Trends of hospitalisations rates in a cohort of HIV-infected persons followed in an Italian hospital from 1998 to 2016.

Here we evaluated hospitalisation rates and associated risk factors of human immunodeficiency virus (HIV)-infected individuals who were followed up in an Italian reference hospital from 1998 to 2016. Incidence rates (IR) of hospitalisations were calculated for five study periods from 1998 to 2016. The random-effects Poisson regression model was used to assess risk factors for hospitalisation including demographic and clinical characteristics. To consider that more events may occur for the same subject, multiple failure-time data analysis was also performed for selected causes using the Cox proportional hazards model. We evaluated 2031 patients. During 13 173 person-years (py) of follow-up, 3356 hospital admissions were carried out for 756 patients (IR: 255 per 1000 py). IR decreased significantly over the study period, from 634 in 1998-2000 to 126 per 1000 py in 2013-2016. Major declines were detected for AIDS-defining events, non-HIV/AIDS-related infections and neurological diseases. Older age, female sex, longer HIV duration and HCV coinfection were associated with a higher hospitalisation risk, whereas higher CD4 nadir and antiretroviral therapy were associated with a reduced risk. Influence of advanced HIV disease markers declined over time. Hospitalisation rates decreased during the study period in most causes. The relative weight of hospitalisations for non-AIDS-related tumours, cardiovascular, respiratory and kidney diseases increased during the study period, whereas those for AIDS-defining events declined.

Diferente captación de 123I-MIBG en los 2 lóbulos hepáticos principales: un misterio persistente sin resolver / Different uptake of 123I-MIBG in the two main liver lobes: A persistant unsolved mistery

Objetivo: Después de la inyección del radiofármaco se observa con frecuencia una concentración incrementada de 123I-MIBG en el lóbulo hepático izquierdo en comparación con el derecho, pero la razón de este hallazgo sigue siendo desconocida. Nuestro objetivo fue analizar retrospectivamente el patrón de absorción de 123I-MIBG entre los 2 lóbulos hepáticos y correlacionar nuestros resultados con algunas características epidemiológicas/clínicas. Material y métodos: Se seleccionaron 94 gammagrafías 123I-MIBG de 71 pacientes. Las regiones de interés se dibujaron en los lóbulos derecho e izquierdo utilizando secciones tomográficas transversales y se calcularon relaciones de actividad de izquierda a derecha (relación I/D) a las 6 y 24horas de la administración del radiofármaco. Resultados: Veintisiete exámenes fueron positivos para lesiones hipermetabólicas, mientras que los 67 restantes fueron negativos. En todos los casos las relaciones medias de I/D temprana y tardía fueron superiores a 1; la relación I/D temprana media fue de 1,37 y la relación I/D tardía de 1,52. La relación I/D tardía fue significativamente mayor que la precoz. No hubo diferencias en la relación I/D con respecto a la edad, sexo, enfermedad primaria y resultado de la gammagrafía. Conclusiones: La absorción de 123I-MIBG fue mayor en el lóbulo hepático izquierdo en comparación con el derecho, y esta relación no se correlacionó con ninguna característica epidemiológica o clínica. La razón de este metabolismo todavía no se ha explicado, y algunas hipótesis biomoleculares podrían ser probadas en modelos 3D dinámicos in vitro

Purpose: After radiopharmaceutical injection, a heightened 123I-MIBG concentration is frequently observed in the left hepatic lobe compared to the right one, but the reason of this finding remains unknown. Our aim was to retrospectively analyze the different 123I-MIBG uptake pattern between the two hepatic lobes and correlate our results with some epidemiological/clinical features. Material and methods: Ninety-four 123I-MIBG scintigraphies from 71 patients were selected. Regions of interest were drawn in the right and left lobes using transverse tomographic sections and left to right activity ratios (L/R ratio) were calculated at 6 and 24h after radiotracer administration. Results: Twenty-seven examinations were positive for hypermetabolic lesions while the remaining 67 were negative. In all cases mean early and delayed L/R ratios were greater than 1.00; average early L/R ratio was 1.37 and delayed L/R ratio 1.52. The delayed L/R ratio was significantly higher than the early one. There was no difference in the L/R ratios with regard to age, gender, primary disease and result of scintigraphy. Conclusions: 123I-MIBG uptake was higher in left hepatic lobe compared to right and this ratio did not correlate with any epidemiological or clinical feature. The reason of this metabolic is not yet explained and some biomolecular hypotheses could be tested in 3D dynamic in vitro models

