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Abstract Purpose Investigations of the quality of life (QoL) of young people have shown that psychological and behavioral problems are associated with lower subjective well-being. The QoL ratings of children and adolescents based on self-reports and proxy reports are significantly different. The aim of the present study was to examine youth self-reported and parent proxy-reported QoL and investigate the effects of age, gender and psychological/behavioral symptoms on the QoL reports of youth. We hypothesized that self-reported emotional and anxiety problems influence self-reported QoL, while proxy-reported behavioral problems influence proxy reports of QoL. Methods The sample consisted of 284 parent–child pairs. Youths were between the ages of 11 and 18 years, the mean age was 14.3 (SD 2.1) years, and 35.6% were males. The Inventory of Life Quality (ILK) scale was used to measure QoL, and the Strengths and Difficulties Questionnaire was used to assess psychological and behavioral problems. Results Males had higher self-reported QoL than females, and younger children had better QoL than older children. Emotional peer problems and hyperactivity reported by youth and hyperactivity and conduct problems reported by parents predicted youth self-rated ILK. Only parent-reported psychological/behavioral problems predicted proxy-rated ILK. Conclusion The evaluation of QoL of children and adolescents should involve both self and proxy reports in order to capture the effects of various psychological/behavioral symptoms and the perspectives of both youth and parents.

The field of neuroeducation, which integrates neuroscience findings into educational practice, has gained significant attention in recent years. Establishing research priorities in neuroeducation is crucial for guiding future studies and ensuring that the field benefits both neuroscience and education. This study aimed to address the need for collaboration between neuroscientists and educators by conducting a priority-setting exercise with early career professionals from both fields. Using the nominal group technique (NGT) with interquartile range (IQR) analysis, we identified seven key priorities in neuroeducation and assessed the level of consensus on these priorities. The top-ranked priorities were “Emotional and Mental Well-being”, “Neurodiversity and Special Education Needs”, and “Active and Inclusive Teaching Methods”, though IQR analysis revealed varying levels of consensus. Lower-ranked priorities, such as “Role of Technology on Learning and the Brain”, showed a higher consensus. This discrepancy between ranking and consensus highlights the complex nature of neuroeducation, reflecting differing perspectives between neuroscientists and educators. These findings suggest the need for interdisciplinary collaboration to bridge these gaps and foster evidence-based practices. We recommend that future research focuses on the specific neural mechanisms underlying emotional well-being, strategies for supporting neurodivergent learners, and practical approaches to integrating inclusive teaching methods in diverse educational contexts.

Abstract (−)-Cannabidiol (CBD) and (−)-cannabigerol (CBG) are two major non-psychotropic phytocannabinoids that have many beneficial biological properties. However, due to their low water solubility and prominent first-pass metabolism, their oral bioavailability is moderate, which is unfavorable for medicinal use. Therefore, there is a great need for appropriate chemical modifications to improve their physicochemical and biological properties. In this study, Mannich-type reaction was used for the synthetic modification of CBD and CBG for the first time, and thus fifteen new cannabinoid derivatives containing one or two tertiary amino groups were prepared. Thereafter the antiviral, antiproliferative and antibacterial properties of the derivatives and their effects on certain skin cells were investigated. Some modified CBD derivatives showed remarkable antiviral activity against SARS-CoV-2 without cytotoxic effect, while synthetic modifications on CBG resulted in a significant increase in antiproliferative activity in some cases compared to the parent compound.

Abstract Drug-resistant Plasmodium falciparum (Pf) infections are a major burden on the population and the healthcare system. The establishment of Pf resistance to most existing antimalarial therapies has complicated the problem, and the emergence of resistance to artemisinin derivatives is even more concerning. It is increasingly difficult to cure malaria patients due to the limited availability of effective antimalarial drugs, resulting in an urgent need for more efficacious and affordable treatments to eradicate this disease. Herein, new nucleoside analogues including morpholino-nucleoside hybrids and thio-substituted nucleoside derivatives were prepared and evaluated for in vitro and in vivo antiparasitic activity that led a few hits especially nucleoside-thiopyranoside conjugates, which are highly effective against Pf3D7 and PfRKL-9 strains in submicromolar concentration. One adenosine derivative and four pyrimidine nucleoside analogues significantly reduced the parasite burden in mouse models infected with Plasmodium berghei ANKA. Importantly, no significant hemolysis and cytotoxicity towards human cell line (RAW) was observed for the hits, suggesting their safety profile. Preliminary research suggested that these thiosugar-nucleoside conjugates could be used to accelerate the antimalarial drug development pipeline and thus deserve further investigation.

