32 research outputs found

    Covid-19 seroprevalence among healthcare workers of a large covid-19 hospital in rome reveals strengths and limits of two different serological tests

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    Healthcare workers are at the forefront against COVID-19, worldwide. Since Fondazione Policlinico Universitario A. Gemelli (FPG) IRCCS was enlisted as a COVID-19 hospital, the healthcare workers deployed to COVID-19 wards were separated from those with limited/no exposure, whereas the administrative staff were designated to work from home. Between 4 June and 3 July 2020, an investigation was conducted to evaluate the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin (IgG) antibodies among the employees of the FPG using point-of-care (POC) and venous blood tests. Sensitivity, specificity, and predictive values were determined with reverse-transcription polymerase chain reaction on nasal/oropharyngeal swabs as the diagnostic gold standard. The participants enrolled amounted to 4777. Seroprevalence was 3.66% using the POC test and 1.19% using the venous blood test, with a significant difference (p < 0.05). The POC test sensitivity and specificity were, respectively, 63.64% (95% confidence interval (CI): 62.20% to 65.04%) and 96.64% (95% CI: 96.05% to 97.13%), while those of the venous blood test were, respectively, 78.79% (95% CI: 77.58% to 79.94%) and 99.36% (95% CI: 99.07% to 99.55%). Among the low-risk populations, the POC test’s predictive values were 58.33% (positive) and 98.23% (negative), whereas those of the venous blood test were 92.86% (positive) and 98.53% (negative). According to our study, these serological tests cannot be a valid alternative to diagnose COVID-19 infection in progress

    Efficacy and safety of growth hormone treatment in children with short stature: the Italian cohort of the GeNeSIS clinical study

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    Purpose: We examined auxological changes in growth hormone (GH)-treated children in Italy using data from the Italian cohort of the multinational observational Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS) of pediatric patients requiring GH treatment. Methods: We studied 711 children (median baseline age 9.6 years). Diagnosis associated with short stature was as determined by the investigator. Height standard deviation score (SDS) was evaluated yearly until final or near-final height (n = 78). Adverse events were assessed in all GH-treated patients. Results: The diagnosis resulting in GH treatment was GH deficiency (GHD) in 85.5 % of patients, followed by Turner syndrome (TS 6.6 %). Median starting GH dose was higher in patients with TS (0.30 mg/kg/week) than patients with GHD (0.23 mg/kg/week). Median (interquartile range) GH treatment duration was 2.6 (0.6\u20133.7) years. Mean (95 % confidence interval) final height SDS gain was 2.00 (1.27\u20132.73) for patients with organic GHD (n = 18) and 1.19 (0.97\u20131.40) for patients with idiopathic GHD (n = 41), but lower for patients with TS, 0.37 ( 120.03 to 0.77, n = 13). Final height SDS was > 122 for 94 % of organic GHD, 88 % of idiopathic GHD and 62 % of TS patients. Mean age at GH start was lower for organic GHD patients, and treatment duration was longer than for other groups, resulting in greater mean final height gain. GH-related adverse events occurred mainly in patients diagnosed with idiopathic GHD. Conclusions: Data from the Italian cohort of GeNeSIS showed auxological changes and safety of GH therapy consistent with results from international surveillance databases

    Processo di risoluzione di 2-ossazolidinoni racemici

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    Si descrive un processo di risoluzione di composti 2-ossazolidinonici 5-sostituiti con OX, dove X ha i significati indicati nella descrizione, mediante cristallizzazione preferenziale da soluzioni sovrassature

    Bio-hydrolysis and bio-hydrogen production from food waste by thermophilic and hyperthermophilic anaerobic process

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    High-temperature pretreatment plays a key role in the anaerobic digestion of food waste (FW). However, the suitable temperature is not yet determined. In this work, a long-term experiment was conducted to compare hydrolysis, acidogenesis, acetogenesis, and hydrogen production at 55\ua0\ub0C and 70\ua0\ub0C, using real FW in CSTR reactors. The results obtained indicated that acidification was the rate-limiting step at both temperatures with similar process kinetics characterizations. However, the thermophilic pretreatment was more advantageous than the hyperthermophilic with suspended solids solubilization of 47.7% and 29.5% and total VFA vs. soluble COD ratio of 15.2% and 4.9%, for thermophilic and hyperthermophilic treatment, respectively, with a hydrolytic reaction time (HRT) of 10\ua0days and an OLR of 14\ua0kg\ua0COD/m3\ua0d. Moreover, stable hydrogen yield (70.7\ua0ml-H2/g\ua0VSin) and content in off gas (58.6%) was achieved at HRT 5\ua0days, pH 5.5, and temperature of 55\ua0\ub0C, as opposed to 70\ua0\ub0C