Different uptake of 123I-MIBG in the two main liver lobes: A persistant unsolved mistery. / Diferente captación de 123I-MIBG en los 2 lóbulos hepáticos principales: un misterio persistente sin resolver.

PURPOSE: After radiopharmaceutical injection, a heightened 123I-MIBG concentration is frequently observed in the left hepatic lobe compared to the right one, but the reason of this finding remains unknown. Our aim was to retrospectively analyze the different 123I-MIBG uptake pattern between the two hepatic lobes and correlate our results with some epidemiological/clinical features. MATERIAL AND METHODS: Ninety-four 123I-MIBG scintigraphies from 71 patients were selected. Regions of interest were drawn in the right and left lobes using transverse tomographic sections and left to right activity ratios (L/R ratio) were calculated at 6 and 24h after radiotracer administration. RESULTS: Twenty-seven examinations were positive for hypermetabolic lesions while the remaining 67 were negative. In all cases mean early and delayed L/R ratios were greater than 1.00; average early L/R ratio was 1.37 and delayed L/R ratio 1.52. The delayed L/R ratio was significantly higher than the early one. There was no difference in the L/R ratios with regard to age, gender, primary disease and result of scintigraphy. CONCLUSIONS: 123I-MIBG uptake was higher in left hepatic lobe compared to right and this ratio did not correlate with any epidemiological or clinical feature. The reason of this metabolic is not yet explained and some biomolecular hypotheses could be tested in 3D dynamic in vitro models.

Incidental meningioma detected by using 99mTc-MIBI SPECT/CT / Detección incidental de meningioma con 99mTc-MIBI SPECT/TC

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The persistent problem of late HIV diagnosis in people with AIDS: a population-based study in Italy, 1999-2013.

OBJECTIVES: Despite the wide accessibility to free human immunodeficiency virus (HIV) testing and combined antiretroviral therapy (cART), late HIV diagnosis remains common with severe consequences at individual and population level. This study aimed to describe trends of late HIV testing and to identify their determinants in the late cART era in Italy. STUDY DESIGN: We conducted a population-based, nationwide analysis of the Italian National AIDS Registry data (AIDS - acquired immune deficiency syndrome) for the years 1999-2013. METHODS: Late testers (LTs) were defined as people with AIDS (PWA) whose first HIV-positive test preceded AIDS diagnosis by 3 months or less. Odds ratios (ORs) with the corresponding 95% confidence intervals (CIs) were estimated to examine factors associated with being LTs. Joinpoint analysis was used to estimate annual percent changes (APCs) of LTs' proportion over time. RESULTS: Among 20,753 adult PWA, 50.8% were LTs. Italian PWA showed a lower proportion of LTs than non-Italian PWA (46.5% vs 68.2%). Among Italian PWA, the odds of being LTs was higher in men than in women (OR = 2.62, 95% CI: 2.38-2.90); in the age groups below 35 years and over 49 years at diagnosis (OR = 1.24, 95% CI: 1.12-1.37 and OR = 1.51, 95% CI: 1.38-1.67, respectively) vs PWA aged 35-49 years; and in those infected through sexual contact as compared with injecting drug use (OR = 13.34, 95% CI: 12.06-14.76 for heterosexual contact and OR = 8.13, 95% CI: 7.30-9.06 for male-to-male sexual contact). The proportion of LTs increased over time among Italians, especially in the latest period (APC2006-2013 = 5.3, 95% CI: 3.8-6.9). The LTs' proportion resulted higher, though stable, among PWA aged ≥50 years. Conversely, an increasing trend was observed among PWA aged 18-34 years (APC = 5.3, 95% CI: 4.5-6.1). The LTs' proportion was persistently higher among PWA who acquired HIV infection through sexual contact, even if a marked increase among injecting drug users was observed after 2005 (APC = 11.4, 95% CI: 5.7-17.5). CONCLUSIONS: The increasing trend of LTs' proportion in the late cART era highlights the need of new strategies tailored to groups who may not consider themselves to be at a high risk of infection. Active promotion of early testing and continuous education of infection, especially among young people, need to be implemented.

