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1. On the Hessian of cubic hypersurfaces

Author

Bricalli, D., Favale, F. F., and Pirola, G. P.

Subjects
Mathematics - Algebraic Geometry, Primary: 14M12, Secondary: 14J70, 14J17, 13E10, 14J35
Abstract

In this paper, we analyze the Hessian locus associated to a general cubic hypersurface, by describing for every $n$ its singular locus and its desingularization. The strategy is based on strong connections between the Hessian and the quadrics defined as partial derivatives of the cubic polynomial. In particular, we focus our attention on the singularities of the Hessian hypersurface associated to the general cubic fourfold. It turns out to be a minimal surface of general type: its analysis is developed by exploiting the nature of this surface as a degeneracy locus of a symmetric vector bundle map and by describing an unramified double cover, which is constructed in a more general setting., Comment: 25 pages. Comments are welcome

Published
2023
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2. The geometry of the Hessian locus: from a theorem of Gordan and Noether to cubic fourfolds, via Gorenstein rings

Author

Bricalli, D, BRICALLI, DAVIDE, Bricalli, D, and BRICALLI, DAVIDE

Abstract

In questa tesi, verrà analizzato il luogo hessiano di ipersuperfici proiettive, che per molto tempo ha suscitato l'interesse di diversi studiosi nell'ambito della geometria algebrica. Ad esempio nel 1876 Gordan e Noether mostrarono che un'ipersuperficie X definita da un polinomio omogeneo f in uno spazio proiettivo di dimensione al più 3 è un cono se e soltanto se l'hessiano di f (cioè il determinante della matrice Hessiana di f) è identicamente nullo. Nel primo capitolo della tesi daremo una nuova dimostrazione di tale risultato: mostreremo, infatti, un teorema, che è, come classicamente noto, equivalente al risultato di Gordan e Noether. Tale teorema sarà dimostrato con un approccio assolutamente geometrico, nonostante sia caratterizzato da un aspetto decisamente algebrico: esso afferma infatti la validità di certe proprietà di Lefschetz per specifiche algebre Artiniane standard di Gorenstein. Le tecniche utilizzate in questo ambito (come la descrizione, tramite ad esempio un'opportuna varietà di incidenza, di un framework geometrico equivalente al fallimento di specifiche proprietà di Lefschetz) verranno dunque migliorate e sfruttate nel capitolo 2 per dimostrare alcune proprietà di Lefschetz per specifiche algebre di Gorenstein, come anelli Jacobiani di ipersuperfici cubiche lisce in uno spazio proiettivo di dimensione 4 e 5 (cubic threefold e cubic fourfold). Infine, nel capitolo 3, analizzeremo l'ipersuperficie Hessiana H(f) associata a un'ipersuperficie cubica liscia X=V(f), dove H(f) è quindi il luogo degli zeri del determinante della matrice Hessiana di f. Tramite strumenti derivanti dallo studio di certe algebre di Gorenstein e grazie a una naturale identificazione tra forme quadratiche e punti dell'ipersuperficie Hessiana, studieremo le singolarità di H(f) e una sua naturale desingolarizzazione. Analizzeremo infine l'Hessiana associata a un generico cubic fourfold liscio, descrivendo tramite proprietà geometriche e invarianti birazionali la, In this thesis, we will analyze the hessian locus associated to a projective hypersurface: the interest in algebraic geometry for such a topic has been alive for centuries. For example, in 1876 Gordan and Noether showed that a hypersurface X defined by a homogeneous polynomial f in a projective space of dimension at most 3 is a cone if and only if the hessian polynomial of f (i.e. the determinant of the Hessian matrix of f) is identically zero. In the first chapter of this thesis, we will give a new proof of this fundamental result due to Gordan and Noether: indeed, we will show a theorem, which, by classical theories, turns out to be equivalent to Gordan and Noether's result. We will prove this theorem with a very geometrical approach, despite the statement being characterized by a strong algebraic flavour: indeed it states the validity of some Lefschetz properties for specific standard Artinian Gorenstein algebras. The techniques used in this setting (as for example the construction and the description, through a suitable incidence variety, of a geometrical framework, which will be equivalent to the failure of a specific Lefschetz property) will be then improved and exploited in chapter 2, where we will show some Lefschetz properties for specific Gorenstein algebras, as Jacobian rings of smooth cubic hypersurfaces in a projective space of dimension 4 and 5 (i.e. cubic threefolds and cubic fourfolds). Finally, in chapter 3, we will analyze the Hessian hypersurface H(f) associated to a smooth cubic hypersurface X=V(f), i.e. H(f) is the zero locus of the hessian of f. By exploiting properties coming from some Gorenstein algebras and by using a natural identification between quadratic forms and points of the Hessian hypersurface, we will study the singular loci of H(f) and a natural desingularization for it. We will finally study the Hessian associated to a generic smooth cubic fourfold, by describing geometrical properties and birational invariants of the smooth surf

Published
2023

3. Lefschetz properties for jacobian rings of cubic fourfolds and other Artinian algebras

Author

Bricalli, D, Francesco Favale, F, Davide Bricalli, Filippo Francesco Favale, Bricalli, D, Francesco Favale, F, Davide Bricalli, and Filippo Francesco Favale

Abstract

In this paper, we exploit some geometric-differential techniques to prove the strong Lefschetz property in degree 1 for a complete intersection standard Artinian Gorenstein algebra of codimension 6 presented by quadrics. We prove also some strong Lefschetz properties for the same kind of Artinian algebras in higher codimensions. Moreover, we analyze some loci that come naturally into the picture of “special” Artinian algebras: for them we give some geometric descriptions and show a connection between the non emptiness of the so-called non-Lefschetz locus in degree 1 and the “lifting” of a weak Lefschetz property to an algebra from one of its quotients.

