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Background and aim: Burnout and post-traumatic stress disorder (PTSD) among frontline nurses working with COVID-19 patients during the initial phase of the pandemic (2020) have been described by several studies. Therefore, this study aimed to systematically synthesize evidence regarding burnout and PTSD among nurses engaged in the frontline during the COVID-19 pandemic, highlighting their risk and protective factors. Methods: A systematic review was performed (PROSPERO: CRD42021227939), searching literature published in 2020 on Pubmed, Scopus, CINAHL, and PsycInfo. We quantitatively pooled means of included studies measuring burnout and PTSD with the same tools. Results: Twenty-five studies were included in this review. Seven (3766 nurses) were included in the meta-analysis for estimating means of depersonalization and emotional exhaustion assessed using the Maslach Burnout Inventory, respectively: 7,40 (95%CI=6,00-8,80) and 22,82 (95%CI=19,24-26,41). Likely, 12 studies were used to estimate two pooled means for PTSD, one for six studies adopting the Impact of Event Scale-Revised (1551 nurses), and six adopting the PTSD Scale for DSM-5 (8547 nurses). The main risk and protective factors of both outcomes were female sex and younger age, work-related variables, and physical and mental factors, such as concerns, skin lesions from wearing personal protective equipment. Conclusions: This systematic review portrayed the situation described in literature during 2020 on nurses’ burnout and PTSD during the COVID-19 pandemic. Although the outcomes’ levels described in the included studies are diverse, the broad situation appears alarming, and supportive multi-level strategies, considering individual and system-level, should be planned to decrease the described worsening scenario within the clinical settings avoid middle and long-term negative consequences.

Conformational restriction applied to dihydrobenzylpyrimidin-4-(3H)-ones (DABOs) by the intoduction of a methyl group at the alpha-benzylic position is known to massively improve the anti-HIV-1 activity of these compounds. Here, we report the effects of methoxy substitution at the alpha-benzylic position in S-, NH-, and N,N-DABOs carrying 2,6-difluoro, 2-chloro-6-fluoro, or 2,6-dichloro substituted benzyl moieties. The various alpha-methoxy DABO series (12-14) present different SAR at the dihalo benzyl substitution, with the most potent compounds (12d,e and 13c) showing similar (picomolar/nanomolar) anti-HIV-1 potency as the corresponding alpha-methyl analogues against wt HIV-1, and 10-100-fold increased potency (up to low nanomolar) against clinically relevant K103N, Y181C, Y188L, IRLL98, and K103N+Y181C HIV-1 mutant strains, highlighting the importance of the a-methoxy substitution to provide highly efficient DABOs as "second generation" NNRTIs. HPLC enantioseparation of three of the most potent derivatives (12d, 13c, and 14c) provided single enantiomers with significant enantioselectivity in HIV-1 inhibition. Computational studies allowed to correlate the best antiviral activity with the (R) absolute configuration at the a-methoxy stereogenic center.

Enteroviruses (EVs) are among the most frequent infectious agents in humans worldwide and represent the leading cause of upper respiratory tract infections. No drugs for the treatment of EV infections are currently available. Recent studies have also linked enterovirus infection with pulmonary exacerbations, especially in cystic fibrosis (CF) patients, and the importance of this link is probably underestimated. The aim of this work was to develop a new class of multi-target agents active both as broad-spectrum antivirals and as correctors of the F508del-CFTR folding defect responsible for >90% of CF cases. We report herein the discovery of the first small-molecules able to simultaneously act as correctors of the F508del-CFTR folding defect and as broad-spectrum antivirals against a panel of enteroviruses representative of all major species.

