38 results on '"S. Timpano"'
Search Results
2. Mapping internal strain fields of fused filament fabrication metal filled polylactic acid structure using digital volume correlation
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Abhinav Goyal, Cristofaro S Timpano, and Garrett W Melenka
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Mechanics of Materials ,Mechanical Engineering ,Materials Chemistry ,Ceramics and Composites - Abstract
With the advancement in Fused Filament Fabrication (FFF), its application is increasing widely across different industries such as aeronautical, biomedical, robotics, etc. The internal structure is becoming more complex and intricate with varying materials of reinforcement which are used to improve mechanical properties. Current measurement techniques like Digital Image Correlation (DIC) are non-destructive testing methods that do not provide enough information on the behaviour of internal microstructure for anisotropic FFF materials. Digital Volume Correlation (DVC) is non-destructive testing technique which provides full field internal 3D deformation and strain fields. Copper particle filled PLA samples manufactured using FFF method with 20, 40, 60 and 80 infill percentages were loaded in tension inside Micro-CT. X-rays were passed through the sample to get a volumetric dataset for different loadings. Using DVC method on the dataset, internal displacement and strain fields were generated for 20, 40, 60 and 80 infill percentage FFF sample.
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- 2023
3. Digital volume correlation analysis of polylactic acid based fused filament fabrication printed composites
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Cristofaro S. Timpano and Garrett W. Melenka
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Materials science ,Additive manufacturing ,Fused filament fabrication ,02 engineering and technology ,composites ,chemistry.chemical_compound ,0203 mechanical engineering ,Polylactic acid ,Materials Chemistry ,micro-computed tomography ,Composite material ,digital volume correlation ,Rapid manufacturing ,Mechanical Engineering ,Micro computed tomography ,Articles ,021001 nanoscience & nanotechnology ,020303 mechanical engineering & transports ,chemistry ,Mechanics of Materials ,Correlation analysis ,Ceramics and Composites ,fused filament fabrication ,0210 nano-technology ,Thermoplastic polymer ,Volume (compression) - Abstract
Fused filament fabrication (FFF) has rapidly begun to see implementation in industrial fields as a method of rapid manufacturing. Traditional FFF parts are made from a single thermoplastic polymer. The polymer is heated to its melting point and deposited on a work bed where a model is gradually built from the base up. While traditional FFF parts have low mechanical properties, a reinforcing phase allows for improved mechanical properties. The addition of a reinforcing material to the base polymer and complex internal microstructure of the 3 D printed party leads to anisotropic mechanical properties. Thus, these materials’ mechanical properties become challenging to characterize using traditional measurement techniques due to the previously mentioned factors. Therefore, it is essential to develop a method in which mechanical properties can be measured and analyzed. This study aims to characterize the mechanical behaviour under a uniaxial tensile load of an FFF produced polylactic acid (PLA)-copper particulate composite. The internal response of the FFF sample was imaged using micro-computed tomography at predetermined loads. The μ-CT images were input into an open-source digital volume correlation (DVC) software to measure the internal displacements and strain tensor fields. The study results show the development of different strain fields and interior features of the FFF parts.
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- 2021
4. Artificial seeding for micro-computed tomography image contrast enhancement for digital volume correlation
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Garrett W. Melenka and Cristofaro S. Timpano
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Materials science ,Mechanical Engineering ,02 engineering and technology ,Epoxy ,Image segmentation ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Microstructure ,01 natural sciences ,Sample (graphics) ,Industrial and Manufacturing Engineering ,0104 chemical sciences ,Mechanics of Materials ,visual_art ,Ceramics and Composites ,visual_art.visual_art_medium ,Particle ,Seeding ,Tomography ,Composite material ,0210 nano-technology ,Biomedical engineering ,Volume (compression) - Abstract
Digital volume correlation (DVC) can be implemented via micro-computed tomography (μ-CT) to resolve 3D strains. For proper correlation, microstructure detail is required. This study aims to provide a methodology for obtaining optimal DVC image datasets for composite materials by adding contrast particles to an epoxy resin. Image segmentation was utilized to ensure each particle met analysis DVC baselines. Particles with sizes of 10, 25, 50 and 200 μm were investigated. The 25 μm copper particles provided the greatest accuracy. These particles were embedded into an epoxy sample with a hole and subjected to uniaxial compression. Downsampled μ-CT and full-resolution datasets were compared to demonstrate processing strategies for DVC analysis.
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- 2021
5. Characterization of open-cellular polymeric foams using micro-computed tomography
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Cristofaro S. Timpano, Hossein Abdoli, Siu N. Leung, and Garrett W. Melenka
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Materials science ,Polymers and Plastics ,Scanning electron microscope ,Micro computed tomography ,Organic Chemistry ,02 engineering and technology ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,Polyvinylidene fluoride ,0104 chemical sciences ,Characterization (materials science) ,chemistry.chemical_compound ,chemistry ,Materials Chemistry ,Tomography ,Composite material ,0210 nano-technology ,Triboelectric effect - Abstract
Utilization of Polyvinylidene fluoride (PVDF) open-cellular foam allows for the creation of high-efficiency Triboelectric nanogenerators (TENG). The micro-structure of TENG devices can be problematic to characterize accurately using conventional methods like scanning electron microscope (SEM). This work aims to provide a methodology in which representative 3D measurements can be made on open-cellular PVDF foams. Open-cell PVDF foams were produced through a salt-leeching procedure. Analysis of the PVDF foams was done by imaging the sample through a desktop micro-computed tomography (μ-CT) machine to allow for a full 3D dataset to be obtained. Foams were produced with salt sizes of 250–500 μm, 106–250 μm, 53–106 μm, and
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- 2020
6. HIV-1 viral load and CD4 cell count in untreated children with vertically acquired asymptomatic or mild disease. Paediatric European Network for Treatment of AIDS (PENTA)
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J. Levy, A. Alimenti, M. Della Negra, W. Queiroz, Y. C. Lian, C. S. Soares, D. Zarowny, S. Korasheh, J. Forbes, T. Jadavji, W. Vaudry, F. Mechinaud, S. Billaudel, S. Auger, J. Nicolas V. Wahn, S. Kropp, C. Bode, A. Bru Capdeville, T. Niehues, D. Richter, S. Freude, G. Horneff, K. Balley, N. Vente, A. Seibt, C. Dammann, A. Sobanjo, G. Notheis, B. Heeren, B. Hinkelmann, K. Butler, E. Hayes, C. Giaquinto, S. Cozzani, V. Giacomet, E. Ruga, O. Rampon, F. Zacchello, L. Chieco Bianchi, A. de Rossi, A. De Manzini, C. Salvatore, A. Mazza, M. Duse, A. Soresina, M. Pernici, S. Timpano, A. Manca, A. Loy, A. de Maria, A. Plebani, M. G. Clerici, S. Alberti, M. Bray, R. Pinzani, G. Castelli Gattinara, S. Bernardi, S. Scaccia, S. Liviadiotti, A. Krzysztofiak, A. Angioni, P. Orlandi, M. Cellini, C. Baraldi, M. Portolani, P. A. Tovo, E. Palomba, D. Caselli, A. Maccabruni, S. Russo, A. Castaldo, P. Osimani, M. Vignini, H. Scherpbier, P. Leeuwen, A. Delgado, J. Aristegui, R. Cisterna, D. Suarez, I. De José Gomez, M. Herranz Aguirre, M. C. Garcia Rodriguez, J. Echeverria Lecuona, E. Perez Trallero, P. Echaniz Aizpuru, P. Martin Fontelos, M. J. Mellado Pena, A. Bernal, J. M. Perez Gonzales, M. Gracia Casanova, J. A. Leon Leal, J. Ruiz Contreras, J. T. Ramos Amador, C. Canosa, A. Mur Sierra, L. Ciria Calavia, C. Rodrigo, C. Fortuny Guasch, A. Bohlin, D. Nadal, J. Mok, K. Barlow, S. King, J. Hailey, J. Isiah, K. Reynolds, K. Barclay, F. Mitchell, C. Smith, S. Burns, J. Evans, M. S. Walters, R. Booy, S. Marriage, H. Lyall, G. Tudor Williams, J. Weber, C. Stainsby, S. Bingham, S. Galpin, D. Gibb, V. Novelli, J. Crawley, R. Gilbert, N. Klein, L. Nokes, K. Formica, S. Kaye, M. Sharland, W. Faulkner, K. Sloper, GUARINO, ALFREDO, J., Levy, A., Alimenti, M., Della Negra, W., Queiroz, Y. C., Lian, C. S., Soare, D., Zarowny, S., Korasheh, J., Forbe, T., Jadavji, W., Vaudry, F., Mechinaud, S., Billaudel, S., Auger, J. Nicolas V., Wahn, S., Kropp, C., Bode, A., Bru Capdeville, T., Niehue, D., Richter, S., Freude, G., Horneff, K., Balley, N., Vente, A., Seibt, C., Dammann, A., Sobanjo, G., Nothei, B., Heeren, B., Hinkelmann, K., Butler, E., Haye, C., Giaquinto, S., Cozzani, V., Giacomet, E., Ruga, O., Rampon, F., Zacchello, L., Chieco Bianchi, A., de Rossi, A., De Manzini, C., Salvatore, A., Mazza, M., Duse, A., Soresina, M., Pernici, S., Timpano, A., Manca, A., Loy, A., de Maria, A., Plebani, M. G., Clerici, S., Alberti, M., Bray, R., Pinzani, G., Castelli Gattinara, S., Bernardi, S., Scaccia, S., Liviadiotti, A., Krzysztofiak, A., Angioni, P., Orlandi, M., Cellini, C., Baraldi, M., Portolani, P. A., Tovo, E., Palomba, D., Caselli, A., Maccabruni, Guarino, Alfredo, S., Russo, A., Castaldo, P., Osimani, M., Vignini, H., Scherpbier, P., Leeuwen, A., Delgado, J., Aristegui, R., Cisterna, D., Suarez, I., De José Gomez, M., Herranz Aguirre, M. C., Garcia Rodriguez, J., Echeverria Lecuona, E., Perez Trallero, P., Echaniz Aizpuru, P., Martin Fontelo, M. J., Mellado Pena, A., Bernal, J. M., Perez Gonzale, M., Gracia Casanova, J. A., Leon Leal, J., Ruiz Contrera, J. T., Ramos Amador, C., Canosa, A., Mur Sierra, L., Ciria Calavia, C., Rodrigo, C., Fortuny Guasch, A., Bohlin, D., Nadal, J., Mok, K., Barlow, S., King, J., Hailey, J., Isiah, K., Reynold, K., Barclay, F., Mitchell, C., Smith, S., Burn, J., Evan, M. S., Walter, R., Booy, S., Marriage, H., Lyall, G., Tudor William, J., Weber, C., Stainsby, S., Bingham, S., Galpin, D., Gibb, V., Novelli, J., Crawley, R., Gilbert, N., Klein, L., Noke, K., Formica, S., Kaye, M., Sharland, W., Faulkner, and K., Sloper
