 months). Most cases occurred during March-July. Honey consumption was reported in 1 case, and possible environmental risk factors (living nearby rural or construction areas, dust exposure, and having a father who works as a farmer) were reported in 6 cases. Although IB is rare, its incidence in Israel may have increased over recent years, and its epidemiology and risk factors differ from cases reported previously in Israel.
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- 2023
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39. Stable nanovesicles formed by intrinsically planar bilayers.
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Köber M, Illa-Tuset S, Ferrer-Tasies L, Moreno-Calvo E, Tatkiewicz WI, Grimaldi N, Piña D, Pérez AP, Lloveras V, Vidal-Gancedo J, Bulone D, Ratera I, Pedersen JS, Danino D, Veciana J, Faraudo J, and Ventosa N
- Subjects
- Cetrimonium, Cryoelectron Microscopy, Cholesterol chemistry, Lipid Bilayers chemistry, Cetrimonium Compounds chemistry, Molecular Dynamics Simulation
- Abstract
Hypothesis: Quatsome nanovesicles, formed through the self-assembly of cholesterol (CHOL) and cetyltrimethylammonium bromide (CTAB) in water, have shown long-term stability in terms of size and morphology, while at the same time exhibiting high CHOL-CTAB intermolecular binding energies. We hypothesize that CHOL/CTAB quatsomes are indeed thermodynamically stable nanovesicles, and investigate the mechanism underlying their formation., Experiments: A systematic study was performed to determine whether CHOL/CTAB quatsomes satisfy the experimental requisites of thermodynamically stable vesicles. Coarse-grain molecular dynamics simulations were used to investigate the molecular organization in the vesicle membrane, and the characteristics of the simulated vesicle were corroborated with experimental data obtained by cryo-electron microscopy, small- and wide-angle X-ray scattering, and multi-angle static light scattering., Findings: CHOL/CTAB quatsomes fulfill the requisites of thermodynamically stable nanovesicles, but they do not exhibit the classical membrane curvature induced by a composition asymmetry between the bilayer leaflets, like catanionic nanovesicles. Instead, CHOL/CTAB quatsomes are formed through the association of intrinsically planar bilayers in a faceted vesicle with defects, indicating that distortions in the organization and orientation of molecules can play a major role in the formation of thermodynamically stable nanovesicles., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)
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- 2023
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40. Introduction: Cryo-EM in Biology and Materials Research.
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Subramaniam S and Danino D
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- Cryoelectron Microscopy, Models, Molecular, Biology
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- 2022
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41. Decline in Pneumococcal Disease in Young Children During the Coronavirus Disease 2019 (COVID-19) Pandemic in Israel Associated With Suppression of Seasonal Respiratory Viruses, Despite Persistent Pneumococcal Carriage: A Prospective Cohort Study.
- Author
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Danino D, Ben-Shimol S, van der Beek BA, Givon-Lavi N, Avni YS, Greenberg D, Weinberger DM, and Dagan R
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- Child, Child, Preschool, Cohort Studies, Communicable Disease Control, Humans, Infant, Israel epidemiology, Pandemics, Pneumococcal Vaccines, Prospective Studies, SARS-CoV-2, Seasons, Streptococcus pneumoniae, COVID-19 epidemiology, Community-Acquired Infections epidemiology, Pneumococcal Infections epidemiology, Respiratory Syncytial Virus, Human, Viruses
- Abstract