Abstract This study aims to understand healthcare professionals’ thoughts and motivations about optimal management and treatment of patients with chronic obstructive pulmonary disease (COPD). We conducted a DELPHI survey through an online questionnaire distributed to 220 panellists from six European countries and a discrete choice experiment to describe the relationship between selected clinical criteria and the initial COPD treatment of choice. One hundred twenty-seven panellists (general practitioners [GPs] and pulmonologists) completed the survey. Despite the familiarity and use (89.8%) of the GOLD classification for initial treatment selection, a frequent use of LAMA/LABA/ICS was noted. In fact, panellists agreed that inhaled corticosteroids (ICS) are over-prescribed in the primary care setting. Our study showed that GPs felt less confident than pulmonologists with ICS withdrawal. This mismatch observed between best practice and behaviour indicates the need to increase awareness and efforts to improve the adherence to guidelines in clinical practice.

Abstract Gram-negative bacteria possess intrinsic resistance to glycopeptide antibiotics so these important antibacterial medications are only suitable for the treatment of Gram-positive bacterial infections. At the same time, polymyxins are peptide antibiotics, structurally related to glycopeptides, with remarkable activity against Gram-negative bacteria. With the aim of breaking the intrinsic resistance of Gram-negative bacteria against glycopeptides, a polycationic vancomycin aglycone derivative carrying an n-decanoyl side chain and five aminoethyl groups, which resembles the structure of polymyxins, was prepared. Although the compound by itself was not active against the Gram-negative bacteria tested, it synergized with teicoplanin against Escherichia coli, Pseudomonas aeruginosa and Acinetobacter baumannii, and it was able to potentiate vancomycin against these Gram-negative strains. Moreover, it proved to be active against vancomycin- and teicoplanin-resistant Gram-positive bacteria.

Abstract Patients infected with SARS-CoV-2 risk co-infection with Gram-positive bacteria, which severely affects their prognosis. Antimicrobial drugs with dual antiviral and antibacterial activity would be very useful in this setting. Although glycopeptide antibiotics are well-known as strong antibacterial drugs, some of them are also active against RNA viruses like SARS-CoV-2. It has been shown that the antiviral and antibacterial efficacy can be enhanced by synthetic modifications. We here report the synthesis and biological evaluation of seven derivatives of teicoplanin bearing hydrophobic or superbasic side chain. All but one teicoplanin derivatives were effective in inhibiting SARS-CoV-2 replication in VeroE6 cells. One lipophilic and three perfluoroalkyl conjugates showed activity against SARS-CoV-2 in human Calu-3 cells and against HCoV-229E, an endemic human coronavirus, in HEL cells. Pseudovirus entry and enzyme inhibition assays established that the teicoplanin derivatives efficiently prevent the cathepsin-mediated endosomal entry of SARS-CoV-2, with some compounds inhibiting also the TMPRSS2-mediated surface entry route. The teicoplanin derivatives showed good to excellent activity against Gram-positive bacteria resistant to all approved glycopeptide antibiotics, due to their ability to dually bind to the bacterial membrane and cell-wall. To conclude, we identified three perfluoralkyl and one monoguanidine analog of teicoplanin as dual inhibitors of Gram-positive bacteria and SARS-CoV-2.