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Male ,Quality Control ,Aging ,Anti-HIV Agents ,Infant ,Drug Resistance, Microbial ,HIV Infections ,Viral Load ,Infectious Disease Transmission, Vertical ,CD4 Lymphocyte Count ,Double-Blind Method ,Child, Preschool ,HIV-1 ,Humans ,Point Mutation ,RNA, Viral ,Female ,Viremia ,Child ,Zidovudine - Abstract
BACKGROUND: Plasma HIV-1 RNA levels are high in vertically infected infants. Information in older children is limited, particularly in those who have not received antiretroviral therapy. OBJECTIVES: To describe the relationships between HIV-1 RNA, age and CD4 cell count in untreated vertically infected children. DESIGN: HIV-1 RNA was measured in 70 children [median age, 3.5 years (range, 0.4-11.9 years); median CD4 cell count, 881 x 10(6)/l (interquartile range, 576-1347 x 10(6) cells/l)] enrolled in a randomized placebo-controlled trial comparing immediate with deferred zidovudine in asymptomatic or mildly symptomatic vertically infected children (PENTA-1 trial). Short-term variability was assessed by comparing HIV-1 RNA at -2 and 0 weeks (prior to randomization). The relationship between age and HIV-1 RNA, and CD4 cell count was analysed using data from all children prior to randomization and sequential samples from 35 remaining on placebo for up to 105 weeks, by fitting mixed linear models. RESULTS: The within-individual SD in viral load was 0.26 log10 copies/ml. The median plasma HIV-1 RNA at enrollment was 4.61 log10 (range, 2.3-6.56 log10 copies/ml), significantly higher in children aged < or = 2 years (median, 5.23 log10 copies/ml) than in those aged > 2 years (4.51 log10 copies/ml; P < 0.0001). Mean HIV-1 RNA fell by 0.38 log10 copies/ml per year up to 2 years of age, by 0.21 log10 copies/ml per year from 2 to 4 years of age, and by 0.03 log10 copies/ml per year from 4 to 6 years of age reaching a nadir of 4.25 log10 copies/ml at 6 years. Mean log10 CD4 cell count declined steadily with age and was not significantly correlated with HIV-1 RNA, although there was some evidence that the rate of log10 CD4 cell decline was negatively correlated with the initial rate of HIV-1 RNA decline. No mutations associated with resistance to zidovudine were observed. CONCLUSIONS: Age is a key factor in the interpretation of both viral load and CD4 cell count in vertically infected children
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- 1998
7. Comparison of dual nucleoside-analogue reverse-transcriptase inhibitor regimens with HIV-1 who have not previously been treated: the PENTA 5 randomized trial
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J. P. Aboulker, A. Babiker, A. Compagnucci, J. H. Darbyshire, M. Debré, C. Giaquinto, D. M. Gibb, L. Harper, Y. Saidi, AS Walker, J. Darbyshire, D. Johnson, P. Kelleher, L. McGee, A Newberry, A. Poland, A. S. Walker, J P. Aboulker, I. Carrière, V. Eliette, S. Leonardo, M. Gersten, A. Jones, S. Blanche, A. B. Bohlin, K Butler, G. Castelli Gattinara, P. Clayden, R De Groot, A. Faye, C. Griscelli, I Grosch Wörner, C. Kind, H. Lyall, J. Levy, M. Mellado Pena, D. Nadal, C Peckham, J. T. Ramos Amador, L. Rosado, C. Rudin, H. Scherpbier, M Sharland, P. A. Tovo, G. Tudor Williams, N. Valerius, A. Volny Anne, U Wintergerst, V. Wahn, C. Hill, P Lepage, A. Pozniak, S. Vella, M. Hainaut, A. Peltier, S. Carlier, G. Zissis, M. Della Negra, W. Queiroz, L. P. Feitosa, D Oliveira, F. Mechinaud, F. Ballerau, A. Lepelletier, S. Billaudel, V. Ferre, I. Grosch Wörner, R. Weigel, K. Seel, C. Feiterna Sperling, D. Ohlendorf, G. Riße, C. Müller, T. Niehues, J. Ndagijimana, G. Horneff, N. Vente, R. Ganschow, T. Simon, R. Vossen, H Pfister, U. Wintergerst, G. Notheis, G. Strotmann, S Schlieben, K. Butler, E. Hayes, M. O’Mara, J. Fanning, F. Goggins, S. Moriarty, M. Byrne, L. Battisti, M. Duse, S. Timpano, E. Uberti, P. Crispino, P. Carrara, F. Fomia, A. Manca, L. Galli, M. de Martino, F. Fioredda, E. Pontali, M. Cellini, C. Baraldi, M. Portolani, M. Meacci, P. Pietrosemoli, R. Berni Canani, P. Laccetti, M. Gobbo, V. Giacomet, R. D’Elia, O. Rampon, E. Ruga, A. de Rossi, M. Zanchetta, D. Caselli, A. Maccabruni, E. Cattaneo, V Landini, S. Bernardi, A. Krzysztofiak, C. Tancredi, P. Rossi, L. Pansani, E. Palomba, C. Gabiano, A. Mazza, G. Rossetti, R. Nicolin, A. Timillero, F. Candeias, G Santos, M. L. Ramos Ribeiro, M. C. Almeida, M. H. Lourenço, R. Antunes, M. J. Mellado Pena, M L. Carillo de Albornoz, P. Martinez Santos, L. Ciria Calavia, J. Serra Devecchi, O. Delgado, N. Matamoros, A. Foot, H. Kershaw, C. Kelly, O. Caul, W. Tarnow Mordi, J. Petrie, A. McDowell, P. McIntyre, K. Appleyard, K. Sloper, V. Shah, K. Cheema, A. Aali, J. Mok, R. Russell, A. Brewster, N. Richardson, S. Burns, D. Gibb, V. Novelli, N. Klein, S. Ewen, V. Yeung, C. Ball, K. Himid, D. Nayagam, D. Graham, A. Barrie, K. Stringer, S. Jones, N. Weerasooriya, M. Zuckerman, P. Bracken, E. Cooper, T. Fisher, R. Barrie, U. Patel, V. Van Someren, K. Moshal, L. Perry, T. Gundlach, J. Norman, M. Sharland, M. Richardson, S. Donaghy, Z. Mitchla, C. Wells, J. Booth, A. Shipp, J. White, S. Head, S. Lambers, K. O’Hara, C. Stainsby, G. Du Mont, T. Solanki, S. Swanton, S. O’Shea, A. Tilsey, S. Kaye, A. Finn, S. Choo, R. Lakshman, L. Barr, G. Bell, A. Siddens, GUARINO, ALFREDO, SPAGNUOLO, MARIA IMMACOLATA, Aboulker, J. P., Babiker, A., Compagnucci, A., Darbyshire, J. H., Debré, M., Giaquinto, C., Gibb, D. M., Harper, L., Saidi, Y., Walker, A, Darbyshire, J., Johnson, D., Kelleher, P., Mcgee, L., Newberry, A, Poland, A., Walker, A. S., Aboulker, J P., Carrière, I., Eliette, V., Leonardo, S., Gersten, M., Jones, A., Blanche, S., Bohlin, A. B., Butler, K, Castelli Gattinara, G., Clayden, P., R De Groot, Faye, A., Griscelli, C., I Grosch Wörner, Kind, C., Lyall, H., Levy, J., Mellado Pena, M., Nadal, D., Peckham, C, Ramos Amador, J. T., Rosado, L., Rudin, C., Scherpbier, H., Sharland, M, Tovo, P. A., Tudor Williams, G., Valerius, N., Volny Anne, A., Wintergerst, U, Wahn, V., Hill, C., Lepage, P, Pozniak, A., Vella, S., Hainaut, M., Peltier, A., Carlier, S., Zissis, G., Della Negra, M., Queiroz, W., Feitosa, L. P., Oliveira, D, Mechinaud, F., Ballerau, F., Lepelletier, A., Billaudel, S., Ferre, V., Grosch Wörner, I., Weigel, R., Seel, K., Feiterna Sperling, C., Ohlendorf, D., Riße, G., Müller, C., Niehues, T., Ndagijimana, J., Horneff, G., Vente, N., Ganschow, R., Simon, T., Vossen, R., Pfister, H, Wintergerst, U., Notheis, G., Strotmann, G., Schlieben, S, Butler, K., Hayes, E., O’Mara, M., Fanning, J., Goggins, F., Moriarty, S., Byrne, M., Battisti, L., Duse, M., Timpano, S., Uberti, E., Crispino, P., Carrara, P., Fomia, F., Manca, A., Galli, L., de Martino, M., Fioredda, F., Pontali, E., Cellini, M., Baraldi, C., Portolani, M., Meacci, M., Pietrosemoli, P., Guarino, Alfredo, Spagnuolo, MARIA IMMACOLATA, Berni Canani, R., Laccetti, P., Gobbo, M., Giacomet, V., D’Elia, R., Rampon, O., Ruga, E., de Rossi, A., Zanchetta, M., Caselli, D., Maccabruni, A., Cattaneo, E., Landini, V, Bernardi, S., Krzysztofiak, A., Tancredi, C., Rossi, P., Pansani, L., Palomba, E., Gabiano, C., Mazza, A., Rossetti, G., Nicolin, R., Timillero, A., Candeias, F., Santos, G, Ramos Ribeiro, M. L., Almeida, M. C., Lourenço, M. H., Antunes, R., Mellado Pena, M. J., Carillo de Albornoz, M L., Martinez Santos, P., Ciria Calavia, L., Serra Devecchi, J., Delgado, O., Matamoros, N., Foot, A., Kershaw, H., Kelly, C., Caul, O., Tarnow Mordi, W., Petrie, J., Mcdowell, A., Mcintyre, P., Appleyard, K., Sloper, K., Shah, V., Cheema, K., Aali, A., Mok, J., Russell, R., Brewster, A., Richardson, N., Burns, S., Gibb, D., Novelli, V., Klein, N., Ewen, S., Yeung, V., Ball, C., Himid, K., Nayagam, D., Graham, D., Barrie, A., Stringer, K., Jones, S., Weerasooriya, N., Zuckerman, M., Bracken, P., Cooper, E., Fisher, T., Barrie, R., Patel, U., Van Someren, V., Moshal, K., Perry, L., Gundlach, T., Norman, J., Sharland, M., Richardson, M., Donaghy, S., Mitchla, Z., Wells, C., Booth, J., Shipp, A., White, J., Head, S., Lambers, S., O’Hara, K., Stainsby, C., Du Mont, G., Solanki, T., Swanton, S., O’Shea, S., Tilsey, A., Kaye, S., Finn, A., Choo, S., Lakshman, R., Barr, L., Bell, G., and Siddens, A.
