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2. Ultrafast structural changes direct the first molecular events of vision

Author

Gruhl, Thomas, Weinert, Tobias, Rodrigues, Matthew J., Milne, Christopher J., Ortolani, Giorgia, Nass, Karol, Nango, Eriko, Sen, Saumik, Johnson, Philip J. M., Cirelli, Claudio, Furrer, Antonia, Mous, Sandra, Skopintsev, Petr, James, Daniel, Dworkowski, Florian, Båth, Petra, Kekilli, Demet, Ozerov, Dmitry, Tanaka, Rie, Glover, Hannah, Bacellar, Camila, Brünle, Steffen, Casadei, Cecilia M., Diethelm, Azeglio D., Gashi, Dardan, Gotthard, Guillaume, Guixà-González, Ramon, Joti, Yasumasa, Kabanova, Victoria, Knopp, Gregor, Lesca, Elena, Ma, Pikyee, Martiel, Isabelle, Mühle, Jonas, Owada, Shigeki, Pamula, Filip, Sarabi, Daniel, Tejero, Oliver, Tsai, Ching-Ju, Varma, Niranjan, Wach, Anna, Boutet, Sébastien, Tono, Kensuke, Nogly, Przemyslaw, Deupi, Xavier, Iwata, So, Neutze, Richard, Standfuss, Jörg, Schertler, Gebhard, and Panneels, Valerie

Published
2023
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3. Structure-factor amplitude reconstruction from serial femtosecond crystallography of two-dimensional membrane-protein crystals

Author

Casadei, Cecilia M, Nass, Karol, Barty, Anton, Hunter, Mark S, Padeste, Celestino, Tsai, Ching-Ju, Boutet, Sébastien, Messerschmidt, Marc, Sala, Leonardo, Williams, Garth J, Ozerov, Dmitry, Coleman, Matthew, Li, Xiao-Dan, Frank, Matthias, and Pedrini, Bill

Subjects
Inorganic Chemistry, Chemical Sciences, Vaccine Related, free-electron lasers, serial femtosecond crystallography, membrane proteins, two-dimensional crystals, serial femto­second crystallography, Atomic, Molecular, Nuclear, Particle and Plasma Physics, Condensed Matter Physics, Physical Chemistry (incl. Structural), Physical chemistry, Condensed matter physics
Abstract

Serial femtosecond crystallography of two-dimensional membrane-protein crystals at X-ray free-electron lasers has the potential to address the dynamics of functionally relevant large-scale motions, which can be sterically hindered in three-dimensional crystals and suppressed in cryocooled samples. In previous work, diffraction data limited to a two-dimensional reciprocal-space slice were evaluated and it was demonstrated that the low intensity of the diffraction signal can be overcome by collecting highly redundant data, thus enhancing the achievable resolution. Here, the application of a newly developed method to analyze diffraction data covering three reciprocal-space dimensions, extracting the reciprocal-space map of the structure-factor amplitudes, is presented. Despite the low resolution and completeness of the data set, it is shown by molecular replacement that the reconstructed amplitudes carry meaningful structural information. Therefore, it appears that these intrinsic limitations in resolution and completeness from two-dimensional crystal diffraction may be overcome by collecting highly redundant data along the three reciprocal-space axes, thus allowing the measurement of large-scale dynamics in pump-probe experiments.

Published
2019

4. Resolution extension by image summing in serial femtosecond crystallography of two-dimensional membrane-protein crystals

Author

Casadei, Cecilia M, Tsai, Ching-Ju, Barty, Anton, Hunter, Mark S, Zatsepin, Nadia A, Padeste, Celestino, Capitani, Guido, Benner, W Henry, Boutet, Sébastien, Hau-Riege, Stefan P, Kupitz, Christopher, Messerschmidt, Marc, Ogren, John I, Pardini, Tom, Rothschild, Kenneth J, Sala, Leonardo, Segelke, Brent, Williams, Garth J, Evans, James E, Li, Xiao-Dan, Coleman, Matthew, Pedrini, Bill, and Frank, Matthias

Subjects
Inorganic Chemistry, Chemical Sciences, Physical Sciences, Bioengineering, serial crystallography, free-electron lasers, membrane proteins, two-dimensional crystals, Atomic, Molecular, Nuclear, Particle and Plasma Physics, Condensed Matter Physics, Physical Chemistry (incl. Structural), Physical chemistry, Condensed matter physics
Abstract

Previous proof-of-concept measurements on single-layer two-dimensional membrane-protein crystals performed at X-ray free-electron lasers (FELs) have demonstrated that the collection of meaningful diffraction patterns, which is not possible at synchrotrons because of radiation-damage issues, is feasible. Here, the results obtained from the analysis of a thousand single-shot, room-temperature X-ray FEL diffraction images from two-dimensional crystals of a bacteriorhodopsin mutant are reported in detail. The high redundancy in the measurements boosts the intensity signal-to-noise ratio, so that the values of the diffracted intensities can be reliably determined down to the detector-edge resolution of 4 Å. The results show that two-dimensional serial crystallography at X-ray FELs is a suitable method to study membrane proteins to near-atomic length scales at ambient temperature. The method presented here can be extended to pump-probe studies of optically triggered structural changes on submillisecond timescales in two-dimensional crystals, which allow functionally relevant large-scale motions that may be quenched in three-dimensional crystals.

Published
2018

5. Ultrafast structural changes direct the first molecular events of vision

Author

60452330, Gruhl, Thomas, Weinert, Tobias, Rodrigues, Matthew J., Milne, Christopher J., Ortolani, Giorgia, Nass, Karol, Nango, Eriko, Sen, Saumik, Johnson, Philip J. M., Cirelli, Claudio, Furrer, Antonia, Mous, Sandra, Skopintsev, Petr, James, Daniel, Dworkowski, Florian, Båth, Petra, Kekilli, Demet, Ozerov, Dmitry, Tanaka, Rie, Glover, Hannah, Bacellar, Camila, Brünle, Steffen, Casadei, Cecilia M., Diethelm, Azeglio D., Gashi, Dardan, Gotthard, Guillaume, Guixà-González, Ramon, Joti, Yasumasa, Kabanova, Victoria, Knopp, Gregor, Lesca, Elena, Ma, Pikyee, Martiel, Isabelle, Mühle, Jonas, Owada, Shigeki, Pamula, Filip, Sarabi, Daniel, Tejero, Oliver, Tsai, Ching-Ju, Varma, Niranjan, Wach, Anna, Boutet, Sébastien, Tono, Kensuke, Nogly, Przemyslaw, Deupi, Xavier, Iwata, So, Neutze, Richard, Standfuss, Jörg, Schertler, Gebhard, Panneels, Valerie, 60452330, Gruhl, Thomas, Weinert, Tobias, Rodrigues, Matthew J., Milne, Christopher J., Ortolani, Giorgia, Nass, Karol, Nango, Eriko, Sen, Saumik, Johnson, Philip J. M., Cirelli, Claudio, Furrer, Antonia, Mous, Sandra, Skopintsev, Petr, James, Daniel, Dworkowski, Florian, Båth, Petra, Kekilli, Demet, Ozerov, Dmitry, Tanaka, Rie, Glover, Hannah, Bacellar, Camila, Brünle, Steffen, Casadei, Cecilia M., Diethelm, Azeglio D., Gashi, Dardan, Gotthard, Guillaume, Guixà-González, Ramon, Joti, Yasumasa, Kabanova, Victoria, Knopp, Gregor, Lesca, Elena, Ma, Pikyee, Martiel, Isabelle, Mühle, Jonas, Owada, Shigeki, Pamula, Filip, Sarabi, Daniel, Tejero, Oliver, Tsai, Ching-Ju, Varma, Niranjan, Wach, Anna, Boutet, Sébastien, Tono, Kensuke, Nogly, Przemyslaw, Deupi, Xavier, Iwata, So, Neutze, Richard, Standfuss, Jörg, Schertler, Gebhard, and Panneels, Valerie

Abstract

Vision is initiated by the rhodopsin family of light-sensitive G protein-coupled receptors (GPCRs). A photon is absorbed by the 11-cis retinal chromophore of rhodopsin, which isomerizes within 200 femtoseconds to the all-trans conformation, thereby initiating the cellular signal transduction processes that ultimately lead to vision. However, the intramolecular mechanism by which the photoactivated retinal induces the activation events inside rhodopsin remains experimentally unclear. Here we use ultrafast time-resolved crystallography at room temperature to determine how an isomerized twisted all-trans retinal stores the photon energy that is required to initiate the protein conformational changes associated with the formation of the G protein-binding signalling state. The distorted retinal at a 1-ps time delay after photoactivation has pulled away from half of its numerous interactions with its binding pocket, and the excess of the photon energy is released through an anisotropic protein breathing motion in the direction of the extracellular space. Notably, the very early structural motions in the protein side chains of rhodopsin appear in regions that are involved in later stages of the conserved class A GPCR activation mechanism. Our study sheds light on the earliest stages of vision in vertebrates and points to fundamental aspects of the molecular mechanisms of agonist-mediated GPCR activation.

Published
2023

9. ULTRAFAST STRUCTURAL CHANGES DIRECT THE FIRST MOLECULAR EVENTS OF VISION

Author

Gruhl, Thomas, primary, Weinert, Tobias, additional, Rodrigues, Matthew, additional, Milne, Christopher J, additional, Ortolani, Giorgia, additional, Nass, Karol, additional, Nango, Eriko, additional, Sen, Saumik, additional, Johnson, Philip J M, additional, Cirelli, Claudio, additional, Furrer, Antonia, additional, Mous, Sandra, additional, Skopintsev, Petr, additional, James, Daniel, additional, Dworkowski, Florian, additional, Båth, Petra, additional, Kekilli, Demet, additional, Ozerov, Dmitry, additional, Tanaka, Rie, additional, Glover, Hannah, additional, Bacellar, Camila, additional, Brünle, Steffen, additional, Casadei, Cecilia M, additional, Diethelm, Azeglio D, additional, Gashi, Dardan, additional, Gotthard, Guillaume, additional, Guixà-González, Ramon, additional, Joti, Yasumasa, additional, Kabanova, Victoria, additional, Knopp, Gregor, additional, Lesca, Elena, additional, Ma, Pikyee, additional, Martiel, Isabelle, additional, Mühle, Jonas, additional, Owada, Shigeki, additional, Pamula, Filip, additional, Sarabi, Daniel, additional, Tejero, Oliver, additional, Tsai, Ching-Ju, additional, Varma, Niranjan, additional, Wach, Anna, additional, Boutet, Sébastien, additional, Tono, Kensuke, additional, Nogly, Przemyslaw, additional, Deupi, Xavier, additional, Iwata, So, additional, Neutze, Richard, additional, Standfuss, Jörg, additional, Schertler, Gebhard FX, additional, and Panneels, Valerie, additional

Published
2022
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13. Weight Gain during Pregnancy in Women with HIV Receiving Different Antiretroviral Regimens

Author

Floridia, M., Masuelli, G., Tassis, B., Franceschetti, L., Savasi, V. M., Spinillo, A., Tamburrini, E., Guaraldi, G., Dalzero, S., Sansone, M., Chiodo, A., Degli Antoni, A. M., Pinnetti, C., Liuzzi, G., Ravizza, M., Di Lorenzo, F., Sterrantino, G., Meli, M., Campolmi, I., Vichi, F., Del Pin, B., Marocco, R., Mastroianni, C., Mercurio, V. S., Zanaboni, D., Nardini, G., Stentarelli, C., Beghetto, B., Molinari, A., Crisalli, M. P., Donisi, A., Ruggieri, A., Piepoli, M., Cerri, V., Zuccotti, G., Giacomet, V., Paradiso, L., Forlanini, F., Longoni, E., Placido, G., Milini, P., Savalli, F., Portelli, V., Sabbatini, F., Francisci, D., Papalini, C., Bernini, L., Grossi, P., Rizzi, L., Maso, G., Bernardon, M., Bussolaro, S., della Pieta, I., Sorz, A., Meloni, A., Dedoni, M., Ortu, F., Piano, P., Citernesi, A., Vicini, I. B., Luzi, K., Roccio, M., Vimercati, A., Calabretti, D., Gigante, S., Guerra, B., Cervi, F., Simonazzi, G., Margarito, E., Capretti, M. G., Marsico, C., Faldella, G., Martinelli, P., Agangi, A., Capone, A., Maruotti, G. M., Tibaldi, C., Trentini, L., Todros, T., Frisina, V., Cardellicchio, E., Giaquinto, C., Fiscon, M., Rubino, E., Badolato, R., Forleo, M. A., Ruggiero, M., Genovese, O., Cafforio, C., Casadei, A. M., Cavaliere, A. F., Cellini, M., Marconi, A. M., Ierardi, M., Simonetti, S. C., Alfieri, N., Agrati, S., Polizzi, C., Mattei, A., Pirillo, M. F., Amici, R., Galluzzo, C. M., Donnini, S., Baroncelli, S., Cerioli, A., de Martino, M., Parazzini, F., and Vella, S.

Subjects
medicine.medical_specialty, Multivariate analysis, Anti-HIV Agents, Integrase inhibitor, HIV Infections, Overweight, Weight Gain, Cohort Studies, Pregnancy, Internal medicine, medicine, Humans, Pharmacology (medical), Settore MED/38 - Pediatria Generale e Specialistica, Pharmacology, business.industry, Weight change, Odds ratio, medicine.disease, Obesity, Infectious Diseases, Reverse Transcriptase Inhibitors, Female, medicine.symptom, business, Weight gain
Abstract

Background No published studies have evaluated in pregnant women with HIV weight gain with different antiretroviral drug classes. Methods Data from a national cohort study were used. We compared absolute weight gain and occurrence of excessive weight gain in women with HIV who received during pregnancy integrase inhibitors (INSTI), protease inhibitors (PI), or non-nucleoside reverse transcriptase inhibitors (NNRTI). Excessive weight gain was defined according to the Institute of Medicine recommendations. Possible predictors of weight gain were assessed using univariate and multivariate analyses. Results Among 273 cases (PI: 191, NNRTI: 43, INSTI: 39), the mean weight increase was 11.3 kg, and 25.4% of the mothers had an excessive weight increase. No significant differences were found among the three treatment groups for absolute weight increase, occurrence of excessive weight gain, infant birthweight, and other pregnancy and laboratory outcomes. The comparisons of individual drugs, although based on a limited number of cases, suggested no major differences. A significant positive correlation was found between weight gain and CD4+ T-cell increase during pregnancy. In multivariate analyses, drug class and nucleoside backbone were not associated with absolute or excessive weight increase. Excessive weight increase was significantly associated with week of delivery (adjusted odds ratio: 1.74, 95% CI 1.15, 2.63), obesity (5.21, 95% CI 1.85, 14.64), overweight (7.95, 95% CI 3.26, 19.39), recent substance use (5.96, 95% CI 1.13, 31.40) and fasting 2nd trimester hyperglycaemia (3.94, 95% CI 1.14, 13.65). Conclusions No significant differences in absolute weight change or occurrence of excessive weight gain were found among women with HIV who received during pregnancy different classes of antiretroviral drugs.