Objectives: Reducing the microbial level in the aerosol created during dental procedures is essential to avoiding infections. The aim of this study was to examine the change in Streptococcus mutans (S. mutans) and the total bacterial load in human saliva in vivo after a single rinse with different mouthwashes. Material and methods: One mL of unstimulated saliva was collected from volunteers with poor oral hygiene at baseline and 5 min after a 1-min rinsing with diluted Solumium Oral® (hyper-pure 0.0015% chlorine dioxide; ClO2), Listerine Total Care®, Corsodyl® (0.2% chlorhexidine-digluconate; CHX), or BioGate Si*CLEAN for bacterial investigation. In a second study, volunteers rinsed with 0.003% ClO2 or CHX for 1 min, and saliva was collected at baseline, after 5 min, and after 90 min. After plating, the total plate and S. mutans colony numbers were determined. Results: In the first study, ClO2 and CHX similarly reduced both total germ and S. mutans numbers, while Listerine Total Care® decreased only the S. mutans counts. BioGate Si*Clean had no effect on either the total germ or S. mutans numbers. In the second study, an increasing tendency toward bacterial regrowth was observed with CHX after 90 min compared to the 5-min value, while no change was measured after ClO2 rinsing. Conclusion: Hyper-pure ClO2 rinsing may be a new promising preventive and therapeutic adjuvant in dental practice, as it is similar in effectiveness to the gold standard CHX-containing mouthwashes, especially in patients concerned with taste or tooth discoloration during oral health therapy.

Cannabidiol (CBD) is a nonpsychoactive phytocannabinoid that can be found in Cannabis sativa and possesses numerous pharmacological effects. Due to these promising effects, CBD can be used in a wide variety of diseases, for instance cardiovascular diseases. However, CBD, like tetrahydrocannabinol (THC), has low bioavailability, poor water solubility, and a variable pharmacokinetic profile, which hinders its therapeutic use. Chemical derivatization of CBD offers us potential ways to overcome these issues. We prepared three new CBD derivatives substituted on the aromatic ring by Mannich-type reactions, which have not been described so far for the modification of cannabinoids, and studied the protective effect they have on cardiomyocytes exposed to oxidative stress and hypoxia/reoxygenation (H/R) compared to the parent compound. An MTT assay was performed to determine the viability of rat cardiomyocytes treated with test compounds. Trypan blue exclusion and lactate dehydrogenase (LDH) release assays were carried out to study the effect of the new compounds in cells exposed to H2O2 or hypoxia/reoxygenation (H/R). Direct antioxidant activity was evaluated by a total antioxidant capacity (TAC) assay. To study antioxidant protein levels, HO-1, SOD, catalase, and Western blot analysis were carried out. pIC50 (the negative log of the IC50) values were as follows: CBD1: 4.113, CBD2: 3.995, CBD3: 4.190, and CBD: 4.671. The newly synthesized CBD derivatives prevented cell death induced by H/R, especially CBD2. CBD has the largest direct antioxidant activity. The levels of antioxidant proteins were increased differently after pretreatment with synthetic CBD derivatives and CBD. Taken together, our newly synthesized CBD derivatives are able to decrease cytotoxicity during oxidative stress and H/R. The compounds have similar or better effects than CBD on H9c2 cells.