Published
2022

4. Determinants of mother-to-infant human immunodeficiency virus 1 transmission before and after the introduction of zidovudine prophylaxis

Author

de Martino, M, Galli, L, Tovo, PA, Gabiano, C, Pezzotti, P, Wagner, TM, Rezza, G, Osimani, P, De Mattia, D, Di Bari, C, Ruggeri, M, Baldi, F, Ciccia, M, Lanari, M, Masi, M, Venturi, V, Battisti, L, Duse, M, Chiriaco, PG, Cavallini, R, Dessi, C, Pintor, C, Anastasio, E, SABATINO, GIOVANNI, Sticca, M, Pomero, G, Bezzi, T, Chiappini, E, De Luca, M, Gervaso, P, Cecchi, MT, Bassetti, D, Gotta, C, Rosso, R, Timitilli, A, Tondo, U, Mussini, P, Bricalli, D, BUCCERI, ANDREA, Ferraris, G, Giovannini, M, Mosca, F, Lipreri, R, Guarino, A, Plebani, A, Riva, E, RIVA, SILVIA, Vigano, A, Zuccotti, GV, Cellini, M, Buffolano, W, Tarallo, L, D'Elia, R, Giaquinto, C, Rampon, O, Dalle Nogare, ER, Romano, A, Caselli, D, Maccabruni, A, Consolini, R, Benaglia, G, Magnani, C, Anzidei, G, Pistilli, AMC, Gattinara, GC, Catania, S, Facente, C, Falconieri, P, Fundaro, C, Genovese, O, Rendeli, C, Bionda, S, Cristiano, L, Garetto, S, Riva, C, PALOMBA, ERIKA, Portelli, V, Mazza, A, SALVATORE, CLAUDIO, Pellegatta, A, Molesini, M, de Martino, M, Galli, L, Tovo, PA, Gabiano, C, Pezzotti, P, Wagner, TM, Rezza, G, Osimani, P, De Mattia, D, Di Bari, C, Ruggeri, M, Baldi, F, Ciccia, M, Lanari, M, Masi, M, Venturi, V, Battisti, L, Duse, M, Chiriaco, PG, Cavallini, R, Dessi, C, Pintor, C, Anastasio, E, Sabatino, G, Sticca, M, Pomero, G, Bezzi, T, Chiappini, E, De Luca, M, Gervaso, P, Cecchi, MT, Bassetti, D, Gotta, C, Rosso, R, Timitilli, A, Tondo, U, Mussini, P, Bricalli, D, Bucceri, A, Ferraris, G, Giovannini, M, Mosca, F, Lipreri, R, Guarino, A, Plebani, A, Riva, E, Riva, S, Vigano, A, Zuccotti, GV, Cellini, M, Buffolano, W, Tarallo, L, D'Elia, R, Giaquinto, C, Rampon, O, Dalle Nogare, ER, Romano, A, Caselli, D, Maccabruni, A, Consolini, R, Benaglia, G, Magnani, C, Anzidei, G, Pistilli, AMC, Gattinara, GC, Catania, S, Facente, C, Falconieri, P, Fundaro, C, Genovese, O, Rendeli, C, Bionda, S, Cristiano, L, Garetto, S, Riva, C, Palomba, E, Portelli, V, Mazza, A, Salvatore, C, Pellegatta, A, and Molesini, M

Subjects
immunodeficiency virus 1
Abstract

Background: Randomized controlled trials have demonstrated that zidovudine therapy decreases the mother-to-infant transmission of human immunodeficiency virus 1 (HIV-1). Data from large observational studies may provide further important findings on the effectiveness at the population level of combined treatments in decreasing transmission.Objective: To evaluate time trends in prophylactic interventions and the determinants of transmission both before and after the introduction of antiretroviral prophylaxis, and in treated and untreated mother-infant pairs after 1995.Design and Setting: Analysis of prospective data on 3770 children born to HIV-1-infected women between 1985 and 1999 and reported to the Italian Register for HIV Infection in Children.Main Outcome Measures: Logistic regression random effects models were used to estimate crude and adjusted odds ratios for several factors potentially influencing vertical transmission for 2periods-1985 through 1995 (January 1, 1985, through December 31,1995) and 1996 through 1999 (January 1, 1996, through December 31, 1999), and between treated and untreated children after 1995.Results: The transmission rate was 15.5% in the 19851995 period and 5.8% in the 1996-1999 period. By 1999, prophylactic interventions had greatly increased. Antiretroviral treatment (ART) usage was 89.9%, (55.1% combination ART) and the elective cesarean delivery rate was 81.3%. In multivariate analysis, only elective cesarean delivery was associated with a lower risk of mother-to-infant transmission before 1995. After 1995, nonbreastfeeding and receipt of ART were protective whereas elective cesarean delivery was not significantly protective in multivariate analysis. Transmission risk was reduced by 76% with an incomplete zidovudine regimen, 88% with a complete regimen, and 93% when the mother received combination ART. In the 1996-1999 period, the transmission rate for nonbreastfeeding mother-infant pairs was 8.6% with elective cesarean delivery, 4.4% with any ART, and 2.4% with these interventions combined.Conclusion: Prophylactic interventions, and in particular ART, reduced perinatal HIV-1 transmission at a population level in Italy.

Published
2004

6. Clinical and immuno-virologic characterization of the efficacy of stavudine, lamivudine, and indinavir in human immunodeficiency virus infection

Author

Vigano, A., Dally, L., Bricalli, D., Sala, N., Pirillo, M., Saresella, M., Trabattoni, D., Vella, S., Clerici, M., and Principi, N.

Abstract

Clinical, virologic, and immunologic outcomes were analyzed in children with vertically transmitted human immunodeficiency virus (HIV) infection (n = 25) and clinical symptoms and evidence of immunosuppression to establish the efficacy of 18 months' treatment with stavudine, lamivudine, and indinavir. Children were naive for treatment with protease inhibitors and lamivudine and had minimal exposure to stavudine. At 1, 6, 12, and 18 months, the proportions of patients with HIV-RNA <400 copies/mL were 79%, 100%, 94%, 87% in Centers for Disease Control and Prevention (CDC) immunologic class 2 and 50%, 67%, 67%, 72% in CDC immunologic class 3. At 12 months, the median CD4^+ count and percent increased significantly in both CDC immunologic class groups, but to a greater extent in the class 3 group. In the 12- to 18-month period, there were no significant changes within the groups. In both groups there was a steady increase in the proportion and number of children with positive skin test responses. Children in class 2 were more likely to have a positive delayed-type hypersensitivity response and a greater number of positive responses. Lymphocyte proliferative response to recall antigens improved significantly in all patients. The rate of increase in positive test results was faster in children in class 2 than in those in class 3. Only minor clinical events occurred during 18 months of therapy. Potent antiretroviral therapy achieves a sustained benefit in HIV-infected children, but immune reconstitution is more likely achieved in children with less advanced disease. (J Pediatr 1999;135:675-82)