- Abstract
Introduction Treatment options for children with HIV-1 are limited. We aimed to compare activity and safety of three dualnucleoside analogue reverse-transcriptase inhibitor (NRTI) regimens with or without a protease inhibitor in previously untreated children with HIV-1. Methods In our multicentre trial, we randomly assigned 36 children to zidovudine and lamivudine, 45 to zidovudine and abacavir, and 47 to lamivudine and abacavir. Children who were symptomfree (n=55) were also randomly assigned to receive nelfinavir or placebo. Children with more advanced disease received open-label nelfinavir (73). Primary endpoints were change in plasma HIV-1 RNA at 24 and 48 weeks for the NRTI comparison and occurrence of serious adverse events for both randomised comparisons. Analyses were by intention to treat. Findings Children had a median CD4 percentage of 22% (IQR 15–29) and a mean HIV-1 RNA concentration of 5·0 log copies/mL (SD 0·8). One child was lost to follow-up and one died of sepsis. At 48 weeks, in the zidovudine/lamivudine, zidovudine/abacavir, and lamivudine/abacavir groups, mean HIV-1 RNA had decreased by 1·71, 2·19, and 2·63 log copies/mL, respectively (estimated in absence of nelfinavir) (p=0·02 after adjustment for baseline factors). One child had a hypersensitivity reaction to abacavir; and three with possible reactions stopped abacavir. There were 24 serious adverse events—six in the symptom-free children (all on nelfinavir), but none were attributed to nelfinavir. Interpretation Regimens containing abacavir were more effective than zidovudine/lamivudine. Such regimens could be combined with protease inhibitors and non-nucleoside reverse transcriptase inhibitors for safe and effective treatment of previously untreated children with HIV-1.
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- 2002
8. CD8+CD28-Tcells in vertically HIV-infected children
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Marzia Duse, Roberto Cattaneo, Duilio Brugnoni, Paolo Airò, Alberto G. Ugazio, S. Timpano, and Fabio Malacarne
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CD4-Positive T-Lymphocytes ,Editorial Review ,Immunology ,Apoptosis ,HIV Infections ,CD8-Positive T-Lymphocytes ,Virus ,Antigen ,CD28 Antigens ,Immunopathology ,HIV Seropositivity ,Immunology and Allergy ,Humans ,Lymphocyte Count ,Sida ,Child ,biology ,Age Factors ,CD28 ,Infant ,T lymphocyte ,biology.organism_classification ,Infectious Disease Transmission, Vertical ,CD4 Lymphocyte Count ,Child, Preschool ,Viral disease ,CD8 - Abstract
SUMMARY To evaluate whether vertical HIV infection interferes with the expression of CD28 on T lymphocytes, 25 HIV-infected children and 29 seroreverted children born to HIV+ mothers were studied. The percentage of CD28− cells among CD8+ T lymphocytes was higher in HIV-infected children than in controls (P
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- 1997
9. [The inhalational therapy of respiratory pathology]
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S, Guarnaccia, M A, Muraro, C, Aparicio, C, Fazi, M G, Laffranchi, S, Marini, S, Timpano, M, Gardenghi, A, Brunori, and A G, Ugazio
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Aerosols ,Pharmaceutical Preparations ,Nebulizers and Vaporizers ,Administration, Inhalation ,Respiratory Tract Diseases ,Humans ,Equipment Design ,Child - Abstract
The inhalation of aerosolized drugs for therapeutic purpose has been used for many years in respiratory diseases as asthma, chronic bronchitis, cystic fibrosis. Therapeutic aerosols have the advantages to deliver active substances directly to the site of disease, without systemic side effects, to produce a more rapid clinical response, to avoid barriers to the absorption of drugs such as the gastrointestinal tract. We review the mechanisms and the site of lung deposition and the range of devices that can provide an effective aerosol such as metered dose-inhaler and spacers. Besides drugs as cromolyn, beta-2-agonists and topical steroids, recently new inhalation therapies were proposed using antiviral drugs (interferon), pentamidine for Pneumocystis carinii in immunocompromised host, inhalation of attenuated virus (measles) for active immunization. However there is a need for further work in this area.
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- 1994
10. Risk of CFTR-related disorders and cystic fibrosis in an Italian cohort of CRMS/CFSPID subjects in preschool and school age.
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Fevola C, Dolce D, Tosco A, Padoan R, Daccò V, Claut L, Schgor T, Sepe A, Timpano S, Fabrizzi B, Piccinini P, Taccetti G, Bonomi P, and Terlizzi V
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- Infant, Infant, Newborn, Child, Humans, Child, Preschool, Cystic Fibrosis Transmembrane Conductance Regulator genetics, Neonatal Screening, Genetic Testing, Italy epidemiology, Cystic Fibrosis diagnosis, Cystic Fibrosis genetics
- Abstract
The identification of cystic fibrosis screening-positive, inconclusive diagnosis (CFSPID) in infants is a controversial outcome of newborn screening for cystic fibrosis (CF). Today, despite improvements in the knowledge of CFSPID and the description of several cohorts, little data are available on cohorts with a follow-up period of more than 6 years. In this study, we report the outcomes of an Italian cohort of CFSPID individuals with CFSPID or formerly CFTR-related disorders (CFTR-RD) (CFSPID > CFTR-RD) or diagnosed with CF (CFSPID > CF). This was an observational and multicentre Italian study collecting clinical data on CFSPID born between the period January 1, 2011, and December 13, 2019. A total of 268 participants were included: 243 with persistent CFSPID, 7 with CFSPID > CFTR-RD, and 18 with CFSPID > CF. The trend of sweat chloride (SC) values, percentage of definitive diagnoses, lung function in school-aged children, and development of CF-related complications were evaluated. At the end of the observation period, almost 80% of the individuals with CFSPID did not have a conclusive diagnosis. A total of 29 children (10.8%) transitioned to a diagnosis of CF for pathological SC values (≥ 60 mmol/L) or multi-organ involvement, and 18 (6.7%) to CFTR-RD. Children who were followed up for > 6 years (median age, 7.5 years; range, 6.04-10.5) had normal lung function and were pancreatic sufficient, and the evolution in CF was only present in two cases., Conclusion: Most Italian preschool and school-aged children with CFSPID did not have a conclusive diagnosis, and progression to CF was unlikely in children > 6 years of age. An annual follow-up could be indicated to identify early evolution in clinical features consistent with a CFTR-RD., What Is Known: • Cystic Fibrosis newborn screening identifies also subjects with an inconclusive diagnosis (CFSPID). • Over time a variable percentage of CFSPIDs will be diagnosed as CF. • Little data is available on CFSPIDs with a follow-up period of more than six years., What Is New: • 80% of Italian preschool and school-age CFSPIDs not have a conclusive diagnosis. • Italian preschool and school-age CFSPIDs have normal lung function and are pancreatic sufficient. • Annual follow-up after 6 years is recommended in CFSPID with abnormal LCI2.5 or with a CF-causing variant in trans with a VVCC., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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11. Hyperbilirubinemia and Gilbert's syndrome in Cystic Fibrosis patients treated with elexacaftor/tezacaftor/ivacaftor.