Arschang Valipour,1 Michael Tamm,2 Jana Kociánová,3 Valentina Bayer,4 Maria Sanzharovskaya,5 Alexey Medvedchikov,6 Monika Haaksma-Herczegh,6 János Mucsi,7 Zvi Fridlender,8 Claudia Toma,9,10 Andrey Belevskiy,11 Bohumil Matula,12 Jurij Šorli13 1Department of Respiratory and Critical Care Medicine, Karl-Landsteiner-Institute for Lung Research and Pulmonary Oncology, Krankenhaus Nord – Klinik Floridsdorf, Vienna, Austria; 2Lung Centre/Pneumology Department, University Hospital Basel, Basel, Switzerland; 3Pneumological Outpatient Department, MephaCentrum, a.s., Ostrava-Poruba, Czech Republic; 4Biostatistics and Data Sciences, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA; 5Respiratory TA, Boehringer Ingelheim RCV GmbH & Co. KG, Vienna, Austria; 6Medical Affairs Regional Center, Boehringer Ingelheim RCV GmbH & Co. KG, Vienna, Austria; 7Elizabeth Nursing Home, Gödöllő, Hungary; 8Department of Internal Medicine, Hebrew University Hadassah Medical School, Jerusalem, Israel; 9Department of Pneumology, Institute of Pneumatology “Marius Nasta”, Bucharest, Romania; 10Department Of Pneumology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania; 11Department of Pulmonology, Pirogov Russian National Research Medical University, Pletnev Hospital, Moscow, Russian Federation; 12Department of Functional Diagnostics, Specialized Hospital of Saint Zoerardus, Teaching Facility of the Slovak Medical University, Nitra, Slovakia; 13Topolšica Hospital, Topolšica, SloveniaCorrespondence: Arschang ValipourDepartment of Respiratory and Critical Care Medicine, Karl-Landsteiner-Institute for Lung Research and Pulmonary Oncology, Krankenhaus Nord-Klinik, Floridsdorf Brünnerstrasse 68, Wien, Vienna 1210, AustriaTel +43 1 910 600Email arschang.valipour@wienkav.atBackground: Reduced physical activity is associated with increased morbidity and mortality in patients with COPD. Studies suggest that treatment with the long-acting muscarinic antagonist tiotropium and the long-acting β2-agonist olodaterol increases exercise capacity. This study assessed the effects of a fixed-dose combination (FDC) of tiotropium/olodaterol (delivered via Respimat®) on physical functioning in patients with stable COPD in a “real-world setting”.Methods: An international, open-label, single-arm, non-interventional study conducted in nine countries measuring changes in self-reported physical functioning in COPD patients treated with tiotropium/olodaterol 5/5 μg FDC for approximately 6 weeks. The primary endpoint was therapeutic success, defined as a minimum 10-point increase in the 10-question Physical Functioning Questionnaire (PF-10) score. Secondary endpoints included absolute change in PF-10 from Visit 1 to Visit 2, patient general condition (measured by Physician’s Global Evaluation score) and patient satisfaction with the treatment and device (assessed by Patient Satisfaction Questionnaire at the end of the study period).Results: Therapeutic success was observed in 67.8% of 7218 patients (95% CI 66.7, 68.8) in the final analysis set after approximately 6 weeks of treatment with tiotropium/olodaterol. Mean change in PF-10 score between Visit 1 and Visit 2 was 16.6 points (95% CI 16.2, 17.0). Therapeutic success was 64.3% (95% CI 63.0–65.6%) in patients with infrequent (≤1) and 76.1% (95% CI 74.3–77.9%) in patients with frequent (≥2) exacerbations (p

Background: Preventing infectious diseases has become particularly relevant in the past few years. Therefore, antiseptics that are harmless and insusceptible to microbial resistance mechanisms are desired in medicine and public health. In our recent work, a poly(ethylene oxide)-based nanofibrous mat loaded with sodium chlorite was formulated. Methods: We tested the chlorine dioxide production and bacterial inactivation of the fibers in a medium, modeling the parameters of human exhaled air (ca. 5% (v/v) CO2, T = 37 °C, RH > 95%). The morphology and microstructure of the fibers were investigated via scanning electron microscopy and infrared spectroscopy. Results: Smooth-surfaced, nanoscale fibers were produced. The ClO2-producing ability of the fibers decreased from 65.8 ppm/mg to 4.8 ppm/mg with the increase of the sample weight from 1 to 30 mg. The effect of CO2 concentration and exposure time was also evaluated. The antibacterial activity of the fibers was tested in a 24 h experiment. The sodium-chlorite-loaded fibers showed substantial antibacterial activity. Conclusions: Chlorine dioxide was liberated into the gas phase in the presence of CO2 and water vapor, eliminating the bacteria. Sodium-chlorite-loaded nanofibers can be sources of prolonged chlorine dioxide production and subsequent pathogen inactivation in a CO2-rich and humid environment. Based on the results, further evaluation of the possible application of the formulation in face-mask filters as medical devices is encouraged.