Published
1999
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7. Determinants of mother-to-infant human immunodeficiency virus 1 transmission before and after the introduction of zidovudine prophylaxis

Author

Martino, M., Galli, L., Tovo, P. -A, Gabiano, C., Pezzotti, P., Wagner, T. M., Rezza, G., Osimani, P., Mattia, D., Di Bari, C., Ruggeri, M., Baldi, F., Ciccia, M., Lanari, M., Masi, M., Venturi, V., Battisti, L., Duse, M., Chiriacò, P. G., Cavallini, R., Dessí, C., Pintor, C., Anastasio, E., Sabatino, G., Sticca, M., Pomero, G., Bezzi, T., Chiappini, E., Luca, M., Gervaso, P., Cecchi, M. T., Bassetti, D., Gotta, C., Rosso, R., Timitilli, A., Tondo, U., Mussini, P., Bricalli, D., Bucceri, A., Ferraris, G., Giovannini, M., Mosca, F., Lipreri, R., Plebani, A., Riva, E., Riva, S., Viganò, A., Gianvincenzo Zuccotti, Cellini, M., Buffolano, W., Guarino, A., Tarallo, L., D Elia, R., Giaquinto, C., Rampon, O., Dalle Nogare, E. R., Romano, A., Caselli, D., Maccabruni, A., Consolini, R., Benaglia, G., Magnani, C., Anzidei, G., Casadei Pistilli, A. M., Castelli Gattinara, G., Catania, S., Facente, C., Falconieri, P., Fundarò, C., Genovese, O., Rendeli, C., Bionda, S., Cristiano, L., Garetto, S., Riva, C., Palomba, E., Portelli, V., Mazza, A., Salvatore, C., Pellegatta, A., and Molesini, M.

10. The geometry of the Hessian locus: from a theorem of Gordan and Noether to cubic fourfolds, via Gorenstein rings

Author

BRICALLI, DAVIDE and Bricalli, D

Subjects
ipersuperfici, anelli jacobiani, cubiche, cubic, geometria algebrica, jacobian rings, hessiano, hypersurface, hessian, MAT/03 - GEOMETRIA, algebraic geometry
Abstract

In questa tesi, verrà analizzato il luogo hessiano di ipersuperfici proiettive, che per molto tempo ha suscitato l'interesse di diversi studiosi nell'ambito della geometria algebrica. Ad esempio nel 1876 Gordan e Noether mostrarono che un'ipersuperficie X definita da un polinomio omogeneo f in uno spazio proiettivo di dimensione al più 3 è un cono se e soltanto se l'hessiano di f (cioè il determinante della matrice Hessiana di f) è identicamente nullo. Nel primo capitolo della tesi daremo una nuova dimostrazione di tale risultato: mostreremo, infatti, un teorema, che è, come classicamente noto, equivalente al risultato di Gordan e Noether. Tale teorema sarà dimostrato con un approccio assolutamente geometrico, nonostante sia caratterizzato da un aspetto decisamente algebrico: esso afferma infatti la validità di certe proprietà di Lefschetz per specifiche algebre Artiniane standard di Gorenstein. Le tecniche utilizzate in questo ambito (come la descrizione, tramite ad esempio un'opportuna varietà di incidenza, di un framework geometrico equivalente al fallimento di specifiche proprietà di Lefschetz) verranno dunque migliorate e sfruttate nel capitolo 2 per dimostrare alcune proprietà di Lefschetz per specifiche algebre di Gorenstein, come anelli Jacobiani di ipersuperfici cubiche lisce in uno spazio proiettivo di dimensione 4 e 5 (cubic threefold e cubic fourfold). Infine, nel capitolo 3, analizzeremo l'ipersuperficie Hessiana H(f) associata a un'ipersuperficie cubica liscia X=V(f), dove H(f) è quindi il luogo degli zeri del determinante della matrice Hessiana di f. Tramite strumenti derivanti dallo studio di certe algebre di Gorenstein e grazie a una naturale identificazione tra forme quadratiche e punti dell'ipersuperficie Hessiana, studieremo le singolarità di H(f) e una sua naturale desingolarizzazione. Analizzeremo infine l'Hessiana associata a un generico cubic fourfold liscio, descrivendo tramite proprietà geometriche e invarianti birazionali la superficie liscia su cui H(f) è singolare e costruendo per tale superficie un naturale ricoprimento doppio e non ramificato, che mostreremo anche essere connesso tramite strumenti di teoria delle rappresentazioni. In this thesis, we will analyze the hessian locus associated to a projective hypersurface: the interest in algebraic geometry for such a topic has been alive for centuries. For example, in 1876 Gordan and Noether showed that a hypersurface X defined by a homogeneous polynomial f in a projective space of dimension at most 3 is a cone if and only if the hessian polynomial of f (i.e. the determinant of the Hessian matrix of f) is identically zero. In the first chapter of this thesis, we will give a new proof of this fundamental result due to Gordan and Noether: indeed, we will show a theorem, which, by classical theories, turns out to be equivalent to Gordan and Noether's result. We will prove this theorem with a very geometrical approach, despite the statement being characterized by a strong algebraic flavour: indeed it states the validity of some Lefschetz properties for specific standard Artinian Gorenstein algebras. The techniques used in this setting (as for example the construction and the description, through a suitable incidence variety, of a geometrical framework, which will be equivalent to the failure of a specific Lefschetz property) will be then improved and exploited in chapter 2, where we will show some Lefschetz properties for specific Gorenstein algebras, as Jacobian rings of smooth cubic hypersurfaces in a projective space of dimension 4 and 5 (i.e. cubic threefolds and cubic fourfolds). Finally, in chapter 3, we will analyze the Hessian hypersurface H(f) associated to a smooth cubic hypersurface X=V(f), i.e. H(f) is the zero locus of the hessian of f. By exploiting properties coming from some Gorenstein algebras and by using a natural identification between quadratic forms and points of the Hessian hypersurface, we will study the singular loci of H(f) and a natural desingularization for it. We will finally study the Hessian associated to a generic smooth cubic fourfold, by describing geometrical properties and birational invariants of the smooth surface over which the Hessian locus is singular; moreover, for such a surface, we will construct a natural unramified double cover, which will turn out to be also connected, by using tools coming from representation theory.