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Terlizzi V, Timpano S, Salvi M, Tosco A, Castaldo A, Fevola C, Leonetti G, Vitullo P, Sepe A, Badolato R, and Salvatore D
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- Humans, Hyperbilirubinemia, Aminophenols adverse effects, Benzodioxoles adverse effects, Cystic Fibrosis Transmembrane Conductance Regulator genetics, Mutation, Chloride Channel Agonists adverse effects, Drug Combinations, Cystic Fibrosis complications, Cystic Fibrosis drug therapy, Cystic Fibrosis genetics, Gilbert Disease diagnosis, Gilbert Disease drug therapy, Gilbert Disease genetics
- Abstract
Competing Interests: Declaration of Competing Interest The authors disclose no conflicts of interest or financial relationships relevant to this article.
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- 2023
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12. Pathogenic variants in SMARCA1 cause an X-linked neurodevelopmental disorder modulated by NURF complex composition.
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Picketts D, Mirzaa G, Yan K, Relator R, Timpano S, Yalcin B, Collins S, Ziegler A, Pao E, Oyama N, Brischoux-Boucher E, Piard J, Monaghan K, Sacoto MG, Dobyns W, Park K, Fernández-Mayoralas D, Fernández-Jaén A, Jayakar P, Brusco A, Antona V, Giorgio E, Kvarnung M, Isidor B, Conrad S, Cogné B, Deb W, Stuurman KE, Sterbova K, Smal N, Weckhuysen S, Oegema R, Innes M, Latsko M, Ben-Omran T, Yeh R, Kruer M, Bakhtiari S, Papavasiliou A, Moutton S, Nambot S, Chanprasert S, Paolucci S, Miller K, Burton B, Kim K, O'Heir E, Bruwer Z, Donald K, Kleefstra T, Goldstein A, Angle B, Bontempo K, Miny P, Joset P, Demurger F, Hobson E, Pang L, Carpenter L, Li D, Bonneau D, and Sadikovic B
- Abstract
Pathogenic variants in ATP-dependent chromatin remodeling proteins are a recurrent cause of neurodevelopmental disorders (NDDs). The NURF complex consists of BPTF and either the SNF2H ( SMARCA5 ) or SNF2L ( SMARCA1 ) ISWI-chromatin remodeling enzyme. Pathogenic variants in BPTF and SMARCA5 were previously implicated in NDDs. Here, we describe 40 individuals from 30 families with de novo or maternally inherited pathogenic variants in SMARCA1 . This novel NDD was associated with mild to severe ID/DD, delayed or regressive speech development, and some recurrent facial dysmorphisms. Individuals carrying SMARCA1 loss-of-function variants exhibited a mild genome-wide DNA methylation profile and a high penetrance of macrocephaly. Genetic dissection of the NURF complex using Smarca1, Smarca5 , and Bptfsingle and double mouse knockouts revealed the importance of NURF composition and dosage for proper forebrain development. Finally, we propose that genetic alterations affecting different NURF components result in a NDD with a broad clinical spectrum., Competing Interests: KGM and MJGS are employees of GeneDX, LLC. All remaining authors declare no competing financial interests.
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- 2023
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13. The Role of Bronchoscopy in the Management of Children With Cystic Fibrosis.
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Tosco A, Poli P, Casale A, De Gregorio F, Sepe A, Buonpensiero P, Di Pasqua A, Castaldo A, Cimbalo C, Buzzetti R, Raia V, Berlucchi M, Timpano S, Badolato R, Padoan R, and Orlando C
- Subjects
- Adolescent, Child, Humans, Anti-Bacterial Agents therapeutic use, Bronchoalveolar Lavage, Bronchoscopy, Prospective Studies, Cystic Fibrosis drug therapy
- Abstract
Background: Currently, no consensus guidelines recommend routine bronchoscopy procedure in cystic fibrosis (CF), as no evidence is available concerning its use as either a diagnostic or therapeutic tool. Its efficacy is controversial, and no randomized controlled prospective trials are available to check its effectiveness. The aims of the present study were to evaluate the effectiveness of bronchoscopy as a diagnostic/therapeutic tool in CF children and adolescents; and to verify the effect of serial bronchoscopy on lung disease progression in subjects with CF not responding to a single procedure., Methods: Data of patients who received bronchoscopy at 2 Italian CF centers were collected. Bronchoalveolar lavage was performed during the procedure including airway clearance with mucolytics, inhaled antibiotics, and/or surfactant instillation., Results: A total of 16 patients in center 1 and 17 in center 2 underwent, respectively, 28 and 23 bronchoscopic procedure in the study period. Five patients in each center underwent >1 procedure. All procedures were generally well tolerated. No patient required admission to the pediatric intensive therapy unit. In 19.6% of bronchoalveolar lavages, growth of Aspergillus fumigatus was evident, although not detected by sputum analyses. After the procedure, an increase in mean percent predicted forced expiratory volume in the 1 second >10% was observed, and a significant decrease in pulmonary exacerbations yearly was evident., Conclusion: Based on the results, we suggest bronchoscopy is not to be considered an obsolete tool, and it remains useful in CF management, although in selected cases. We encourage to support longitudinal observational studies to standardize the procedure, focusing on the choice of drugs to be instilled, modalities and timing of serial bronchoscopy and subsequent follow-up in selected severe clinical conditions., Competing Interests: Disclosure: There is no conflict of interest or other disclosures., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2023
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14. Longitudinal Characterization of Immune Response in a Cohort of Children Hospitalized with Multisystem Inflammatory Syndrome.
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Dotta L, Moratto D, Cattalini M, Brambilla S, Giustini V, Meini A, Girelli MF, Cortesi M, Timpano S, Galvagni A, Viola A, Crotti B, Manerba A, Pierelli G, Verzura G, Serana F, Brugnoni D, Garrafa E, Ricci F, Tomasi C, Chiarini M, and Badolato R
- Abstract
Background: Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe complication of SARS-CoV-2 infection caused by hyperactivation of the immune system., Methods: this is a retrospective analysis of clinical data, biochemical parameters, and immune cell subsets in 40 MIS-C patients from hospital admission to outpatient long-term follow-up., Results: MIS-C patients had elevated inflammatory markers, associated with T- and NK-cell lymphopenia, a profound depletion of dendritic cells, and altered monocyte phenotype at disease onset, while the subacute phase of the disease was characterized by a significant increase in T- and B-cell counts and a rapid decline in activated T cells and terminally differentiated B cells. Most of the immunological parameters returned to values close to the normal range during the remission phase (20-60 days after hospital admission). Nevertheless, we observed a significantly reduced ratio between recently generated and more differentiated CD8+ T- and B-cell subsets, which partially settled at longer-term follow-up determinations., Conclusions: The characterization of lymphocyte distribution in different phases of MIS-C may help to understand the course of diseases that are associated with dysregulated immune responses and to calibrate prompt and targeted treatments.
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- 2023
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15. Different management approaches and outcome for infants with an inconclusive diagnosis following newborn screening for cystic fibrosis (CRMS/CFSPID) and Pseudomonas aeruginosa isolation.
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Dolce D, Claut L, Colombo C, Tosco A, Castaldo A, Padoan R, Timpano S, Fabrizzi B, Bonomi P, Taccetti G, and Terlizzi V
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- Infant, Newborn, Humans, Infant, Child, Preschool, Neonatal Screening, Pseudomonas aeruginosa, Retrospective Studies, Cystic Fibrosis Transmembrane Conductance Regulator, Cystic Fibrosis diagnosis
- Abstract
Introduction: Evidence is currently lacking to guide the management of cystic fibrosis (CF) transmembrane conductance regulator-related metabolic syndrome CF screen-positive inconclusive diagnosis (CRMS/CFSPID) with Pseudomonas aeruginosa (Pa)-positive respiratory culture. This study assessed the clinical data, management, and outcomes of an Italian cohort of CRMS/CFSPID infants with Pa isolated from their airways., Methods: Data of Pa-positive CRMS/CFSPID infants born between January 2011 and August 2018 and followed at five CF Italian centres were retrospectively extracted. Further data were collected until June 2021 to assess outcomes, prevalence of subjects treated with antimicrobials, and treatment type and duration., Results: Forty-three asymptomatic CRMS/CFSPID patients (median age on 30 June 2021, 82 months; interquartile range [IQR], 63-98 months) with at least one positive airway culture for non-mucoid Pa (median age at first isolation, 18.7 months; IQR, 7-25 months) were enrolled. Of them, 24 (55.8%) underwent anti-Pa therapy. Pa clearance occurred in 22 (91.6%) of 24 patients versus spontaneous clearance in 16 of 19 (84.2%) untreated patients (chi-square, 0.5737; p = 0.44878). After a median follow-up of 6.2 years (IQR, 3.0-9.9), 7 (16.3%) were diagnosed with CF after a pathological sweat test (median age, 43 months; IQR, 28-77 months), 3 (7%) developed recurrent pancreatitis or isolated bronchiectasis consistent with CFTR-related disorder, and the CRMS/CFSPID classification remained in 33 (76.7%)., Conclusions: Pa detection frequently occurs in asymptomatic infants with CRMS/CFSPID but tends to clear spontaneously. More studies are needed to determine if Pa isolation can predict evolution., Competing Interests: Declaration of Competing Interest The authors disclose no conflicts of interest or financial relationships relevant to this article., (Copyright © 2022. Published by Elsevier B.V.)
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- 2023
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16. Outcomes of early repeat sweat testing in infants with cystic fibrosis transmembrane conductance regulator-related metabolic syndrome/CF screen-positive, inconclusive diagnosis.
