Influenza vaccination in health-care workers: an evaluation of an on-site vaccination strategy to increase vaccination uptake in HCWs of a South Italy Hospital.

Despite the international recommendation and specific programs, and although the vaccination of health-care workers (HCWs) is considered the main measure to prevent nosocomial influenza, vaccination coverage (VC) among HCWs remains low. One of the most important barriers to vaccination uptake is the time required to attend a vaccination clinic. Centers for Disease Control and Prevention (CDC) recommends on-site influenza vaccination as a proven and cost-effective strategy that increases productivity, reduces overall absenteeism and prevents direct health-care costs. In order to increase vaccine compliance in the HCWs, the Hygiene and the Occupational Medicine departments of Bari Policlinico General University-Hospital, in the 2017/18 influenza season, promoted an on-site vaccination program in eight Operative Units (OUs). We investigated the influenza VC among HCWs of Bari Policlinico (n = 3,397), comparing VC after implementation of the on-site strategy by the Hygiene department during the 2017/18 influenza season to VC in 2016/17 season. For 2017/18 season, we also compared VC in OUs target of on-site strategy with data from in eight "control" Units (choose by simple random sampling) not included in the on-site offer. In the 2016/17 influenza season, 295/3,397 HCWs were vaccinated (VC: 8.7%) while in the 2017/18 season 482 HCWs (VC: 14.2%) received the vaccination. In OUs target of on-site vaccination, 71 HCWs (VC: 10.0%) were vaccinated in the 2016/17 season and 126 (18.0%) in the 2017/18 season, of which 101/126 (80.2%) were vaccinated in an on-site clinic. VC in OUs target of on-site vaccination increased between 2016/17 and 2017/18 seasons of 16.8 ± 10.4% (range: 5.5-37.1), while the coverage in OUs of the control group increased of 1.6 ± 2.2% (range: -1.7-4.5), with a significant difference (p < .05). Our study suggests that the offer of on-site vaccination during the 2017/18 season led to an increase of VC in HCWs compared to the classical vaccination clinic approach. The determinants of adhesion and not-adhesion must be analyzed in dept, to experiment, in the future, new good clinical practices to increase the vaccination coverage in HCWs.

Design and Synthesis of Metabolically Stable tRNA Synthetase Inhibitors Derived from Cladosporin.

Selective and specific inhibitors of Plasmodium falciparum lysyl-tRNA synthetase represent promising therapeutic antimalarial avenues. Cladosporin was identified as a potent P. falciparum lysyl-tRNA synthetase inhibitor, with an activity against parasite lysyl-tRNA synthetase >100-fold more potent than that of the activity registered against the human enzyme. Despite its compelling activity, cladosporin exhibits poor oral bioavailability; a critical requirement for antimalarial drugs. Thus, the quest to develop metabolically stable cladosporin-derived analogues, while retaining similar selectivity and potency to that of the natural compound, has begun. Chemogenomic profiling of a designed library allowed an entirely innovative structure-activity relationship study to be initiated; this shed light on structural evidence of a privileged scaffold with a unique activity against tRNA synthetases.

Enantioselective Synthesis of Cyclobutenes by Intermolecular [2+2] Cycloaddition with Non-C2 Symmetric Digold Catalysts.

The enantioselective intermolecular gold(I)-catalyzed [2+2] cycloaddition of terminal alkynes and alkenes has been achieved using non-C2-chiral Josiphos digold(I) complexes as catalysts, by the formation of the monocationic complex. This new approach has been applied to the enantioselective total synthesis of rumphellaone A.

α,ß-Unsaturated Gold(I) Carbenes by Tandem Cyclization and 1,5-Alkoxy Migration of 1,6-Enynes: Mechanisms and Applications.

1,6-Enynes bearing OR groups at the propargyl position generate α,ß-unsaturated gold(I)-carbenes/ gold(I) stabilized allyl cations that can be trapped by alkenes to form cyclopropanes or 1,3-diketones to give products of α-alkylation. The best migrating group is p-nitrophenyl ether, which leads to the corresponding products without racemization. Thus, an improved formal synthesis of (+)-schisanwilsonene A has been accomplished. The different competitive reaction pathways have been delineated computationally.