Published
2023

11. Lefschetz properties for jacobian rings of cubic fourfolds and other Artinian algebras

Author

Davide Bricalli, Filippo Francesco Favale, Bricalli, D, and Francesco Favale, F

Subjects
Lefschetz propertie, Mathematics::Commutative Algebra, Applied Mathematics, General Mathematics, Cubic fourfold, Artinian Gorenstein algebra, Mathematics - Commutative Algebra, Commutative Algebra (math.AC), Mathematics - Algebraic Geometry, Mathematics::Algebraic Geometry, FOS: Mathematics, Mathematics::Symplectic Geometry, Algebraic Geometry (math.AG), Complete intersection, MAT/03 - GEOMETRIA, 14J35, 13E10, 14J70, 14M10, 13F20, 14N05, Jacobian ring
Abstract

In this paper, we exploit some geometric-differential techniques to prove the strong Lefschetz property in degree $1$ for a complete intersection standard Artinian Gorenstein algebra of codimension $6$ presented by quadrics. We prove also some strong Lefschetz properties for the same kind of Artinian algebras in higher codimensions. Moreover, we analyze some loci that come naturally into the picture of "special" Artinian algebras: for them, we give some geometric descriptions and show a connection between the non emptiness of the so-called non-Lefschetz locus in degree $1$ and the "lifting" of a weak Lefschetz property to an algebra from one of its quotients., Comment: 21 pages

Published
2022

12. Serotype distribution and antimicrobial susceptibilities of nasopharyngeal isolates of Streptococcus pneumoniae from healthy children in the 13-valent pneumococcal conjugate vaccine era.

Author

Zuccotti G, Mameli C, Daprai L, Garlaschi ML, Dilillo D, Bedogni G, Faccini M, Gramegna M, Torresani E, Ballerini E, Benincaso A, Bonvissuto M, Bricalli D, Brioschi M, Calloni CS, Camiletti MI, Colella G, De Angelis L, Decarlis S, Di Nello F, Dozzi M, Galli E, Gandini V, Giuliani MG, Laviola F, Loda B, Macedoni M, Mazzucchi E, Metta MG, Moscatiello A, Nannini P, Petruzzi M, Picicco D, Picciotti M, Pisanelli S, Porta N, Ramponi G, Redaelli F, Rubini R, Sala N, Saitta V, Scelza G, Tiso RM, Tomasetto M, Torcoletti M, Travaini M, Valentini M, and Vessia C

Subjects
Child, Preschool, Cross-Sectional Studies, Drug Resistance, Bacterial, Female, Humans, Infant, Italy, Male, Microbial Sensitivity Tests, Pneumococcal Vaccines administration & dosage, Streptococcus pneumoniae drug effects, Streptococcus pneumoniae isolation & purification, Carrier State microbiology, Nasopharynx microbiology, Pneumococcal Infections epidemiology, Streptococcus pneumoniae classification
Abstract

Few epidemiological data are available since the introduction of 13-valent pneumococcal vaccine (PCV13) in 2010. We conducted a cross-sectional study to estimate the prevalence of Streptococcus pneumoniae (SP) nasopharyngeal carriage in healthy Italian infants and young children and to evaluate the impact of PCV13 on pneumococcal colonization. In the trimester September-December 2011 nasopharyngeal swabs were collected from healthy children aged 3-59 months presenting for routine well careat 16 primary care pediatricians in Milan. SP carriage isolates were serotyped and tested for antimicrobial resistance using EUCAST breakpoints. Among 1250 enrolled children, 618 had received at least 1 dose of PCV13, 292 at least 1 dose of PCV7, 94 a combination of the two vaccines and 246 were not vaccinated. The prevalence of SP carriage was 27% (95% confidence interval [CI] 25-30). At multivariable analysis, age≥25 months (prevalence ratio [PR]=0.74) and use of antibiotics in the previous 3 months (PR=0.67) were associated with lower SP carriage prevalence. Having siblings (PR=1.79 for 1 sibling and PR=2.23 for ≥2 siblings), day-care attendance (PR=2.27) and respiratory tract infections in the previous 3 months (PR=1.39) were associated with higher SP carriage prevalence. The immunization status for SP was not associated with SP carriage at univariable or at multivariable analysis. The most common carriage isolates were 6C, 19A and 23A. The prevalence of the six additional PCV13 serotypes carriage in children appropriately vaccinated with PCV13 was lower than in children appropriately vaccinated with PCV7 (0 vs. 0.060); the greater reduction in prevalence of carriage was observed for serotype 19A (0 vs. 0.041). Serotype 6C was the most common drug-resistant serotype (17.2%). Further epidemiological studies are needed to assess changes in circulating SP serotypes following the large-scale introduction of PCV13., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Published
2014
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13. Increased lipodystrophy is associated with increased exposure to highly active antiretroviral therapy in HIV-infected children.

Author

Viganò A, Mora S, Testolin C, Beccio S, Schneider L, Bricalli D, Vanzulli A, Manzoni P, and Brambilla P

Subjects
Abdomen, Absorptiometry, Photon, Adipose Tissue, Adolescent, Body Composition, Child, Female, HIV Infections complications, Humans, Magnetic Resonance Imaging, Male, Prospective Studies, Protease Inhibitors adverse effects, Antiretroviral Therapy, Highly Active adverse effects, HIV Infections drug therapy, HIV-Associated Lipodystrophy Syndrome epidemiology
Abstract

Objective: To assess body composition changes in HIV-infected children receiving highly active antiretroviral therapy (HAART)., Methods: Thirty-seven HIV-positive children were enrolled. Dual-energy X-ray absorptiometry (DXA) scans were performed in all HIV-infected children at baseline and after an additional 12 months of HAART and in 54 matched (for sex, age, body mass index [BMI], and pubertal stage) healthy controls. Abdominal MRI was performed in 14 of 37 HIV-positive children at baseline and in 28 of 37 HIV-positive children after additional 12 months of HAART., Results: During the study period, mean HAART exposure increased from 39.3 to 50.9 months and the number of HIV-infected children with clinical lipodystrophy (LD) increased from 6 to 8, whereas mean BMI, CD4 percentage, and percentage of HIV-infected children with HIV RNA <50 copies/mL did not change. DXA scans showed an increase in lean mass, peripheral fat loss, and central fat accumulation in all HIV-infected children. As compared with controls, 70% and 84% of HIV-infected children showed DXA-detectable LD at baseline and at 12 months of follow-up, respectively. Mixed LD and central fat accumulation were the most common LD phenotype. At baseline and at 12 months of follow-up, intra-abdominal adipose tissue (IAT) was greater than in controls in 33% and 35% of HIV-infected children, and it was greater in those with LD than in those without. Peripheral fat loss and IAT content were associated with duration of HAART and were independent of immunologic stage of disease and immunologic response., Conclusions: Changes in body composition related to LD in HAART-treated children are frequent, precocious, and progressive. Duration of HAART negatively influences visceral adiposity and peripheral fat loss.

