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Since June 2016, an outbreak of hepatitis A has been reported in Europe. Here we report the HAV outbreak in Brescia (Northern Italy) from July 2016 to July 2017. We actively recorded all HAV cases defined by detection of HAV IgM antibodies in serum. Data on sexual behaviour, travel attitudes, concomitant sexually transmitted diseases (STDs), clinical presentation and laboratory results were collected. Forty-two confirmed cases were recorded: 25 (60%) were MSM and reported sexual contact at risk of STDs. Compared to 2015 and the first half of 2016, when only three hepatitis A cases were recorded, in the 12 months in question the number of cases rose 14-fold. Among 25 MSM, 14 were HIV-infected. Hepatitis A is usually a self-limiting disease, but it could be more serious in the case of HIV co-infection, immunosuppression and chronic hepatitis. HAV infection has a high outbreak potential in MSM because of more common oro-anal practices compared to HS, a high interconnectedness global network, chemsex practices and a new tendency to travel abroad to attend group sex events. In our experience, most cases occurred in MSM and 56% of them were HIV-infected, suggesting the need to promote active screening, immunization and education in this population.

The analysis of the interaction phenomena occurring between biorobots and biological tissues requires in-depth knowledge of the biomechanical response of tissues. Most phenomenological models are based on hyperelastic formulation and this entails a careful evaluation of the model constitutive parameters, which are defined on the basis of data obtained from experimental tests. The choice of the test to be developed depends on the tissue characteristics to be studied and the procedure to be used to define the parameters . The aim of the present work is to describe a procedure used to define constitutive parameters for hyperelastic soft tissue constitutive models by considering combinations of data from uniaxial, equi-biaxial and shear testing conditions of tissue specimens and to discuss the results obtained. The parameters are estimated using a stochastic optimization procedure, considering the complex behaviour of the cost function. The mechanical tests to be adopted and their combination are discussed with regard to the reliability and efficiency of the procedure to be used in the numerical modelling of tissue-robot interaction phenomena

Two families of hexameric cyclic peptoids decorated with linear N-alkyl and alternated N-alkyl/N-benzyl side chains (2 a–d and 3 a–c, respectively) were designed and synthesized in order to correlate their logP values (from 2.55 to 6.83) to their ionophoric activities. The present contribution confirms the general ability of hexameric cyclic peptoids to behave as efficient cation carriers, corroborates their preference for Na+ ion, among the tested alkali metals, and suggests a Na+/H+ antiport transport mechanism (rate limited by the transport of the proton) for these new ionophores. Our observations indicate that in order to attain an efficient ionophoric activity, a narrow range of liphophilicity is required (4

A novel asymmetric phase-transfer-catalyzed γ-alkylation of phthalide 3-carboxylic esters has been developed, giving access to 3,3-disubstituted phthalide derivatives, which present a chiral quaternary γ-carbon in good to excellent yields and good enantioselectivities (74–88% ee). The enantiomeric purity could be substantially enhanced to 94–95% ee by recrystallization. Both electron-withdrawing and electron-releasing substituents are well tolerated on the phthalide core as well as on the aromatic moiety of the alkylating agent. This methodology, enabling the introduction of an unfunctionalized group at the phthalide γ-position, fully complements previously reported organocatalytic strategies involving functionalized electrophiles, thus expanding the scope of accessible 3,3-disubstituted products. The high synthetic value of this asymmetric reaction has been proven by the formal synthesis of the naturally occurring alkaloid (+)-(9S,13R)-13-hydroxyisocyclocelabenzine.

Five new cyclic peptoids containing (2S,4R)-4-hydroxyproline (Hyp) residues have been designed and synthesized using a mixed "submonomer/monomer" approach. Alkali metal cation affinities and ion transport activities were assessed by experimental (NMR and HPTS assay in liposomes) and computational methods. Easy functionalization of hydroxyproline residues afforded a bouquet of cyclic oligomers showing correlation between ion transport abilities and cytotoxic activities on selected human cancer cell lines.

SUMMARYThis study assessed changes in prevalence and distribution of HIV-1 non-subtype B viruses in Italian and immigrant patients over two decades in a province in Italy. All HIV-positive patients who underwent genotypic resistance testing were selected. Prevalence of non-subtype B viruses in 3-year periods was calculated. All sequences of non-subtype B and those provided by REGA as unassigned were analysed for phylogenetic relationships. In total, 250/1563 (16%) individuals were infected with a non-subtype B virus. Prevalence increased over time, reaching a peak (31·5%) in 2004–2006. In Italian patients, the most frequent subtypes were B (92·5%) and F1 (4%). F1 subtype was also prevalent in patients from South America (13·6%); in patients of African origin, CRF02_AG (54·9%) and G (12·3%) were the most frequent. HIV-1 non-subtype B infections in Italians were mostly found in patients who acquired HIV sexually. A phylogenetic relationship between F subtypes in Italian and representative HIV-1 sequences from Brazil was found. C subtypes in Italians were phylogenetically related to subtypes circulating in Brazil. Inter-subtype recombinants were also found in the latest years. The HIV-1 epidemic in Brescia province evolved to the point where about 1/3 patients recently diagnosed harboured non-B HIV subtypes. The distribution of HIV-1 non-B subtypes in Italian patients resembled that in South American patients and phylogenetic relatedness between some Italian and South American HIV-1 strains was found. The possible epidemiological link between these two populations would have been missed by looking only at risk factors for HIV acquisition declared by patients. The evidence of inter-subtype recombinants points to significant genetic assortment. Overall our results support phylogenetic analysis as a tool for epidemiological investigation in order to guide targeted prevention strategies.