alpha-Dicarbonyl compounds are intermediate substances occurring in thermally treated foods as reaction products of caramelization, Maillard reaction, and lipid peroxidation, in fermented foods and beverages, where are produced by microorganism metabolisms, in plants, produced in response to stress conditions, in water, in tobacco smoke, and in medical products (peritoneal dialysis fluids). Glyoxal (G) and methylglyoxal (MG) can be produced also by many strains of bacteria present in the intestinal tract, and are endogenous compounds because are human physiological metabolites. Alpha-Oxoaldehydes are highly reactive alkilating agents, that have been found to rapidly modify side chains of protein and form reversible Schiff’s base that after subsequent rearrangements, oxidations and dehydratations, yields relatively stable Amadori products, known as Maillard reaction products (MRPs) if occur in foods, or advanced glycation products (AGEs) if are endogenously formed. Recent publications reported that both alpha-dicarbonyl compounds and AGEs induced several cellular damages, mainly attributed to their interaction with essential cellular macromolecules, leading to the alteration in structure and function of some kind of cells. In recent years the role of exogenous alpha-dicarbonyl compounds in gastrointestinal tract is under investigation to understand whether excess consumption of such dietary compounds might be a risk for human health. Nevertheless, to our knowledge, the influence of the digestion process on food derived alpha-dicarbonyl compounds has not been investigated. Therefore, a mixture of alpha-dicarbonyl compounds, commonly occurring in foods (G, MG and diacetyl), before and after in vitro simulated gastrointestinal digestion process, was evaluated for its ability to induce cytotoxicity against three different cultured cell lines and to inhibit the function of selected enzymes responsible for DNA repair in human cells. Then these properties were correlated both to the alpha-dicarbonyl compound content (determined by a validated RP-HPLC-DAD method) before and after digestion and with the digestive enzyme carbonylation induced by alpha-dicarbonyl compounds. The digested alpha-dicarbonyl mixtures was found to contain compound(s) with apparent selective in vitro antiproliferative activity against colon cancer cells, but not other cell lines. Overall, the results showed that digested alpha-dicarbonyl compounds should not be cytotoxic towards normal cells, but may display specific anticancer activity.

With the aim of identifying novel lead compounds active against emergent human infectious diseases, a series of 2,3-dihydro-4H-pyridinone derivatives has been prepared and evaluated for antiviral activity. Compounds were evaluated in vitro in cell-based assays for cytotoxicity and against a wide spectrum of viruses. In the antiviral screening, several compounds showed to be fairly active against viruses belonging to the Flaviviridae family. The Pestiviruses (bovine viral diarrhoea virus) were inhibited by 4acis (CC(50) > 100 mu m; EC(50) = 14 mu m), compounds 4ccis and 6a showed a significant activity against Flaviviruses (Yellow Fever Virus) (CC(50) > 100 mu m; EC(50) = 18 mu m, CC(50) > 100 mu m; EC(50) = 10 mu m). Among these, compound 6a displayed great inhibitory activity against Hepaciviruses (hepatitis C virus) in replicon assay [CC(50) > 100 mu m; EC(50)(1b) = 4 mu m]. In vitro inhibitory activity against the HCV RNA-dependent RNA polymerase (NS5B) of title compounds is discussed. The antiviral screening of viral strains indicated that compound 6a can be selected as promising tool in novel anti-flaviviruses development.

New potent indolyl aryl sulfone (IAS) HIV-1 NNRTIs were obtained by coupling natural and unnatural aminoacids to the 2-carboxamide, and introducing different electron-withdrawing substituent(s) at the position(s) 4 and 5 of the indole nucleus. The new IASs inhibited the HIV-1 replication in human T-lymphocyte (CEM) cells at low/sub-nanomolar concentration, and were weakly cytostatic. Against the mutant L100I and K103N RT HIV-1 strain, sulfones 3, 4, 19, 27 and 31 were superior to EFV, and equipotent to MKC-4965 and TMC120, and were as potent as EFV against the mutant Y181C strain. The new IASs proved to be effective inhibitors of Coxackie B4 virus with an EC50 = 2 M. In view of this particular therapeutic profile, these agents might be useful for the treatment of HIV seropositive patients with pathological conditions associated Coxsackie B virus. Superimposition of PLANTS docked conformations of 19 and the highly active derivative 9 revealed different hydrophobic interactions of the 3,5-dimethylphenyl group, for which a staking interaction with Tyr181 aromatic side chain was observed. In L100I mutated RT the mutation of leucine to isoleucine does not affect the binding mode confirming all the interactions reported for the WT strain.