Epidemiological and clinical characteristics and behaviours of individuals with newly diagnosed HIV infection: a multicentre study in north Italy.

INTRODUCTION: We aimed to investigate socio-demographic, clinical and epidemiological characteristics and behaviours of subjects with new HIV diagnosis. METHODS: We carried out a multi-centre cross-sectional study comprising 17 infectious diseases units in the Lombardy Region, North Italy. All subjects with a first positive test for HIV infection examined in 2008-09 were interviewed using a structured questionnaire. RESULTS: 472 patients were enrolled (mean age 39.8 years, standard deviation [SD] 11.5), mostly males (78%), and born in Italy (77%). The most common routes of HIV transmission were heterosexual intercourse (49%) and sex among men who have sex with men (MSM) (40%). Never/sometimes use of a condom with occasional partners was associated with male gender, heterosexual transmission route, and with >10 sexual partners in their lifetime. 47% had previous HIV negative tests. Having had more than 2 previous HIV negative tests was associated with younger age, MSM transmission route, CD4+ lymphocyte count >350/microl and self-perception of risk. DISCUSSION: This study shows that there is a large portion of the adult population, especially heterosexual men aged 45 years and over, who are at high risk of acquiring and transmitting HIV infection and undergoing the HIV diagnostic test late, due to risk behaviours combined with a low perception of being at risk. Compared to people infected by heterosexual contacts, MSM show a greater awareness of being at risk of infection, but this knowledge has a low impact in reducing at-risk behaviours.

Few Italian drug users undergo HIV testing.

We estimated the proportion of drug users at treatment centres in Italy who had undergone HIV testing and the correlates of testing. Of the 1,917 drug injectors, 37.4% had been tested in the current year; of the 665 non-injectors, 28% had been tested. Among injectors, testing was associated with: being older than 35, foreign nationality, residing in central Italy, drug use for over 2 years, and having undergone both pharmacological and psychological treatment. Among non-injectors, an association was found for foreign nationality and not having been treated at other facilities. The results stress the need to facilitate access to testing.

[Proportion of drug users in treatment who have never undergone serological testing for HIV, HBV and HCV and correlates of failure to undergo testing: Italy, 2005-2007]. / Proporzione di tossicodipendenti in trattamento che non hanno mai eseguito i test sierologici per HIV, HBV e HCV e fattori correlati alla mancata esecuzione: Italia, 2005-2007.

In Italy, although the most recent guidelines stress the importance of screening for the human immunodeficiency virus (HIV) and the hepatitis B and C viruses (HBV and HCV) those subjects considered to be at high risk (e.g., injecting drug users), not all drug users being treated at public drug dependency centres are regularly tested for these infections. The results of the present study show that 7.2%, 13.0%, and 7.4% of injecting drug users seeking treatment at public drug dependency centres are not tested for, respectively, HIV, HBV and HCV infections and while corresponding figures for drug users who do not inject drugs are 20.3%, 25.1% and 16.2%. The failure to undergo testing among injectors was associated with a shorter history of drug use and with drug centres in central or southern Italy; these associations were also found among non-injectors, with the addition of low level of education. The results stress the importance of facilitating access to testing, of providing the drug dependency centres with the necessary resources for taking blood samples at the centres themselves, of making access to (and performance of) testing uniform throughout the country, and of removing obstacles that can lead to the drug user's refusal to undergo testing.

Tyrosine phosphorylation inhibits the interaction of 14-3-3 proteins with the plant plasma membrane H+-ATPase.