Various dimeric derivatives of the glycopeptide antibiotic teicoplanin were prepared with the aim of increasing the activity of the parent compound against glycopeptide-resistant bacteria, primarily vancomycin-resistant enterococci. Starting from teicoplanin, four covalent dimers were prepared in two orientations, using an α,ω-bis-isothiocyanate linker. Formation of a dimeric cobalt coordination complex of an N-terminal L-histidyl derivative of teicoplanin pseudoaglycone has been detected and its antibacterial activity evaluated. The Co(III)-induced dimerization of the histidyl derivative was demonstrated by DOSY experiments. Both the covalent and the complex dimeric derivatives showed high activity against VanA teicoplanin-resistant enterococci, but their activity against other tested bacterial strains did not exceed that of the monomeric compounds.

The increase in antibiotic resistance among Gram-positive bacteria underscores the urgent need to develop new antibiotics. New antibiotics should target actively growing susceptible bacteria that are resistant to clinically accepted antibiotics including bacteria that are not growing or are protected in a biofilm environment. In this paper, we compare the in vitro activities of two new semisynthetic glycopeptide antibiotics, MA79 and ERJ390, with two clinically used glycopeptide antibiotics—vancomycin and teicoplanin. The new antibiotics effectively killed not only exponentially growing cells of Staphylococcus aureus, but also cells in the stationary growth phase and biofilm.

Pleuromutilin is a fungal diterpene natural product with antimicrobial properties, semisynthetic derivatives of which are used in veterinary and human medicine. The development of bacterial resistance to pleuromutilins is known to be very slow, which makes the tricyclic diterpene skeleton of pleuromutilin a very attractive starting structure for the development of new antibiotic derivatives that are unlikely to induce resistance. Here, we report the very first synthetic modifications of pleuromutilin and lefamulin at alkene position C19–C20, by two different photoinduced addition reactions, the radical thiol-ene coupling reaction, and the atom transfer radical additions (ATRAs) of perfluoroalkyl iodides. Pleuromutilin were modified with the addition of several alkyl- and aryl-thiols, thiol-containing amino acids and nucleoside and carbohydrate thiols, as well as perfluoroalkylated side chains. The antibacterial properties of the novel semisynthetic pleuromutilin derivatives were investigated on a panel of bacterial strains, including susceptible and multiresistant pathogens and normal flora members. We have identified some novel semisynthetic pleuromutilin and lefamulin derivatives with promising antimicrobial properties.

The protracted global COVID-19 pandemic urges the development of new drugs against the causative agent SARS-CoV-2. The clinically used glycopeptide antibiotic, teicoplanin, emerged as a potential antiviral, and its efficacy was improved with lipophilic modifications. This prompted us to prepare new lipophilic apocarotenoid conjugates of teicoplanin, its pseudoaglycone and the related ristocetin aglycone. Their antiviral effect was tested against SARS-CoV-2 in Vero E6 cells, using a cell viability assay and quantitative PCR of the viral RNA, confirming their micromolar inhibitory activity against viral replication. Interestingly, two of the parent apocarotenoids, bixin and β-apo-8′carotenoic acid, exerted remarkable anti-SARS-CoV-2 activity. Mechanistic studies involved cathepsin L and B, as well as the main protease 3CLPro, and the results were rationalized by computational studies. Glycopeptide conjugates show dual inhibitory action, while apocarotenoids have mostly cathepsin B and L affinity. Since teicoplanin is a marketed antibiotic and the natural bixin is an approved, cheap and widely used red colorant food additive, these readily available compounds and their conjugates as potential antivirals are worthy of further exploration.