Background: The incidence of invasive pneumococcal disease (IPD) declined during the COVID-19 pandemic. Previous studies hypothesized that this was due to reduced pneumococcal transmission resulting from nonpharmaceutical interventions. We used multiple ongoing cohort surveillance projects in children <5 years to test this hypothesis., Methods: The first SARS-CoV-2 cases were detected in February 2020, resulting in a full lockdown, followed by several partial restrictions. Data from ongoing surveillance projects captured the incidence dynamics of community-acquired alveolar pneumonia (CAAP), nonalveolar lower respiratory infections necessitating chest X-rays (NA-LRIs), nasopharyngeal pneumococcal carriage in nonrespiratory visits, nasopharyngeal respiratory virus detection (by polymerase chain reaction), and nationwide IPD. Monthly rates (January 2020 through February 2021 vs mean monthly rates 2016-2019 [expected rates]) adjusted for age and ethnicity were compared., Results: CAAP and bacteremic pneumococcal pneumonia were strongly reduced (incidence rate ratios [IRRs]: .07 and .19, respectively); NA-LRIs and nonpneumonia IPD were also reduced by a lesser magnitude (IRRs: .46 and .42, respectively). In contrast, pneumococcal carriage prevalence was only slightly reduced, and density of colonization and pneumococcal serotype distributions were similar to previous years. The decline in pneumococcus-associated disease was temporally associated with a full suppression of respiratory syncytial virus, influenza viruses, and human metapneumovirus, often implicated as co-pathogens with pneumococcus. In contrast, adenovirus, rhinovirus, and parainfluenza activities were within or above expected levels., Conclusions: Reductions in pneumococcal and pneumococcus-associated diseases occurring during the COVID-19 pandemic in Israel were not predominantly related to reduced pneumococcal carriage and density but were strongly associated with the disappearance of specific respiratory viruses., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
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- 2022
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42. Remote Versus In-person Outpatient Clinic Visits and Antibiotic Use Among Children During the COVID-19 Pandemic.
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Danino D, Ben-Shimol S, Sharf A, Greenberg D, and Givon-Lavi N
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- Ambulatory Care, Ambulatory Care Facilities, Anti-Bacterial Agents therapeutic use, Child, Humans, Pandemics, COVID-19 epidemiology, COVID-19 Drug Treatment
- Abstract
Background: The proportion of remote clinic visits was expected to increase among children during the COVID-19 pandemic which might result in antibiotic overuse., Methods: In southern Israel, 2 ethnic groups, Jewish and Bedouin, live side-by-side. Computerized data on visits for children <18 years were examined from clinics with ≥50 insured children, active both pre-COVID-19 and during the COVID-19 pandemic. Visits were divided into in-person and remote. Monthly infectious diagnoses and dispensed antibiotic prescription rates were calculated by age (<5, 5-17 years) and ethnic groups. Mean monthly rates of 2 parallel seasons (pre-COVID-19 and COVID-19 periods) were compared., Results: Overall 2,120,253 outpatient clinic visits were recorded. Remote clinic visit rates (per 1000 children) increased from 97.04 and 33.86 in the pre-COVID-19 to 179.75 and 50.05 in the COVID-19 period in Jewish and Bedouin children, respectively ( P < 0.01) along with a reduction of in-person visit rates in both populations. Comparing pre-COVID-19 and COVID-19 periods, the rates of overall infectious diagnoses in remote visits increased. Nevertheless, dispensed antibiotic prescription rates in remote visits (per 1000 visits) remained unchanged (9.84 vs. 8.67, P = 0.70, in the Jewish population and 14.32 vs. 14.17, P = 1.00, in the Bedouin population in the pre-COVID-19 and COVID-19 periods, respectively) with a similar distribution of antibiotic categories., Conclusions: COVID-19 pandemic resulted in an expansion of remote visits of children <18 years with an increase in infectious diagnoses. However, remote dispensed antibiotic prescription rates remained unchanged. These dynamics were more accentuated in Jewish children, characterized by higher socio-economic conditions, compared to Bedouin children., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2022
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43. The Pneumococcus-Respiratory Virus Connection-Unexpected Lessons From the COVID-19 Pandemic.
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Dagan R, Danino D, and Weinberger DM
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- Humans, Pandemics, Streptococcus pneumoniae, COVID-19 epidemiology, Influenza A Virus, H1N1 Subtype, Influenza, Human epidemiology
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- 2022
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44. Disproportionate reduction in respiratory vs. non-respiratory outpatient clinic visits and antibiotic use in children during the COVID-19 pandemic.