Published
2003
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14. Mitochondrial functionality and mitochondrial DNA content in lymphocytes of vertically infected human immunodeficiency virus-positive children with highly active antiretroviral therapy-related lipodystrophy.

Author

Cossarizza A, Pinti M, Moretti L, Bricalli D, Bianchi R, Troiano L, Fernandez MG, Balli F, Brambilla P, Mussini C, and Viganò A

Subjects
Acquired Immunodeficiency Syndrome immunology, Acquired Immunodeficiency Syndrome transmission, Adolescent, Child, Child, Preschool, Female, Flow Cytometry, Humans, Male, Mitochondria physiology, Acquired Immunodeficiency Syndrome drug therapy, Antiretroviral Therapy, Highly Active adverse effects, DNA, Mitochondrial analysis, Infectious Disease Transmission, Vertical, Lipodystrophy chemically induced, Lymphocytes drug effects, Mitochondria drug effects
Abstract

Mitochondria functionality and apoptosis were studied in peripheral blood lymphocytes (PBL) of human immunodeficiency virus type 1-infected children, with or without lipodystrophy (LD), who were receiving highly active antiretroviral therapy (HAART) and in PBL of healthy control subjects (HCs). By flow cytometry, mitochondrial (mt) membrane potential, mt mass, intra-mt cardiolipin distribution, and early and late apoptosis in fresh PBL or in PBL cultured with different stimuli were assessed. mtDNA content was evaluated in fresh PBL by an original double-competitive quantitative polymerase chain reaction method, which enabled direct quantification of the number of mtDNA copies present in human lymphocytes. PBL from LD-positive and LD-negative children and from HCs were similar in mt functionality and in their tendency to undergo apoptosis. mtDNA content was also similar in PBL of LD-positive children and HCs, suggesting that normal mt functionality and normal tendency to undergo apoptosis are present in PBL of children with HAART-associated LD.

Published
2002
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15. Highly active antiretroviral-treated HIV-infected children show fat distribution changes even in absence of lipodystrophy.

Author

Brambilla P, Bricalli D, Sala N, Renzetti F, Manzoni P, Vanzulli A, Chiumello G, di Natale B, and Viganò A

Subjects
Absorptiometry, Photon, Adipose Tissue pathology, Adolescent, Body Composition physiology, Child, Female, HIV Infections pathology, HIV-1 pathogenicity, Humans, Magnetic Resonance Imaging, Male, Adipose Tissue drug effects, Antiretroviral Therapy, Highly Active adverse effects, Body Composition drug effects, HIV Infections drug therapy, Lipodystrophy chemically induced
Abstract

Background: Combined use of dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI) allows a precise estimate of regional body composition and intra-abdominal adipose tissue (IAT). Data on body composition in HIV-infected children (HIV+) receiving highly active antiretroviral therapy (HAART) with (LD+) and without (LD-) lipodystrophy are lacking., Methods: DXA scans were performed in 34 HIV+: six LD+, 28 LD- and 34 pair-matched (age, sex and body mass index) healthy controls (HC): six for LD+ (HC+) and 28 for LD- (HC-). MRI scans were performed in 16 HIV+: six LD+, 10 LD- and 16 pair-matched (age and sex) HC. Data were analysed by analysis of variance, post hoc Fisher test and Mann-Whitney test., Results: LD+ and LD- were similar for: previous exposure to zidovudine/zidovudine + didanosine, months on HAART (stavudine + lamuvidine + one protease inhibitor), CD4+ cells, patients with HIV-RNA < 50 copies/ml. In HIV+ and HC, fat mass and distribution were significantly different, whereas lean mass was comparable. Thus, LD+ and LD- as compared to HC+ and HC- respectively showed: (1) reduced fat amount and percentage; (2) lower truncal fat mass; (3) markedly reduced limbs fat mass. Within the HIV+ group, (4) LD+ showed higher fat trunk/fat total (P = 0.04) and lower fat limbs/ fat total ratios (P = 0.009) than LD-; (5) LD+ showed larger IAT areas than LD- and HC (P < 0.0003)., Conclusions: Increased central fat and peripheral lipoatrophy are distinctive features of all HAART-treated children. Changes in body fat composition are detectable by DXA even in the absence of signs of Lipodystrophy. Only LD+ show true central obesity.

Published
2001
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16. Bone mineral loss through increased bone turnover in HIV-infected children treated with highly active antiretroviral therapy.

Author

Mora S, Sala N, Bricalli D, Zuin G, Chiumello G, and Viganò A

Subjects
Absorptiometry, Photon, Adolescent, Bone Remodeling, Bone Resorption, Child, Child, Preschool, Female, Humans, Infectious Disease Transmission, Vertical, Lipodystrophy chemically induced, Male, Antiretroviral Therapy, Highly Active adverse effects, Bone Density, Bone Diseases, Metabolic chemically induced, HIV Infections drug therapy
Abstract

Objectives: To evaluate the occurrence and define the aetiology of osteopenia in children receiving highly active antiretroviral therapy (HAART)., Methods: Bone mineral density (BMD) of total body and lumbar spine (L2-L4) was assessed by dual-energy X-ray absorptiometry in 40 children vertically infected with HIV: 35 taking HAART and five naive to any antiretroviral treatment (untreated). Six HAART-treated children showed clinical evidence of lipodystrophy. N-terminal propeptide of type-I procollagen (PINP), bone-specific alkaline phosphatase (BALP) and N-terminal telopeptide of type I collagen (NTx) were measured. Results were compared with those obtained in 314 healthy controls. Differences between HIV-positive and healthy children and within the HIV-positive group were assessed by multivariate analyses, controlling for confounding variables (age, sex, weight and height)., Results: HAART-treated children showed lower spine BMD values than untreated (P = 0.045) and healthy (P = 0.004) children and lower total body BMD values than untreated (P = 0.012) and healthy (P < 0.0001) children. Spine and total body BMD were similar between untreated and healthy children. Total body BMD was lower (P < 0.005) in HAART-treated children with lipodystrophy than in untreated patients, while children on HAART but without lipodystrophy had intermediate values. BALP, PINP and NTx were similar among untreated and healthy children. HAART-treated children had higher BALP levels than healthy (P = 0.0007) and untreated (P = 0.045) children. PINP values showed the same trend as BALP. HAART-treated children had higher NTx urine levels than healthy (P < 0.0001) and untreated (P = 0.041) children., Conclusions: HAART seems a new risk factor for life-long osteoporosis in children. An increased rate of bone turnover causes BMD decrease. Severity of osteopenia seems to be related to lipodystrophy.