Microplastic pollution is prevalent in the Ottawa River, with all open water samples (n = 62) and sediment samples (n = 10) containing microplastics. The median microplastic concentration of nearshore 100 L water samples was 0.1 fragments per L (ranged between 0.05 and 0.24 fragments per L). The larger volume Manta trawls samples taken in the middle of the Ottawa River had an overall mean concentration of plastics of 1.35 fragments per m3. Plastic concentrations were significantly higher downstream of the wastewater treatment plant (1.99 fragments per m3) compared with upstream of the effluent output (0.71 fragments per m3), suggesting that the effluent plume is a pathway for plastic pollution to the Ottawa River. The mean concentration of microplastic fragments recovered in the sediment samples was 0.22 fragments per g dry weight. The abundance of microplastics in the sediment was not significantly related to the mean particle size or the organic content of the sediment. The most common form of plastic particles found was microfibers. These made up between 70% and 100% of all plastic particles observed, although plastic microbeads and secondary plastic fragments were also recovered.

Herein 1H and 13C NMR spectra of ERJ-500, a new hybrid aspirin derivative, covalently conjugated to nitrogen monoxide donor linsidomine are presented as well as NMR spectra of its synthetic intermediate compounds. HPLC-MS measurements data are also included, demonstrating the stability of the linsidomine-aspirin hybrid in oxidation reactions. This data article also concerns miscellaneous myocardial parameters of isolated rat hearts as a complementation of the tables shown in the paper entitled “A new, vasoactive hybrid aspirin containing nitrogen monoxide-releasing molsidomine moiety” Szoke et al., 2019. Column tables represent data of aorta flow, aortic pressure, derivated aortic pressure and cardiac output. Keywords: ERJ-500, Hybrid aspirin, Molsidomine

For some time, glycopeptide antibiotics have been considered the last line of defense against Methicillin-resistant Staphylococcus aureus (MRSA). However, vancomycin resistance of Gram-positive bacteria is an increasingly emerging worldwide health problem. The mode of action of glycopeptide antibiotics is essentially the binding of peptidoglycan cell-wall fragments terminating in the d-Ala-d-Ala sequence to the carboxylate anion binding pocket of the antibiotic. Dimerization of these antibiotics in aqueous solution was shown to persist and even to enhance the antibacterial effect in a co-operative manner. Some works based on solid state (ss) Nuclear Magnetic Resonance (NMR) studies questioned the presence of dimers under the conditions of ssNMR while in a few cases, higher-order oligomers associated with contiguous back-to-back and face-to-face dimers were observed in the crystal phase. However, it is not proved if such oligomers persist in aqueous solutions. With the aid of 15N-labelled eremomycin using 15N relaxation and diffusion NMR methods, we observed tetramers and octamers when the N-Ac-d-Ala-d-Ala dipeptide was added. To the contrary, the N-Ac-d-Ala or (N-Ac)2-l-Lys-d-Ala-d-Ala tripeptide did not induce higher-order oligomers. These observations are interesting examples of tailored supramolecular self-organization. New antimicrobial tests have also been carried out with these self-assemblies against MRSA and VRE (resistant) strains.

Background: Cardioprotective effects of H2S are being suggested by numerous studies. Furthermore, H2S plays a role in relaxation of vascular smooth muscle, protects against oxidative stress, and modulates inflammation. Long-term high-dose use of NSAIDs, such as ibuprofen, have been associated with enhanced cardiovascular risk. The goal of the present work is the synthesis and basic pharmacological characterization of a newly designed H2S-releasing ibuprofen derivative. Methods: Following the synthesis of EV-34, a new H2S-releasing derivative of ibuprofen, oxidative stability assays were performed (Fenton and porphyrin assays). Furthermore, stability of the molecule was studied in rat serum and liver lysates. H2S-releasing ability of the EC-34 was studied with a hydrogen sulfide sensor. MTT (3-(4,5-dimethylthiazol 2-yl)-2,5-(diphenyltetrazolium bromide)) assay was carried out to monitor the possible cytotoxic effect of the compound. Cyclooxygenase (COX) inhibitory property of EV-34 was also evaluated. Carrageenan assay was carried out to compare the anti-inflammatory effect of EV-34 to ibuprofen in rat paws. Results: The results revealed that the molecule is stable under oxidative condition of Fenton reaction. However, EV-34 undergoes biodegradation in rat serum and liver lysates. In cell culture medium H2S is being released from EV-34. No cytotoxic effect was observed at concentrations of 10, 100, 500 µM. The COX-1 and COX-2 inhibitory effects of the molecule are comparable to those of ibuprofen. Furthermore, based on the carrageenan assay, EV-34 exhibits the same anti-inflammatory effect to that of equimolar amount of ibuprofen (100 mg/bwkg). Conclusion: The results indicate that EV-34 is a safe H2S releasing ibuprofen derivative bearing anti-inflammatory properties.