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Terlizzi V, Claut L, Colombo C, Tosco A, Castaldo A, Fabrizzi B, Lucarelli M, Cimino G, Carducci C, Dolce D, Biffi A, Bonomi P, Timpano S, and Padoan R
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- Cystic Fibrosis Transmembrane Conductance Regulator genetics, Humans, Infant, Infant, Newborn, Mutation, Neonatal Screening, Prospective Studies, Sweat, Cystic Fibrosis diagnosis, Metabolic Syndrome
- Abstract
Background: Reaching early and definitive diagnosis in infants with cystic fibrosis (CF) transmembrane conductance regulator-related metabolic syndrome (CRMS)/CF screen-positive, inconclusive diagnosis (CFSPID) is a priority of all CF newborn screening programs. Currently, sweat testing (ST) is the gold standard for CF diagnosis or exclusion. We assessed outcomes in a cohort of Italian CRMS/CFSPID infants who underwent repeat ST in the 1st year of life., Methods: This multicentre, prospective study analysed clinical data and outcomes in CRMS/CFSPID infants born between September 1, 2018, and December 31, 2019, and followed until June 30, 2020. All subjects underwent CF transmembrane conductance regulator (CFTR) gene sequencing and the search for CFTR macrodeletions/macroduplications, and repeat ST in the 1st year of life., Results: Fifty subjects (median age at end of follow-up, 16 months [range, 7-21 months]) were enrolled. Forty-one (82%) had the first sweat chloride (SC) in the intermediate range. During follow up, 150 STs were performed (range, 1-7/infant). After a median follow-up of 8.5 months (range, 1-16.2 months), 11 (22%) subjects were definitively diagnosed as follows: CF (n = 2 [4%]) at 2 and 5 months, respectively; healthy carrier (n = 8 [16%]), at a median age of 4 months (range, 2-8 months); and healthy (n = 1 [2%]) at 2 months of age. Inconclusive diagnosis remained in 39 (78%) infants., Conclusions: Early repeat ST in the 1st year of life can shorten the time to definitive diagnosis in screening positive subjects with initial SC levels in the intermediate range., (© 2021 Wiley Periodicals LLC.)
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- 2021
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17. Paranasal mucoceles in children with cystic fibrosis: Management of a not so rare clinical condition.
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Rampinelli V, Ferrari M, Poli P, Lancini D, Mattavelli D, Timpano S, Redaelli de Zinis LO, Badolato R, Padoan R, and Berlucchi M
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- Adolescent, Age Factors, Child, Child, Preschool, Female, Humans, Infant, Male, Mucocele diagnosis, Mucocele etiology, Mucocele pathology, Paranasal Sinus Diseases diagnosis, Paranasal Sinus Diseases etiology, Paranasal Sinus Diseases pathology, Paranasal Sinuses diagnostic imaging, Paranasal Sinuses surgery, Rare Diseases, Retrospective Studies, Tomography, X-Ray Computed, Treatment Outcome, Cystic Fibrosis complications, Endoscopy methods, Mucocele surgery, Nasal Surgical Procedures methods, Paranasal Sinus Diseases surgery
- Abstract
Purpose: Paranasal mucocele (PM) is reported as a complication in children with cystic fibrosis (CF) in up to 4% of patients. The objective of this study was to identify PMs in the personal large series of children with CF and to assess their diagnosis and treatment., Material and Methods: Medical records of children with CF and PM who were admitted and treated by means of endoscopic nasal surgery between 2004 and 2020 were retrospectively reviewed., Results: Thirty-four patients were included in the study (mean age 7.7 years). CT scan of sinuses showed a total of 53 PMs. Nasal endoscopic findings suggestive for PM were present in almost 80% of patients. PMs were located in the maxillary, ethmoid, and sphenoid sinuses in 29/34 (85.3%, bilateral in 17 cases), 4/34 (11.8%) and 1/34 (2.9%) patients, respectively. Marsupialization of PMs was performed in all patients using an endoscopic transnasal approach. No complications were observed. Resolution of symptoms and normalization of the endoscopic nasal picture was evident in all patients. After a mean follow-up of 85 months, no recurrences were observed., Conclusions: To the best of our knowledge, this is the largest series of CF patients with PMs. Even if not frequently reported in the literature, PMs should not be considered an uncommon finding in patients affected by CF. Routine nasal endoscopy is mandatory to favor early diagnosis. Endoscopic transnasal marsupialization represents the gold standard of care for patients with CF and PM(s)., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
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18. A survey of the prevalence, management and outcome of infants with an inconclusive diagnosis following newborn bloodspot screening for cystic fibrosis (CRMS/CFSPID) in six Italian centres.
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Terlizzi V, Claut L, Tosco A, Colombo C, Raia V, Fabrizzi B, Lucarelli M, Angeloni A, Cimino G, Castaldo A, Marsiglio L, Timpano S, Cirilli N, Moroni L, Festini F, Piccinini P, Zavataro L, Bonomi P, Taccetti G, Southern KW, and Padoan R
- Subjects
- Child, Preschool, Cystic Fibrosis Transmembrane Conductance Regulator, Diagnosis, Differential, Female, Humans, Infant, Infant, Newborn, Italy epidemiology, Male, Metabolic Syndrome diagnosis, Metabolic Syndrome epidemiology, Prevalence, Surveys and Questionnaires, Cystic Fibrosis diagnosis, Cystic Fibrosis epidemiology, Neonatal Screening methods
- Abstract
Objective: We evaluated the prevalence, Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene profile, clinical data, management and outcome for infants with a CFTR-related metabolic syndrome/CF Screen Positive, Inconclusive Diagnosis (CRMS/CFSPID) designation from six Italian centres., Methods: All newborn bloodspot screening (NBS) positive infants born from January 2011 to August 2018 with a CF diagnosis or a CRMS/CFSPID designation were enrolled. Data on sweat testing, genetics, clinical course and management were collected., Results: We enrolled 257 CF patientsand 336 infants with a CRMS/CFSPID designation (CF: CRMS/CFSPID ratio of 1:1.30).Blood immuno-reactive trypsinogen (IRT) was significantly lower in CRMS/CFSPID infants and the F508del variant accounted for only 20% of alleles. Children with CRMS/CFSPID showed a milder clinical course, pancreatic sufficiency compared to CF infants. Varied practice across centres was identified regarding sweat testing, chest radiograph (8-100%) and salt supplementation (11-90%). Eighteen (5.3%) CRMS/CFSPID infants converted or were reclassified to diagnosis of CF. Four infants (1.3%) developed a clinical feature consistent with a CFTR-related disorder (1.2%). Twenty-seven were re-classified as healthy carriers (8.0%) and 16 as healthy infants (4.8%)., Conclusions: We have identified considerable variability in the evaluation and management of infants with an inconclusive diagnosis following NBS across six Italian centres. CRMS/CFSPID is more regularly seen in this population compared to countries with higher prevalence of F508del.Conversion to a CF diagnosis was recorded in 18 (5.3%) of CRMS/CFSPID infants and in 16 was as a result of increasing sweat chloride concentration., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest and no financial relationships relevant to this article to disclose., (Copyright © 2021 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)
- Published
- 2021
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19. Impaired SNF2L Chromatin Remodeling Prolongs Accessibility at Promoters Enriched for Fos/Jun Binding Sites and Delays Granule Neuron Differentiation.
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Goodwin LR, Zapata G, Timpano S, Marenger J, and Picketts DJ
- Abstract
Chromatin remodeling proteins utilize the energy from ATP hydrolysis to mobilize nucleosomes often creating accessibility for transcription factors within gene regulatory elements. Aberrant chromatin remodeling has diverse effects on neuroprogenitor homeostasis altering progenitor competence, proliferation, survival, or cell fate. Previous work has shown that inactivation of the ISWI genes, Smarca5 (encoding Snf2h) and Smarca1 (encoding Snf2l) have dramatic effects on brain development. Smarca5 conditional knockout mice have reduced progenitor expansion and severe forebrain hypoplasia, with a similar effect on the postnatal growth of the cerebellum. In contrast, Smarca1 mutants exhibited enlarged forebrains with delayed progenitor differentiation and increased neuronal output. Here, we utilized cerebellar granule neuron precursor (GNP) cultures from Smarca1 mutant mice (Ex6DEL) to explore the requirement for Snf2l on progenitor homeostasis. The Ex6DEL GNPs showed delayed differentiation upon plating that was not attributed to changes in the Sonic Hedgehog pathway but was associated with overexpression of numerous positive effectors of proliferation, including targets of Wnt activation. Transcriptome analysis identified increased expression of Fosb and Fosl2 while ATACseq experiments identified a large increase in chromatin accessibility at promoters many enriched for Fos/Jun binding sites. Nonetheless, the elevated proliferation index was transient and the Ex6DEL cultures initiated differentiation with a high concordance in gene expression changes to the wild type cultures. Genes specific to Ex6DEL differentiation were associated with an increased activation of the ERK signaling pathway. Taken together, this data provides the first indication of how Smarca1 mutations alter progenitor cell homeostasis and contribute to changes in brain size., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Goodwin, Zapata, Timpano, Marenger and Picketts.)
- Published
- 2021
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20. Case Report: Analysis of Inflammatory Cytokines IL-6, CCL2/MCP1, CCL5/RANTES, CXCL9/MIG, and CXCL10/IP10 in a Cystic Fibrosis Patient Cohort During the First Wave of the COVID-19 Pandemic.