Published
2021

14. CD4/CD8 ratio in pregnant women with HIV and its association with pregnancy outcome: data from a national study in Italy

Author

Floridia, M., Pinnetti, C., Masuelli, G., Spinillo, A., Savasi, V. M., Liuzzi, G., Degli Antoni, A. M., Sansone, M., Guaraldi, G., Dalzero, S., Maso, G., Francisci, D., Sterrantino, G., Ravizza, M., Tamburrini, E., Di Lorenzo, F., Meli, M., Campolmi, I., Vichi, F., Del Pin, B., Marocco, R., Mastroianni, C., Mercurio, V. S., Zanaboni, D., Nardini, G., Stentarelli, C., Beghetto, B., Molinari, A., Crisalli, M. P., Donisi, A., Ruggieri, A., Piepoli, M., Cerri, V., Zuccotti, G., Giacomet, V., Paradiso, L., Forlanini, F., Longoni, E., Placido, G., Milini, P., Savalli, F., Sabbatini, F., Papalini, C., Bernini, L., Grossi, P., Rizzi, L., Portelli, V., Bernardon, M., Bussolaro, S., Della Pieta, I., Sorz, A., Meloni, A., Chiodo, A., Dedoni, M., Ortu, F., Piano, P., Citernesi, A., Bordoni Vicini, I., Luzi, K., Roccio, M., Vimercati, A., Calabretti, D., Gigante, S., Guerra, B., Cervi, F., Simonazzi, G., Margarito, E., Capretti, M. G., Marsico, C., Faldella, G., Martinelli, P., Agangi, A., Capone, A., Maruotti, G. M., Tibaldi, C., Trentini, L., Todros, T., Frisina, V., Savasi, V., Cardellicchio, E., Giaquinto, C., Fiscon, M., Rubino, E., Franceschetti, L., Badolato, R., Forleo, M. A., Tassis, B., Ruggiero, M., Genovese, O., Cafforio, C., Casadei, A. M., Cavaliere, A. F., Cellini, M., Marconi, A. M., Ierardi, M., Simonetti, S. C., Alfieri, N., Agrati, S., Polizzi, C., Mattei, A., Pirillo, M. F., Amici, R., Galluzzo, C. M., Donnini, S., Baroncelli, S., Cerioli, A., De Martino, M., Parazzini, F., Vella, S., Floridia M., Pinnetti C., Masuelli G., Spinillo A., Savasi V.M., Liuzzi G., Degli Antoni A.M., Sansone M., Guaraldi G., Dalzero S., Maso G., Francisci D., Sterrantino G., Ravizza M., Tamburrini E., Di Lorenzo F., Meli M., Campolmi I., Vichi F., Del Pin B., Marocco R., Mastroianni C., Mercurio V.S., Zanaboni D., Nardini G., Stentarelli C., Beghetto B., Molinari A., Crisalli M.P., Donisi A., Ruggieri A., Piepoli M., Cerri V., Zuccotti G., Giacomet V., Paradiso L., Forlanini F., Longoni E., Placido G., Milini P., Savalli F., Sabbatini F., Papalini C., Bernini L., Grossi P., Rizzi L., Portelli V., Bernardon M., Bussolaro S., Della Pieta I., Sorz A., Meloni A., Chiodo A., Dedoni M., Ortu F., Piano P., Citernesi A., Bordoni Vicini I., Luzi K., Roccio M., Vimercati A., Calabretti D., Gigante S., Guerra B., Cervi F., Simonazzi G., Margarito E., Capretti M.G., Marsico C., Faldella G., Martinelli P., Agangi A., Capone A., Maruotti G.M., Tibaldi C., Trentini L., Todros T., Frisina V., Savasi V., Cardellicchio E., Giaquinto C., Fiscon M., Rubino E., Franceschetti L., Badolato R., Forleo M.A., Tassis B., Ruggiero M., Genovese O., Cafforio C., Casadei A.M., Cavaliere A.F., Cellini M., Marconi A.M., Ierardi M., Simonetti S.C., Alfieri N., Agrati S., Polizzi C., Mattei A., Pirillo M.F., Amici R., Galluzzo C.M., Donnini S., Baroncelli S., Cerioli A., De Martino M., Parazzini F., and Vella S.

Subjects
0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Multivariate analysis, 030106 microbiology, CD4-CD8 Ratio, Human immunodeficiency virus (HIV), HIV Infections, CD8-Positive T-Lymphocytes, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, CD4/CD8 ratio, Pregnancy, CD4, CD8, HIV suppression, Preterm delivery, Female, Humans, Infant, Newborn, Pregnancy Outcome, Pregnant Women, Viral Load, Pregnancy Complications, Infectious, medicine, 030212 general & internal medicine, business.industry, Obstetrics, Infectious, Infant, General Medicine, Newborn, medicine.disease, Pregnancy Complications, Infectious Diseases, Increased risk, National study, Outcome data, business
Abstract

Purpose: To evaluate associations between CD4/CD8 ratio and pregnancy outcomes in women with HIV. Methods: We evaluated, in a national study of pregnant women with HIV receiving antiretroviral treatment (ART), values of CD4/CD8 ratio at entry in pregnancy, changes between first and third trimester, and possible associations with preterm delivery, low birthweight, and HIV-RNA < 50 copies/ml at third trimester in univariate and multivariate analyses. Results: Among 934 women, 536 (57.4%) were already on ART at conception. CD4/CD8 ratio (baseline value 0.570) increased significantly between the first and third trimesters, particularly in women who started ART in pregnancy (+ 0.163, vs. + 0.036 in women already on treatment). The rate of CD4/CD8 ratio normalization, defined by achieving a ratio ≥ 1 at the third trimester, was 13.2%. In multivariable analyses, women who entered pregnancy with a CD4/CD8 ratio < 0.3, compared to women with ratio ≥ 1, were almost four-times less likely to have third-trimester HIV-RNA < 50 copies/ml (AOR 0.258, 95%CI 0.111–0.601), and more than twice as likely to have preterm delivery (AOR 2.379, 95%CI 1.082–5.232). For preterm delivery, also a baseline CD4/CD8 ratio between 0.3 and 0.45 was significantly associated with an increased risk (AOR: 3.415, 95%CI 1.690–6.900). Conclusion: We described for the first time independent associations of low CD4/CD8 ratio with preterm delivery and HIV-RNA suppression.

Published
2021

16. Atazanavir and darunavir in pregnant women with HIV: evaluation of laboratory and clinical outcomes from an observational national study

Author

Floridia, M., Masuelli, G., Ravizza, M., Tassis, B., Cetin, I., Sansone, M., Antoni, A. D., Simonazzi, G., Maccabruni, A., Francisci, D., Frisina, V., Liuzzi, G., Dalzero, S., Tamburrini, E., Di Lorenzo, F., Sterrantino, G., Meli, M., Campolmi, I., Vichi, F., Del Pin, B., Marocco, R., Mastroianni, C., S. Mercurio V., Zanaboni, D., Guaraldi, G., Nardini, G., Stentarelli, C., Beghetto, B., Antoni, A. M. D., Molinari, A., Crisalli, M. P., Donisi, A., Piepoli, M., Cerri, V., Zuccotti, G., Giacomet, V., Coletto, S., Di Nello, F., Madia, C., Placido, G., Milini, P., Savalli, F., Portelli, V., Sabbatini, F., Papalini, C., Bernini, L., Grossi, P., Rizzi, L., Bernardon, M., Maso, G., Rizzante, E., Belcaro, C., Meloni, A., Dedoni, M., Ortu, F., Piano, P., Citernesi, A., Bordonivicini, I., Luzi, K., Spinillo, A., Roccio, M., Vimercati, A., Crupano, F. M., Calabretti, D., Cervi, F., Margarito, E., Capretti, M. G., Marsico, C., Faldella, G., Martinelli, P., Agangi, A., Capone, A., Maruotti, G. M., Tibaldi, C., Trentini, L., Todros, T., Brambilla, T., Savasi, V., Personeni, C., Giaquinto, C., Fiscon, M., Rubino, E., Franceschetti, L., Badolato, R., Tiso, G. C., Genovese, O., Cafforio, C., Pinnetti, C., Casadei, A. M., Cavaliere, A. F., Cellini, M., Marconi, A. M., Sacchi, V., Ierardi, M., Polizzi, C., Mattei, A., Pirillo, M. F., Amici, R., Galluzzo, C. M., Donnini, S., Baroncelli, S., Villani, P., Cusato, M., Cerioli, A., De Martino, M., Parazzini, F., Vella, S., Floridia, M., Masuelli, G., Ravizza, M., Tassis, B., Cetin, I., Sansone, M., Antoni, A. Degli, Simonazzi, G., Maccabruni, A., Francisci, D., Frisina, V., Liuzzi, G., Dalzero, S., Tamburrini, E., Di Lorenzo, F., Sterrantino, G., Meli, M., Campolmi, I., Vichi, F., Del Pin, B., Marocco, R., Mastroianni, C., S.Mercurio, V., Zanaboni, D., Guaraldi, G., Nardini, G., Stentarelli, C., Beghetto, B., Antoni, A.M. Degli, Molinari, A., Crisalli, M.P., Donisi, A., Piepoli, M., Cerri, V., Zuccotti, G., Giacomet, V., Coletto, S., Di Nello, F., Madia, C., Placido, G., Milini, P., Savalli, F., Portelli, V., Sabbatini, F., Papalini, C., Bernini, L., Grossi, P., Rizzi, L., Bernardon, M., Maso, G., Rizzante, E., Belcaro, C., Meloni, A., Dedoni, M., Ortu, F., Piano, P., Citernesi, A., BordoniVicini, I., Luzi, K., Spinillo, A., Roccio, M., Vimercati, A., Crupano, F.M., Calabretti, D., Cervi, F., Margarito, E., Capretti, M.G., Marsico, C., Faldella, G., Martinelli, P., Agangi, A., Capone, A., Maruotti, G.M., Tibaldi, C., Trentini, L., Todros, T., Brambilla, T., Savasi, V., Personeni, C., Giaquinto, C., Fiscon, M., Rubino, E., Franceschetti, L., Badolato, R., Tiso, G.C., Genovese, O., Cafforio, C., Pinnetti, C., Casadei, A.M., Cavaliere, A.F., Cellini, M., Marconi, A.M., Sacchi, V., Ierardi, M., Polizzi, C., Mattei, A., Pirillo, M.F., Amici, R., Galluzzo, C.M., Donnini, S., Baroncelli, S., Villani, P., Cusato, M., Cerioli, A., De Martino, M., Parazzini, F., and Vella, S.

Subjects
Male, 0301 basic medicine, medicine.medical_treatment, HIV Infections, 0302 clinical medicine, Pregnancy, Pharmacology (medical), 030212 general & internal medicine, Pregnancy Complications, Infectious, Darunavir, medicine.diagnostic_test, Obstetrics, Pregnancy Outcome, virus diseases, Alanine Transaminase, Viral Load, Cholesterol, Treatment Outcome, Infectious Diseases, Premature birth, Gestation, Female, Drugs in pregnancy, medicine.drug, Adult, Microbiology (medical), medicine.medical_specialty, Drug-Related Side Effects and Adverse Reactions, Anti-HIV Agents, Atazanavir Sulfate, Settore MED/17 - MALATTIE INFETTIVE, 03 medical and health sciences, pharmacology, pharmacology (medical), infectious diseases, medicine, Humans, Caesarean section, Triglycerides, Pharmacology, business.industry, Infant, Newborn, Infant, Bilirubin, medicine.disease, 030112 virology, Atazanavir, azatanavir sulfate, Lipid profile, business
Abstract

Background Atazanavir and darunavir represent the main HIV PIs recommended in pregnancy, but comparative data in pregnant women are limited. We assessed the safety and activity profile of these two drugs in pregnancy using data from a national observational study. Methods Women with atazanavir or darunavir exposure in pregnancy were evaluated for laboratory measures and main pregnancy outcomes (e.g. preterm delivery, low birthweight, non-elective caesarean section and neonatal gestational age-adjusted birthweight Z-score). Results Final analysis included 500 pregnancies with either atazanavir (n = 409) or darunavir (n = 91) exposure. No differences in pregnancy outcomes, weight gain in pregnancy, drug discontinuations, undetectable HIV-RNA, haemoglobin, ALT, total cholesterol, HDL cholesterol and LDL cholesterol were observed between the two groups. At third trimester, exposure to darunavir was associated with higher levels of plasma triglycerides (median 235.5 versus 179 mg/dL; P = 0.032) and a higher total cholesterol/HDL cholesterol ratio (median 4.03 versus 3.27; P = 0.028) and exposure to atazanavir was associated with higher levels of plasma bilirubin (1.54 versus 0.32 mg/dL; P

Published
2017
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18. Magnetic properties and hyperfine interactions in Cr8, Cr7Cd, and Cr7Ni molecular rings from 19F-NMR.

Author

Bordonali, L., Garlatti, E., Casadei, C. M., Furukawa, Y., Lascialfari, A., Carretta, S., Troiani, F., Timco, G., Winpenny, R. E. P., and Borsa, F.

