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Objectives: To describe how SARS-CoV-2 infection at the time of delivery affected maternal and neonatal outcomes across four major waves of the COVID-19 pandemic in Italy. Methods: This is a large, prospective, nationwide cohort study collecting maternal and neonatal data in case of maternal peripartum SARS-CoV-2 infection between February 2020 and March 2022. Data were stratified across the four observed pandemic waves. Results: Among 5201 COVID-19-positive mothers, the risk of being symptomatic at delivery was significantly higher in the first and third waves (20.8-20.8%) than in the second and fourth (13.2-12.2%). Among their 5284 neonates, the risk of prematurity (gestational age

Background/Objectives: Gestational diabetes mellitus (GDM) is one of the most common morbidities of pregnancy. The impact of increased maternal blood glucose on fetoplacental hemodynamics is not fully elucidated, especially in patients with uncontrolled GDM necessitating insulin therapy. The objective of this study was to assess the impact of insulin therapy on the umbilical artery dopplers in GDM pregnancies adequate for gestational-age fetuses. Methods: Retrospective observational study among 447 GDM pregnant women, divided according to their treatment (nutritional therapy (NT), long acting (LA) insulin, combined insulin) and 100 healthy controls with the same gestational age. The umbilical artery pulsatility index (UA-PI) was recorded at 28, 32 and 36 weeks. Results: UA-PI values declined in both GDM and healthy controls at all three time intervals. The combined insulin group showed reduced UA-PI values in comparison to the LA insulin group, but the difference never reached statistical significance. The combined insulin group exhibited significantly reduced UA-PI values at 32- and 36-weeks’ gestation compared to the NT groups. Conclusions: A decreased impedance to blood flow in the umbilical artery of diabetic mothers on insulin therapy was observed. This was more pronounced during the last trimester. The extent to which umbilical artery PI can predict unfavorable outcomes has yet to be determined. Further additional studies are necessary to confirm the precise impact of glucose levels and medical interventions on the circulation of both the fetus and the mother.

La letteratura dedicata all’analisi dei manuali didattici ha da tempo evidenziato una serie di lacune nei materiali input in termini di modello conversazionale suggerendo l’impiego di corpora come fonte per la costruzione di risorse didattiche. Con l’intento di contribuire al dibattito sul tema, il presente lavoro discute uno studio pilota mirato a confrontare parlato spontaneo e dialoghi didattici in interazioni task-based orientate al compito Ordinare al tavolo di un ristorante. L’analisi pragmatica dei due tipi di dialogo ha portato all’identificazione della struttura sequenziale di questo tipo di interazione, oltre che al riconoscimento dei ruoli interazionali del cameriere e del cliente nelle diverse fasi della conversazione. Il confronto ha evidenziato inoltre come i dialoghi dei manuali e le interazioni spontanee rappresentino due diversi modelli interazionali: il parlato spontaneo prevede un’agenda nascosta e rappresenta un tipo peculiare di parlato istituzionale; i dialoghi didattici trattano invece il task come una conversazione ordinaria di tipo simmetrico. Questi primi risultati, oltre ad aprire la strada ad ulteriori indagini, offrono una serie di indicazioni operative per la didattica, sia in termini di selezione degli input che di progettazione di attività. A pragmatic analysis of a task-based corpus of spontaneous speech and instructional dialogues The literature dedicated to the analysis of teaching materials has highlighted a series of limitations in the input materials in terms of conversational model, suggesting the use of corpora as a source for the effective planning of teaching resources. With the aim of contributing to the current debate, the present work discusses a pilot study aimed at comparing spontaneous speech and teaching dialogues in task-based interactions oriented to the task of Ordering at a restaurant table. The pragmatic analysis of the two types of data led to the identification of the sequential structure of the interactions considered, as well as the recognition of waiter and customer interactional roles at different stages of this kind of interaction. The comparison also highlighted how teaching dialogues and spontaneous interactions represent two different interactional models: spontaneous speech involves a hidden agenda and it is structured as a peculiar institutional speech; didactic dialogues instead treat the task as an ordinary symmetrical conversation. These first results pave the way for further investigations and offer a series of practical suggestions for teaching, both in terms of input selection and activities development.

The intrinsic steady-state and time-resolved fluorescence of Leishmania major pteridine reductase 1, a tetrameric protein target for anti-infective agents, is investigated and deciphered in terms of the contributions from populations of the two tryptophans included in each protein monomer. Signals from these local fluorometric reporters contain molecular-level information on the conformational landscape of this protein and on its interaction with a nanomolar pteridinic inhibitor.

Abstract There is growing interest on the potential clinical relevance of the endometrial microbiome. However, insufficient attention has been given to the methodology of sampling. To minimize contamination, we advocate the use of the double-lumen catheters commonly employed for the embryo transfer. Endometrial fluid samples obtained from 53 women scheduled for IVF were studied for microbiome characterization. Control samples from the vagina of these same women were concomitantly obtained. Samples were analysed by V3–V4–V6 regions of 16S rRNA gene sequencing with Next Generation Sequencing technique. Endometrial Lactobacillus-dominant cases were uncommon compared to previous evidence, being observed in only 4 (8%) women. Taxonomy markedly differed between the endometrial and vaginal microbiomes composition. The most common bacterial genera coincided in only 4 (8%) women. The comparison between women who did and did not subsequently become pregnant failed to identify any microorganism associated with the success of the procedure. However, the endometrial biodiversity resulted higher among pregnant women. Shannon’s Equitability index in pregnant and non pregnant women was 0.76 [0.57–0.87] and 0.55 [0.51–0.64], respectively (p = 0.002). In conclusion, the use of embryo transfer catheters for testing the endometrial microbiome is promising. The scant concordance with vaginal samples supports the validity of this approach. Moreover, our study highlighted a possible beneficial role of a higher biodiversity on endometrial receptivity.

Poly(methyl methacrylate) (PMMA) is characterized by high CO2 capture yield under mild pressures and temperatures. A morphological modification of powdery amorphous PMMA (pPMMA) is carried out by electrospinning to increase the surface/volume ratio of the resulting electrospun PMMAs (ePMMAs). This modification improves the kinetics and the capture yields. The rate constants observed for ePMMAs are two to three times higher than those for pPMMA, reaching 90% saturation values within 5–7 s. The amount of sorbed CO2 is up to eleven times higher for ePMMAs at 1 °C, and the highest difference in captured CO2 amount is observed at the lowest tested pressure of 1 MPa. The operating life of the ePMMAs shows a 5% yield loss after ten consecutive runs, indicating good durability. Spent electrospun PMMAs after several cycles of CO2 sorption-desorption can be regenerated by melting and again electrospinning the molten mass, resulting in a CO2 capture performance that is undistinguishable from that observed with fresh ePMMA. Scanning electron and atomic force microscopies show a reduction in surface roughness after gas exposure, possibly due to the plasticization effect of CO2. This study shows the potential of electrospun PMMAs as solid sorbents for carbon capture from natural gas or pre-combustion and oxyfuel combustion processes.

In questo contributo viene presentato uno studio di caso dedicato al tema della revisione collaborativa tra pari per la scrittura. La ricerca ha coinvolto una classe quarta di una scuola primaria ad alta densità migratoria, impegnata nella sperimentazione di un percorso di scrittura narrativa tratto dal sillabo di Osservare l'Interlingua (Pallotti, Borghetti, Rosi, 2022; Pallotti, Ferrari, 2019). L'indagine dà conto dei comportamenti correttivi di docente e allievi, concentrandosi in particolare sull'interazione tra istruzioni procedurali dell'insegnante, attualizzazione delle consegne nella fase di revisione ed eventuale accoglienza delle proposte nella fase di riscrittura da parte degli studenti. The collaborative revision of the written text. Acquisitional observations from a case study in a multilingual primary school This paper presents a case study on collaborative peer review for writing. The research involved fourth graders of a primary school in a north-Italian urban context. The pupils were engaged in experimenting with a narrative writing protocol taken from the syllabus of Osservare l'Interlingua (Pallotti, Borghetti, Rosi, 2022; Pallotti, Ferrari, 2019). The analysis considers the corrective behaviors of teacher and students, focusing in particular on the interaction between the teacher's procedural instructions to the revision phase and on the acceptance of the revision proposals in the rewriting phase by the authors.

Drugs that target human thymidylate synthase (hTS), a dimeric enzyme, are widely used in anticancer therapy. However, treatment with classical substrate-site-directed TS inhibitors induces over-expression of this protein and development of drug resistance. We thus pursued an alternative strategy that led us to the discovery of TS-dimer destabilizers. These compounds bind at the monomer-monomer interface and shift the dimerization equilibrium of both the recombinant and the intracellular protein toward the inactive monomers. A structural, spectroscopic, and kinetic investigation has provided evidence and quantitative information on the effects of the interaction of these small molecules with hTS. Focusing on the best among them, E7, we have shown that it inhibits hTS in cancer cells and accelerates its proteasomal degradation, thus causing a decrease in the enzyme intracellular level. E7 also showed a superior anticancer profile to fluorouracil in a mouse model of human pancreatic and ovarian cancer. Thus, over sixty years after the discovery of the first TS prodrug inhibitor, fluorouracil, E7 breaks the link between TS inhibition and enhanced expression in response, providing a strategy to fight drug-resistant cancers.

This paper reports the results of an investigation into the teaching of L2 Italian in mainstream schools in the school year 2019/2020 during the Covid-19 pandemic. The teachers’ perspective on the online teaching experience is explored through semi-structured interviews focusing on the challenges and the didactic and organisa-tion strategies connected to distance teaching, conducted with 14 teachers of L2 Ital-ian working in three different municipalities of the Emilia Romagna Region.

Objective To evaluate whether telomere length (TL), mitochondrial-DNA (mt-DNA) or epigenetic age estimators based on DNA methylation (DNAm) pattern could be considered reliable predictors of in-vitro-fertilization (IVF) success in terms of live birth rate. Design Prospective cohort study Setting Infertility Unit of the Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Patients 181 women aged 37–39 years who underwent IVF at a single-centre between January 2017 and December 2018. Interventions On the day of recruitment, blood samples were collected, and genomic DNA was isolated from white blood cells. TL, mt-DNA and DNAm assessment was performed using quantitative real-time polymerase chain reaction (qPCR). Biological age (DNAm age) was computed as the algorithm based on methylation pattern of five genes. Epigenetic age acceleration was estimated from the residuals of the linear model of epigenetic age regressed on chronological age. Long Interspersed Nuclear Elements (LINE)-1 methylation pattern was used as a surrogate for global DNA methylation. Main outcome measures This study investigated whether peripheral TL, mt-DNA and DNAm could predict live birth in IVF cycles. Results TL, mt-DNA and LINE-1 methylation were not associated with IVF success. Conversely, DNAm age resulted significantly lower in women who had a live birth compared to women who did not (36.1 ± 4.2 and 37.3 ± 3.3 years, respectively, p = 0.04). For DNAm age, odds ratio (OR) for live birth per year of age was 0.90 (95%CI: 0.82–0.99, p = 0.036) after adjusting for FSH and antral follicle count (AFC) and 0.90 (95%CI: 0.82–0.99, p = 0.028) after adjusting also for number of oocytes retrieved. A significant association also emerged for epigenetic age acceleration after adjustments (OR = 0.91, 95%CI: 0.83–1.00, p = 0.048). Conclusion DNAm age is associated with IVF success but the magnitude of this association is insufficient to claim a clinical use. However, our findings are promising and warrant further investigation. Assessment of biological age using different epigenetic clocks or focusing on different tissues may reveal new predictors of IVF success.

In this work we investigated the synthesis and the characterization of electrospun polyacrylonitrile (PAN) and polymethyl methacrylate (PMMA) stabilized in air, made in a 5:1 ratio, used as sorbent for the solid-phase extraction of fluoroquinolones in plasma samples and the following quantification in UHPLC-PDA. Preliminary analyses of viscosity were carried out on the polymer solution to be sure about the electrospinability. Characterizations were performed on the electrospun membrane to evaluate the morphology (SEM scanning electron microscopy and AFM atomic force microscopy), the thermal degradation behavior (TGA thermogravimetric analysis), the porosity and the surface area (BET, Brunauer Emmett Teller), and the quantitative and qualitative distribution of atomic structures (FTIR infrared analysis in Fourier transform and EDX Energy Dispersive X-ray analysis). A solid-phase extraction method was developed by studying parameters such as the amount of sorbent and the pH of the sample. Finally, a UHPLC-PDA method for the analysis of fluoroquinolones was developed and validated in accordance with the guidelines and successfully applied. The use of the prepared sorbent combined with UHPLC-PDA has allowed the development of a method whose strengths are its speed, accuracy, sensitivity, and high recoveries.

In this work, a sorbent was prepared from wastepaper samples enriched with iron oxide particles and graphene oxide and used in the solid phase extraction of antibiotics. The precursor underwent a carbothermal reduction to promote the formation of paramagnetic phases useful for the recovery of the sorbent during the analysis, and to disperse and fix graphene and the iron oxide in a durable way throughout the cellulose structure. Characterizations were carried out to evaluate the composition (Raman, XRD and EDX) and the morphological structure (SEM) of the material. A UHPLC-PDA method was developed for the simultaneous determination of antibiotics from different drug families (carbapenems, fluoroquinolones, β-lactams) using a 120 SB-C 18 poroshell column (50 × 2.1 mm I.D., 2.7 um particle size) and a mobile phase consisting of 10 mM acetate buffer at pH 5 (Line A) and acetonitrile (Line B) both containing 0.1% of triethylamine. A gradient elution was used for the separation of the analytes, while for the quantitative analysis each analyte was determined at its maximum wavelength. Several experiments were carried out to evaluate the influence of different parameters involving the dispersive magnetic solid phase extraction of these analytes. Samples were extracted using 25 mg of sorbent at pH 5 and desorbed in 5 min using methanol. We report herein on some of the outstanding advantages of using carbon-based sorbent, such as lower toxicity, scalability, improved absorption capacity, target selectivity and stability in acidic medium. Moreover, from the results obtained it is evident that, despite the use of some recycled materials, the performances obtained were comparable or even superior to the methods reported in the literature.

Several studies suggested that male's diet affects fertility. This cross-sectional analysis from a prospective cohort study aims to explore the relation between antioxidants intake and sperm parameters in sub-fertile couples referring to a Fertility center. Socio-demographic characteristics, health history, lifestyle habits, and diet information were obtained. A semen sample was analyzed to proceed with assisted reproduction. Three hundred and twenty-three men were enrolled: 19.1% had semen volume (SV) < 1.5 mL, 31.4% sperm concentration (SC) < 15.0 mil/mL, 26.8% sperm motility < 32%, and 33.0% had total sperm count (TSC) < 39.0 mil. Higher levels of α-carotene were associated to lower risk of low SC [4th vs. 1st quartile, adjusted OR (aOR) 0.43, 95% CI 0.20–0.91) and low TSC (aOR 0.46, 95% CI 0.22–0.95). Higher intake of β-carotene was inversely associated with risk of low TSC. Lycopene intake was associated with higher risk for these conditions (aOR 2.46, 95%CI 1.01–5.98, SC), and (aOR 3.11, 95%CI 1.29–7.50, TSC). Risk of low semen volume was lower in men with higher level of vitamin D intake (aOR 0.25, 95%CI 0.09–0.66)]. Further research, especially, well-designed randomized clinical trials (RCT), is needed to understand how diet modifications may have a role in modulating male fertility and fecundability.

Abstract Background Vitamin D plays an important role in human physiology and pathology. The receptor for vitamin D regulates 0.5–5% of the human genome. Accordingly, vitamin D insufficiency has been shown to increase the risk of several diseases. In recent years, based on growing evidence, on a role of vitamin D has been also postulated in reproductive health both in animals and humans, especially in female fertility female fertility. In vitro fertilization success was shown to be higher in women with appropriate reserves of vitamin D. However a causal relation has not been demonstrated and randomized controlled trials testing the effectiveness of vitamin D supplementation in IVF are warranted. Methods This is a multicenter randomized double blinded placebo controlled study aimed at determining the benefits of vitamin D [25(OH)D] supplementation in improving clinical pregnancy rate in women undergoing IVF. Eligible women with a serum level of 25-hydroxyvitamin D [25(OH)D]