The preparation of a new class of backbone-modified PNA mimetic incorporating thymine is described. Target dipeptoid monomer 21 was synthesised from an N-[2-(thymin-1-yl)ethyl]glycinate ester and a properly protected iminodiacetic acid. The distinctive structural motif in the backbone is acarboxy group, inserted to impart water solubility to the oligomer. Two achiral oligopeptoid sequences (8-mer and 12-mer), characterised by the shift of the amide carbonyl group away from the nucleobase, were efficiently assembled according to solid-phase synthesis protocols. Thermal denaturation studies showed that the two homopyrimidine oligopeptoids do not effectively hybridise with complementary sequences of DNA and RNA or fully synthetic (2,4-diamino)triazin-6-yl-tagged peptoid 22. A possible reason could reside in the concurrent unfavourable influence of the anionic N-(carboxymethyl) moieties and the flexible nucleobase/backbone ethylene linker.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Continuous surveillance of HIV primary resistance mutations is highly important due to their potential clinical impact. All patients naive to antiretrovirals who had ≥1 genotypic resistance testing at the Institute of Infectious Diseases (Brescia, Northern Italy) between 2001 and 2006 were analyzed. Primary resistance mutations were defined using epidemiological and clinical criteria. Mutations were interpreted using the Stanford University Algorithm. Logistic regression analysis was used to assess possible predictors of primary resistance mutations. Among 569 patients, 11% presented ≥1 mutation. Prevalence of primary resistance mutations to nucleoside reverse-transcriptase inhibitors (NRTI), non-nucleoside reverse-transcriptase inhibitors (NNRTI), and protease inhibitors (PI) was 6.3%, 6%, and 1.6%, respectively. The most frequent mutations to NRTI were substitutions at position 215 (215Y in 3 patients, and 215 revertants in 16), 41L (13), 219Q (12), and 210W (10). Among mutations to NNRTI, 103N was found in 21 patients, while 181C, 188L, and 190A/S in 8, 3, and 4 patients, respectively. Fifty-one patients (9%) had high-to-intermediate resistance to ≥1 antiretroviral drug before starting the treatment. Regarding the new generation drugs, nine patients had intermediate resistance to etravirine, five patients had intermediate resistance to tipranavir, while five, one, and seven patients had low resistance to etravirine, tipranavir, and darunavir. Homosexuals were more likely to harbor a virus with primary resistance mutations (OR:2.68; 95% CI:1.44-5.00; P=0.002) while non-Italian nationality was protective (OR:0.38; 95% CI:0.17-0.86; P=0.020). Prevalence of primary resistance mutations suggests that genotypic resistance testing should be performed before starting treatment in naïve patients in Italy, particularly when NNRTI are prescribed. © 2008 Wiley-Liss, Inc.

A new class of artificial ionophores has been rationally designed and synthesized linking to a tetrafunctionalized l -treitol spacer two rigid hydrophobic 3β-hydroxy-5α-23,24-bisnorcholanic units and two flexible hydrophilic oligo(ethylene glycol) chains. Compounds 1a and 1b were incorporated into phospholipid vesicles and shown to facilitate Na+-transport.

This report regards the case of a 43 year-old HIV-positive woman who developed an episode of serious transaminase elevation during stavudine-including antiretroviral therapy. Diagnostic assessment ruled out hepatitis virus co-infection, alcohol abuse besides other possible causes of liver damage. No signs of lactic acidosis were present. Liver biopsy showed portal inflammatory infiltrate, spotty necrosis, vacuoles of macro- and micro-vesicular steatosis, acidophil and foamy hepatocytes degeneration with organelles clumping, poorly formed Mallory bodies and neutrophil granulocytes attraction (satellitosis). A dramatic improvement in liver function tests occurred when stavudine was discontinued and a new antiretroviral regimen with different nucleoside reverse transcriptase inhibitors was used. The importance of considering hepatotoxicity as an adverse event of HAART including stavudine, even in absence of other signs of mitochondrial toxicity should therefore be underlined. Liver biopsy may provide further important information regarding patients with severe transaminase elevation, for a better understanding of the etiology of liver damage.

The Na+ transporting properties of the first member of a new class of artificial ionophores, based on a C-2-symmetric polyhydroxylated steroid dimer, are described.

The synthesis of a new class of amphiphilic calix[ 4] arene-based ionophores, relying on direct reductive amination as a key step, and the evaluation of their H+ and Na+ transporting properties is described.

A quantitative measurement of laser-beam quality can be performed by determination of the presence of multiple transverse modes of the laser oscillator and by calculation of their power content. Along this line of argument, we discuss a new approach that, starting from near-field and far-field intensity measurements, can evaluate the complex excitation coefficients of the transverse modes in a laser beam. The exploitation of near-field measurements sharply improves the performances of the technique in those cases in which only far-field measurements are used. The validity of the method is confirmed by several accurate numerical simulations and by some experimental results relative to a multimode Q-switched Nd:YAG laser.