Subjects
MAGNETIC properties, HYPERFINE interactions, NUCLEAR magnetic resonance, METAL ions, BOLTZMANN factor
Abstract

A detailed experimental investigation of the 19F nuclear magnetic resonance is made on single crystals of the homometallic Cr8 antiferromagnetic molecular ring and heterometallic Cr7Cd and Cr7Ni rings in the low temperature ground state. Since the F- ion is located midway between neighboring magnetic metal ions in the ring, the 19F-NMR spectra yield information about the local electronic spin density and 19F hyperfine interactions. In Cr8, where the ground state is a singlet with total spin ST = 0, the 19F-NMR spectra at 1.7 K and low external magnetic field display a single narrow line, while when the magnetic field is increased towards the first level crossing field, satellite lines appear in the 19F-NMR spectrum, indicating a progressive increase in the Boltzmann population of the first excited state ST = 1. In the heterometallic rings, Cr7Cd and Cr7Ni, whose ground state is magnetic with ST = 3/2 and ST = 1/2, respectively, the 19F-NMR spectrum has a complicated structure which depends on the strength and orientation of the magnetic field, due to both isotropic and anisotropic transferred hyperfine interactions and classical dipolar interactions. From the 19F-NMR spectra in single crystals we estimated the transferred hyperfine constants for both the F--Ni2+ and the F--Cd2+ bonds. The values of the hyperfine constants compare well to the ones known for F--Ni2+ in KNiF3 and NiF2 and for F--Cr3+ in K2NaCrF6. The results are discussed in terms of hybridization of the 2s, 2p orbitals of the F- ion and the d orbitals of the magnetic ion. Finally, we discuss the implications of our results for the electron-spin decoherence. [ABSTRACT FROM AUTHOR]

Published
2014
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19. Wnt7b signalling through Frizzled-7 receptor promotes dendrite development by coactivating CaMKII and JNK

Author

Ferrari, María E, Bernis, María E, McLeod, Faye, Podpolny, Marina, Coullery, Romina P, Casadei, Inelia M, Salinas, Patricia C, and Rosso, Silvana B

Subjects
enzymology [Dendrites], MAP Kinase Kinase 4, metabolism [Receptors, G-Protein-Coupled], Dishevelled Proteins, metabolism [Hippocampus], genetics [Dishevelled Proteins], Hippocampus, Fzd7 protein, mouse, Receptors, G-Protein-Coupled, genetics [Calcium-Calmodulin-Dependent Protein Kinase Type 2], genetics [Dendrites], Mice, metabolism [Wnt Proteins], ddc:570, Proto-Oncogene Proteins, Neurites, metabolism [Dishevelled Proteins], genetics [MAP Kinase Kinase 4], Animals, metabolism [Dendrites], metabolism [Proto-Oncogene Proteins], Rats, Wistar, Wnt Signaling Pathway, genetics [Receptors, G-Protein-Coupled], genetics [Wnt Proteins], metabolism [Calcium-Calmodulin-Dependent Protein Kinase Type 2], metabolism [Neurites], Wnt7b protein, mouse, Dendrites, metabolism [MAP Kinase Kinase 4], growth & development [Hippocampus], Frizzled Receptors, Rats, Mice, Inbred C57BL, Wnt Proteins, Dvl1 protein, mouse, genetics [Proto-Oncogene Proteins], Calcium-Calmodulin-Dependent Protein Kinase Type 2, Protein Binding
Abstract

The formation of complex dendritic arbors is crucial for the assembly of functional networks as abnormal dendrite formation underlies several neurodevelopmental and psychiatric disorders. Many extracellular factors have been postulated as regulators of dendritic growth. Wnt proteins play a critical role in neuronal development and circuit formation. We previously demonstrated that Wnt7b acts through the scaffold protein dishevelled 1 (Dvl1) to modulate dendrite arborisation by activating a non-canonical Wnt signalling pathway. Here, we identify the seven-transmembrane frizzled-7 (Fz7, also known as FZD7) as the receptor for Wnt7b-mediated dendrite growth and complexity. Importantly, Fz7 is developmentally regulated in the intact hippocampus, and is localised along neurites and at dendritic growth cones, suggesting a role in dendrite formation and maturation. Fz7 loss-of-function studies demonstrated that Wnt7b requires Fz7 to promote dendritic arborisation. Moreover, in vivo Fz7 loss of function results in dendritic defects in the intact mouse hippocampus. Furthermore, our findings reveal that Wnt7b and Fz7 induce the phosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and JNK proteins, which are required for dendritic development. Here, we demonstrate that Wnt7b-Fz7 signals through two non-canonical Wnt pathways to modulate dendritic growth and complexity.

Published
2018
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20. Abacavir/Lamivudine and Tenofovir/Emtricitabine in Pregnant Women with Hiv: Laboratory and Clinical Outcomes in an Observational National Study

Author

Floridia, M., Pinnetti, C., Ravizza, M., Masuelli, G., Personeni, C., Sansone, M., Antoni, A. D., Guaraldi, G., Spinillo, A., Tassis, B., Dalzero, S., Liuzzi, G., Tamburrini, E., Di Lorenzo, F., Sterrantino, G., Meli, M., Campolmi, I., Vichi, F., Del Pin, B., Marocco, R., Mastroianni, C., Mercurio, V. S., Maccabruni, A., Zaramella, M., Mariani, B., Nardini, G., Stentarelli, C., Beghetto, B., Degli Antoni, A. M., Molinari, A., Crisalli, M. P., Donisi, A., Piepoli, M., Cerri, V., Zuccotti, G., Giacomet, V., Coletto, S., Di Nello, F., Madia, C., Placido, G., Milini, P., Savalli, F., Portelli, V., Sabbatini, F., Francisci, D., Papalini, C., Bernini, L., Grossi, P., Rizzi, L., Bernardon, M., Maso, G., Rizzante, E., Belcaro, C., Meloni, A., Dedoni, M., Ortu, F., Piano, P., Citernesi, A., Vicini, I. B., Luzi, K., Roccio, M., Vimercati, A., Miccolis, A., De Gennaro, A., Guerra, B., Cervi, F., Simonazzi, G., Margarito, E., Capretti, M. G., Marsico, C., Faldella, G., Martinelli, P., Agangi, A., Capone, A., Maruotti, G. M., Tibaldi, C., Trentini, L., Todros, T., Frisina, V., Cetin, I., Brambilla, T., Savasi, V., Giaquinto, C., Fiscon, M., Rubino, E., Franceschetti, L., Badolato, R., Tiso, G. C., Genovese, O., Cafforio, C., Casadei, A. M., Cavaliere, A. F., Cellini, M., Marconi, A. M., Sacchi, V., Ierardi, M., Polizzi, C., Mattei, A., Pirillo, M. F., Amici, R., Galluzzo, C. M., Donnini, S., and Baroncelli, S.

Subjects
0301 basic medicine, HIV Infections, Hemoglobins, 0302 clinical medicine, Abacavir, Anemia, Cholesterol, Emtricitabine, HIV-RNA, Lamivudine, Low birthweight, Pregnancy, Preterm delivery, Tenofovir, immune system diseases, Antiretroviral Therapy, Highly Active, Pharmacology (medical), 030212 general & internal medicine, Pregnancy Outcome, virus diseases, Lipoproteins, LDL, Drug Combinations, Infectious Diseases, Hypertension, RNA, Viral, Female, medicine.drug, Adult, medicine.medical_specialty, Anti-HIV Agents, Pregnancy Trimester, Third, 03 medical and health sciences, Internal medicine, medicine, Humans, AIDS-Associated Nephropathy, Cesarean Section, business.industry, Abacavir/Lamivudine, medicine.disease, 030112 virology, Dideoxynucleosides, CD4 Lymphocyte Count, Pregnancy Complications, HIV-1, Observational study, business
Abstract

Abacavir-lamivudine (ABC/3TC) and tenofovir-emtricitabine (TDF/FTC) represent in the guidelines of several countries, including Italy and United States, the preferred nucleoside/nucleotide backbones of antiretroviral regimens. We assessed their profile in pregnancy using data from a national observational study.Laboratory measures (CD4, HIV-RNA, lipid profile, glucose, hemoglobin, and alanine transferase) and pregnancy outcomes (preterm delivery, low birthweight, nonelective cesarean section, birthweight Z-score, congenital defects, HIV transmission, maternal weight gain, and pregnancy complications) were compared after prenatal exposure to ABC/3TC or TDF/FTC.The study evaluated 913 pregnancies (ABC/3TC: 252; TDF/FTC: 661). At entry in pregnancy, women on TDF/FTC were older (33.6 vs. 32.4 years, P = 0.005), less frequently on treatment (66.9% vs. 80.2%, P0.001), and had lower CD4 counts (475/mm vs. 533/mm, P = 0.003) and higher plasma HIV-RNA levels (2.48 vs. 2.22 log10 copies/mL, P = 0.003). Women on ABC/3TC had more commonly hypertension/nephropathy (5.2% vs. 2.0%, P = 0.013). No major differences were observed in the main pregnancy outcomes and in rates of undetectable HIV-RNA at third trimester. In a subgroup analysis that evaluated at third trimester only cases with regular 3-drug treatment during pregnancy, women on TDF/FTC had lower hemoglobin levels (median: 11.1 vs. 11.8 g/dL, P = 0.002) and women on ABC/3TC had higher levels of total cholesterol (median: 230 vs. 216 mg/dL, P = 0.023) and low-density lipoprotein-cholesterol (133 vs. 111 mg/dL, P = 0.030).In this study, use of TDF/FTC and ABC/3TC in pregnancy was associated with similar pregnancy outcomes and with some differences in laboratory measures that might guide physicians' prescriptions in mothers with hematologic or metabolic risk factors.

Published
2018

21. Second-line therapy in paediatric warm autoimmune haemolytic anaemia. Guidelines from the Associazione Italiana Onco-Ematologia Pediatrica (AIEOP)

Author

Ladogana S., Maruzzi M., Samperi P., Condorelli A., Casale M., Giordano P., Notarangelo L. D., Farruggia P., Giona F., Nocerino A., Fasoli S., Casciana M. L., Miano M., Tucci F., Casini T., Saracco P., Barcellini W., Zanella A., Perrotta S., Russo G., Baronci C., Casadei A. M., Cazzaniga G., Coluzzi S., Ciliberti A., Del Vecchio G. C., Facchini E., Girelli G., Lazzareschi I., Masera N., Perseghin P., Peruccio D., Petrone A., Sau A., Schiro R., Tumino M., Vasta I., Verzegnassi F., Ladogana, Saverio, Maruzzi, Matteo, Samperi, Piera, Condorelli, Annalisa, Casale, Maddalena, Giordano, Paola, Notarangelo, Lucia D., Farruggia, Piero, Giona, Fiorina, Nocerino, Agostino, Fasoli, Silvia, Casciana, Maria L., Miano, Maurizio, Tucci, Fabio, Casini, Tommaso, Saracco, Paola, Barcellini, Wilma, Zanella, Alberto, Perrotta, Silverio, Russo, Giovanna, Baronci, Carlo, Casadei, Anna Maria, Cazzaniga, Giovanni, Coluzzi, Serelina, Corti, Paola, Del Vecchio, Giovanni C., Facchini, Elena, Girelli, Gabriella, Lazzareschi, Ilaria, Masera, Nicoletta, Perseghin, Paolo, Peruccio, Daniela, Petrone, Angelamaria, Sau, Antonella, Schirò, Raffaella, Tumino, Manuela, Vasta, Isabella, Verzegnassi, Federico, Ladogana, S, Maruzzi, M, Samperi, P, Condorelli, A, Casale, M, Giordano, P, Notarangelo, L, Farruggia, P, Giona, F, Nocerino, A, Fasoli, S, Casciana, M, Miano, M, Tucci, F, Casini, T, Saracco, P, Barcellini, W, Zanella, A, Perrotta, S, Russo, G, Baronci, C, Casadei, A, Cazzaniga, G, Coluzzi, S, Ciliberti, A, Del Vecchio, G, Facchini, E, Girelli, G, Lazzareschi, I, Masera, N, Perseghin, P, Peruccio, D, Petrone, A, Sau, A, Schiro, R, Tumino, M, Vasta, I, and Verzegnassi, F

Subjects
Male, autoimmune haemolytic anaemia, child, therapy, rituximab, mycophenolate mofetil, splenectomy, therapy, Erythrocytes, Adolescent, Incidence, mycophenolate mofetil, Infant, Hematology, Guideline, splenectomy, rituximab, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, Child, Preschool, Humans, Immunology and Allergy, autoimmune haemolytic anaemia, Female, Anemia, Hemolytic, Autoimmune, Child, Autoantibodies
Published
2018

22. Second-line therapy in paediatric warm autoimmune haemolytic anaemia. Guidelines from the Associazione Italiana Onco-Ematologia Pediatrica (AIEOP)

Author

Ladogana, S, Maruzzi, M, Samperi, P, Condorelli, A, Casale, M, Giordano, P, Notarangelo, L, Farruggia, P, Giona, F, Nocerino, A, Fasoli, S, Casciana, M, Miano, M, Tucci, F, Casini, T, Saracco, P, Barcellini, W, Zanella, A, Perrotta, S, Russo, G, Baronci, C, Casadei, A, Cazzaniga, G, Coluzzi, S, Ciliberti, A, Del Vecchio, G, Facchini, E, Girelli, G, Lazzareschi, I, Masera, N, Perseghin, P, Peruccio, D, Petrone, A, Sau, A, Schiro, R, Tumino, M, Vasta, I, Verzegnassi, F, Ladogana S., Maruzzi M., Samperi P., Condorelli A., Casale M., Giordano P., Notarangelo L. D., Farruggia P., Giona F., Nocerino A., Fasoli S., Casciana M. L., Miano M., Tucci F., Casini T., Saracco P., Barcellini W., Zanella A., Perrotta S., Russo G., Baronci C., Casadei A. M., Cazzaniga G., Coluzzi S., Ciliberti A., Del Vecchio G. C., Facchini E., Girelli G., Lazzareschi I., Masera N., Perseghin P., Peruccio D., Petrone A., Sau A., Schiro R., Tumino M., Vasta I., Verzegnassi F., Ladogana, S, Maruzzi, M, Samperi, P, Condorelli, A, Casale, M, Giordano, P, Notarangelo, L, Farruggia, P, Giona, F, Nocerino, A, Fasoli, S, Casciana, M, Miano, M, Tucci, F, Casini, T, Saracco, P, Barcellini, W, Zanella, A, Perrotta, S, Russo, G, Baronci, C, Casadei, A, Cazzaniga, G, Coluzzi, S, Ciliberti, A, Del Vecchio, G, Facchini, E, Girelli, G, Lazzareschi, I, Masera, N, Perseghin, P, Peruccio, D, Petrone, A, Sau, A, Schiro, R, Tumino, M, Vasta, I, Verzegnassi, F, Ladogana S., Maruzzi M., Samperi P., Condorelli A., Casale M., Giordano P., Notarangelo L. D., Farruggia P., Giona F., Nocerino A., Fasoli S., Casciana M. L., Miano M., Tucci F., Casini T., Saracco P., Barcellini W., Zanella A., Perrotta S., Russo G., Baronci C., Casadei A. M., Cazzaniga G., Coluzzi S., Ciliberti A., Del Vecchio G. C., Facchini E., Girelli G., Lazzareschi I., Masera N., Perseghin P., Peruccio D., Petrone A., Sau A., Schiro R., Tumino M., Vasta I., and Verzegnassi F.