Synthesis of Rumphellaone A and Hushinone by a Gold-Catalyzed [2 + 2] Cycloaddition.

The enantioselective total synthesis of rumphellaone A has been accomplished in 12 steps via a diastereoselective gold(I)-catalyzed [2 + 2] macrocyclization of a 1,10-enyne as the key step to build the cyclobutene moiety. This concise approach has also led to the total synthesis of husinone.

Anatomy of gold catalysts: facts and myths.

This review article covers the main types of gold(i) complexes used as precatalysts under homogeneous conditions in organic synthesis and discusses the different ways of catalyst activation as well as ligand, silver, and anion effects.

3-Alkenyl-2-silyloxyindoles in vinylogous Mannich reactions: synthesis of aminated indole-based scaffolds and products.

The first Lewis acid catalyzed vinylogous Mukaiyama-type Mannich addition of 3-alkenyl-2-silyloxyindoles to in situ generated N-Boc imines has been established, which affords chiral α-alkylidene-δ-amino-2-oxindole products with good efficiency and complete γ-site- and Z-selectivity. The reaction is wide in scope, as it can be applied with equal convenience to different silyloxyindole donors and aromatic or aliphatic aminal-derived aldimine acceptors. The utility of these scaffolds is demonstrated by their easy transformation into either spirocyclopropane oxindole or homotryptamine-like products, featuring nontraditional indole-based skeleton connections.

Synthesis of substituted indenones and indanones by a Suzuki-Miyaura coupling/acid-promoted cyclisation sequence.

A one-pot Suzuki-Miyaura cross-coupling/acid-catalyzed cyclisation leading to indenones and indanones in modest to good yields is reported.

Concise synthesis of the isothiourea organocatalysts homobenzotetramisole and derivatives.

A concise approach to the synthesis of homobenzotetramisole and derivatives is described. Our strategy features a one-pot acylation-cyclization of 2-aminobenzothiazole with α,ß-unsaturated acid chlorides to afford annulated pyrimidones. Subsequent Grignard addition followed by acid-promoted dehydration and reduction provides good overall yields of the title compounds in three steps and in quantities up to 10 g. The synthesis employs low-cost and readily available starting materials and enables access to both optical antipodes of these increasingly useful nucleophilic catalysts following chiral separation.

Diastereo- and enantioselective catalytic vinylogous Mukaiyama-Mannich reactions of pyrrole-based silyl dienolates with alkyl-substituted aldehydes.

A reliable, catalytic asymmetric vinylogous Mukaiyama-Mannich reaction of pyrrole-based silyl dienolates is introduced that is particularly apt for alkyl- and α-alkoxyalkyl-substituted aldehydes. The reaction course is effectively orchestrated by the Hoveyda-Snapper amino acid-based chiral ligand/silver(I) catalyst combination to produce valuable vicinal diamino carbonyl compounds in high yields, with virtually complete γ-site- and anti-selectivity and significant catalyst-to-product chirality transfer. The utility of the Mannich products can be seen in the synthesis of an unprecedented perhydrofuro[3,2-b]pyrrolone product, an aza-analogue of naturally occurring (+)-goniofufurone.

anti-Selective, catalytic asymmetric vinylogous Mukaiyama Mannich reactions of pyrrole-based silyl dienolates with N-aryl aldimines.

Pyrrole-based silyl dienolates undergo asymmetric vinylogous Mukaiyama Mannich reactions with a series of N-aryl aldimines in the presence of the Hoveyda-Snapper amino acid-derived silver(I) catalysts. The Mannich products-α,ß-unsaturated δ-amino-γ-butyrolactams-are typically obtained in high yields, excellent γ-site selectivities and anti-diastereoselectivities, and up to 80% enantioselectivity.