- Author
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Givon-Lavi N, Danino D, van der Beek BA, Sharf A, Greenberg D, and Ben-Shimol S
- Subjects
- Ambulatory Care, Ambulatory Care Facilities, Anti-Bacterial Agents therapeutic use, Child, Communicable Disease Control, Humans, Pandemics, SARS-CoV-2, COVID-19 epidemiology
- Abstract
Background: The COVID-19 pandemic led to improved hygiene and reduced social encounters. Near elimination of the activity of respiratory syncytial virus and influenza viruses were observed, worldwide. Therefore, we assessed the rates of pediatric outpatient clinic visits and medications prescribed at those visits during the coronavirus disease 2019 (COVID-19) pandemic and pre-COVID-19 period (2016-2019)., Methods: Monthly and annual incidence rates for respiratory and non-respiratory diagnoses and dispensed prescription rates were calculated. Acute gastroenteritis (AGE) visits were analyzed separately since the mode of transmission is influenced by hygiene and social distancing., Results: Overall, 5,588,702 visits were recorded. Respiratory and AGE visits declined by 49.9% and 47.3% comparing the COVID-19 and pre-COVID-19 periods. The respective rate reductions for urinary tract infections, trauma, and skin and soft tissue infections were 18.2%, 19.9%, and 21.8%. Epilepsy visits increased by 8.2%. Overall visits rates declined by 21.6%. Dispensed prescription rates of antibiotics and non-antibiotics respiratory medications declined by 49.3% and 44.4%, respectively. The respective declines for non-respiratory antibiotics and non-antibiotics were 15.1% and 0.2%. Clinic visits and prescription rates reductions were highest in April-May, following the first lockdown in Israel., Conclusions: COVID-19 pandemic resulted in a substantial reduction in respiratory outpatient clinic visits and dispensed respiratory drugs, with only a mild reduction seen for non-respiratory visits. These trends were probably driven by COVID-19 mitigation measures and by the profound disruption to non-SARS COV-2 respiratory virus activity., (© 2022. The Author(s).)
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- 2022
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45. Severe Pneumonia Caused by Methicillin-Resistant Staphylococcus pseudintermedius in an Oncology Patient: Case Report and Literature Review.
- Author
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Asleh M, Feinstein Y, Lazar I, Rokney A, Baum M, Sagi O, Leibovitz E, and Danino D
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- Bacteremia complications, Child, Drug Resistance, Multiple, Bacterial, Ependymoma complications, Female, Humans, Immunocompromised Host, Pneumonia, Bacterial complications, Staphylococcal Infections microbiology, Bacteremia microbiology, Methicillin Resistance, Pneumonia, Bacterial microbiology, Staphylococcus
- Abstract
Staphylococcus pseudintermedius is usually a commensal bacterium of microbiota of dogs and cats that can become pathogenic in these animals. In the past two decades, an increasing number of human infections caused by this pathogen was reported; only two pediatric cases were due to methicillin-susceptible isolates. We describe the first case of methicillin-resistant S. pseudintermedius diagnosed in a 12-year-old immunocompromised girl with refractory anaplastic ependymoma, presented with life-threatening pneumonia and bacteremia. The girl had close contact with her two pet dogs. This case emphasizes that immunocompromised children should be advised on proper handling of household pets to minimize the risk of infection, which could be life threatening.
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- 2022
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46. Engineering pH-Sensitive Stable Nanovesicles for Delivery of MicroRNA Therapeutics.