Published
2018

23. Second-line therapy in paediatric warm autoimmune haemolytic anaemia. Guidelines from the Associazione Italiana Onco-Ematologia Pediatrica (AIEOP)

Author

Ladogana, S., Maruzzi, M., Samperi, P., Condorelli, A., Casale, M., Giordano, P., Notarangelo, L. D., Farruggia, P., Giona, F., Nocerino, A., Fasoli, S., Casciana, M. L., Miano, M., Tucci, F., Casini, T., Saracco, P., Barcellini, W., Zanella, A., Perrotta, S., Russo, G., Baronci, C., Casadei, A. M., Cazzaniga, G., Coluzzi, S., Ciliberti, A., Del Vecchio, G. C., Facchini, E., Girelli, G., Lazzareschi, I., Masera, N., Perseghin, P., Peruccio, D., Petrone, A., Sau, A., Schiro, R., Tumino, M., Vasta, I., Verzegnassi, F., Zanella A., Cazzaniga G., Ciliberti A., Facchini E., Lazzareschi I. (ORCID:0000-0001-7221-2983), Vasta I., Ladogana, S., Maruzzi, M., Samperi, P., Condorelli, A., Casale, M., Giordano, P., Notarangelo, L. D., Farruggia, P., Giona, F., Nocerino, A., Fasoli, S., Casciana, M. L., Miano, M., Tucci, F., Casini, T., Saracco, P., Barcellini, W., Zanella, A., Perrotta, S., Russo, G., Baronci, C., Casadei, A. M., Cazzaniga, G., Coluzzi, S., Ciliberti, A., Del Vecchio, G. C., Facchini, E., Girelli, G., Lazzareschi, I., Masera, N., Perseghin, P., Peruccio, D., Petrone, A., Sau, A., Schiro, R., Tumino, M., Vasta, I., Verzegnassi, F., Zanella A., Cazzaniga G., Ciliberti A., Facchini E., Lazzareschi I. (ORCID:0000-0001-7221-2983), and Vasta I.

Abstract

No abstract available

Published
2018

24. Molecular monitoring in chronic myeloid leukemia (CML)

Author

Izzo B., Accetta R., Caruso S., De Angelis B., Del Prete C., Errichiello S., Galdiero A., Casadei G. M., Musella F., Quintarelli C., Visconti R., Pane F., Izzo, B., Accetta, R., Caruso, S., De Angelis, B., Del Prete, C., Errichiello, S., Galdiero, A., Casadei, G. M., Musella, F., Quintarelli, C., Visconti, R., and Pane, F.

Abstract

The pathognomonic genetic alteration in CML is the formation of the BCR-ABL fusion gene, which produces a constitutively active tyrosine kinase that drives leukemic transformation. Targeted tyrosine kinase inhibitor treatment is the cornerstone of modern therapy for this hematologic malignancy. Analysis of BCR-ABL [through reverse transcriptase-quantitative polymerase chain reaction (RT-QPCR)] is the gold standard approach for quantitatively assessing minimal residual disease and monitoring the efficacy of tyrosine kinase inhibitor therapy in CML patients. The continuous therapeutic improvement has led to increasingly ambitious treatment endpoints, which, in turn, require more and more refined measurement and definition of molecular response levels. For these reasons standardization efforts of monitoring by RT-QPCR are now focused on ensuring reliable and harmonized expression of quantitative results.

Published
2015

25. Pregnant with HIV before age 25: Data from a large national study in Italy, 2001-2016

Author

Floridia, M., Masuelli, G., Tamburrini, E., Cetin, I., Liuzzi, G., Martinelli, Paolo, Guaraldi, G., Spinillo, A., Vimercati, A., Maso, G., Pinnetti, C., Frisina, V., Dalzero, S., Ravizza, M., Di Lorenzo, F., Sterrantino, G., Meli, M., Campolmi, I., Vichi, F., Del Pin, B., Marocco, R., Mastroianni, C., Mercurio, V. S., Maccabruni, A., Zaramella, M., Mariani, Bianca, Nardini, G., Stentarelli, C., Beghetto, B., Antoni, A. M. Degli, Molinari, A., Crisalli, M. P., Donisi, A., Piepoli, M., Cerri, V., Zuccotti, G., Giacomet, V., Coletto, S., Di Nello, F., Madia, C., Placido, G., Milini, P., Savalli, F., Portelli, V., Sabbatini, F., Francisci, D., Angeli, G., Bernini, L., Grossi, P., Rizzi, L., Bernardon, M., Rizzante, E., Belcaro, C., Meloni, Antonio, Dedoni, M., Ortu, F., Piano, Pierluigi, Citernesi, A., Vicini, I. Bordoni, Luzi, K., Roccio, M., Miccolis, A., De Gennaro, A., Guerra, B., Cervi, Filippo, Simonazzi, G., Margarito, E., Capretti, M. G., Marsico, C., Faldella, G., Sansone, M., Agangi, A., Capone, A., Maruotti, G. M., Tibaldi, C., Trentini, L., Todros, T., Brambilla, T., Savasi, V., Personeni, C., Giaquinto, C., Fiscon, M., Rubino, E., Franceschetti, L., Tassis, B., Genovese, O., Cafforio, C., Casadei, A. M., Cavaliere, A. F., Cellini, Matteo, Marconi, A. M., Sacchi, V., Ierardi, M., Polizzi, C., Mattei, A., Pirillo, M. F., Amici, R., Galluzzo, C. M., Donnini, S., Baroncelli, S., Cerioli, A., DE MARTINO, MARIA CRISTINA, Parazzini, F., and Vella, S.

Subjects
Antiretroviral treatment, HIV diagnosis, HIV testing, pregnancy, women's health, medicine.medical_specialty, Pediatrics, Longitudinal study, Adolescent, Epidemiology, Short Report, HIV Infections, Cohort Studies, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Pregnancy, medicine, Odds Ratio, Humans, 030212 general & internal medicine, Young adult, 030219 obstetrics & reproductive medicine, business.industry, Odds ratio, medicine.disease, Female, Italy, Infectious Diseases, Confidence interval, Family planning, business, Cohort study
Abstract

SUMMARYYoung pregnant women with HIV may be at significant risk of unplanned pregnancy, lower treatment coverage, and other adverse pregnancy outcomes. In a large cohort of pregnant women with HIV in Italy, among 2979 pregnancies followed in 2001–2016, 9·0% were in women P< 0·001). Younger women had a lower rate of planned pregnancy (23·2%vs.37·7%, odds ratio (OR) 0·50, 95% confidence interval (CI) 0·36–0·69), were more frequently diagnosed with HIV in pregnancy (46·5%vs.20·9%, OR 3·29, 95% CI 2·54–4·25), and, if already diagnosed with HIV before pregnancy, were less frequently on antiretroviral treatment at conception (vs.99·3%), with no differences in rate of HIV viral suppression at third trimester and adverse pregnancy outcomes. The data show that young women represent a growing proportion of pregnant women with HIV, and are significantly more likely to have unplanned pregnancy, undiagnosed HIV infection, and lower treatment coverage at conception. During pregnancy, antiretroviral treatment, HIV suppression, and pregnancy outcomes are similar compared with older women. Earlier intervention strategies may provide additional benefits in the quality of care for women with HIV.

Published
2017

26. Direct visualization of a Fe(IV)-OH intermediate in a heme enzyme

Author

Kwon, Hanna, Basran, Jaswir, Raven, Emma L., Casadei, Cecilia M., Fielding, Alistair J., Schrader, Tobias E., Ostermann, Andreas, Devos, Juliette M., Aller, Pierre, Blakeley, Matthew P., and Moody, Peter C. E.

Subjects
Science, Iron, Electron Spin Resonance Spectroscopy, Heme, Crystallography, X-Ray, Article, QH301, Neutron Diffraction, Cytochrome P-450 Enzyme System, Peroxidases, biological sciences, QD, ddc:500, Crystallization
Abstract

Catalytic heme enzymes carry out a wide range of oxidations in biology. They have in common a mechanism that requires formation of highly oxidized ferryl intermediates. It is these ferryl intermediates that provide the catalytic engine to drive the biological activity. Unravelling the nature of the ferryl species is of fundamental and widespread importance. The essential question is whether the ferryl is best described as a Fe(IV)=O or a Fe(IV)–OH species, but previous spectroscopic and X-ray crystallographic studies have not been able to unambiguously differentiate between the two species. Here we use a different approach. We report a neutron crystal structure of the ferryl intermediate in Compound II of a heme peroxidase; the structure allows the protonation states of the ferryl heme to be directly observed. This, together with pre-steady state kinetic analyses, electron paramagnetic resonance spectroscopy and single crystal X-ray fluorescence, identifies a Fe(IV)–OH species as the reactive intermediate. The structure establishes a precedent for the formation of Fe(IV)–OH in a peroxidase., The nature of the ferryl intermediate generated in reactions catalysed by heme-containing enzymes is uncertain, due to the ambiguity of X-ray crystallography data. Here, the authors apply neutron diffraction, kinetics and other spectroscopy to directly observe a protonated ferryl intermediate in a heme peroxidase.

Published
2016
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27. Resolution extension by image summing in serial femtosecond crystallography of two-dimensional membrane-protein crystals

Author

Casadei, Cecilia M., primary, Tsai, Ching-Ju, additional, Barty, Anton, additional, Hunter, Mark S., additional, Zatsepin, Nadia A., additional, Padeste, Celestino, additional, Capitani, Guido, additional, Benner, W. Henry, additional, Boutet, Sébastien, additional, Hau-Riege, Stefan P., additional, Kupitz, Christopher, additional, Messerschmidt, Marc, additional, Ogren, John I., additional, Pardini, Tom, additional, Rothschild, Kenneth J., additional, Sala, Leonardo, additional, Segelke, Brent, additional, Williams, Garth J., additional, Evans, James E., additional, Li, Xiao-Dan, additional, Coleman, Matthew, additional, Pedrini, Bill, additional, and Frank, Matthias, additional

Published
2018
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29. Rate, correlates and outcomes of repeat pregnancy in HIV-infected women

Author

Floridia, M., Tamburrini, E., Masuelli, G., Martinelli, P., Spinillo, A., Liuzzi, G., Vimercati, A., Alberico, S., Maccabruni, A., Pinnetti, C., Frisina, V., Dalzero, S., Ravizza, M., Mori, F., Ortolani, P., dalle Nogare, E. R., Di Lorenzo, F., Sterrantino, G., Meli, M., Polemi, S., Nocentini, J., Baldini, M., Montorzi, G., Mazzetti, M., Rogasi, P., Borchi, B., Vichi, F., Del Pin, B., Pinter, E., Anzalone, E., Marocco, R., Mastroianni, C., Mercurio, V. S., Carocci, A., Grilli, E., Zaramella, M., Mariani, B., Natalini Raponi, G., Guaraldi, G., Nardini, G., Stentarelli, C., Beghetto, B., Degli Antoni, A. M., Molinari, A., Crisalli, M. P., Donisi, A., Piepoli, M., Cerri, V., Zuccotti, G., Giacomet, V., Coletto, S., Di Nello, F., Madia, C., Placido, G., Vivarelli, A., Castelli, P., Savalli, F., Portelli, V., Sabbatini, F., Francisci, D., Bernini, L., Grossi, P., Rizzi, L., Maso, G., Airoud, M., Soppelsa, G., Meloni, A., Dedoni, M., Cuboni, C., Ortu, F., Piano, P., Citernesi, A., Bordoni Vicini, I., Luzi, K., Roccio, M., Miccolis, A., De Gennaro, A., Guerra, B., Cervi, F., Simonazzi, G., Margarito, E., Capretti, M. G., Marsico, C., Faldella, G., Sansone, M., Agangi, A., Capone, A., Maruotti, M., Tibaldi, C., Trentini, L., Todros, T., Cetin, I., Brambilla, T., Savasi, V., Personeni, C., Giaquinto, C., Fiscon, M., Rubino, E., Bucceri, A., Matrone, R., Scaravelli, G., Genovese, O., Cafforio, C., Tozzi, V., Massetti, P., Casadei, A. M., Cavaliere, A. F., Cellini, M., Castelli Gattinara, G., Marconi, A. M., Sacchi, V., Ierardi, M., Polizzi, C., Mattei, A., Pirillo, M. F., Amici, R., Galluzzo, C. M., Donnini, S., Baroncelli, S., Villani, P., Cusato, M., Cerioli, A., De Martino, M., Mastroiacovo, P., Parazzini, F., Vella, S., Floridia, M, Tamburrini, E., Masuelli, G., Martinelli, P., Spinillo, A., Liuzzi, G., Vimercati, A., Alberico, S., Maccabruni, A., Pinnetti, C., Frisina, V., Dalzero, S., Ravizza, M. [, Faldella G., and ]

Subjects
0301 basic medicine, Adult, medicine.medical_specialty, HIV RNA, Anti-HIV Agents, birth weight, HIV, pregnancy, preterm delivery, Health Policy, Infectious Diseases, Pharmacology (medical), Birth weight, Emigrants and Immigrants, HIV Infections, Settore MED/17 - MALATTIE INFETTIVE, Pregnancy, Preterm delivery, CD4 Lymphocyte Count, Female, HIV-1, Humans, Premature Birth, Viral Load, Infant, Low Birth Weight, 03 medical and health sciences, medicine, Obstetrics, business.industry, Low Birth Weight, Infant, Odds ratio, medicine.disease, 030112 virology, Confidence interval, Pregnancy rate, Low birth weight, Premature birth, medicine.symptom, business, Viral load
Abstract

Objectives The aim of the study was to assess the rate, determinants, and outcomes of repeat pregnancies in women with HIV infection. Methods Data from a national study of pregnant women with HIV infection were used. Main outcomes were preterm delivery, low birth weight, CD4 cell count and HIV plasma viral load. Results The rate of repeat pregnancy among 3007 women was 16.2%. Women with a repeat pregnancy were on average younger than those with a single pregnancy (median age 30 vs. 33 years, respectively), more recently diagnosed with HIV infection (median time since diagnosis 25 vs. 51 months, respectively), and more frequently of foreign origin [odds ratio (OR) 1.36; 95% confidence interval (CI) 1.10–1.68], diagnosed with HIV infection in the current pregnancy (OR: 1.69; 95% CI: 1.35–2.11), and at their first pregnancy (OR: 1.33; 95% CI: 1.06–1.66). In women with sequential pregnancies, compared with the first pregnancy, several outcomes showed a significant improvement in the second pregnancy, with a higher rate of antiretroviral treatment at conception (39.0 vs. 65.4%, respectively), better median maternal weight at the start of pregnancy (60 vs. 61 kg, respectively), a higher rate of end-of-pregnancy undetectable HIV RNA (60.7 vs. 71.6%, respectively), a higher median birth weight (2815 vs. 2885 g, respectively), lower rates of preterm delivery (23.0 vs. 17.7%, respectively) and of low birth weight (23.4 vs. 15.4%, respectively), and a higher median CD4 cell count (+47 cells/μL), with almost no clinical progression to Centers for Disease Control and Prevention stage C (CDC-C) HIV disease (0.3%). The second pregnancy was significantly more likely to end in voluntary termination than the first pregnancy (11.4 vs. 6.1%, respectively). Conclusions Younger and foreign women were more likely to have a repeat pregnancy; in women with sequential pregnancies, the second pregnancy was characterized by a significant improvement in several outcomes, suggesting that women with HIV infection who desire multiple children may proceed safely and confidently with subsequent pregnancies.

