Fattori genetici coinvolti nella trasmissione del virus HIV-1

2010/2011Nel mondo la quasi totalità delle infezioni pediatriche da HIV-1 avvengono per trasmissione verticale. È stata dimostrata l’importanza dei fattori genetici dell’ospite, in particolare quelli legati all’immunità innata, nella suscettibilità alla trasmissione verticale dell’HIV. Un ruolo rilevante in questo senso, sembra essere determinato dai recettori DC-SIGN (dendritic cell-specific intracellular adhesion molecules-3 (ICAM-3)-grabbing non-integrin) e L-SIGN (liver/lymph node-specific intracellular adhesion molecules-3 (ICAM-3)-grabbing non-integrin), mediatori della cattura virale da parte delle cellule dendritiche e dei macrofagi specializzati a livello di placenta che potrebbero contribuire a spiegare la suscettibilità/protezione all’infezione da HIV-1. Un’altra proteina dell’immunità innata importante nella protezione immunitaria del feto e del bambino è la proteina legante il mannosio, MBL (mannose binding lectin): prodotta nella fase acuta dell’infezione, è in grado di mediare la cattura del virus rappresentando anch’essa un fattore di suscettibilità/protezione alla trasmissione verticale. In questo lavoro di tesi si è deciso di studiare polimorfismi con un ruolo (presunto o comprovato) funzionale nei due geni codificanti per DC-SIGN e L-SIGN, in una popolazione pediatrica del nord- est brasiliano esposta al virus HIV-1, allo scopo di individuare un loro eventuale coinvolgimento nella trasmissione verticale del virus HIV-1. Come popolazione controllo sono stati selezionati bambini della stessa etnia, senza esposizione nota al virus. Gli stessi polimorfismi sono stati successivamente analizzati in una popolazione italiana costituita da soggetti adulti sieropositivi e soggetti sieronegativi senza esposizione nota al virus, per verificare l’eventuale coinvolgimento dei due geni anche nella trasmissione orizzontale dell’HIV-1. Inoltre, sono stati studiati cinque diversi polimorfismi nel gene MBL2, in un gruppo di bambini africani nati da madri sieropositive per HIV-1, reclutati per lo studio “Zambia Exclusive Breastfeeding Study” con lo scopo di definire un ruolo di questi SNPs nella trasmissione verticale, ed in particolare relativamente al tipo di trasmissione: intrauterina, intrapartum o post-partum (attraverso l’allattamento al seno). Da questo studio è emerso che i geni codificanti per DC-SIGN e L-SIGN possono rivestire un ruolo nella trasmissione verticale del virus HIV-1 nella popolazione pediatrica brasiliana da noi studiata, dal momento che polimorfismi localizzati nella regione del promotore di DC-SIGN (-871G/G, -336G/G, -201G/T, -201T, -139G e -139G/G) e nell’esone 4 di L-SIGN (genotipi 5/5, 6/6 e genotipi omozigoti) sono risultati essere plausibili marcatori di protezione/suscettibilità per l’infezione verticale. Inoltre, uno di questi polimorfismi di DC-SIGN (-336G/A) è un possibile marcatore di rischio/suscettibilità anche per l’infezione orizzontale di HIV-1 nella popolazione italiana da noi analizzata, così pure come un ulteriore polimorfismo nell’esone 5 di L-SIGN (rs2277998). Anche per quanto riguarda MBL2, è stato confermato un ruolo di questo gene nella trasmissione verticale del virus, in particolare si è vista un’associazione ad una particolare modalità di trasmissione verticale: nella popolazione pediatrica africana da noi analizzata, infatti, essere portatori della allele mutato A e del genotipo G/A al codone 54, è risultato essere un fattore di rischio per l’acquisizione dell’infezione intrauterina, così come la variante allelica 0 (ed i genotipi A/0 e 0/0) si associa ad una maggiore suscettibilità all’infezione intrauterina da HIV-1 in presenza di conta linfocitaria (CD4+) materna inferiore a 350 mmc. Chiarire come queste molecole intervengono nelle diverse modalità di trasmissione potrà essere utile al clinico al fine di individuare nuovi target terapeutici.XXIV Cicl

Estimation of biological parameters for germination of Abutilon theophrasti Medik.