Interaction of 14-3-3 proteins with their targets depends not only on the phosphorylation status of the target but also on that of 14-3-3 (Fu et al., 2000). In this work we demonstrated that the maize 14-3-3 isoform GF14-6 is a substrate of the tyrosine kinase insulin growth factor receptor 1. By means of site-directed mutants of GF14-6, we identified Tyr-137 as the specific tyrosine residue phosphorylated by the insulin growth factor receptor 1. Phosphorylation of GF14-6 on Tyr-137 lowered its affinity for a peptide mimicking the 14-3-3 binding site of the plant plasma membrane H+-ATPase. Moreover, phosphorylation in planta of 14-3-3 tyrosine residues, resulting from incubation with the tyrosine phosphatase inhibitor, phenylarsine oxide, decreased their association to the H+-ATPase.

Adenosine 5'-monophosphate inhibits the association of 14-3-3 proteins with the plant plasma membrane H(+)-ATPase.

Although a well ascertained evidence proves that the activity of the plant plasma membrane H(+)-ATPase is regulated by 14-3-3 proteins, information about physiological factors modulating the phosphorylation-dependent association between 14-3-3 proteins and the proton pump is largely incomplete. In this paper we show that the 5'-AMP-mimetic, 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), inhibits the fusicoccin-promoted proton extrusion in maize roots. We also demonstrate that 5'-AMP inhibits the association of 14-3-3 proteins with the C-terminal domain of the H(+)-ATPase in an overlay assay as well as the 14-3-3-dependent stimulation of the Arabidopsis thaliana H(+)-ATPase AHA1 isoform expressed in yeast membranes. Finally, by means of affinity chromatography with immobilized 5'-AMP and trinitrophenyl-AMP fluorescence analysis, we demonstrate that the 14-3-3 isoform GF14-6 from maize is able to bind 5'-AMP. The possible role of 5'-AMP as a general regulator of 14-3-3 functions in the plant cell is discussed.

Phosphorylation-dependent interaction between plant plasma membrane H(+)-ATPase and 14-3-3 proteins.

The H(+)-ATPase is a key enzyme for the establishment and maintenance of plasma membrane potential and energization of secondary active transport in the plant cell. The phytotoxin fusicoccin induces H(+)-ATPase activation by promoting the association of 14-3-3 proteins. It is still unclear whether 14-3-3 proteins can represent natural regulators of the proton pump, and factors regulating 14-3-3 binding to the H(+)-ATPase under physiological conditions are unknown as well. In the present study in vivo and in vitro evidence is provided that 14-3-3 proteins can associate with the H(+)-ATPase from maize roots also in a fusicoccin-independent manner and that the interaction depends on the phosphorylation status of the proton pump. Furthermore, results indicate that phosphorylation of H(+)-ATPase influences also the fusicoccin-dependent interaction of 14-3-3 proteins. Finally, a protein phosphatase 2A able to impair the interaction between H(+)-ATPase and 14-3-3 proteins was identified and partially purified from maize root.

Immigration and health: the Italian National Focal Point experience.

This report is a description of the situation of migrant populations in Italy. It was written by a committed team of experts from public institutions, non-governmental organisations (NGO) and volunteer associations that for three years have been part of the Italian National Focal Point (NFP) within the European Project "AIDS & Mobility", which is being co-ordinated by the Netherlands Institute for Health Promotion and Disease Prevention (the Netherlands) and financed by the European Commission DG/V. This year the Italian National Focal Point, co-ordinated by the Telefono Verde AIDS of the Istituto Superiore di Sanità, has produced a second report (the first one was published in 1998) on health issues related to migrant populations. Besides providing an updated picture on the presence of foreigners in Italy, such report illustrates the present legislative situation within the sanitary area and some interventions regarding prevention, treatment and rehabilitation provided by each structure in the Italian NFP to foreign citizens. The initiatives carried out during the year 1999 by public institutions, NGO and volunteer associations are also reported in order to detect the psycho-social-sanitary needs of immigrants and target prevention programmes to their particular and specific needs.

Corpeptins, new bioactive lipodepsipeptides from cultures of Pseudomonas corrugata.