Published
2016

30. Good prenatal detection rate of major birth defects in HIV-infected pregnant women in Italy

Author

Floridia, M, Mastroiacovo, P., Ravizza, M., Todros, T., Chiadò Fiorio Tin, M., Marconi, A. M., Cetin, I., Maruotti, G. M., Liuzzi, G., Pinnetti, C., Degli Antoni, A., Spinillo, A., Guerra, B., Tamburrini, E., Floridia, M., Mori, F., Ortolani, P., dalle Nogare, E. R., Di Lorenzo, F., Sterrantino, G., Meli, M., Polemi, S., Nocentini, J., Baldini, M., Montorzi, G., Mazzetti, M., Rogasi, P., Borchi, B., Vichi, F., Del Pin, B., Pinter, E., Anzalone, E., Marocco, R., Mastroianni, C., Mercurio, V. S., Carocci, A., Grilli, E., Maccabruni, A., Zaramella, M., Mariani, B., Natalini Raponi, G., Guaraldi, G., Nardini, G., Stentarelli, C., Beghetto, B., Degli Antoni, A. M., Molinari, A., Crisalli, M. P., Donisi, A., Piepoli, M., Cerri, V., Zuccotti, G., Giacomet, V., Coletto, S., Di Nello, F., Madia, C., Placido, G., Vivarelli, A., Castelli, P., Savalli, F., Portelli, V., Sabbatini, F., Francisci, Daniela, Bernini, L., Grossi, P., Rizzi, L., Alberico, S., Maso, G., Airoud, M., Soppelsa, G., Meloni, A., Dedoni, M., Cuboni, C., Ortu, F., Piano, P., Citernesi, A., Bordoni Vicini, I., Luzi, K., Roccio, M., Vimercati, A., Miccolis, A., De Gennaro, A., Cervi, F., Puccetti, C., Margarito, E., Contoli, M., Capretti, M. G., Marsico, C., Faldella, G., Sansone, M., Martinelli, P., Agangi, A., Capone, A., Tibaldi, C., Trentini, L., Masuelli, G., Frisina, V., Brambilla, T., Savasi, V., Personeni, C., Giaquinto, C., Fiscon, M., Rinaldi, R., Rubino, E., Bucceri, A., Matrone, R., Scaravelli, G., Fundarò, C., Genovese, O., Cafforio, C., Tozzi, V., Massetti, P., Casadei, A. M., Cavaliere, A. F., Finelli, V., Cellini, M., Castelli Gattinara, G., Dalzero, S., Sacchi, V., Ierardi, M., Polizzi, C., Mattei, A., Pirillo, M. F., Amici, R., Galluzzo, C. M., Donnini, S., Baroncelli, S., Villani, P., Cusato, M., Cerioli, A., De Martino, M., Parazzini, F., and Vella, S.

Subjects
Adult, Infectious, Obstetrics and Gynecology, HIV Infections, Congenital Abnormalities, Pregnancy Complications, Italy, Pregnancy, Humans, Female, Pregnancy Complications, Infectious, Genetics (clinical)
Published
2015

31. Pregnancy outcomes and cytomegalovirus DNAaemia in HIV-infected pregnant women with CMV

Author

Ravizza, M., Tamburrini, Enrica, Mori, F., Ortolani, P., dalle Nogare, E. R., Di Lorenzo, F., Sterrantino, G., Meli, M., Polemi, S., Nocentini, J., Baldini, M., Montorzi, G., Mazzetti, M., Rogasi, P., Borchi, B., Vichi, F., Del Pin, B., Pinter, E., Anzalone, E., Marocco, R., Mastroianni, C., Mercurio, V. S., Carocci, A., Grilli, E., Maccabruni, A., Zaramella, M., Mariani, B., Natalini Raponi, G., Guaraldi, G., Nardini, G., Stentarelli, C., Beghetto, B., Degli Antoni, A. M., Molinari, A., Crisalli, M. P., Donisi, A., Piepoli, M., Cerri, V., Zuccotti, G., Giacomet, V., Coletto, S., Di Nello, F., Madia, C., Placido, G., Vivarelli, A., Castelli, P., Savalli, F., Portelli, V., Sabbatini, F., Francisci, D., Bernini, L., Grossi, P., Rizzi, L., Alberico, S., Maso, G., Airoud, M., Soppelsa, G., Meloni, A., Dedoni, M., Cuboni, C., Ortu, F., Piano, P., Citernesi, A., Bordoni Vicini, I., Luzi, K., Spinillo, A., Roccio, M., Vimercati, A., Miccolis, A., De Gennaro, A., Guerra, B., Cervi, F., Simonazzi, G., Margarito, E., Capretti, M. G., Marsico, C., Faldella, G., Sansone, M., Martinelli, P., Agangi, A., Capone, A., Maruotti, G. M., Tibaldi, C., Trentini, L., Todros, T., Masuelli, G., Frisina, V., Cetin, I., Brambilla, T., Savasi, V., Personeni, C., Giaquinto, C., Fiscon, M., Rubino, E., Bucceri, A., Matrone, R., Scaravelli, G., Genovese, O., Cafforio, C., Pinnetti, C., Liuzzi, G., Tozzi, V., Massetti, P., Casadei, A. M., Cavaliere, Anna Franca, Cellini, M., Castelli Gattinara, G., Marconi, A. M., Dalzero, S., Sacchi, V., Ierardi, M., Polizzi, C., Mattei, A., Pirillo, M. F., Amici, R., Galluzzo, C. M., Donnini, S., Baroncelli, S., Floridia, M., Villani, P., Cusato, M., Cerioli, A., De Martino, M., Mastroiacovo, P., Parazzini, F., Vella, S., Tamburrini, Enrica (ORCID:0000-0003-4930-426X), Ravizza, M., Tamburrini, Enrica, Mori, F., Ortolani, P., dalle Nogare, E. R., Di Lorenzo, F., Sterrantino, G., Meli, M., Polemi, S., Nocentini, J., Baldini, M., Montorzi, G., Mazzetti, M., Rogasi, P., Borchi, B., Vichi, F., Del Pin, B., Pinter, E., Anzalone, E., Marocco, R., Mastroianni, C., Mercurio, V. S., Carocci, A., Grilli, E., Maccabruni, A., Zaramella, M., Mariani, B., Natalini Raponi, G., Guaraldi, G., Nardini, G., Stentarelli, C., Beghetto, B., Degli Antoni, A. M., Molinari, A., Crisalli, M. P., Donisi, A., Piepoli, M., Cerri, V., Zuccotti, G., Giacomet, V., Coletto, S., Di Nello, F., Madia, C., Placido, G., Vivarelli, A., Castelli, P., Savalli, F., Portelli, V., Sabbatini, F., Francisci, D., Bernini, L., Grossi, P., Rizzi, L., Alberico, S., Maso, G., Airoud, M., Soppelsa, G., Meloni, A., Dedoni, M., Cuboni, C., Ortu, F., Piano, P., Citernesi, A., Bordoni Vicini, I., Luzi, K., Spinillo, A., Roccio, M., Vimercati, A., Miccolis, A., De Gennaro, A., Guerra, B., Cervi, F., Simonazzi, G., Margarito, E., Capretti, M. G., Marsico, C., Faldella, G., Sansone, M., Martinelli, P., Agangi, A., Capone, A., Maruotti, G. M., Tibaldi, C., Trentini, L., Todros, T., Masuelli, G., Frisina, V., Cetin, I., Brambilla, T., Savasi, V., Personeni, C., Giaquinto, C., Fiscon, M., Rubino, E., Bucceri, A., Matrone, R., Scaravelli, G., Genovese, O., Cafforio, C., Pinnetti, C., Liuzzi, G., Tozzi, V., Massetti, P., Casadei, A. M., Cavaliere, Anna Franca, Cellini, M., Castelli Gattinara, G., Marconi, A. M., Dalzero, S., Sacchi, V., Ierardi, M., Polizzi, C., Mattei, A., Pirillo, M. F., Amici, R., Galluzzo, C. M., Donnini, S., Baroncelli, S., Floridia, M., Villani, P., Cusato, M., Cerioli, A., De Martino, M., Mastroiacovo, P., Parazzini, F., Vella, S., and Tamburrini, Enrica (ORCID:0000-0003-4930-426X)

Abstract

not available

Published
2016

35. Atazanavir and lopinavir profile in pregnant women with HIV: tolerability, activity and pregnancy outcomes in an observational national study

Author

Floridia, M., Ravizza, M., Masuelli, G., Giacomet, V., Martinelli, P., Degli Antoni, A., Spinillo, A., Fiscon, M., Francisci, D., Liuzzi, G., Pinnetti, C., Marconi, A. M., Tamburrini, E., Mori, F., Ortolani, P., dalle Nogare, E. R., Di Lorenzo, F., Sterrantino, G., Meli, M., Polemi, S., Nocentini, J., Baldini, M., Montorzi, G., Mazzetti, M., Rogasi, P., Borchi, B., Vichi, F., Del Pin, B., Pinter, E., Anzalone, E., Marocco, R., Mastroianni, C., Mercurio, V. S., Carocci, A., Grilli, E., Maccabruni, A., Zaramella, M., Mariani, B., Natalini Raponi, G., Guaraldi, Giovanni, Nardini, Giulia, Stentarelli, Chiara, Beghetto, Barbara, Degli Antoni, A. M., Molinari, A., Crisalli, M. P., Donisi, A., Piepoli, M., Cerri, V., Zuccotti, G., Fabiano, V., Placido, G., Vivarelli, A., Castelli, P., Savalli, F., Portelli, V., Sabbatini, F., Bernini, L., Grossi, P., Rizzi, L., Alberico, S., Maso, G., Airoud, M., Soppelsa, G., Meloni, A., Dedoni, M., Cuboni, C., Ortu, F., Piano, P., Citernesi, A., Bordoni Vicini, I., Luzi, K., Roccio, M., Vimercati, A., Miccolis, A., Bassi, E., Guerra, B., Cervi, F., Puccetti, C., Murano, P., Contoli, M., Capretti, M. G., Marsico, C., Faldella, G., Sansone, M., Agangi, A., Tibaldi, C., Trentini, L., Todros, T., Frisina, V., Cetin, I., Brambilla, T., Savasi, V., Personeni, C., Giaquinto, C., Rinaldi, R., Rubino, E., Bucceri, A., Matrone, R., Scaravelli, G., Fundaro, C., Genovese, O., Cafforio, C., Tozzi, V., Massetti, P., Casadei, A. M., Cavaliere, A. F., Finelli, V., Cellini, M., Castelli Gattinara, G., Dalzero, S., Sacchi, V., De Pirro, A., Polizzi, C., Mattei, A., Pirillo, M. F., Amici, R., Galluzzo, C. M., Donnini, S., Baroncelli, S., Regazzi, M., Villani, P., Cusato, M., Cerioli, A., De Martino, M., Mastroiacovo, P., Moroni, M., Parazzini, F., Vella, S., Floridia, M, Ravizza, M, Masuelli, G, Giacomet, V, Martinelli, Pasquale, Degli Antoni, A, Spinillo, A, Fiscon, M, Francisci, D, Liuzzi, G, Pinnetti, C, Marconi, Am, Tamburrini, E, on behalf of The Italian Group on Surveillance on Antiretroviral Treatment in, Pregnancy, Floridia, M1, Italian Group on Surveillance on Antiretroviral Treatment in, P. r. e. g. n. a. n. c. y., Marco Floridia, Marina Ravizza, Giulia Masuelli, Vania Giacomet, Pasquale Martinelli, Anna Degli Antoni, Arsenio Spinillo, Marta Fiscon, Daniela Francisci, Giuseppina Liuzzi, Carmela Pinnetti, Anna Maria Marconi, Enrica Tamburrini, on behalf of The Italian Group on Surveillance on Antiretroviral Treatment in Pregnancy [.., Capretti, M.G., Marsico, C., Faldella, G., and ].

Subjects
Pyridines, Pyridine, HIV Infections, Triglyceride, Lopinavir, Liver Function Tests, Pregnancy, HIV Infection, Pharmacology (medical), Viral, Pregnancy Complications, Infectious, triglycerides, pre-term delivery, medicine.diagnostic_test, Liver Function Test, Obstetrics, Medicine (all), Pregnancy Outcome, Infectious, virus diseases, HIV, pregnancy, RNA, Lipid, Viral Load, Lipids, Infectious Diseases, Tolerability, Oligopeptide, Population study, RNA, Viral, Female, medicine.symptom, bilirubin, Viral load, Oligopeptides, Human, medicine.drug, Microbiology (medical), Adult, medicine.medical_specialty, HIV RNA, Anti-HIV Agents, Atazanavir Sulfate, Infectious Disease, Bilirubin, Cholesterol, Pre-term delivery, Triglycerides, Pharmacology, cholesterol, Settore MED/17 - MALATTIE INFETTIVE, medicine, Humans, business.industry, Anti-HIV Agent, medicine.disease, Atazanavir, CD4 Lymphocyte Count, Pregnancy Complications, Immunology, Pregnancy Complications, Infectiou, business, Liver function tests, Weight gain
Abstract

BACKGROUND: Atazanavir and lopinavir represent the main HIV protease inhibitors recommended in pregnancy, but comparative data in pregnant women are limited. METHODS: Women from a national observational study, exposed in pregnancy to either atazanavir or lopinavir, were compared for glucose and lipid profiles, liver function tests, CD4 count, HIV RNA and main pregnancy outcomes. Statistical methods included univariate and multivariable analyses. RESULTS: The study population included 428 pregnancies (lopinavir, 322; atazanavir, 106). The lopinavir group was characterized by higher rates of HIV diagnosis in pregnancy and treatment indication for maternal health, lower CD4 counts, higher HIV RNA levels, less frequent antiretroviral treatment at conception and shorter duration of drug exposure during pregnancy. No differences in pregnancy outcomes, glucose metabolism and weight gain were observed. The two groups also showed in a multivariable analysis similar odds for detectable HIV RNA in the third trimester (adjusted OR 0.85, 95% CI 0.35-2.10, P = 0.730). Total lipid levels were significantly higher in the lopinavir group (median values in the third trimester 239 versus 221 mg/dL for total cholesterol and 226 versus 181 mg/dL for triglycerides; P < 0.001 for both comparisons) and bilirubin levels were significantly higher in the atazanavir group (1.53 versus 0.46 mg/dL, P < 0.001). CONCLUSIONS: In this observational study atazanavir and lopinavir showed similar safety and activity in pregnancy, with no differences in the main pregnancy outcomes. Atazanavir use was associated with a better lipid profile and with higher bilirubin levels. Overall, the study findings confirm that these two HIV protease inhibitors represent equally valid alternative options.