Background and Purpose: Velvetleaf seed longevity and prolonged emergence complicate assessing appropriate time for its control. Estimating biological parameters (base temperature and base water potential) is a first step towards development of emergence predictive model for this weed species in summer crops. Since, development of new model is time consuming, the aim of the research was to provide the data set of biological thresholds for Croatian ecotype and then to compare it with Italian velvetleaf thresholds to assess the implementation of AlertInf predictive weed emergence model from Italy to Croatia. Materials and methods: Laboratory experiments were conducted with 100 seeds per three replicates at seven constant temperatures (4, 8, 12, 16, 20, 24, 28°C) to estimate base temperature (Tb) and at seven water stress levels (0.00, -0.05, -0.10, -0.25, -0.38, -0.50, -0.80, -1.00 MPa) to estimate base water potential (Ψb). Results: The highest germination occurred at temperature > 20°C with 3.6 days and at water stress level >- 0.25 MPa with 4.9 days to complete 50% of germination (t50). The slowest t50 occurred at 4°C (41.9 days) and b) and – 0.67 MPa (Ψb) with no significant difference compared to Italian ecotype, according to 95% confidence intervals overlapping. Conclusion: The results indicate that it could be possible to implement AlertInf model from Italy to Croatia for this weed species without additional adjustment. Nevertheless, next step of this implementation should include validation of estimated results in the field conditions.    Key words: invasive weed species, velvetleaf, germination modelling, integrated weed management, base temperature, base water potential</p

Spectrally multimode squeezed states generation at telecom wavelengths

We report on the experimental demonstration of a source that generates spectrally multimode squeezed states of light over the infrared C-Band. This is achieved using a single-pass Spontaneous Parametric Down Conversion (SPDC) process in a periodically-poled KTP waveguide that is pumped with the second harmonic of a femtosecond laser. Our measurements show significant squeezing in more than 21 frequency modes, with a maximum squeezing value over 2.5 dB. Moreover, we demonstrate multiparty entanglement across 8 individual frequency bands by measuring the covariance matrix of their quadratures. Finally, we use reconfigurable mode-selective homodyne detection to mold the output into cluster states of various shapes. This result paves the way for the implementation of continuous variable quantum information protocols at telecommunication wavelengths, with applications in multiparty, entanglement-based quantum communication and computation

Letter to the Editor: Acute Effects of Intravenous Administration of Pamidronate in Patients with Osteoporosis

We read the interesting article “Acute Effects of Intravenous Administration of Pamidronate in Patients with Osteoporosis” in the Journal of Korean Medical Science by Lim et al. (1). We would like to comment and compare these data to a study recently published by our research group (2). The two studies had different initial aims, but still they share the same results in determining the modulatory effect of inflammation of aminobisphosphonates, such as pamidronate. The pamidronate belongs to the family of aminobisphosphonates (N-BPs), currently the major class of drugs used for the treatment of osteoporosis and other diseases characterized by increased bone resorption. The immune modulation exerted by pamidronate has not yet fully been understood (3). In vitro experiments have shown an anti-inflammatory effect of this N-BP; (4, 5) as well as a pro-inflammatory one (6, 7). Moreover contrasting results were obtained when pamidronate was used for the treatment of different inflammatory or immunologic diseases, such as rheumatoid arthritis (8,9) or systemic sclerosis. The aminobiphosphonates act on farnesylpyrophosphate synthase (FPPS) and inhibit the mevalonate pathway, the latter being responsible for production of cholesterol and isoprenoid lipids. In particular we can hypothesize that the inflammatory phenotype is due to lack of enzymes downstream the FPPS, and in particular the lack of geranylgeranyl-pyrophosphate (GGPP) could be associated to the activation of caspase-1 and the high IL-1β release. Lim et al. (1) emphasized that in vivo infusion of pamidronate at a therapeutic dose of 30 mg increased production of two inflammatory cytokines, IL-6 and TNF-α in serum. The increase is an acute effect after intravenous injection (1). Recently, our group demonstrated that pamidronate is able to increase the sensitivity to bacterial compounds both in the murine macrophagic cell line (Raw 264.7) and in Balb/c mice, by an incremental release of IL1β. These findings are in agreement with published data concerning inflammatory modulation in alendronate treated-mice (2). Moreover the effect of pamidronate does not depend on its concentration, whereas it may be involved in the increase of susceptibility to pro-inflammatory compounds such as muramildipeptide or lipopolysaccaride (2). In summary, we agree with the study by Lim et al. (1) and we emphasize the pivotal role of pamidronate in the modulation of inflammatory response

Upper limb function in Duchenne muscular dystrophy: 24 month longitudinal data

The aim of the study was to establish 24 month changes in upper limb function using a revised version of the performance of upper limb test (PUL 2.0) in a large cohort of ambulant and non-ambulant boys with Duchenne muscular dystrophy and to identify possible trajectories of progression. Of the 187 patients studied, 87 were ambulant (age range: 7\u201315.8 years), and 90 non-ambulant (age range: 9.08\u201324.78). The total scores changed significantly over time (p&lt;0.001). Non-ambulant patients had lower total scores at baseline (mean 19.7) when compared to the ambulant ones (mean 38.4). They also had also a bigger decrease in total scores over 24 months compared to the ambulant boys (4.36 vs 2.07 points). Multivariate model analysis showed that the Performance of Upper Limb changes reflected the entry level and ambulation status, that were independently associated to the slope of Performance of Upper Limb changes. This information will be of help both in clinical practice and at the time of designing clinical trials

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries