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The current study aimed to examine the relationships between item-based tests and a narrative retelling by analyzing concurrent associations, regression coefficients, language progress, and sex differences. Thirty-one kindergarteners with typical language development were assessed at the beginning (Mage = 64.77 months) and the end of the school year. The statistically significant associations and predictive relations between the item-based tests and narrative retelling were scarce and occurred mainly at the same language level (words and sentences). Accordingly, language progression was mirrored differently by the two assessment conditions. Sex was not related to language skills. Overall, the results indicate these two kinds of tools assess different language constructs and should be used complementarily. Additionally, two relatively innovative trends emerged: errors produced in the narrative seem to be a good discriminative metric for this age range, and testing language by units (words and sentences) might be appropriate to assess language development.

Novel multicomponent crystal forms were obtained from reactions of trans-disubstituted cyclam derivatives with flufenamic and salicylic acids. The reactions of H2(4-CF3PhCH2)2cyclam with those acids led to the formation of salts of the formulae [H2{H2(4-CF3PhCH2)2cyclam}](3-CF3PhNHC6H4COO)2 and [H2{H2(4-CF3PhCH2)2cyclam}](HOC6H4COO)2, respectively. The reaction of H2(PhCH2)2cyclam with flufenamic acid led to the formation of the salt [H2{H2(PhCH2)2cyclam}](3-CF3PhNHC6H4COO)2, whereas its reaction with salicylic acid afforded the ionic cocrystal [H2(PhCH2)2cyclam](HOC6H4COOH)2·[H2{H2(PhCH2)2cyclam}](HOC6H4COO)2. The compounds obtained were fully characterized and tested against several yeasts as well as Gram-positive and Gram-negative bacterial strains. The results have shown that the new multicomponent forms display relevant antimicrobial activity when compared to their parent cyclam derivatives, highlighting the importance of exploring synergistic effects to unveil new and efficient antimicrobial agents. [ABSTRACT FROM AUTHOR]

Mechanochemistry has been assuming a major role in chemistry over the last years. Its potential in a wide variety of reactions is undeniable nowadays, contributing to sustainable chemistry and, at the same time, leading to lower reaction time, higher selectivity and novel reactivity. Herein we disclose new solid forms of pipemidic acid, an antibiotic against which bacteria have been developing resistance mechanisms, obtained by mechanochemistry. These forms are molecular salts with glycolic, oxalic and (R)- and (S)-camphorsulfonic acids, as well as a Cu(II) complex exhibiting a 1D hydrogen bonded network. To prove the importance of the technique, we present here also the rapid and high yielding mechanochemical synthesis of a previously reported Ag metal–organic framework with pipemidic acid. [ABSTRACT FROM AUTHOR]

Background: The inherent potential of filamentous fungi, especially of Ascomycota, for producing diverse bioactive metabolites remains largely silent under standard laboratory culture conditions. Innumerable strategies have been described to trigger their production, one of the simplest being manipulation of the growth media composition. Supplementing media with ionic liquids surprisingly enhanced the diversity of extracellular metabolites generated by penicillia. This finding led us to evaluate the impact of ionic liquids' stimuli on the fungal metabolism in Aspergillus nidulans and how it reflects on the biosynthesis of secondary metabolites (SMs). Results: Whole transcriptional profiling showed that exposure to 0.7 M cholinium chloride or 1-ethyl-3- methylimidazolium chloride dramatically affected expression of genes encoding both primary and secondary metabolism. Both ionic liquids apparently induced stress responses and detoxification mechanisms but response profiles to each stimulus were unique. Primary metabolism was up-regulated by choline, but down-regulated by 1- ethyl-3-methylimidazolium chloride; both stimulated production of acetyl-CoA (key precursor to numerous SMs) and non proteinogenic amino acids (building blocks of bioactive classes of SMs). In total, twenty one of the sixty six described backbone genes underwent up-regulation. Accordingly, differential analysis of the fungal metabolome showed that supplementing growth media with ionic liquids resulted in ca. 40 differentially accumulated ion masses compared to control conditions. In particular, it stimulated production of monodictyphenone and orsellinic acid, otherwise cryptic. Expression levels of genes encoding corresponding polyketide biosynthetic enzymes (i.e. backbone genes) increased compared to control conditions. The corresponding metabolite extracts showed increased cell polarity modulation potential in an ex vivo whole tissue assay (Thelial Live Targeted Epithelia; theLiTE™). Conclusions: Ionic liquids, a diverse class of chemicals composed solely of ions, can provide an unexpected means to further resolve the diversity of natural compounds, guiding discovery of fungal metabolites with clinical potential. [ABSTRACT FROM AUTHOR]

Background: The backstage of research projects is seldom presented to the general audience, in particular, how the research questions emerged, how the team interacted and how the methods and design were decided upon. Aim: In this paper we will recount the story behind an international practice‐based research network for personalising health assessment, the joint journey of researchers and therapists from three different countries in creating the Individualised Patient‐Progress System (IPPS). Results: We first describe how the idea of the IPPS emerged; then we show how IPPS is being piloted and integrated into clinical practice. Next, we present the views of therapists and researchers who have been part of this project. Conclusions: We discuss some lessons learned from this 14‐year collaborative research programme. [ABSTRACT FROM AUTHOR]

Background: Lipid polymers in plant cell walls, such as cutin and suberin, build recalcitrant hydrophobic protective barriers. Their degradation is of foremost importance for both plant pathogenic and saprophytic fungi. Regardless of numerous reports on fungal degradation of emulsified fatty acids or cutin, and on fungi–plant interactions, the pathways involved in the degradation and utilisation of suberin remain largely overlooked. As a structural component of the plant cell wall, suberin isolation, in general, uses harsh depolymerisation methods that destroy its macromolecular structure. We recently overcame this limitation isolating suberin macromolecules in a near-native state. Results: Suberin macromolecules were used here to analyse the pathways involved in suberin degradation and utilisation by Aspergillus nidulans. Whole-genome profiling data revealed the complex degrading enzymatic machinery used by this saprophytic fungus. Initial suberin modification involved ester hydrolysis and ω-hydroxy fatty acid oxidation that released long chain fatty acids. These fatty acids were processed through peroxisomal β-oxidation, leading to up-regulation of genes encoding the major enzymes of these pathways (e.g. faaB and aoxA). The obtained transcriptome data was further complemented by secretome, microscopic and spectroscopic analyses. Conclusions: Data support that during fungal growth on suberin, cutinase 1 and some lipases (e.g. AN8046) acted as the major suberin degrading enzymes (regulated by FarA and possibly by some unknown regulatory elements). Suberin also induced the onset of sexual development and the boost of secondary metabolism. [ABSTRACT FROM AUTHOR]

Background Involving patients in treatment is becoming increasingly popular in mental health [Sales & Alves: Personalized evaluation of psychological treatments: A review of tools and research designs, submitted]. However, in substance misuse treatment settings, the patient perspective about treatment tends to be overlooked. This has been cited as a key priority by Orford et al. [Addiction, 103: 875-885, 2008] who included patient feedback about treatment as one of ten areas requiring an urgent paradigm shift in addiction research and practice. This project will apply an innovative method to involve substance misuse patients in psychological therapies, by asking them to suggest topics to evaluate their treatment. These topics suggested by patients can be written as a list of personalized items, so-called as patient-generated outcome measures (PGOM). Despite its patient-friendly features, PGOM's have never been used in this population, which is what this project aims to overcome. Methods/design This project is part of an International Exchange Platform on Personalising Addiction Treatment. Data will be collected in two phases (pre-post study and focus groups with patients) to explore the following: 1) How reliable and sensitive to change are PGOM's and standardised measures in substance misuse treatment? 2) Do PGOM's add relevant information to standardised measures? 3) What are the views of substance misuse patients about personalized outcome assessment? 4) Development of guidelines on using PGOM's in this population Discussion This research will potentially demonstrate the diversity of personal problems among patients seeking substance misuse treatment, suggesting the relevance of PGOM as a method to personalise outcome measurement and, ultimately, guiding treatment provision. It is expected that, as in previous studies, PGOM's will be perceived as helpful and patient-friendly tools, where patients may express their own concerns in a semi-structured setting. Similarly to other populations, we also expect PGOM's to be reliable, valid and sensitive to clinical changes in substance misuse treatment, as well as more content informative than their standardized counterparts. If these results are achieved, we might hypothesize that PGOM's are a potentially valid supplement to traditional standardised scales, by providing a closer insight to what motivates patients to participate in substance misuse treatment programmes. [ABSTRACT FROM AUTHOR]

The urge for the development of a more efficient antibiotic crystalline forms led us to the disclosure of new antibiotic coordination frameworks of pyrazinamide, a well-known drug used for the treatment of tuberculosis, with some of the novel compounds unravelling improved antimycobacterial activity. Mechanochemistry was the preferred synthetic technique to yield novel compounds, allowing the reproduction of a 1D zinc framework, the synthesis of a novel hydrogen bonding manganese framework, and three new compounds with silver. The structural characterization of the novel forms is presented along with stability studies. The increased antimicrobial activity of the new silver-based frameworks against Escherichia coli, Staphylococcus aureus, and Mycobacterium smegmatis is particularly relevant. [ABSTRACT FROM AUTHOR]

Tazobactam (TazoH) is a penicillinate sulfone β-lactamase inhibitor with negligible antimicrobial activity, commonly used with other antibiotics to provide an effective combination against many susceptible organisms expressing β-lactamases. Two novel Ag(I)-tazobactam frameworks ([Ag(I)-Tazo] and [Ag(I)-Tazo 2 ]) prepared by mechanochemistry are presented herein as alternative forms to improve the antimicrobial activity of tazobactam by exploring synergistic effects with silver, being the first crystal structures reported of tazobactam coordinating to a metal site. The topological analysis of the 3D ([Ag(I)-Tazo]) and 2D+1D ([Ag(I)-Tazo 2 ]) frameworks revealed underlying nets with the cbs (CrB self-dual) and decorated sql topologies, respectively. These novel frameworks are stable and show an enhanced antimicrobial activity when compared to tazobactam alone. Amongst the tested microorganisms, Pseudomonas aeruginosa is the most sensitive to tazobactam and the new compounds. This study thus unveils novel facets of tazobactam chemistry and opens up its application as a multifunctional linker for the design of antibiotic coordination frameworks and related materials., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ferreira, Alves, Kirillov, Rijo and André.)

We report herein three novel complexes whose design was based on the approach that consists of combining commercially available antibiotics with metals to attain different physicochemical properties and promote antimicrobial activity. Thus, new isostructural three-dimensional (3D) hydrogen bonding frameworks of pipemidic acid with manganese (II), zinc (II) and calcium (II) have been synthesised by mechanochemistry and are stable under shelf conditions. Notably, the antimicrobial activity of the compounds is maintained or even increased; in particular, the activity of the complexes is augmented against Escherichia coli , a representative of Gram-negative bacteria that have emerged as a major concern in drug resistance. Moreover, the synthesised compounds display similar general toxicity ( Artemia salina model) levels to the original antibiotic, pipemidic acid. The increased antibacterial activity of the synthesised compounds, together with their appropriate toxicity levels, are promising outcomes.

A homologous series of novel nitro-catechol structures (7a-7e) were synthesized and tested as inhibitors of the enzyme catechol-O-methyltransferase (COMT). Increasing chain length was found to have significant impact on both brain penetration and duration of COMT inhibition in the rat. Of this series, compound 7b (1-(3,4-dihydroxy-5-nitrophenyl)-2-phenyl-ethanone) was found to exhibit the most potent and selective inhibition of peripheral COMT, with an inhibition profile more similar to entacapone 2 than tolcapone 1 (an equipotent peripheral and central inhibitor) but with much improved duration of action (7b, 70% inhibition and 2, 25% inhibition at 9 h after administration). The effects of structural modifications to 7b on COMT inhibitory profile were investigated, and it is concluded that the carbonyl group and preferably unsubstituted aromatic ring are essential features to maintain prolonged peripheral COMT inhibition. The introduction of the alpha-methylene group, the major structural difference between 7b and 1, would appear responsible for the observed enhancement in selectivity of peripheral COMT inhibition of 7b, which has more limited access to the brain than 1.