Published
2014

36. Wnt7b signalling through Frizzled-7 receptor promotes dendrite development by coactivating CaMKII and JNK.

Author

McLeod, Faye, Salinas, Patricia C., Ferrari, María E., Coullery, Romina P., Casadei, Inelia M., Rosso, Silvana B., Bernis, María E., and Podpolny, Marina

Subjects
DENDRITIC cells, MENTAL illness, SCAFFOLD proteins, LECTINS, NEURONS, PHOSPHORYLATION, PROTEIN kinases, PROTEINS
Abstract

The formation of complex dendritic arbors is crucial for the assembly of functional networks as abnormal dendrite formation underlies several neurodevelopmental and psychiatric disorders. Many extracellular factors have been postulated as regulators of dendritic growth. Wnt proteins play a critical role in neuronal development and circuit formation. We previously demonstrated that Wnt7b acts through the scaffold protein dishevelled 1 (Dvl1) to modulate dendrite arborisation by activating a non-canonical Wnt signalling pathway. Here,we identify the seven-transmembrane frizzled-7 (Fz7, also known as FZD7) as the receptor for Wnt7b-mediated dendrite growth and complexity. Importantly, Fz7 is developmentally regulated in the intact hippocampus, and is localised along neurites and at dendritic growth cones, suggesting a role in dendrite formation andmaturation. Fz7 lossof-function studies demonstrated that Wnt7b requires Fz7 to promote dendritic arborisation. Moreover, in vivo Fz7 loss of function results in dendritic defects in the intact mouse hippocampus. Furthermore, our findings reveal that Wnt7b and Fz7 induce the phosphorylation of Ca² +/calmodulin-dependent protein kinase II (CaMKII) and JNK proteins, which are required for dendritic development. Here, we demonstrate that Wnt7b--Fz7 signals through two non-canonical Wnt pathways to modulate dendritic growth and complexity. [ABSTRACT FROM AUTHOR]

Published
2018
Full Text
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37. Body Mass Index and Weight Gain in Pregnant Women With HIV: A National Study in Italy

Author

Floridia, M., Ravizza, M., Masuelli, G., Dalzero, S., Pinnetti, C., Cetin, I., Meloni, A., Spinillo, A., Rubino, E., Francisci, D., Tamburrini, E., Mori, F., Ortolani, P., Dalle Nogare, E. R., Di Lorenzo, F., Sterrantino, G., Meli, M., Polemi, S., Nocentini, J., Baldini, M., Montorzi, G., Mazzetti, M., Rogasi, P., Borchi, B., Vichi, F., Pinter, E., Anzalone, E., Marocco, R., Mastroianni, Claudio Maria, Mercurio, V. S., Carocci, A., Grilli, E., Maccabruni, A., Zaramella, M., Mariani, B., Natalini Raponi, G., Guaraldi, G., Luzi, K., Nardini, G., Stentarelli, C., Degli Antoni, A. M., Molinari, A., Crisalli, M. P., Donisi, A., Piepoli, M., Cerri, V., Zuccotti, G., Giacomet, V., Fabiano, V., Placido, G., Vivarelli, A., Castelli, P., Savalli, F., Portelli, V., Sabbatini, F., Bernini, L., Alberico, S., Maso, G., Tropea, M., Dedoni, M., Cuboni, C., Ortu, F., Piano, P., Citernesi, A., Vicini, I., Roccio, M., Vimercati, A., Miccolis, A., Bassi, E., Guerra, B., Cervi, F., Puccetti, C., Murano, P., Contoli, M., Capretti, M. G., Marsico, C., Faldella, G., Sansone, M., Martinelli, P., Agangi, A., Tibaldi, C., Trentini, L., Todros, T., Garetto, S., Brambilla, T., Savasi, V., Crepaldi, A., Giaquinto, C., Fiscon, M., Rinaldi, R., Bucceri, A., Matrone, R., Scaravelli, G., Fundaro, C., Genovese, O., Cafforio, C., Liuzzi, G., Tozzi, V., Massetti, Anna Paola, Anceschi, M., Casadei, A. M., Cavaliere, A. F., Finelli, V., Cellini, M., Castelli Gattinara, G., Marconi, A. M., Sacchi, V., De Pirro, A., Polizzi, C., Mattei, A., Pirillo, M. F., Amici, R., Galluzzo, C. M., Donnini, S., Baroncelli, S., Villani, P., Cusato, M., Cerioli, A., De Martino, M., Mastroiacovo, P., Moroni, M., Parazzini, F., Vella, S., Floridia, M, Ravizza, M, Masuelli, G, Dalzero, S, Pinnetti, C, Cetin, I, Meloni, A, Spinillo, A, Rubino, E, Francisci, D, Tamburrini, E, Italian Group on Surveillance on Antiretroviral Treatment in, Pregnancy, Martinelli, Pasquale, Floridia M, Ravizza M, Masuelli G, Dalzero S, Pinnetti C, Cetin I, Meloni A, Spinillo A, Rubino E, Francisci D, Tamburrini E, Faldella G, Guerra B, and for the Italian Group on Surveillance on Antiretroviral Treatment in Pregnancy

Subjects
Microbiology (medical), medicine.medical_specialty, antiretroviral therapy, MEDLINE, Human immunodeficiency virus (HIV), HIV Infections, body mass index, medicine.disease_cause, Settore MED/17 - MALATTIE INFETTIVE, Body Mass Index, BMI, weight gain, HIV-1, Pregnancy, Medicine, Humans, HIV infection, pregnancy, Pregnancy Complications, Infectious, business.industry, Obstetrics, Cesarean Section, Infectious, Pregnancy Outcome, HIV, medicine.disease, Pregnancy Complications, Infectious Diseases, Italy, National study, Female, medicine.symptom, business, Weight gain, Body mass index
Abstract

Although most of the women (69.4%) had a normal BMI at start of pregnancy, only 37% had an adequate weight gain during pregnancy. Inadequate body weight gain was more common (44.8%) than excessive weight gain (18.2%), but 40% of overweight women and 50% of obese women had an excessive weight gain in pregnancy, with about 9% of the women in these categories gaining >18 kg during pregnancy (Table 1). Only 1.9% of the women had a vaginal delivery; elective and nonelective cesarean deliveries accounted for 81.3% and 16.7% of deliveries, respectively. Compared to underweight/normal women, overweight/obese women had similar occurrences of preterm delivery (23.4% vs 22.7%, P = .871), significantly lower rates of low birthweight (14.2% vs 24.2%, P = .007) and nonelective cesarean deliveries (11.7% vs 18.3%, P = .042), and a significantly higher occurrence of fasting plasma glucose >92 mg/dL at 20–28 weeks (12.1% vs 6.6%, P = .027), hypertension during pregnancy (6.4% vs 2.7%, P = .019), and gestational age–adjusted birthweight >90th percentile (15.5% vs 5.0%, P < .001). Complications of delivery, major birth defects, and HIV transmission were similar between the 2 groups (7.3% vs 7.6%, P = .881; 2.6% vs 3.5%, P = .589; and 0.8% vs 0.5%, P = .661, respectively). An inadequate weight gain during pregnancy was associated with an increased risk of nonelective cesarean delivery (OR, 1.589 [95% CI, 1.077–2.346], P = .020). Excessive weight gain during pregnancy was not associated with either hypertension (OR, 1.364 [95% CI, .537–3.465], P = .514) or 20–28 week glucose level of >92 mg/dL (OR, 0.841 [95% CI, .399–1.772], P = .648), but was significantly associated with birthweight >90th percentile (OR, 2.271 [95% CI, 1.229–4.195], P = .009), and appeared to be protective against low birthweight (OR, 0.544 [95% CI, .323–.918], P = .023) and birthweight

Published
2013

38. Birth defects in a national cohort of pregnant women with HIV infection in Italy, 2001-2011

Author

Floridia, M., Mastroiacovo, P., Tamburrini, E., Tibaldi, C., Todros, T., Crepaldi, A., Sansone, M., Fiscon, M., Liuzzi, G., Guerra, B., Vimercati, A., Vichi, F., Vicini, I., Pinnetti, C., Marconi, A. M., Ravizza, M., Mori, F., Ortolani, P., dalle Nogare, E. R., Di Lorenzo, F., Sterrantino, G., Meli, M., Polemi, S., Nocentini, J., Baldini, M., Montorzi, G., Mazzetti, M., Rogasi, P., Borchi, B., Pinter, E., Anzalone, E., Marocco, R., Mastroianni, C., Mercurio, V. S., Carocci, A., Grilli, E., Maccabruni, A., Zaramella, M., Mariani, B., Natalini Raponi, G., Guaraldi, G., Luzi, K., Nardini, G., Stentarelli, C., Degli Antoni, A. M., Molinari, A., Crisalli, M. P., Donisi, A., Piepoli, M., Cerri, V., Zuccotti, G., Giacomet, V., Fabiano, V., Coletto, S., Placido, G., Vivarelli, A., Castelli, P., Savalli, F., Portelli, V., Sabbatini, F., Francisci, D., Bernini, L., Alberico, S., Maso, G., Tropea, M., Meloni, A., Dedoni, M., Cuboni, C., Ortu, F., Piano, P., Citernesi, A., Spinillo, A., Roccio, M., Miccolis, A., Bassi, E., Cervi, F., Puccetti, C., Murano, P., Contoli, M., Capretti, M. G., Marsico, C., Faldella, G., Martinelli, P., Agangi, A., Trentini, L., Masuelli, G., Garetto, S., Cetin, I., Brambilla, T., Savasi, V., Giaquinto, C., Rinaldi, R., Rubino, E., Bucceri, A., Matrone, R., Scaravelli, G., Fundaro, C., Genovese, O., Cafforio, C., Tozzi, V., Massetti, P., Anceschi, M., Casadei, A. M., Cavaliere, A. F., Finelli, V., Cellini, M., Castelli Gattinara, G., Dalzero, S., Sacchi, V., De Pirro, A., Polizzi, C., Mattei, A., Pirillo, M. F., Amici, R., Galluzzo, C. M., Donnini, S., Baroncelli, S., Regazzi, M., Villani, P., Cusato, M., Cerioli, A., De Martino, M., Moroni, M., Parazzini, F., Vella, S., Floridia, M, Mastroiacovo, P, Tamburrini, E, Tibaldi, C, Todros, T, Crepaldi, A, Sansone, M, Fiscon, M, Liuzzi, G, Guerra, B, Vimercati, A, Vichi, F, Vicini, I, Pinnetti, C, Marconi, A, Ravizza, M, Martinelli, Pasquale, and The Italian Group on Surveillance on Antiretroviral Treatment in, Pregnancy

Subjects
Male, HIV Infections, transcriptase inhibitors, Cohort Studies, chemistry.chemical_compound, Pregnancy, Prevalence, Birth Weight, Young adult, Pregnancy Complications, Infectious, education.field_of_study, Obstetrics, Coinfection, Antiretroviral therapy, birth defects, efavirenz, HIV, non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, pregnancy, protease inhibitors, women, Obstetrics and Gynecology, Abnormalities, Drug-Induced, Middle Aged, Italy, Maternal Exposure, Reverse Transcriptase Inhibitors, Female, Cohort study, Adult, medicine.medical_specialty, Efavirenz, Adolescent, Anti-HIV Agents, Birth weight, Population, Antiretroviral Therapy, Birth defects, HIV-1, Young Adult, Hepatitis B, Chronic, medicine, Humans, education, business.industry, Infant, Newborn, Odds ratio, Hepatitis C, Chronic, medicine.disease, Infectious Disease Transmission, Vertical, Surgery, Pregnancy Trimester, First, chemistry, business
Abstract

Objective We used data from a national study of pregnant women with HIV to evaluate the prevalence of congenital abnormalities in newborns from women with HIV infection. Design Observational study. Setting University and hospital clinics. Population Pregnant women with HIV exposed to antiretroviral treatment at any time during pregnancy. Methods The total prevalence of birth defects was assessed on live births, stillbirths, and elective terminations for fetal anomaly. The associations between potentially predictive variables and the occurrence of birth defects were expressed as odds ratios (ORs) with 95% confidence intervals (95% CIs) for exposed versus unexposed cases, calculated in univariate and multivariate logistic regression analyses. Main outcome measures Birth defects, defined according to the Antiretroviral Pregnancy Registry criteria. Results A total of 1257 pregnancies with exposure at any time to antiretroviral therapy were evaluated. Forty-two cases with major defects were observed. The total prevalence was 3.2% (95% CI 1.9–4.5) for exposure to any antiretroviral drug during the first trimester (23 cases with defects) and 3.4% (95% CI 1.9–4.9) for no antiretroviral exposure during the first trimester (19 cases). No associations were found between major birth defects and first-trimester exposure to any antiretroviral treatment (OR 0.94, 95% CI 0.51–1.75), main drug classes (nucleoside reverse transcriptase inhibitors, OR 0.95, 95% CI 0.51–1.76; non-nucleoside reverse transcriptase inhibitors, OR 1.20, 95% CI 0.56–2.55; protease inhibitors, OR 0.92, 95% CI 0.43–1.95), and individual drugs, including efavirenz (prevalence for efavirenz, 2.5%). Conclusions This study adds further support to the assumption that first-trimester exposure to antiretroviral treatment does not increase the risk of congenital abnormalities.