The structure of the corpeptins, bioactive lipodepsipeptides produced in culture by Pseudomonas corrugata, the causal agent of tomato pith necrosis, has been determined. The combined use of FAB-mass spectrometry, NMR spectroscopy and chemical procedures has allowed us to assign the following primary structure to the peptide moiety: Dhb-Pro-Ala-Ala-Ala-Val-Val-Dhb-Hse-Val-alle-Dhp-Ala-Ala-Ala-Val-D hb-aThr-Ala-Dab-Ser-Ile with the terminal carboxy group closing a macrocyclic ring on the hydroxy group of the allo-threonine residue. The N-terminus is in turn acylated by 3-hydroxydecanoate in corpeptin A and by cis-3-hydroxy-5-dodecenoate in corpeptin B. Some preliminary data on the biological activity of corpeptins are included.

14-3-3 proteins activate a plant calcium-dependent protein kinase (CDPK).

Plants and protozoa contain a unique family of calcium-dependent protein kinases (CDPKs) which are defined by the presence of a carboxyl-terminal calmodulin-like regulatory domain. We present biochemical evidence indicating that at least one member of this kinase family can be stimulated by 14-3-3 proteins. Isoform CPK-1 from the model plant Arabidopsis thaliana was expressed as a fusion protein in E. coli and purified. The calcium-dependent activity of this recombinant CPK-1 was shown to be stimulated almost twofold by three different 14-3-3 isoforms with 50% activation around 200 nM. 14-3-3 proteins bound to the purified CPK-1, as shown by binding assays in which either the 14-3-3 or CPK-1 were immobilized on a matrix. Both the 14-3-3 binding and activation of CPK-1 were specifically disrupted by a known 14-3-3 binding peptide LSQRQRSTpSTPNVHMV (IC50 = 30 microM). These results raise the question of whether 14-3-3 can modulate the activity of CDPK signal transduction pathways in plants.

Biological activities of pseudomycin A, a lipodepsinonapeptide from Pseudomonas syringae MSU 16H.

Similarly to other Pseudomonas lipodepsinonapeptides, pseudomycin A inhibits proton extrusion from maize roots, promotes closure of stomata in Vicia faba, necrosis of tobacco leaves, haemolysis of human erythrocytes, affects H(+)-ATPase activity and proton translocation in plasma membrane vesicles, and stimulates succinate respiration in pea mitochondria. In general, the biological activities of pseudomycin A are lower than those of syringomycin-E, the prototype member of this family of bacterial metabolities. This difference might depend on the diverse number and distribution of charged residues in the peptide moiety of these compounds.

Structure of fuscopeptins, phytotoxic metabolites of Pseudomonas fuscovaginae.

The structure of the fuscopeptins, bioactive lipodepsipeptides produced in culture by the gramineae pathogen Pseudomonas fuscovaginae, has been determined. The combined use of FAB mass spectroscopy NMR spectroscopy and chemical and enzymatic procedures allowed one to define a peptide moiety corresponding to Z-Dhb-D-Pro-L-Leu-D-Ala-D-Ala-D-Ala-D-Ala-D-Val-Gly-D-Ala-D-Val-D-Ala-D- Val-Z-Dhb-Da-Thr-L-Ala-L-Dab-D-Dab-L-Phe with the terminal carboxyl group closing a macrocyclic ring on the hydroxyl group of the allothreonine residue. The N-terminus is in turn acylated by 3-hydroxyoctanoate in fuscopeptin A and 3-hydroxydecanoate in fuscopeptin B. Some preliminary data on the biological activity of fuscopeptins are also reported.

Pseudomonas syringae pv. syringae phytotoxins reversibly inhibit the plasma membrane H(+)-ATPase and disrupt unilamellar liposomes.

The Pseudomonas syringae pv. syringae phytotoxins syringomycin-E and syringopeptins 22-A and 25-A reversibly and noncompetitively inhibit purified H(+)-ATPase solubilized from plasma membrane of maize roots. Moreover, they increase the passive permeability to protons in phosphatidylcholine/phosphatidylethanolamine liposomes. Both effects are more pronounced with syringopeptins than with syringomycin-E. Activity on phospholipid bilayers is detectable at phytotoxin concentrations not affecting H(+)-ATPase activity.