Published
2001
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17. Markers of cell death-activation in lymphocytes of vertically HIV-infected children naive to highly active antiretroviral therapy: the role of age.

Author

Viganò A, Pinti M, Nasi M, Moretti L, Balli F, Mussini C, Bricalli D, Sala N, Bugarini R, Vella S, Principi N, and Cossarizza A

Subjects
Adolescent, Age Factors, CD28 Antigens isolation & purification, Child, Child, Preschool, Female, Humans, Infectious Disease Transmission, Vertical, Leukocyte Common Antigens isolation & purification, Male, Membrane Potentials, Mitochondria metabolism, Phenotype, fas Receptor isolation & purification, Antigens, Differentiation, T-Lymphocyte isolation & purification, Antiretroviral Therapy, Highly Active, Apoptosis, HIV Infections immunology, HIV Infections transmission, T-Lymphocytes immunology
Abstract

Background: Apoptosis plays a major role in depleting CD4(+) lymphocytes during infection with HIV-1. Few data exist on its role during HIV infection of children. Sensitivity of peripheral blood lymphocytes (PBLs) to apoptotic stimuli and the importance of the patient's age remain unclear., Objectives: We sought to analyze the following: (1) markers of cell death-activation (CD95, CD45 isoforms, and CD28) in PBLs from vertically HIV-infected children of different ages before highly active antiretroviral therapy; (2) changes in other PBL populations; (3) PBL sensitivity to cell death and mitochondrial damages; and (4) role of age during progression of infection., Methods: Cell culture techniques and flow cytometry were used to analyze surface antigens, PBL susceptibility to apoptosis, or PBL susceptibility to change of mitochondrial membrane potential., Results: Donor age had a strong negative correlation with numbers of CD4(+) and CD8(+) T cells. Virgin T lymphocyte (CD45RA(+), CD95(-)) levels and those of CD95(+) cells showed no correlation with the children's clinical status but did show a correlation with patient age. CD28(-) T lymphocytes were markedly augmented in HIV-infected children but were unrelated to stage of infection or age. A relevant decrease in B lymphocytes and an increase in natural killer cells were also found. Finally, PBLs from HIV-positive children had a marked tendency to undergo apoptosis and mitochondrial damage., Conclusion: Changes in PBL phenotype, increased expression of CD95, and high sensitivity to apoptosis suggest that a precocious aging of the immune system occurs in HIV-infected children.

Published
2001
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18. T-lymphocyte maturation abnormalities in uninfected newborns and children with vertical exposure to HIV.

Author

Clerici M, Saresella M, Colombo F, Fossati S, Sala N, Bricalli D, Villa ML, Ferrante P, Dally L, and Vigano' A

Subjects
Adult, Age Factors, Antigens, Surface blood, CD4 Antigens blood, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes metabolism, Child, Child, Preschool, Cohort Studies, Female, HIV Envelope Protein gp160 pharmacology, HIV Infections immunology, HIV Seropositivity, Humans, Immunity, Cellular immunology, Infant, Newborn, Infectious Disease Transmission, Vertical, Interferon-gamma metabolism, Interleukin-7 blood, Lymphocyte Activation drug effects, Male, Mitogens pharmacology, Mothers, Cell Differentiation immunology, HIV Infections transmission, T-Lymphocytes pathology
Abstract

Cell-mediated immunity and T-lymphocyte maturation are impaired in HIV-infected children. These abnormalities would be detected in HIV-uninfected offspring of HIV women (seroreverters [SR]) if HIV or its soluble proteins could cross the placental barrier. Immunophenotypic analyses were performed in 20 healthy HIV-uninfected newborns of HIV-infected mothers (SR), and in 14 healthy newborns of HIV-negative women (UC). The same analyses were performed in 3 groups of older children: SR (n = 41); UC (n = 15); and HIV-infected children (n = 25). Antigen-specific cells were evaluated with ELISpot and fluorimetric analyses; IL-7 serum concentration was measured by enzyme-linked immunosorbent assay (ELISA). Results showed that in SR newborns: (1) the CD4/CD8 ratio was reduced, (2) CD4(+) and CD8(+) naive T-cell percentages were decreased, (3) percentage of activated CD8(+) T cells was increased, and (4) percentages of CD3(+)/4(-)/8(-) (DN) and DN/25(-)/44(+) were augmented. These abnormalities were partially retained in older SR children. CD4(+) and CD8(+) HIV-specific cells were detected in a portion of newborn SRs but not in older SRs. Serum IL-7 was augmented both in newborn and older SRs. Cell-mediated immunity and T-cell maturation are altered even in HIV-uninfected newborns of HIV-infected mothers; these abnormalities persist over time. The biologic significance of these observations and potential subsequent clinical events should be investigated in larger cohorts of seroreverters. (Blood. 2000;96:3866-3871)

Published
2000

19. Early immune reconstitution after potent antiretroviral therapy in HIV-infected children correlates with the increase in thymus volume.