Published
2013

39. Changing patterns of clinical events in perinatally HIV-1-infected children during the era of HAART. The Italian Register for HIV Infection in Children

Author

WRITING COMMITTEE CHIAPPINI, E, Galli, L, Tovo, Pa, Gabiano, C, Lisi, C, Gattinara, Gc, Esposito, S, Viganò, A, Giaquinto, C, Rosso, R, Guarino, A, Osimani, DE MARTINO M. MEMBERS OF THE ITALIAN REGISTER FOR HIV INFECTION IN CHILDREN P., Cordiali, R., DE MATTIA, D., Manzionna, M., DI BARI, C., Ruggeri, M., Masi, M., Miniaci, A., Specchia, F., Ciccia, M., Lanari, M., Baldi, F., Battisti, L., Schumacher, R., Duse, M., Sinelli, M., Bennato, V., Dessì, C., Dedoni, M., Fenu, M. L., Cavallini, R., Anastasio, E., Zicchinella, D., Sticca, M., Pomero, G., Contiero, R., Fiumana, E., Gervaso, P., Gabrielli, G., Braccesi, G., Becherucci, S., DE GAUDIO, M., Innocenti, L., Cecchi, M. T., Ginocchio, F., Nicolini, L. A., Ciravegna, B. W., Cosso, D., Timitilli, A., Stronati, M., Plebani, A., Bojanin, J., Porta, A., Principi, N., Giacomet, V., Bianchi, R., Zuccotti, G. V., Giovannini, M., Ferraris, G., Lipreri, R., MORETTI MILANO, C., Cellini, M., Cano, M. C., Palazzi, G., Bruzzese, E., Giannattazio, A., Tarallo, L., Tancredi, F., D'Elia, R., Rampon, O., DALLE NOGARE, E. R., Sanfilippo, A., Romano, A., Saitta, M., Dodi, I., Barone, A., Consolini, Rita, Legitimo, Annalisa, Magnani, C., Falconieri, P., Fundarò, C., Salvucci, P. VALENTINI S., Casadei, A. M., Bernardi, S., Palma, P., Anzidei, M., Cerilli, S., Ajassa, C., Ganau, A., Cristiano, L., Mazza, A., Gentilini, L., Mignone, F., Versace, A., Antonielli, E., Sovatzis, S., Scolfaro, C., Palomba, E., Portelli, V., Rabusin, M., Pellegatta, A., and Fortunati, P.

Published
2007

40. Cancer rates after year 2000 significantly decrease in children with perinatal HIV infection: A study by the Italian Register for HIV Infection in Children

Author

Chiappini, E, Galli, L, Tovo, Pa, Gabiano, C, Lisi, C, Giaquinto, C, Rampon, O, Gattinara, Gc, De Marco, G, Osimani, P, Manzionna, M, Miniaci, A, Pintor, C, Rosso, R, Esposito, S, Viganò, A, Dodi, I, Maccabruni, A, Fundarò, C, de Martino, M, Osimani, P., Cordiali, R., De Mattia, D., Manzionna, M., Di Bari, C., Ruggeri, M., Masi, M., Miniaci, A., Specchia, F., Ciccia, M., Lanari, M., Baldi, F., Battisti, L., Fiorino, C., Dessı`, C., Pintor, C., Dedoni, M., Fenu, M. L., Cavallini, R., Anastasio, E., Merolla, F., Sticca, M., Pomero, G., Bezzi, Teresa Maria, Fiumana, Elisa, Bonsignori, F., Gervaso, P., Seini, E., Cecchi, M. T., Cosso, D., Timitilli, A., Stronati, M., Plebani, A., Pinzani, R., Bongianin, I., Vigano`, A., Giacomet, V., Erba, P., Salvini, F., Zuccotti, G. V., Giovannini, M., Ferraris, G., Lipreri, R., Moretti, C., Cellini, M., Cano, M. C., Paolucci, P., Bruzzese, E., De Marco, G., Tarallo, L., Tancredi, F., Pennazzato, M., Rampon, O., Dalle Nogare, E. R., Sanfilippo, A., Romano, A., Saitta, M., Dodi, I., Barone, A., Maccabruni, A., Consolini, R., Legitimo, A., Magnani, C., Falconieri, P., Fundaro`, C., Genovese, O., Panzanella, A., Casadei, A. M., Martino, A., Concato, C., Anzidei, G., Bove, G., Cerilli, S., Catania, S., Ajassa, C., Ganau, A., Cristiano, L., Mazza, A., Di Palma, A., Mignone, F., Riva, C., Scorfaro, C., Portelli, V., Rabusin, M., Pellegatta, A., Molesini, M., Chiappini, Elena, Galli, Luisa, Tovo, Pier-Angelo, Gabiano, Clara, Lisi, Catiuscia, Giaquinto, Carlo, Rampon, Osvalda, Gattinara, Guido Castelli, De Marco, Giulio, Osimani, Patrizia, Manzionna, Mariano, Miniaci, Angela, Pintor, Carlo, Rosso, Raffaella, Esposito, Susanna, Viganò, Alessandra, Dodi, Icilio, Maccabruni, Anna, Fundarò, Carlo, De Martino, Maurizio, Italian Register for HIV Infection in, Children, and Lanari, M.

Subjects
Registrie, Pediatrics, Cancer Research, Time Factors, HIV Infections, Antiretroviral Therapy, Highly Active, Neoplasms, HIV Infection, Registries, Sida, Child, biology, Incidence (epidemiology), Medicine (all), Incidence, Child, Preschool, Disease Progression, Humans, Infant, Infant, Newborn, Italy, Treatment Outcome, Oncology, symbols, Population study, Viral disease, Human, medicine.medical_specialty, cancer rates, HIV infection, children, Time Factor, Antiretroviral Therapy, symbols.namesake, Acquired immunodeficiency syndrome (AIDS), medicine, cancer, Highly Active, Poisson regression, Preschool, Settore MED/38 - Pediatria Generale e Specialistica, Perinatal HIV infection, business.industry, Cancer, Newborn, medicine.disease, biology.organism_classification, Italian Register for HIV infection in children, El Niño, Neoplasm, business
Abstract

Purpose To evaluate the impact of highly active antiretroviral therapy (HAART) on cancer incidence in HIV-infected children throughout a 20-year period. Patients and Methods An observational population study was conducted on 1,190 perinatally HIV-infected children enrolled onto the Italian Register for HIV Infection in Children from 1985 to 2004 and never lost to follow-up (total observation time, 10,037.66 years). Cancer rates were calculated in the pre-HAART (1985 to 1995), early HAART (1996 to 1999), and late HAART (2000 to 2004) periods and compared using Poisson regression adjusted for age. The proportion of HAART-treated children increased from 4.1% in 1996 to 60.4% in 1999 and to 81.5% in 2004. In the same time frame, the proportion of children receiving HAART for at least 2 years increased from 3.1% to 77.0%. Results Overall, 35 cancers occurred. Cancer rates were 4.49 (95% CI, 2.37 to 6.64), 4.09 (95% CI, 1.68 to 6.50), and 0.76 (95% CI, 0.00 to 1.80) per 1,000 children per year in 1985 to 1995, 1996 to 1999, and 2000 to 2004, respectively. Notably, there was no significant difference comparing the periods from 1985 to 1995 and 1996 to 1999 (P = .081). By contrast, cancer rates were significantly lower in the period from 2000 to 2004 than in 1996 to 1999 (P < .0001). Results were confirmed by separately analyzing data from children observed from birth (P = .418 for 1985 to 1995 v 1996 to 1999; P = .001 for 1996 to 1999 v 2000 to 2004). Conclusion Dramatically reduced cancer rates were observed only in the late HAART period in parallel to the increasing proportion of children receiving HAART therapy.

Published
2007

41. Virologic, immunologic, and clinical benefits from early combined antiretroviral therapy in infants with perinatal HIV-1 infection

Author

Chiappini, E., Galli, L., Atovo, P. i. e. r., Gabiano, C., Castelli Gattinara, G., Guarino, A., Baddato, R., Giaquinto, C., Lisi, C., de Martino, M., Osimani, P., Cordiali, R., De Mattia, D., Manzionna, M., Di Bari, C., Ruggeri, M., Masi, M., Miniaci, A., Specchia, F., Ciccia, M., Lanari, M., Baldi, F., Battisti, L., Fiorino, C., Dessı`, C., Pintor, C., Dedoni, M., Fenu, M. L., Cavallini, R., Anastasio, E., Merolla, F., Sticca, M., Pomero, G., Bezzi, Teresa Maria, Fiumana, Elisa, Bonsignori, F., Gervaso, P., Seini, E., Cecchi, M. T., Cosso, D., Timitilli, A., Stronati, M., Plebani, A., Pinzani, R., Bongianin, I., Vigano`, A., Giacomet, V., Erba, P., Salvini, F., Zuccotti, G. V., Giovannini, M., Ferraris, G., Lipreri, R., Moretti, C., Cellini, M., Cano, M. C., Paolucci, P., Bruzzese, E., De Marco, G., Tarallo, L., Tancredi, F., Pennazzato, M., Rampon, O., Dalle Nogare, E. R., Sanfilippo, A., Romano, A., Saitta, M., Dodi, I., Barone, A., Maccabruni, A., Consolini, R., Legitimo, A., Magnani, C., Falconieri, P., Fundaro`, C., Genovese, O., Panzanella, A., Casadei, A. M., Martino, A., Concato, C., Anzidei, G., Bove, G., Cerilli, S., Catania, S., Ajassa, C., Ganau, A., Cristiano, L., Mazza, A., Di Palma, A., Mignone, F., Riva, C., Scorfaro, C., Portelli, V., Rabusin, M., Pellegatta, A., Molesini, M., Chiappini, E, Galli, L, Tovo, Pa, Gabiano, C, Gattinara, Gc, Guarino, Alfredo, Baddato, R, Giaquinto, C, Lisi, C, and DE MARTINO, M.

Subjects
medicine.medical_specialty, Pediatrics, Anti-HIV Agents, medicine.medical_treatment, Immunology, combined antiretroviral therapy, CD4-CD8 Ratio, HIV Infections, HIV-1 infection, Asymptomatic, Drug Administration Schedule, Acquired immunodeficiency syndrome (AIDS), Immunopathology, Antiretroviral Therapy, Highly Active, Medicine, Immunology and Allergy, Humans, Sida, ART, infants, Chemotherapy, biology, business.industry, Age Factors, Infant, Viral Load, biology.organism_classification, medicine.disease, Infectious Disease Transmission, Vertical, Surgery, CD4 Lymphocyte Count, Infectious Diseases, Treatment Outcome, Child, Preschool, Lentivirus, Disease Progression, HIV-1, Viral disease, medicine.symptom, business, Epidemiologic Methods, Viral load
Abstract

Objective: To investigate the impact of early versus deferred combined antiretroviral treatment (ART) in asymptomatic or moderately symptomatic [Centers for Disease Control and Prevention (CDC) category N, A or B] infants with perinatal HIV-1 infection. Methods: A multi-centre nationwide case-control study was conducted. Data from 30 infants treated with combined ART with three or more drugs before 6 months of age were compared with data from 103 infants starting ART with three or more drugs after 6 months of age. The median follow-up time was 4.1 years (range, 1.0-6.5 years). Results: No difference was evident in the first available viral load and CD4 T-lymphocyte percentage between the two groups of children. Early-treated infants showed significantly lower viral loads than infants receiving deferred treatment at all the follow-up periods. A higher proportion of early-treated infants than infants receiving deferred treatment (73.3% versus 30.1%; P < 0.0001) reached an undetectable viral load. Higher CD4 T-lymphocyte percentages were found in early-treated infants at 13-24 (P < 0.0001), 25-36 (P < 0.0001), and 37-48 (P = 0.003) months of age. No early-treated infant versus 20 of 103 (19.4%) infants receiving deferred ART (P=0.02) showed a CD4 T-lymphocyte percentage of less than 15% at one time point during follow-up. No CDC category A, B or C clinical event occurred in early-treated infants over the follow-up period while 44 of 103 (42.7%) infants receiving deferred treatment presented a decline in the CDC category. Kaplan-Meier analyses revealed significant differences in CDC category A (P = 0.0002), B (P = 0.0003), and C (P = 0.0018) event-free survivals. Conclusion: The data suggest virologic, immunologic, and clinical benefits from early administration of ART.

Published
2006

42. Early triple therapy vs mono or dual therapy for children with perinatal HIV infection

Author

Chiappini, E, Galli, L, Gabiano, C, Tovo, Pa, de Martino, M, Osimani, P., Cordiali, R., De Mattia, D., Manzionna, M., Di Bari, C., Ruggeri, M., Masi, M., Miniaci, A., Specchia, F., Ciccia, M., Lanari, M., Baldi, F., Battisti, L., Fiorino, C., Dessı`, C., Pintor, C., Dedoni, M., Fenu, M. L., Cavallini, R., Anastasio, E., Merolla, F., Sticca, M., Pomero, G., Bezzi, Teresa Maria, Fiumana, Elisa, Bonsignori, F., Gervaso, P., Seini, E., Cecchi, M. T., Cosso, D., Timitilli, A., Stronati, M., Plebani, A., Pinzani, R., Bongianin, I., Vigano`, A., Giacomet, V., Erba, P., Salvini, F., Zuccotti, G. V., Giovannini, M., Ferraris, G., Lipreri, R., Moretti, C., Cellini, M., Cano, M. C., Paolucci, P., Bruzzese, E., De Marco, G., Tarallo, L., Tancredi, F., Pennazzato, M., Rampon, O., Dalle Nogare, E. R., Sanfilippo, A., Romano, A., Saitta, M., Dodi, I., Barone, A., Maccabruni, A., Consolini, R., Legitimo, A., Magnani, C., Falconieri, P., Fundaro`, C., Genovese, O., Panzanella, A., Casadei, A. M., Martino, A., Concato, C., Anzidei, G., Bove, G., Cerilli, S., Catania, S., Ajassa, C., Ganau, A., Cristiano, L., Mazza, A., Di Palma, A., Mignone, F., Riva, C., Scorfaro, C., Portelli, V., Rabusin, M., Pellegatta, A., Molesini, M., Chiappini E., Galli L., Gabiano C., Tovo P A., De Martino M., for the Italian Register for HIV Infection in Children: [.., Osimani P., Specchia F., Molesini M., and ]

Subjects
Perinatal HIV infection, Pediatrics, medicine.medical_specialty, HIV INFECTIONS, business.industry, Therapy, General Medicine, Virology, Perinatal hiv, medicine, INFANT, Dual therapy, business, MATERNAL-FETAL RELATIONS, DISEASE TRANSMISSION, ANTIHIV AGENTS
Abstract

The time at which antiretroviral therapy (ART) should be initiated in children with perinatal human immunodeficiencyvirus (HIV) infection remains controversial. In a cohort study, Berk et al1 reported clinical benefit from mono/dual ART started before 60 days of life in 10 children compared with treatment administered at 61 to 120 days of life in 16 children. The 23 children who received early triple ART were not investigated because none of them progressed to category C diagnosis by 3 years of age. We performed a similar analysis in a cohort study of a larger data set of children with a longer follow-up to evaluate the outcomes of early and very early triple ART.