    Long-term bio-H2and bio-CH4production from food waste in a continuous two-stage system : Energy efficiency and conversion pathways

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    Anaerobic digestion is a well-established technology for treating organic waste, but it is still under challenge for food waste due to process stability problems. In this work, continuous H2and CH4production from canteen food waste (FW) in a two-stage system were successfully established by optimizing process parameters. The optimal hydraulic retention time was 5 d for H2and 15 d for CH4. Overall, around 59% of the total COD in FW was converted into H2(4%) and into CH4(55%). The fluctuations of FW characteristics did not significantly affect process performance. From the energy point view, the H2reactor contributed much less than the methane reactor to total energy balance, but it played a key role in maintaining the stability of anaerobic treatment of food waste. Microbial characterization indicated that methane formation was through syntrophic acetate oxidation combined with hydrogenotrophic methanogenesis pathway

    Resolution of 5-hydroxymethyl-2-oxazolidinone by preferential crystallization[ 1 ] and investigations on the nature of the racemates of some 2-oxazolidinone derivatives

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    After ascertaining its conglomerate nature by DSC and solid-state IR analyses, 5-hydroxymethyl-2-oxazolidinone 1, whose enantiomers are very important synthons, was efficiently resolved without chiral auxiliaries by preferential crystallization from a supersaturated isopropanolic solution of the racemate, slightly enriched in one enantiomer (3.7% ee). Favourable conditions to the entrainment were defined utilizing the previously constructed ternary phase diagram {( R)-1, ( S)-1, 2-propanol}. Furthermore, the investigations were extended to other chiral 2-oxazolidinones with a functionalized methyl at the 5- or 4-position finding that 5-tosyloxymethyl-2-oxazolidinone is a racemic compound, whereas just the corresponding mesylate is a conglomerate as the parent alcohol 1. Interestingly, 4-hydroxymethyl-2-oxazolidinone 4 proved to be a racemic compound in contrast with its positional isomer 1 demonstrating how a relatively fine variation in the molecular structure can unpredictably influence the crystalline nature of the racemate. The X-ray structure determination carried out on ( S)-(+)-1, (\ub1)-4 and ( R)-(+)-4 enlightened the importance of the hydrogen bond in determining different supramolecular assembling in the two homochiral compounds with respect to the racemic one and allowed a correlation with the stability of the crystal to be made

    DESIGN, SYNTHESIS AND BIOLOGICAL EVALUATION OF NON-PEPTIDIC INHIBITORS OF FARNEYLTRANSFRERASE

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    Ras proteins are plasma membrane\u2013bound GTP-binding proteins which play an important role in normal cellular physiology and pathophysilogy. They are involved in the transmission of signals from extracellular stimuli to the nucleus. Mutations in ras genes, that lead to uncontrolled cell growth, have been identified in human cancers especially those of pancreas, colon, lung and bladder [1]. Ras proteins are initially sinthesized in the cytoplasma where they undergo farnesylation as the first step of the post-translational modifications. Farnesylation of the cysteine unit of the so-called CAAX box is followed by the proteolytic cleavege of the three terminal aminoacids (AAX) and by methyl esterification at the new C terminal Cysteine residue by a protein methyltransferase [2]. The last step is the acylation with palmitic acid of Cysteine residue located upstream of the farnesylated Cysteine. This palmitoylation increses the binding of Ras proteins to the cell membrane. As the farnesylation is catalyzed by farnesyltransferase (Ftase), inhibition of this enzyme represents a potential target for the development of anticancer agents. Many classes of Farnesyltransferase inhibitors (FTIs) have been reported in the literature. They have been designed based on: a) the modification of tetrapeptide CAAX (peptidomimetics); b) the farnesyl moiety of farnesyl pyrophosphate (FPP mimetics); c) the bisubstrate analogues incorporating the structural motif of both farnesyl pyrophosphate and the CAAX tetrapeptide; d) the natural inhibitors. Our studies on FTIs focused on peptidomimetics. On the basis of the structures of known inhibitors and of the results of docking searches [3], the compounds of formula 1were developed. The interaction capabilities of the selected compounds were highlighted with detailed molecular docking searches, using BioDock. More in details, MonteCarlo based conformational scans were combined with docking analyses in order to take in account the ligand flexibility. The preferred conformations for each derivative (15/20 structures per ligand) were docked in the FTase structure and the best obtained complexes were minimized, keeping fixed all residues outside a 10 \uc5 radius sphere around the ligand. This study underlines how these novel inhibitors enclose at least three interacting substructures: 1) the carboxyl moiety, which realizes strong electrostatic interactions with Zn++ ion reinforced by similar interactions with Arg-202\uf062 and Arg-359\uf062; 2) the biphenyl group, which realizes \uf070\uf02d\uf070 stacking with the Tyr-361\uf062 residue; 3) the benzodioxane moiety, which interacts with Lys-294\uf062 and Lys-164\uf061, establishing both charge transfer interaction with the phenyl ring and hydrogen bonds with benzodioxane oxygen atoms. These results seem to indicate that the methylthioethyl chain of Methionine is not involved in the interaction with the active site of the enzyme. Therefore, we have planned the replacement of such an aminoacid with Glycine, Isoleucine or Homoserine. For this new class of FTIs, structure activity relationship will be proposed on the basis of the results of the binding studies