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Baresi G, Giacomelli M, Moratto D, Chiarini M, Conforti IC, Padoan R, Poli P, Timpano S, Caldarale F, and Badolato R
- Abstract
Since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, data registered in the European countries revealed increasing cases of infection in cystic fibrosis (CF) patients. In the course of this pandemic, we enrolled 17 CF patients for a study evaluating inflammatory markers. One of them developed COVID - 19, giving us the possibility to analyze inflammatory markers in the acute phase as compared to levels detected before and after the infectious episode and to levels measured in the other CF patients enrolled to the study who did not experience COVID-19 and 23 patients referred to our center for SARS-CoV-2 infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Baresi, Giacomelli, Moratto, Chiarini, Conforti, Padoan, Poli, Timpano, Caldarale and Badolato.)
- Published
- 2021
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21. Plasmacytoid Dendritic Cells Depletion and Elevation of IFN-γ Dependent Chemokines CXCL9 and CXCL10 in Children With Multisystem Inflammatory Syndrome.
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Caldarale F, Giacomelli M, Garrafa E, Tamassia N, Morreale A, Poli P, Timpano S, Baresi G, Zunica F, Cattalini M, Moratto D, Chiarini M, Cannizzo ES, Marchetti G, Cassatella MA, Taddio A, Tommasini A, and Badolato R
- Subjects
- Child, Child, Preschool, Female, Humans, Infant, Male, Retrospective Studies, COVID-19 immunology, Chemokine CXCL10 immunology, Chemokine CXCL9 immunology, Dendritic Cells immunology, Interferon-gamma immunology, Plasma Cells immunology, SARS-CoV-2 immunology, Systemic Inflammatory Response Syndrome immunology
- Abstract
Background: SARS-CoV-2 occurs in the majority of children as COVID-19, without symptoms or with a paucisymptomatic respiratory syndrome, but a small proportion of children develop the systemic Multi Inflammatory Syndrome (MIS-C), characterized by persistent fever and systemic hyperinflammation, with some clinical features resembling Kawasaki Disease (KD)., Objective: With this study we aimed to shed new light on the pathogenesis of these two SARS-CoV-2-related clinical manifestations., Methods: We investigated lymphocyte and dendritic cells subsets, chemokine/cytokine profiles and evaluated the neutrophil activity mediators, myeloperoxidase (MPO), and reactive oxygen species (ROS), in 10 children with COVID-19 and 9 with MIS-C at the time of hospital admission., Results: Patients with MIS-C showed higher plasma levels of C reactive protein (CRP), MPO, IL-6, and of the pro-inflammatory chemokines CXCL8 and CCL2 than COVID-19 children. In addition, they displayed higher levels of the chemokines CXCL9 and CXCL10, mainly induced by IFN-γ. By contrast, we detected IFN-α in plasma of children with COVID-19, but not in patients with MIS-C. This observation was consistent with the increase of ISG15 and IFIT1 mRNAs in cells of COVID-19 patients, while ISG15 and IFIT1 mRNA were detected in MIS-C at levels comparable to healthy controls. Moreover, quantification of the number of plasmacytoid dendritic cells (pDCs), which constitute the main source of IFN-α, showed profound depletion of this subset in MIS-C, but not in COVID-19., Conclusions: Our results show a pattern of immune response which is suggestive of type I interferon activation in COVID-19 children, probably related to a recent interaction with the virus, while in MIS-C the immune response is characterized by elevation of the inflammatory cytokines/chemokines IL-6, CCL2, and CXCL8 and of the chemokines CXCL9 and CXL10, which are markers of an active Th1 type immune response. We believe that these immunological events, together with neutrophil activation, might be crucial in inducing the multisystem and cardiovascular damage observed in MIS-C., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Caldarale, Giacomelli, Garrafa, Tamassia, Morreale, Poli, Timpano, Baresi, Zunica, Cattalini, Moratto, Chiarini, Cannizzo, Marchetti, Cassatella, Taddio, Tommasini and Badolato.)
- Published
- 2021
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22. Immune response in children with COVID-19 is characterized by lower levels of T-cell activation than infected adults.
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Moratto D, Giacomelli M, Chiarini M, Savarè L, Saccani B, Motta M, Timpano S, Poli P, Paghera S, Imberti L, Cannizzo S, Quiros-Roldan E, Marchetti G, and Badolato R
- Subjects
- Adolescent, COVID-19 immunology, COVID-19 pathology, Chemokine CCL2 blood, Chemokine CCL5 blood, Chemokine CXCL10 blood, Chemokine CXCL9 blood, Child, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Interleukin-8 blood, Lymphocyte Activation, Lymphocyte Count, Lymphopenia pathology, Male, T-Lymphocyte Subsets immunology, CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, COVID-19 blood, Chemokines blood, SARS-CoV-2 immunology
- Abstract
Study of immunological features of immune response in 14 children (aged from 12 days up to 15 years) and of 10 adults who developed COVID-19 show increased number of activated CD4 and CD8 cells expressing DR and higher plasmatic levels of IL-12 and IL-1β in adults with COVID-19, but not in children. In addition, plasmatic levels of CCL5/RANTES are higher in children and adults with COVID-19, while CXCL9/MIG was only increased in adults. Higher number of activated T cells and expression of IL-12 and CXCL9 suggest prominent Th1 polarization of immune response against SARS-CoV2 in infected adults as compared with children., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2020
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23. Neurodevelopmental Disorders Caused by Defective Chromatin Remodeling: Phenotypic Complexity Is Highlighted by a Review of ATRX Function.
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Timpano S and Picketts DJ
- Abstract
The ability to determine the genetic etiology of intellectual disability (ID) and neurodevelopmental disorders (NDD) has improved immensely over the last decade. One prevailing metric from these studies is the large percentage of genes encoding epigenetic regulators, including many members of the ATP-dependent chromatin remodeling enzyme family. Chromatin remodeling proteins can be subdivided into five classes that include SWI/SNF, ISWI, CHD, INO80, and ATRX. These proteins utilize the energy from ATP hydrolysis to alter nucleosome positioning and are implicated in many cellular processes. As such, defining their precise roles and contributions to brain development and disease pathogenesis has proven to be complex. In this review, we illustrate that complexity by reviewing the roles of ATRX on genome stability, replication, and transcriptional regulation and how these mechanisms provide key insight into the phenotype of ATR-X patients., (Copyright © 2020 Timpano and Picketts.)
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- 2020
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24. Asymptomatic case of Covid-19 in an infant with cystic fibrosis.
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Poli P, Timpano S, Goffredo M, Padoan R, and Badolato R
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- Betacoronavirus, COVID-19, Humans, Infant, Infant, Newborn, Neonatologists, SARS-CoV-2, Coronavirus, Coronavirus Infections, Cystic Fibrosis, Pandemics, Pneumonia, Viral
- Abstract
Competing Interests: Declaration of Competing Interest The authors declare that there are no conflict of interests.
- Published
- 2020
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25. Should isolated Pseudo-Bartter syndrome be considered a CFTR-related disorder of infancy?
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Poli P, De Rose DU, Timpano S, Savoldi G, and Padoan R
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- Female, Humans, Infant, Infant, Newborn, Male, Mutation, Bartter Syndrome genetics, Cystic Fibrosis Transmembrane Conductance Regulator genetics, Metabolic Diseases genetics
- Abstract
Background: Infants that are negative to cystic fibrosis (CF) newborn screening (NBS) programs, or in countries without NBS, may present with metabolic alkalosis and severe salt depletion, a well-known clinical manifestation of CF termed Pseudo-Bartter syndrome (PBS). Here, we report the cases of three CF-negative children, who carry rare mutations in the CF transmembrane conductance regulator (CFTR) gene, and, for whom, PBS was the only manifestation of CFTR protein dysfunction. There is no diagnostic label for these cases., Methods: Medical records of patients followed at our Cystic Fibrosis Centre were revised and data were collected for all patients who presented with an isolated PBS. The syndrome was defined as an episode of dehydration with low levels of serum sodium (<134mmol/L), potassium ( <3.4mmol/L), and chloride ( <100mmol/L), with metabolic alkalosis (bicarbonatemia >27mmol/L) in the absence of renal tubulopathy., Results: Three out of 73 (4%) CF infants presented with a severe metabolic alkalosis with salt depletion; two of these required admission to the intensive care unit. Two infants had a negative NBS, and one was identified as a CF carrier. Sweat test was repeatedly in the negative/borderline ranges for all patients. Less than two CF causing mutations were identified (F508del/R1070W, F508del; L467F/P5L, R1066H/P5L). During a mean follow-up of 9 years, the children had no other CF manifestations., Conclusion: We suggest that PBS as the sole manifestation of CFTR dysfunction might be considered a CFTR-related disorder of infancy., (© 2019 Wiley Periodicals, Inc.)
- Published
- 2019
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26. Physioxic human cell culture improves viability, metabolism, and mitochondrial morphology while reducing DNA damage.