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Boloix A, Feiner-Gracia N, Köber M, Repetto J, Pascarella R, Soriano A, Masanas M, Segovia N, Vargas-Nadal G, Merlo-Mas J, Danino D, Abutbul-Ionita I, Foradada L, Roma J, Córdoba A, Sala S, de Toledo JS, Gallego S, Veciana J, Albertazzi L, Segura MF, and Ventosa N
- Subjects
- Humans, Hydrogen-Ion Concentration, MicroRNAs chemistry, Nanoparticles chemistry, Neoplasms drug therapy, Neoplasms therapy
- Abstract
MicroRNAs (miRNAs) are small non-coding endogenous RNAs, which are attracting a growing interest as therapeutic molecules due to their central role in major diseases. However, the transformation of these biomolecules into drugs is limited due to their unstability in the bloodstream, caused by nucleases abundantly present in the blood, and poor capacity to enter cells. The conjugation of miRNAs to nanoparticles (NPs) could be an effective strategy for their clinical delivery. Herein, the engineering of non-liposomal lipid nanovesicles, named quatsomes (QS), for the delivery of miRNAs and other small RNAs into the cytosol of tumor cells, triggering a tumor-suppressive response is reported. The engineered pH-sensitive nanovesicles have controlled structure (unilamellar), size (<150 nm) and composition. These nanovesicles are colloidal stable (>24 weeks), and are prepared by a green, GMP compliant, and scalable one-step procedure, which are all unavoidable requirements for the arrival to the clinical practice of NP based miRNA therapeutics. Furthermore, QS protect miRNAs from RNAses and when injected intravenously, deliver them into liver, lung, and neuroblastoma xenografts tumors. These stable nanovesicles with tunable pH sensitiveness constitute an attractive platform for the efficient delivery of miRNAs and other small RNAs with therapeutic activity and their exploitation in the clinics., (© 2021 The Authors. Small published by Wiley-VCH GmbH.)
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- 2022
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47. Hospitalizations for vaccine-preventable infections among pediatric hematopoietic cell transplantation recipients in the first 5 years after transplantation.
- Author
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Danino D, Stanek JR, Rangarajan H, and Ardura MI
- Subjects
- Child, Hospitalization, Humans, Transplant Recipients, Communicable Diseases etiology, Hematopoietic Stem Cell Transplantation adverse effects, Vaccines
- Abstract
Despite recommendations for vaccination after hematopoietic cell transplantation (HCT), immunization rates remain low leaving children at high risk for vaccine preventable infections (VPIs). However, the burden from VPIs in pediatric HCT recipients is not well known. We describe the prevalence, risk factors, and outcomes of VPI-associated hospitalizations at centers participating in the Pediatric Health Information System database. Children <18 years who underwent allogeneic or autologous-HCT between 1/1/2010-31/12/2018, were identified and prevalence of overall VPI and of each infection were determined at five time-points within 5 years post-HCT. In total, 684 of 9591 pediatric HCT recipients had a VPI-associated hospitalization, most frequently in the first 6-12 months, for an overall prevalence of 7.1% (95% CI: 6.6-7.7%). Influenza, varicella, and invasive pneumococcal infections were the most frequent. Multivariable analyses identified younger age (OR = 0.96 [95% CI: 0.93-0.99]; p = 0.013), primary immune deficiency (PID) (OR = 1.78 [95% CI: 1.11-2.84]; p = 0.016), and GVHD (OR = 1.62 [95% CI: 1.05-2.48]; p = 0.028) as independent risk factors during the initial HCT-hospitalization. Children with VPI had longer duration of hospitalization (55[51] vs 36[24] days, p < 0.001)
, higher rates of ICU admission (42 vs 26%, p < 0.001), and mortality (11% [n = 17) vs 6% [n = 519]; p = 0.003). Continued efforts to improve vaccination early post-HCT are warranted., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2021
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48. Rhodococcus Ventriculoperitoneal Shunt Infection with Meningitis and Peritonitis in an Immunocompetent Child.
- Author
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Faingelernt Y, Leibovitz E, Yerushalmi B, Damari E, Kristal E, Nassar R, and Danino D
- Subjects
- Actinomycetales Infections microbiology, Child, Preschool, Female, Humans, Meningitis, Bacterial microbiology, Peritonitis microbiology, Rhodococcus isolation & purification, Actinomycetales Infections diagnosis, Meningitis, Bacterial diagnosis, Peritonitis diagnosis, Ventriculoperitoneal Shunt adverse effects
- Published
- 2021
49. Unraveling the Impact of Pneumococcal Conjugate Vaccines on Ambulatory Antibiotic Drug Consumption in Young Children: An Interrupted Time-Series Analysis.