West Nile virus (WNV) is an emerging arbovirus that causes infections worldwide. Clinical manifestations of the infection vary from asymptomatic to fatal illness when it reaches the central nervous system. To date, vaccine and specific antiviral treatments are not available. Teicoplanin is already used to treat Gram-positive bacterial infections. Furthermore, it has been reported to block the entry of pseudotyped Ebola, Middle East respiratory syndrome coronavirus and severe acute respiratory syndrome coronavirus. Moreover, teicoplanin derivatives showed anti-influenza virus, anti-human immunodeficiency virus, anti-hepatitis C virus, and anti-dengue virus activity. In total, 12 teicoplanin derivatives have been tested against our West Nile virus isolate. Vero E6 cells were simultaneously treated with 50 µM of teicoplanin derivatives and infected with WNV at the same time. Virus-induced cytopathic effect and cytotoxicity were examined 4 days post-infection. One compound completely blocked virus pathogenesis, while five compounds reduced the viral titer. Further studies will be conducted to unravel the mode of action of these promising derivatives.

Influenza A and B viruses are a global threat to human health and increasing resistance to the existing antiviral drugs necessitates new concepts to expand the therapeutic options. Glycopeptide derivatives have emerged as a promising new class of antiviral agents. To avoid potential antibiotic resistance, these antiviral glycopeptides are preferably devoid of antibiotic activity. We prepared six vancomycin aglycone hexapeptide derivatives with the aim of obtaining compounds having anti-influenza virus but no antibacterial activity. Two of them exerted strong and selective inhibition of influenza A and B virus replication, while antibacterial activity was successfully eliminated by removing the critical N-terminal moiety. In addition, these two molecules offered protection against several other viruses, such as herpes simplex virus, yellow fever virus, Zika virus, and human coronavirus, classifying these glycopeptides as broad antiviral molecules with a favorable therapeutic index.

A small library of 3’-deoxy-C3’-substituted xylofuranosyl-pyrimidine nucleoside analogues were prepared by photoinduced thiol-ene addition of various thiols, including normal and branched alkyl-, 2-hydroxyethyl, benzyl-, and sugar thiols, to 3’-exomethylene derivatives of 2’,5’-di-O-tert-butyldimethylsilyl-protected ribothymidine and uridine. The bioactivity of these derivatives was studied on tumorous SCC (mouse squamous carcinoma cell) and immortalized control HaCaT (human keratinocyte) cell lines. Several alkyl-substituted analogues elicited promising cytostatic activity in low micromolar concentrations with a slight selectivity toward tumor cells. Near-infrared live-cell imaging revealed SCC tumor cell-specific mitotic blockade via genotoxicity of analogue 10, bearing an n-butyl side chain. This analogue essentially affects the chromatin structure of SCC tumor cells, inducing a condensed nuclear material and micronuclei as also supported by fluorescent microscopy. The results highlight that thiol-ene chemistry represents an efficient strategy to discover novel nucleoside analogues with non-natural sugar structures as anticancer agents.

Bona Salut a Cuneo és un projecte d'innovació sanitària que es va posar en marxa l'estiu del 2008 per al sistema regional italià de salut ASL CN1. El projecte proposava noves solucions i estratègies de disseny que volien donar resposta a les necessitats de salut locals dels ciutadans i els proveïdors d'assistència sanitària de la província de Cuneo. Demostrà el valor del disseny com a eina estratègica i de transformació fent servir la recerca per entendre la problemàtica sanitària dels actors interessats i els contextos locals, el design thinking per identificar les oportunitats d'innovació, i les tècniques de disseny per transformar aquestes oportunitats en propostes de salut sostenibles que aprofitin els recursos locals.