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Timpano S, Guild BD, Specker EJ, Melanson G, Medeiros PJ, Sproul SLJ, and Uniacke J
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- Antioxidants metabolism, Cell Line, Tumor, Cell Proliferation genetics, Cells, Cultured, Humans, Oxidation-Reduction, Oxidative Stress genetics, Oxygen metabolism, Cell Survival genetics, DNA Damage genetics, Mitochondria genetics, Mitochondria metabolism
- Abstract
Multicellular organisms balance oxygen delivery and toxicity by having oxygen pass through several barriers before cellular delivery. In human cell culture, these physiologic barriers are removed, exposing cells to higher oxygen levels. Human cells cultured in ambient air may appear normal, but this is difficult to assess without a comparison at physiologic oxygen. Here, we examined the effects of culturing human cells throughout the spectrum of oxygen availability on oxidative damage to macromolecules, viability, proliferation, the antioxidant and DNA damage responses, metabolism, and mitochondrial fusion and morphology. We surveyed 4 human cell lines cultured for 3 d at 7 oxygen conditions between 1 and 21% O
2 . We show that oxygen levels and cellular benefit are not inversely proportional, but the benefit peaks within the physioxic range. Normoxic cells are in a perpetual state of responding to damaged macromolecules and mitochondrial networks relative to physioxic cells, which could compromise an investigation. These data contribute to the concept of an optimal oxygen availability for cell culture in the physioxic range where the oxygen is not too high to reduce oxidative damage, and not too low for efficient oxidative metabolism, but just right: the Goldiloxygen zone.-Timpano, S., Guild, B. D., Specker, E. J., Melanson, G., Medeiros, P. J., Sproul, S. L. J., Uniacke, J. Physioxic human cell culture improves viability, metabolism, and mitochondrial morphology while reducing DNA damage.- Published
- 2019
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27. The eIF4E2-Directed Hypoxic Cap-Dependent Translation Machinery Reveals Novel Therapeutic Potential for Cancer Treatment.
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Melanson G, Timpano S, and Uniacke J
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- Animals, Basic Helix-Loop-Helix Transcription Factors metabolism, Humans, Hypoxia-Inducible Factor 1 metabolism, Mechanistic Target of Rapamycin Complex 1 metabolism, Neoplasms pathology, Protein Biosynthesis, Tumor Microenvironment, Eukaryotic Initiation Factor-4E metabolism, Neoplasms drug therapy, RNA Cap-Binding Proteins metabolism
- Abstract
Hypoxia is an aspect of the tumor microenvironment that is linked to radiation and chemotherapy resistance, metastasis, and poor prognosis. The ability of hypoxic tumor cells to achieve these cancer hallmarks is, in part, due to changes in their gene expression profiles. Cancer cells have a high demand for protein synthesis, and translational control is subsequently deregulated. Various mechanisms of translation initiation are active to improve the translation efficiency of select transcripts to drive cancer progression. This review will focus on a noncanonical cap-dependent translation initiation mechanism that utilizes the eIF4E homolog eIF4E2, a hypoxia-activated cap-binding protein that is implicated in hypoxic cancer cell migration, invasion, and tumor growth in mouse xenografts. A historical perspective about eIF4E2 and its various aliases will be provided followed by an evaluation of potential therapeutic strategies. The recent successes of disabling canonical translation and eIF4E with drugs should highlight the novel therapeutic potential of targeting the homologous eIF4E2 in the treatment of hypoxic solid tumors.
- Published
- 2017
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28. Analysis of Cap-binding Proteins in Human Cells Exposed to Physiological Oxygen Conditions.
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Timpano S, Melanson G, Evagelou SL, Guild BD, Specker EJ, and Uniacke J
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- Culture Media chemistry, Eukaryotic Initiation Factor-4F metabolism, Humans, Protein Biosynthesis, RNA Caps, Cell Culture Techniques, Oxygen physiology, RNA Cap-Binding Proteins metabolism
- Abstract
Translational control is a focal point of gene regulation, especially during periods of cellular stress. Cap-dependent translation via the eIF4F complex is by far the most common pathway to initiate protein synthesis in eukaryotic cells, but stress-specific variations of this complex are now emerging. Purifying cap-binding proteins with an affinity resin composed of Agarose-linked m
7 GTP (a 5' mRNA cap analog) is a useful tool to identify factors involved in the regulation of translation initiation. Hypoxia (low oxygen) is a cellular stress encountered during fetal development and tumor progression, and is highly dependent on translation regulation. Furthermore, it was recently reported that human adult organs have a lower oxygen content (physioxia 1-9% oxygen) that is closer to hypoxia than the ambient air where cells are routinely cultured. With the ongoing characterization of a hypoxic eIF4F complex (eIF4FH ), there is increasing interest in understanding oxygen-dependent translation initiation through the 5' mRNA cap. We have recently developed a human cell culture method to analyze cap-binding proteins that are regulated by oxygen availability. This protocol emphasizes that cell culture and lysis be performed in a hypoxia workstation to eliminate exposure to oxygen. Cells must be incubated for at least 24 hr for the liquid media to equilibrate with the atmosphere within the workstation. To avoid this limitation, pre-conditioned media (de-oxygenated) can be added to cells if shorter time points are required. Certain cap-binding proteins require interactions with a second base or can hydrolyze the m7 GTP, therefore some cap interactors may be missed in the purification process. Agarose-linked to enzymatically resistant cap analogs may be substituted in this protocol. This method allows the user to identify novel oxygen-regulated translation factors involved in cap-dependent translation.- Published
- 2016
- Full Text
- View/download PDF
29. Acute Scedosporium apiospermum Endobronchial Infection in Cystic Fibrosis.
- Author
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Padoan R, Poli P, Colombrita D, Borghi E, Timpano S, and Berlucchi M
- Subjects
- Bronchitis therapy, Bronchoalveolar Lavage, Child, Humans, Male, Mycoses therapy, Bronchitis diagnosis, Bronchitis pathology, Cystic Fibrosis complications, Mycoses diagnosis, Mycoses pathology, Scedosporium isolation & purification
- Abstract
Fungi are known pathogens in cystic fibrosis patients. A boy with cystic fibrosis boy presented with acute respiratory distress. Bronchoscopy showed airways obstruction by mucus plugs and bronchial casts. Scedosporium apiospermum was identified as the only pathogen. Bronchoalveolar lavage successfully resolved the acute obstruction. Plastic bronchitis is a new clinical picture of acute Scedosporium endobronchial colonization in cystic fibrosis patients.
- Published
- 2016
- Full Text
- View/download PDF
30. Human Cells Cultured under Physiological Oxygen Utilize Two Cap-binding Proteins to recruit Distinct mRNAs for Translation.
- Author
-
Timpano S and Uniacke J
- Subjects
- Basic Helix-Loop-Helix Transcription Factors genetics, Cell Line, Tumor, Eukaryotic Initiation Factor-4E, Humans, RNA Cap-Binding Proteins genetics, RNA, Messenger genetics, Basic Helix-Loop-Helix Transcription Factors metabolism, Oxygen metabolism, Peptide Chain Initiation, Translational, RNA Cap-Binding Proteins metabolism, RNA, Messenger metabolism, Tumor Microenvironment
- Abstract
Translation initiation is a focal point of translational control and requires the binding of eIF4E to the 5' cap of mRNA. Under conditions of extreme oxygen depletion (hypoxia), human cells repress eIF4E and switch to an alternative cap-dependent translation mediated by a homolog of eIF4E, eIF4E2. This homolog forms a complex with the oxygen-regulated hypoxia-inducible factor 2α and can escape translation repression. This complex mediates cap-dependent translation under cell culture conditions of 1% oxygen (to mimic tumor microenvironments), whereas eIF4E mediates cap-dependent translation at 21% oxygen (ambient air). However, emerging evidence suggests that culturing cells in ambient air, or "normoxia," is far from physiological or "normal." In fact, oxygen in human tissues ranges from 1-11% or "physioxia." Here we show that two distinct modes of cap-dependent translation initiation are active during physioxia and act on separate pools of mRNAs. The oxygen-dependent activities of eIF4E and eIF4E2 are elucidated by observing their polysome association and the status of mammalian target of rapamycin complex 1 (eIF4E-dependent) or hypoxia-inducible factor 2α expression (eIF4E2-dependent). We have identified oxygen conditions where eIF4E is the dominant cap-binding protein (21% normoxia or standard cell culture conditions), where eIF4E2 is the dominant cap-binding protein (1% hypoxia or ischemic diseases and cancerous tumors), and where both cap-binding proteins act simultaneously to initiate the translation of distinct mRNAs (1-11% physioxia or during development and stem cell differentiation). These data suggest that the physioxic proteome is generated by initiating translation of mRNAs via two distinct but complementary cap-binding proteins., (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)
- Published
- 2016
- Full Text
- View/download PDF
31. Clinical heterogeneity of dominant chronic mucocutaneous candidiasis disease: presenting as treatment-resistant candidiasis and chronic lung disease.
- Author
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Dotta L, Scomodon O, Padoan R, Timpano S, Plebani A, Soresina A, Lougaris V, Concolino D, Nicoletti A, Giardino G, Licari A, Marseglia G, Pignata C, Tamassia N, Facchetti F, Vairo D, and Badolato R
- Subjects
- Adolescent, Adult, Antifungal Agents therapeutic use, Autoimmunity, Azoles therapeutic use, Bacterial Infections complications, Candidiasis, Chronic Mucocutaneous complications, Candidiasis, Chronic Mucocutaneous drug therapy, Child, Chronic Disease, Cryptococcosis complications, Cryptococcus neoformans, Drug Resistance, Female, Humans, Leishmaniasis, Visceral complications, Lung Diseases complications, Lung Diseases drug therapy, Lung Diseases genetics, Lymphopenia complications, Male, Middle Aged, Mutation, Phosphorylation, STAT1 Transcription Factor metabolism, Virus Diseases complications, Young Adult, Candidiasis, Chronic Mucocutaneous genetics, STAT1 Transcription Factor genetics
- Abstract
In gain-of-function STAT1 mutations, chronic mucocutaneous candidiasis disease (CMCD) represents the phenotypic manifestation of a complex immunodeficiency characterized by clinical and immunological heterogeneity. We aimed to study clinical manifestations, long-term complications, molecular basis, and immune profile of patients with dominant CMCD. We identified nine patients with heterozygous mutations in STAT1, including novel amino acid substitutions (L283M, L351F, L400V). High risk of azole-resistance was observed, particularly when intermittent regimens of antifungal treatment or use of suboptimal dosage occurs. We report a case of Cryptococcosis and various bacterial and viral infections. Risk of developing bronchiectasis in early childhood or gradually evolving to chronic lung disease in adolescent or adult ages emerges. Lymphopenia is variable, likely progressing by adulthood. We conclude that continuous antifungal prophylaxis associated to drug monitoring might prevent resistance to treatment; prompt diagnosis and therapy of lung disease might control long-term progression; careful monitoring of lymphopenia-related infections might improve prognosis., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
32. Clinical and immunological data of nine patients with chronic mucocutaneous candidiasis disease.
- Author
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Dotta L, Scomodon O, Padoan R, Timpano S, Plebani A, Soresina A, Lougaris V, Concolino D, Nicoletti A, Giardino G, Licari A, Marseglia G, Pignata C, Tamassia N, Facchetti F, Vairo D, and Badolato R
- Abstract
This paper describes the heterogeneous clinical phenotype of a cohort of nine patients diagnosed with heterozygous mutations in STAT1. We report data of extended immunophenotyping over time and we show lung damage in four patients. The increased phosphorylation of STAT1 in response to IFNγ and IFNα stimulation proves the gain-of-function nature of the defects. The data are supplemental to our original article concurrently published "Clinical heterogeneity of dominant chronic mucocutaneous candidiasis disease: presenting as treatment-resistant candidiasis and chronic lung disease" [1], where additional results and interpretation of our research can be found.