Published
2006

43. The management of HCV infected pregnant women and their children European paediatric HCV network

Author

Pembrey, Lucy, Newell, Marie Louise, Tovo, Pier Angelo, Amoroso, A., Bevilaqua, E., Asensi Botet, F., Pereda, A., Balossini, V., Bona, G., Zaffaroni, M., Bandelloni, A., Coscia, A., Fabris, C., Aime, S., Belloni, C., Bossi, G., Salati, B., Boucher, C., Buffolano, W., Butler, K., Roura, L. Cabero, Sanges, J. M. Bertran, Cigna, P., Ciria, L. M., Ginard, C. Servera, Teruel, G. Claret, Fortuny, C., Coll, O., Corrias, A., Ledda, R., Floris, S., De Maria, A., Echeverria, J., Cilla, G., LANARI, MARCELLO, Tridapalli, E., Venturi, V., Fischler, B., Bohlin, A. B., Lindgren, S., Lindh, G., Giacomet, V., Merlo, M., Figini, C., Erba, P., Viganò, A., Hannam, S., Mieli Vergani, G., Hatzakis, A., Inchley, C., Fjaerli, H. O., Maccabruni, A., Marcellini, M., Sartorelli, M. R., Fontelos, P. Martin, Mazza, A., Mok, J. Y. Q., Mûr, A., Viñolas, M., Paternoster, D. M., Grella, P., Polywka, S., Quinti, I., Casadei, A. M., Rojahn, A., Berg, A., Rosso, R., Ferrando, S., Bassetti, D., Contreras, J. Ruiz, Manzanares, A., Extremera, A. Ruiz, Salvini, F., Zuccotti, G. V., Schmitz, T., Grosch Wörner, I., Sperling, C. Feiterna, Piening, T., Vegnente, A., Iorio, R., Versace, A., Lazier, L., Palomba, E., Gabiano, C., Balbo, L., Zanetti, A., Tanzi, E., FALDELLA, GIACOMO, Pembrey, L., Newell, M. L., Tovo, P. A., Amoroso, A., Bevilacqua, E., Asensi Botet, F., Pereda, A., Balossini, V., Bona, G., Zaffaroni, M., Bandelloni, A., Coscia, A., Fabris, C., Iorio, Raffaele, Vegnente, Angela, Pembrey, Lucy, Newell, Marie-Louise, Tovo, Pier-Angelo, Bevilaqua, E., Asensi-Botet, F., Aime, S., Belloni, C., Bossi, G., Salati, B., Boucher, C., Buffolano, W., Butler, K., Roura, L. Cabero, Sanges, J.M. Bertran, Cigna, P., Ciria, L.M., Ginard, C. Servera, Teruel, G. Claret, Fortuny, C., Coll, O., Corrias, A., Ledda, R., Floris, S., De Maria, A., Echeverria, J., Cilla, G., Faldella, Giacomo, Lanari, M., Tridapalli, E., Venturi, V., Fischler, B., Bohlin, A.-B., Lindgren, S., Lindh, G., Giacomet, V., Merlo, M., Figini, C., Erba, P., Viganò, A., Hannam, S., Mieli-Vergani, G., Hatzakis, A., Inchley, C., Fjaerli, H.O., Maccabruni, A., Marcellini, M., Sartorelli, M.R., Fontelos, P. Martin, Mazza, A., Mok, J.Y.Q., Mûr, A., Viñolas, M., Paternoster, D.M., Grella, P., Polywka, S., Quinti, I., Casadei, A.M., Rojahn, A., Berg, A., Rosso, R., Ferrando, S., Bassetti, D., Contreras, J. Ruiz, Manzanares, A., Extremera, A. Ruiz, Salvini, F., Zuccotti, G.V., Schmitz, T., Grosch-Wörner, I., Sperling, C. Feiterna, Piening, T., Vegnente, A., Iorio, R., Versace, A., Lazier, L., Palomba, E., Gabiano, C., Balbo, L., Zanetti, A., and Tanzi, E.

Subjects
Pediatrics, medicine.medical_specialty, Psychological intervention, Breastfeeding, Pregnancy, Prenatal Diagnosis, Diagnosis, medicine, Humans, Prospective Studies, Pregnancy Complications, Infectious, Prospective cohort study, Hepatitis C, Clinical management, Mother-to-child transmission, Paediatric, Follow-up, Hepatology, business.industry, Transmission (medicine), Gastroenterology, Infant, Newborn, virus diseases, Evidence-based medicine, medicine.disease, digestive system diseases, Infectious Disease Transmission, Vertical, Europe, Immunology, Female, Viral disease, business, Diagnosi
Abstract

Background/Aims: As evidence accumulates relating to mother-to-child (vertical) transmission of hepatitis C virus (HCV), it is timely to draw up guidelines for the clinical management of HCV infected pregnant women and their children. Methods: A review of evidence from the European Paediatric HCV Network (EPHN) prospective study of HCV infected women and their children and other published studies. Meeting of EPHN clinical experts to reach a consensus on recommendations for management. Each recommendation was graded according to the level of evidence. Results/conclusions: Although several risk factors for mother-to-child transmission have been identified, none are modifiable and there are currently no interventions available to prevent vertical transmission of HCV. Data on timing of loss of maternal antibodies and reliability of diagnostic tests inform the optimum follow-up schedule for confirmation or exclusion of infection in children born to HCV infected women. Based on the current evidence, routine antenatal screening for HCV should not be introduced and neither elective caesarean section nor avoidance of breastfeeding should be recommended to HCV infected women to prevent mother-to-child transmission of HCV. HCV/HIV co-infected women should follow existing HIV guidelines. © 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Published
2005

44. Lower mother-to-child HIV-1 transmission in boys is independent of type of delivery and antiretroviral prophylaxis. The Italian register for HIV intection in children

Author

Galli, L., Puliti, D., Chiappini, E., Gabiano, C., Tovo, P. A., Pezzotti, P., de Martino, M., Osimani, P., Cordiali, R., De Mattia, D., Manzionna, M., Di Bari, C., Ruggeri, M., Masi, M., Miniaci, A., Specchia, F., Ciccia, M., Lanari, M., Baldi, F., Battisti, L., Fiorino, C., Dessı`, C., Pintor, C., Dedoni, M., Fenu, M. L., Cavallini, R., Anastasio, E., Merolla, F., Sticca, M., Pomero, G., Bezzi, Teresa Maria, Fiumana, Elisa, Bonsignori, F., Gervaso, P., Seini, E., Cecchi, M. T., Cosso, D., Timitilli, A., Stronati, M., Plebani, A., Pinzani, R., Bongianin, I., Vigano`, A., Giacomet, V., Erba, P., Salvini, F., Zuccotti, G. V., Giovannini, M., Ferraris, G., Lipreri, R., Moretti, C., Cellini, M., Cano, M. C., Paolucci, P., Bruzzese, E., De Marco, G., Tarallo, L., Tancredi, F., Pennazzato, M., Rampon, O., Dalle Nogare, E. R., Sanfilippo, A., Romano, A., Saitta, M., Dodi, I., Barone, A., Maccabruni, A., Consolini, R., Legitimo, A., Magnani, C., Falconieri, P., Fundaro`, C., Genovese, O., Panzanella, A., Casadei, A. M., Martino, A., Concato, C., Anzidei, G., Bove, G., Cerilli, S., Catania, S., Ajassa, C., Ganau, A., Cristiano, L., Mazza, A., Di Palma, A., Mignone, F., Riva, C., Scorfaro, C., Portelli, V., Rabusin, M., Pellegatta, A., and Molesini, M.

Subjects
infant's gender, vertical transmission, antiretroviral prophylaxis
Published
2005

45. Persistently high IgA serum levels are a marker of immunological or virological failure of combined antiretroviral therapy in children with perinatal HIV-1 infection

Author

Chiappini, E., Galli, L., Tovo, P. A., Gabiano, C., de Martino, M., Osimani, P., Cordiali, R., De Mattia, D., Manzionna, M., Di Bari, C., Ruggeri, M., Masi, M., Miniaci, A., Specchia, F., Ciccia, M., Lanari, M., Baldi, F., Battisti, L., Fiorino, C., Dessı`, C., Pintor, C., Dedoni, M., Fenu, M. L., Cavallini, R., Anastasio, E., Merolla, F., Sticca, M., Pomero, G., Bezzi, Teresa Maria, Fiumana, Elisa, Bonsignori, F., Gervaso, P., Seini, E., Cecchi, M. T., Cosso, D., Timitilli, A., Stronati, M., Plebani, A., Pinzani, R., Bongianin, I., Vigano`, A., Giacomet, V., Erba, P., Salvini, F., Zuccotti, G. V., Giovannini, M., Ferraris, G., Lipreri, R., Moretti, C., Cellini, M., Cano, M. C., Paolucci, P., Bruzzese, E., De Marco, G., Tarallo, L., Tancredi, F., Pennazzato, M., Rampon, O., Dalle Nogare, E. R., Sanfilippo, A., Romano, A., Saitta, M., Dodi, I., Barone, A., Maccabruni, A., Consolini, R., Legitimo, A., Magnani, C., Falconieri, P., Fundaro`, C., Genovese, O., Panzanella, A., Casadei, A. M., Martino, A., Concato, C., Anzidei, G., Bove, G., Cerilli, S., Catania, S., Ajassa, C., Ganau, A., Cristiano, L., Mazza, A., Di Palma, A., Mignone, F., Riva, C., Scorfaro, C., Portelli, V., Rabusin, M., Pellegatta, A., Molesini, M., Chiappini E., Galli L., Tovo PA., Gabiano C., de Martino M., Osimani P, Masi M., Specchia F., Molesini M., and The Italian Register for HIV Infection in Children

Subjects
Adolescent, Anti-HIV Agents, Immunology, HIV Infections, HIV-1 infection, Perinatal hiv, Antiretroviral Therapy, Highly Active, Clinical Studies, Immunology and Allergy, Medicine, Humans, Treatment Failure, Child, viremia, business.industry, combinedantiretroviral therapy, hyper-IgA, Infant, Newborn, Normal population, Infant, Viral Load, Antiretroviral therapy, Virological failure, Infectious Disease Transmission, Vertical, CD4 Lymphocyte Count, Immunoglobulin A, Child, Preschool, HIV-1, Drug Monitoring, business, Viral load, Biomarkers, Follow-Up Studies
Abstract

Summary Non-expensive and low-complexity surrogate markers for monitoring the response to combined antiretroviral therapy (combined-ART) are needed in poor-resource settings where routine assessment of CD4+ T-lymphocyte count and viral load can not be afforded. We longitudinally evaluated Ig serum levels in 234 HIV-1 infected children receiving combined-ART with ≥ 3 drugs. Since Ig levels physiologically vary with age, differences at different age periods were evaluated as differences in z-scores calculated using the mean and standard deviation of the normal population for each age period. Data from 17 (7·3%) children with immunological failure and from 54 (23·1%) children with virological failure of combined-ART were compared with data from not-failed children. At baseline children with immunological failure showed higher IgM z-scores (P = 0·042) than children without. After 3–12 months of therapy immunologically failed children displayed higher viral loads (P < 0·0001) and IgA (P = 0·043) z-scores than not-failed children. Similarly, at the same follow-up time, children with virological failure showed lower CD4+ T-lymphocyte percentages (P = 0·005) and higher IgA z-scores (P < 0·0001) than not-failed children. No difference in IgG or IgM z-scores was evidenced between failed and not-failed children after 3–12 months of therapy. In conclusion, IgA serum level is a cheap and low-complexity marker of immunological or virological failure of combined-ART which might be adopted in poor-resource settings.

Published
2005

49. Soluble interleukin 2 receptors in polymyalgia rheumatica/giant cell arteritis. Clinical and laboratory correlations

Author

Carlo Salvarani, Macchioni, P., Boiardi, L., Rossi, F., Casadei Maldini, M., Mancini, R., Beltrandi, E., Spacca, C., Lodi, L., and Portioli, I.

Subjects
Male, Giant Cell Arteritis, Receptors, Interleukin-2, Blood Sedimentation, Middle Aged, C-Reactive Protein, Polymyalgia Rheumatica, Receptors, Humans, Prednisone, Interleukin-2, Biological Markers, Female, Aged, Biomarkers
Abstract

Serum levels of soluble interleukin 2 receptors (sIL-2R) were measured in 21 patients with polymyalgia rheumatica (PMR)/giant cell arteritis (GCA) prior to steroid treatment. These levels were significantly elevated in patients with PMR/GCA compared with healthy controls (p = 0.002). A significantly longer duration of morning stiffness (p = 0.005) was observed in patients with a high concentration of sIL-2R. A significant correlation was observed at diagnosis between sIL-2R and erythrocyte sedimentation rate (ESR) (p = 0.01) and between ESR and C-reactive protein (CRP) (p = 0.005). We investigated prospectively a group of 10 patients over a period of 6 months of prednisone therapy. At the end of the study sIL-2R levels fell significantly compared to pretreatment values (p = 0.02), but remained significantly higher compared to controls (p = 0.02). ESR and CRP values also fell significantly compared to pretreatment levels (p = 0.0001 in both cases). We observed a significant correlation between the decrease in ESR values and the decrease in sIL-2R and CRP levels after 6 weeks (p = 0.01 in both cases) and after 6 months of therapy (p = 0.002 and p = 0.05). sIL-2R may be considered a useful serologic marker for monitoring response to steroid therapy in patients with PMR/GCA. This laboratory variable correlated more closely with ESR than with CRP. The presence of elevated levels of sIL-2R is likely to reflect T cell activation occurring in PMR/GCA. T lymphocyte activation persisted after 6 months of steroid therapy, despite rapid and continuous control of disease manifestations.

Published
1992

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