Author

Vigano A, Vella S, Saresella M, Vanzulli A, Bricalli D, Di Fabio S, Ferrante P, Andreotti M, Pirillo M, Dally LG, Clerici M, and Principi N

Subjects
Anti-HIV Agents administration & dosage, CD4 Lymphocyte Count, Child, Cohort Studies, Didanosine administration & dosage, Didanosine therapeutic use, Drug Therapy, Combination, HIV Infections immunology, HIV Protease Inhibitors administration & dosage, HIV Protease Inhibitors therapeutic use, Humans, Indinavir administration & dosage, Indinavir therapeutic use, Lamivudine administration & dosage, Lamivudine therapeutic use, Organ Size, Reverse Transcriptase Inhibitors administration & dosage, Reverse Transcriptase Inhibitors therapeutic use, Stavudine administration & dosage, Stavudine therapeutic use, Viral Load, Zidovudine administration & dosage, Zidovudine therapeutic use, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, Thymus Gland pathology
Abstract

Design: Despite significant rises in total CD4 T cells, the process of immune reconstitution in adults with HIV infection treated with potent antiretroviral treatment results in a rather slow increase in phenotypically naive lymphocytes. In children more than in adults, thymic function may be at least partly restored when disease-induced immunosuppression is attenuated by pharmacological means., Methods: Twenty-five vertically infected and antiretroviral-experienced [zidovudine (ZDV)/ZDV plus didanosine (ddl)] children were prospectively followed during 12 months of treatment with lamivudine (3TC), stavudine (d4T) and indinavir (IDV). The plasma HIV viral load and phenotypic and functional cellular immunity-defining parameters were examined. The relationship between the degree of immune reconstitution and thymus volume assessed by nuclear magnetic resonance was also examined., Results: An early and steep increase in CD45RA+62L+ T cells was observed in parallel with a sustained decrease in plasma HIV RNA levels and a significant rise in total CD4 T cells. This increase was significantly greater than that observed in CD4+CD45RO+ T cells. Analysis of the CD4 T cell receptor (TCR) beta repertoire and T helper function showed the ability to reconstitute families almost completely absent at baseline, and a substantial improvement of antigen-specific responses by peripheral blood lymphocytes. The rise in CD4 cells and in CD4+CD45RA+62L+ T cells was statistically associated with changes in thymus size observed over time., Conclusion: These data suggest a relevant contribution of the thymus to reconstitution of the peripheral pool of T cells in vertically HIV-infected children treated with potent antiretroviral regimens.

Published
2000
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20. Thymus volume correlates with the progression of vertical HIV infection.

Author

Vigano' A, Vella S, Principi N, Bricalli D, Sala N, Salvaggio A, Saresella M, Vanzulli A, and Clerici M

Subjects
CD4-Positive T-Lymphocytes immunology, Child, Disease Progression, HIV Infections transmission, HIV Infections virology, Humans, Infectious Disease Transmission, Vertical, L-Selectin immunology, Leukocyte Common Antigens immunology, Magnetic Resonance Imaging, Radiography, T-Lymphocytes, Helper-Inducer immunology, Thymus Gland cytology, Thymus Gland diagnostic imaging, Viremia, HIV Infections immunology, Thymus Gland immunology
Abstract

Background: The thymus is the organ responsible for the maturation and selection of T lymphocytes and is thus pivotal in allowing the development of a functional immune system. Because in HIV infection cell-mediated immune responses are severely impaired, we studied the role of thymus in the control of the progression of HIV infection to AIDS., Methods: Thymic volume was analysed by magnetic resonance imaging in 31 vertically HIV-infected children. Plasma HIV viral load and phenotypic and functional cellular immunity-defining parameters were examined in the same patients., Results: Thymic volume was not correlated with age or nutritional status; thymic volume was nevertheless correlated with CD4 T-lymphocyte counts and with the percentage and absolute number of CD45RA+CD62L+ (naive) T lymphocytes. In addition, the ability of peripheral blood mononuclear cells to proliferate upon tetanus stimulation was directly proportional to thymic volume. Finally, a negative correlation was detected between thymic volume and HIV viral load., Conclusion: Because low HIV plasma viraemia and preserved immune function are favourable prognostic indices in HIV disease, these data indicate that an immunological, thymic-dependent control of the progression of HIV infection might be possible, at least in vertically transmitted HIV infection.

Published
1999
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21. Immunization with both T cell-dependent and T cell-independent vaccines augments HIV viral load secondarily to stimulation of tumor necrosis factor alpha.

Author

Viganò A, Bricalli D, Trabattoni D, Salvaggio A, Ruzzante S, Barbi M, Di Sanzo G, Principi N, and Clerici M

Subjects
Bacterial Vaccines administration & dosage, CD4 Lymphocyte Count, Child, Child, Preschool, Cytokines biosynthesis, HIV immunology, HIV physiology, Humans, Influenza Vaccines administration & dosage, Lipopolysaccharides pharmacology, Lymphocyte Activation, Lymphocyte Subsets, RNA, Viral blood, Streptococcus pneumoniae immunology, Time Factors, Vaccination, Viral Load, Viremia, Bacterial Vaccines immunology, HIV Infections immunology, HIV Infections virology, Influenza Vaccines immunology, T-Lymphocytes immunology, Tumor Necrosis Factor-alpha biosynthesis
Abstract

Vaccination of HIV-infected individuals increases HIV viral load, reduces CD4 cell counts, and might influence disease progression. Because these deleterious effects are postulated to be secondary to a direct activation of T lymphocytes induced by the immunogen, we compared immunologic and virologic effects of a T cell-dependent and a T cell-independent vaccine. Seventeen HIV-infected children were immunized with influenza (FLU) (T cell-dependent) or pneumococcal (PNEUMO) (T cell-independent) vaccines. HIV viral load and type 1 (IL-2 and IFN-gamma) and type 2 (IL-4 and IL-10) cytokine production were evaluated before and 7, 14, and 28 days after vaccination. Slopes of CD4 cell counts analyzed 6 months before and 6 months after vaccination were not significantly different. HIV viral load increased in both groups of children despite the fact that type 1 cytokine production and the type 1-to-type 2 ratio increased in FLU-vaccinated but not in PNEUMO-vaccinated patients. Thus, an increase in HIV viral load in the absence of T cell activation (as measured by cytokine production) was observed in PNEUMO-vaccinated children. Because polysaccharides of the bacterial cell wall stimulate TNF-alpha production by monocyte-macrophages and TNF-alpha was shown to stimulate HIV replication directly on activation of NF-kappa b after binding the long terminal repeat (LTR) sequences of HIV, we measured TNF-alpha production and observed a significant increase in both groups of vaccines. These data suggest that an increase in HIV viral load can be observed in vaccinated HIV-infected children even independent of direct antigen-induced activation of T lymphocytes, and that augmented production of TNF-alpha might play a role in this phenomenon.