- Author
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Danino D, van der Beek BA, Givon-Lavi N, Greenberg D, Ben-Shimol S, and Dagan R
- Subjects
- Amoxicillin-Potassium Clavulanate Combination, Arabs, Child, Child, Preschool, Humans, Incidence, Infant, Pneumococcal Vaccines, Vaccines, Conjugate, Anti-Bacterial Agents therapeutic use, Pneumococcal Infections epidemiology, Pneumococcal Infections prevention & control
- Abstract
Background: Pneumococcal conjugate vaccines (PCVs) reduce respiratory infections in young children, the main antibiotic consumers. Following PCV implementation, dispensed antibiotic prescription (DAP) rates in young children were expected to decline., Methods: Computerized data on DAP for children <5 years were examined during a 13-year period (including 4 pre-PCV years). All DAPs from clinics with ≥50 insured children, active both pre- and post-PCV implementation were included. Interrupted time-series with segmented regression was applied to analyze monthly DAP rate trends, adjusted for age, ethnicity, and season. Incidence rate ratios (IRRs) of DAPs during the late PCV13 period versus 4 years pre-PCV were calculated both as absolute rate ratios (aIRRs) and relative to expected rates (rIRRs)., Results: Of 1 090 870 DAPs, 57% were in children <2 years. All-DAP rates peaked in the cold season. Post-PCV7/PCV13 implementation, all DAP rates abruptly and significantly declined, reaching a plateau within 5 years. This was largely driven by amoxicillin/amoxicillin-clavulanate (75% of DAPs). Age <2 years and Bedouin ethnicity were significantly associated with higher pre-PCV DAP rates but with faster and greater decline post-PCV, achieving near elimination of gaps between ages and ethnic groups. Overall reduction (95% CIs) in DAP rates per 1000 was estimated between aIRR (344.7 [370.9-358.4]) and rIRR (110.4 [96.9-123.7]) values., Conclusions: Shortly following PCV implementation, overall DAP rates showed an abrupt, steep decline, stabilizing within 5 years, in parallel to post-PCV respiratory infection trends previously described in this population, suggesting causality. The variable patterns of certain drug categories suggest additional influences beyond PCV., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
- Published
- 2021
- Full Text
- View/download PDF
50. Multifunctional silica-coated mixed polymeric micelles for integrin-targeted therapy of pediatric patient-derived glioblastoma.
- Author
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Chauhan PS, Kumarasamy M, Carcaboso AM, Sosnik A, and Danino D
- Subjects
- Cell Line, Tumor, Child, Endothelial Cells, Humans, Integrins, Micelles, Silicon Dioxide, Brain Neoplasms drug therapy, Glioblastoma drug therapy
- Abstract
Glioblastoma multiforme (GBM) remains a major cause of mortality because treatments are precluded by to the limited transport and penetration of chemotherapeutics across the blood-brain barrier. Pitavastatin (PTV) is a hydrophobic Food and Drug Administration (FDA)-approved anticholesterolemic agent with reported anti-GBM activity. In the present study, we encapsulate PTV in silica-coated polymeric micelles (SiO
2 PMs) surface-modified with the cyclic peptide Arg-Gly-Asp-Phe-Val (cRGDfV) that actively targets the αv β3 integrin overexpressed in the BBB endothelium and GBM. A central composite design is utilized to optimize the preparation process and improve the drug encapsulation ratio from 131 to 780 μg/mL. The silica shell provides full colloidal stability upon extreme dilution and enables a better control of the release kinetics in vitro with 28% of the cargo released after 12 h. Furthermore, SiO2 PMs show excellent compatibility and are internalized by human BBB endothelial cells, astrocytes and pericytes, as shown by confocal laser scanning fluorescence microscopy and flow cytometry. Finally, the anticancer efficacy is assessed in a pediatric patient-derived glioma cell line expressing high levels of the integrin subunits αv, β3 and β5. This PTV-loaded nanocarrier triggers apoptosis by reducing the mRNA level of anti-apoptotic genes NF-kβ, IL-6, BIRC1 and BIRC5 by 89%, 33%, 81% and 63%, respectively, and the cell viability by >60%. Overall, our results suggest the potential of these hybrid nanocarriers for the targeted therapy of GBM and other tumors overexpressing integrin receptors., (Copyright © 2021. Published by Elsevier B.V.)- Published
- 2021
- Full Text
- View/download PDF
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