- Published
- 2016
- Full Text
- View/download PDF
33. Systemic Reprogramming of Translation Efficiencies on Oxygen Stimulus.
- Author
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Ho JJD, Wang M, Audas TE, Kwon D, Carlsson SK, Timpano S, Evagelou SL, Brothers S, Gonzalgo ML, Krieger JR, Chen S, Uniacke J, and Lee S
- Subjects
- Cell Hypoxia, Cell Line, Tumor, Epithelial Cells cytology, Epithelial Cells drug effects, Epithelial Cells metabolism, Eukaryotic Initiation Factor-4F metabolism, Evolution, Molecular, Humans, Neuroglia cytology, Neuroglia drug effects, Neuroglia metabolism, RNA, Messenger metabolism, Eukaryotic Initiation Factor-4F genetics, Oxygen pharmacology, Protein Biosynthesis drug effects, RNA, Messenger genetics
- Abstract
Protein concentrations evolve under greater evolutionary constraint than mRNA levels. Translation efficiency of mRNA represents the chief determinant of basal protein concentrations. This raises a fundamental question of how mRNA and protein levels are coordinated in dynamic systems responding to physiological stimuli. This report examines the contributions of mRNA abundance and translation efficiency to protein output in cells responding to oxygen stimulus. We show that changes in translation efficiencies, and not mRNA levels, represent the major mechanism governing cellular responses to [O2] perturbations. Two distinct cap-dependent protein synthesis machineries select mRNAs for translation: the normoxic eIF4F and the hypoxic eIF4F(H). O2-dependent remodeling of translation efficiencies enables cells to produce adaptive translatomes from preexisting mRNA pools. Differences in mRNA expression observed under different [O2] are likely neutral, given that they occur during evolution. We propose that mRNAs contain translation efficiency determinants for their triage by the translation apparatus on [O2] stimulus., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
34. A conservative treatment for plastic bronchitis in pediatric age.
- Author
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Berlucchi M, Pelucchi F, Timpano S, Zorzi A, and Padoan R
- Subjects
- Bronchitis diagnosis, Bronchoalveolar Lavage Fluid cytology, Child, Preschool, Diagnosis, Differential, Female, Follow-Up Studies, Humans, Male, Oximetry, Radiography, Thoracic, Spirometry, Bronchitis therapy, Bronchoscopy methods, Positive-Pressure Respiration methods, Respiratory Therapy methods
- Abstract
Plastic bronchitis is a rare disorder in pediatric age. This disease can cause life-threatening episodes. Broncoscopy plus bronchial lavage is considered the gold standard therapeutic technique. Knowledge of this disease is mandatory to perform correct diagnosis and provide prompt treatment. The authors report the history of a 5-year-old girl affected by plastic bronchitis who was successfully treated by a conservative therapy avoiding the traditional more invasive management., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
35. Ciliary aplasia associated with hydrocephalus: an extremely rare occurrence.
- Author
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Berlucchi M, de Santi MM, Bertoni E, Spinelli E, Timpano S, and Padoan R
- Subjects
- Bronchi ultrastructure, Child, Chronic Disease, Ciliary Motility Disorders diagnosis, Ciliary Motility Disorders therapy, Female, Humans, Male, Microscopy, Electron, Transmission, Nasal Mucosa ultrastructure, Respiratory Mucosa ultrastructure, Ciliary Motility Disorders complications, Hydrocephalus complications
- Abstract
Ciliary aplasia is a rare congenital disease that alters the normal function of the mucociliary apparatus in several organs. Patients generally present with severe recurrent and chronic infections of the airways. A high suspect of this disorder is mandatory to perform correct diagnosis and provide prompt treatment. The authors describe the history of two siblings affected by primary ciliary aplasia that was associated with hydrocephalus in one case. A careful description of diagnostic procedures and treatment of this extremely rare disorder is also presented.
- Published
- 2012
- Full Text
- View/download PDF
36. 18q deletion in a cystic fibrosis infant, increased morbidity and challenge for correct treatment choices: a case report.
- Author
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Spinelli E, Timpano S, Fogazzi A, Dester S, Milianti S, and Padoan R
- Subjects
- Child, Preschool, Cystic Fibrosis epidemiology, Cystic Fibrosis therapy, Diuretics therapeutic use, Follow-Up Studies, Humans, Male, Morbidity trends, Chromosome Deletion, Chromosomes, Human, Pair 18 genetics, Cystic Fibrosis genetics, Furosemide therapeutic use, Oxygen Inhalation Therapy methods, Pancreatic Extracts administration & dosage
- Abstract
Cystic Fibrosis (CF) is the most frequent recessive disease of Caucasian patients. Association with other diseases or syndromes has previously been reported. Co-morbidity may be a challenge for clinicians, who have to face more severe problems. We have described a CF infant, F508del homozygote, diagnosed by neonatal screening, who also had a chromosome 18q terminal deletion [del (18)(q22-qter)]. Some clinical features of the 18q deletion: e.g., cardiopathy, gastro-oesophageal reflux and severe muscular hypotonia, worsened the CF clinical picture and his quality of life, with repeated pulmonary exacerbations and failure to thrive in the first six months of life. The treatment strategy was chosen following an accurate multi-disciplinary team study of overlapping chromosome syndrome and CF symptoms. The use of a gastrostomy device for enteral nutrition together with a new device (Ez-PAP) for chest physiotherapy led to normal growth, a notably reduced hospitalization rate and improved quality of life. This case shows how co-morbidities worsening the clinical course of a "complicated patient" can be faced thanks to unconventional therapies that represent a challenge for clinicians.
- Published
- 2011
- Full Text
- View/download PDF
37. CD8+CD28- T cells in vertically HIV-infected children.
- Author
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Brugnoni D, Airo P, Timpano S, Malacarne F, Ugazio AG, Cattaneo R, and Duse M
- Subjects
- Age Factors, Apoptosis, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes immunology, Child, Child, Preschool, HIV Seropositivity, Humans, Infant, Infectious Disease Transmission, Vertical, Lymphocyte Count, CD28 Antigens immunology, CD8-Positive T-Lymphocytes immunology, HIV Infections immunology, HIV Infections transmission
- Abstract
To evaluate whether vertical HIV infection interferes with the expression of CD28 on T lymphocytes, 25 HIV-infected children and 29 seroreverted children born to HIV+ mothers were studied. The percentage of CD28- cells among CD8+ T lymphocytes was higher in HIV-infected children than in controls (P < 0.001). In fact, in HIV-infected children, this percentage was elevated from the first year of life, while in healthy seroreverted children, the proportion of CD28- cells among CD8+ cells rose progressively with age (r = 0.49; P = 0.008). In HIV+ children, the CD8+ CD28-, but not CD8+ CD28+ cell proportion was significantly correlated with immunological markers of disease progression, such as CD4+ cell loss (r = -0.65; P < 0.001) and the level of in vitro spontaneous lymphocyte apoptosis (r = 0.53; P = 0.03).
- Published
- 1997
- Full Text
- View/download PDF
38. [The inhalational therapy of respiratory pathology].
- Author
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Guarnaccia S, Muraro MA, Aparicio C, Fazi C, Laffranchi MG, Marini S, Timpano S, Gardenghi M, Brunori A, and Ugazio AG
- Subjects
- Administration, Inhalation, Aerosols, Child, Equipment Design, Humans, Nebulizers and Vaporizers, Pharmaceutical Preparations administration & dosage, Respiratory Tract Diseases drug therapy
- Abstract
The inhalation of aerosolized drugs for therapeutic purpose has been used for many years in respiratory diseases as asthma, chronic bronchitis, cystic fibrosis. Therapeutic aerosols have the advantages to deliver active substances directly to the site of disease, without systemic side effects, to produce a more rapid clinical response, to avoid barriers to the absorption of drugs such as the gastrointestinal tract. We review the mechanisms and the site of lung deposition and the range of devices that can provide an effective aerosol such as metered dose-inhaler and spacers. Besides drugs as cromolyn, beta-2-agonists and topical steroids, recently new inhalation therapies were proposed using antiviral drugs (interferon), pentamidine for Pneumocystis carinii in immunocompromised host, inhalation of attenuated virus (measles) for active immunization. However there is a need for further work in this area.
- Published
- 1994
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