Published
1998
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22. Plasma viremia and virus phenotype are correlates of disease progression in vertically human immunodeficiency virus type 1-infected children.

Author

Balotta C, Colombo MC, Colucci G, Viganò A, Riva C, Papagno L, Violin M, Crupi L, Bricalli D, Salvaggio A, Moroni M, Principi N, and Galli M

Subjects
Anti-HIV Agents therapeutic use, CD4 Lymphocyte Count, Child, Child, Preschool, Disease Progression, HIV Core Protein p24 blood, HIV Infections drug therapy, HIV Infections immunology, Humans, Infant, Phenotype, Polymerase Chain Reaction, RNA, Viral analysis, RNA-Directed DNA Polymerase, Viremia blood, HIV Infections physiopathology, HIV Infections transmission, HIV-1 isolation & purification, Infectious Disease Transmission, Vertical, Viral Load
Abstract

Objective: To analyze the relationships among HIV-1 plasma viremia, phenotype and CD4 T cell counts in vertically infected children., Methods: Plasma viremia was quantified in 37 vertically infected children at different stages of the disease by a standardized molecular assay. Virus isolation and non-syncytia-inducing or syncytia-inducing (SI) HIV-1 phenotype evaluation were performed in parallel., Results: HIV-1 RNA genomes were found to be significantly different in CDC clinical classes N, A, B and C (P = 0.0135) and in immunologic classes 1, 2 and 3 (P = 0.0110). None of the children in Class N or A harbored HIV-1 isolates with SI phenotype, whereas SI primary isolates were detected in 2 of 7 (29%) and 7 of 10 (70%) Class B and C children, respectively. Similarly SI variants were present in only 9 of 13 children in immunologic Class 3 (70%). When stratified according to the increasing severity of virologic status, the children showed a significant difference (P = 0.0458) in viral burden., Conclusions: Clinical symptoms, the most dramatic being reduction in the number of CD4 lymphocytes, and the highest plasma viremia levels were observed in the children in whom fast replicating, highly cytopathic SI variants were isolated. These data extend the virologic characterization of vertically HIV-1 infected children and suggest that both the plasma viremia levels and phenotype of primary isolates are viral correlates of disease progression in vertically infected children.

Published
1997
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23. Long-term resistance to HIV infection in vertical HIV infection: cytokine production, HIV isolation, and HIV phenotype define long-term resistant hosts.

Author

Vigano A, Balotta C, Trabattoni D, Bricalli D, Crupi L, Palomba E, Galli L, Salvaggio A, Fusi ML, Ruzzante S, Massironi E, Colombo MC, Principi N, Galli M, and Clerici M

Subjects
Adolescent, CD4 Lymphocyte Count, CD4-CD8 Ratio, Chemokine CCL4, Chemokine CCL5 metabolism, Child, HIV genetics, HIV immunology, Humans, Immunity, Innate immunology, Immunoglobulin E blood, Interferon-gamma metabolism, Interleukin-10 metabolism, Interleukin-2 metabolism, Leukocytes, Mononuclear drug effects, Leukocytes, Mononuclear metabolism, Macrophage Inflammatory Proteins metabolism, Phenotype, RNA, Viral analysis, Cytokines metabolism, HIV isolation & purification, HIV Infections immunology, HIV Infections transmission, Infectious Disease Transmission, Vertical
Abstract

We analyzed immunologic (CD4 and CD8 slopes; interferon-gamma, interleukin-2, interleukin-10, and chemokines production; concentration of IgE; beta 2-microglobulin) and virologic (p24; HIV isolability and phenotype; plasma viremia) parameters in HIV vertically infected children > or = 8 years of age without disease progression or mild symptoms and an absolute CD4+ count > or = 500/microliter with CD4+ percentage > or = 25%. The results were compared to those of two control groups: (1) slow progressors, children > or = 8 years of age with moderate symptomatology and/or moderate CD4 depletion, and (2) progressors, children > or = 8 years of age with severe clinical disease and/or severe CD4 depletion. Pediatric long-term resistant hosts were characterized by higher production of interleukin-2 and interferon-gamma and lower production of interleukin-10, normal concentration of IgE, HIV isolates with a non-syncytium-inducing phenotype, and lower plasma viremia. This condition was not associated with the concentration of beta 2-microglobulin, p24, and chemokines, or with HIV isolability. The IL-10/IL-2 ratio best correlated with both CD4 counts and disease progression. Thus, vertically infected children showing resistance to disease progression are immunologically and virologically distinct from those in whom progressive HIV infection is observed.

Published
1997
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24. Virologic and immunologic markers of disease progression in pediatric HIV infection.

Author

Viganò A, Balotta C, Trabattoni D, Salvaggio A, Riva C, Bricalli D, Crupi L, Colombo MC, Principi N, Galli M, and Clerici M

Subjects
Biomarkers, Child, Child, Preschool, Cohort Studies, Disease Progression, Giant Cells, HIV isolation & purification, HIV Infections virology, Humans, Interleukin-10 immunology, Interleukin-4 immunology, Phenotype, CD4 Antigens immunology, Cytokines immunology, HIV immunology, HIV Infections immunology
Abstract

Correlates of progression of human immunodeficiency virus (HIV) infection to AIDS include the reduction in CD4+ T cells and the emergence of syncytium-inducing (SI) HIV variants. It has been suggested that progressive defects in interleukin 2 (IL-2), IL-12, and IFN- gamma production (type 1 cytokines), and increased production of IL-4 (and of IL-4-driven hyper-IgE), IL-6, and IL-10 (type 2 cytokines), could provide another correlate of disease progression. To determine the possible association among these markers, viral phenotype, cytokine production, IgE serum concentration, and rate of CD4 depletion were analyzed in a cohort of vertically HIV-infected children. We report that significantly higher production of type 2 cytokines and augmented IgE concentration are observed in children in whom HIV SI is isolated. In addition, we observed that the isolation of HIV SI and the production of high quantities of type 2 cytokines are correlated with increased loss of CD4 T cells in the 12 months preceding the determinations. These data suggest that the virologic and immunologic parameters characteristic of advanced HIV infection may be associated in pediatric HIV infection, and indicate a virologic-immunologic pathogenesis leading to the appearance of AIDS.

Published
1996
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