    The use of the naphthyl probe to scan the alpha-1A/5HT1A receptor binding sites: discovery of novel alpha-1A selective antagonists

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    This study describes the use of a naphtyl moiety as a probe to find out the steric differences in the binding sites of both alpha-1-adrenoreceptors (alpha-ARs) subtypes and 5HT1A receptor; on this ground chiral naphtyl derivatives of WB-4101 were designed, synthesized and then evaluated their binding affinities. This study brings to light the pivotal rules that probably influence the selectivity and, finally, it allows to achieve novel selective alpha-1A antagonists, that bear naphtodioxane moiety in lieu of classical benzodioxane group. The obtained results underline how the upsizing of phenoxyl substructure is negative for the affinity and/or selectivity on the alpha-1A-AR subtype, while the naphtodioxane derivatives show an affinity a bit less than WB-4101, but a selectivity profile significantly favorable. On the contrary the \uf0611D affinity values increase as well as the upsizing of phenoxyl substructure and the 5HT1A binding values show a similar trend. A molecular modeling analysis highlights that the remarkable selectivity of naphtodioxane derivatives could be explained also on the base of its particular conformational profile, that reveals the hypothetic selective conformation for alpha-1A receptor subtype. Finally, this suggestion was verified, docking the so obtained selective conformations in the alpha-1A receptor model

    Lo Spazio Polmone ospedaliero: un approccio multidisciplinare per definire un'area strategica di supporto alle attività sanitarie in regime ordinario ed emergenziale

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    Introduzione: La pandemia ha evidenziato la difficoltà delle strutture sanitarie nel saper rispondere tempestivamente alle emergenze. Gli ospedali hanno dovuto riorganizzare gli spazi con accorpamenti e trasferimenti, sospendendo i servizi ordinari, al solo fine di garantire la gestione emergenziale del sovrannumero di pazienti. è stata condotta un’indagine sul ruolo dello Spazio Polmone (SP) che potrebbe supportare le strutture ospedaliere. Metodi. È stato elaborato un doppio questionario per staff sanitario e progettisti con una serie di quesiti atti a definire le caratteristiche che lo SP dovrebbe avere, sia in un edificio esistente che di nuova realizzazione. Risultati. Il data analysis ha permesso di evidenziare diversi input quali: a) prossimità al Pronto Soccorso (PS), Terapia Intensiva (TI) e Degenze; b) localizzazione all’interno dell’ospedale ma separato dalle altre aree sanitarie; c) accesso autonomo con camera calda; d) caratteristiche organizzative e spaziali simili a PS, TI e Degenze; e) configurazione di uno spazio già operativo pronto all’uso; f) lo SP dovrebbe ospitare circa il 12% dei posti letto del PS di 40 mq per postazione. Conclusioni. Il lavoro di ricerca è uno starting point: infatti risulta necessario ampliare lo studio. Sebbene il lavoro si sia focalizzato in ambito ospedaliero non si può trascurare l’emergenza verificatasi anche in ambito territoriale e pertanto sono state evidenziate possibili strategie da attuate anche in questi contesti
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