This paper presents the results of a study conducted on the written narratives of two fifth-grade primary school classes involved in the project Observing the Interlanguage. The aim was evaluating the effects of a pedagogical intervention in which the pupils were guided to observe the linguistic-discursive properties of oral and written texts (literary and produced by the students themselves) on their choices regarding the use of reported speech. The results show that children in the experimental classes write more vivid narratives than their peers in two control classes, because of their greater use of direct speech. The study demonstrates the effectiveness of pedagogical interventions which give pupils an active role as “little researchers" and involve them in collaborative tasks of observation and manipulation of their own and others' texts.

Questo contributo illustra i risultati di un’indagine esplorativa relativa alle modalità di gestione verbale di situazioni di conflitto da parte di bambini della scuola primaria. L’analisi mira a rilevare come gli allievi monolingui e plurilingui di 7-8 anni gestiscono l’atto di protesta in italiano nell’interazione tra pari. Oltre a descrivere alcuni degli usi pragmatici dei bambini delle classi multilingui coinvolte, l’osservazione sperimentale ha l’obiettivo di offrire indicazioni ai docenti per sviluppare interventi didattici rivolti a questa fascia d’età.

Il contributo riporta uno studio sperimentale basato sul progetto Osservare l’interlingua con l’obiettivo di indagare come la partecipazione alle sperimentazioni educative per l’intero ciclo scolastico possa migliorare la qualità delle produzioni scritte di bambini della scuola primaria. L’indagine coinvolge 71 allievi di classi quinte suddivisi in gruppo sperimentale e di controllo. L’analisi prende il via da produzioni scritte appositamente elicitate attraverso un compito di scrittura su stimolo video. Gli elaborati dei bambini sono stati valutati sia attraverso scale olistiche che misure analitiche relative a contenuto, comprensibilità, coerenza e coesione. I risultati evidenziano come il Progetto sia efficace nel favorire lo sviluppo di competenze di scrittura per tutta la classe, nel rispetto dei bisogni e dei ritmi di ciascun allievo promuovendo di fatto buone pratiche di didattica inclusiva. Learning to write better. An experimental survey on the effects of an educational experience on classes and multilingual students This paper presents a study based on the project Observing Interlanguage which investigates how participation in a research-action project for five years influenced the quality of the written production of mainstream primary school students. The study involved 71 10-year-old learners, both monolingual and multilingual, divided in experimental and control groups. The analysis is based on written productions elicited by a writing task about a video. The written texts were analyzed using holistic assessment scales and analytical measures of content, comprehensibility, coherence and cohesion. The results show how the project enhanced the development of writing abilities of the whole class, respecting individual needs and promoting inclusive teaching practices.

In the present society, the recycling and reuse of valuable substances are of utmost importance for economic and environmental purposes. At the same time, there is a pressing need to develop new methods to protect the ecosystem from many human activities, including those that have contributed to an ever-increasing presence of pharmaceutical pollutants. In this study, a straightforward approach that applies a magnetic carbon composite for the effective removal of NSAIDs from biological fluids is reported. The composite was produced by recycling wasted handkerchiefs, to provide cellulose to the reactive system and then transformed into carbon via calcination at high temperature. The morphological and structural features of the prepared “Fe3O4@-activated carbon” samples were investigated via thermal analysis, X-ray diffraction, Raman spectroscopy, and scanning electron microscopy. Magnetic solid-state extraction was carried out to reveal the adsorption capabilities of the magnetic carbon composite and then combined with UHPLC–PDA for the determination and quantification of five NSAIDs (furprofen, indoprofen, ketoprofen, flurbiprofen, and indomethacin). The method developed herein proved to be fast and accurate. The adsorbent could be reused for up to 10 cycles, without any decrease in performance; thus, it contributes to an intelligent and sustainable economic strategy projected toward minimal waste generation.

Objective We investigated whether lifestyle affects assisted reproduction technology (ART) outcomes.Design Cohort study.Setting Italian fertility unit.Participants From September 2014 to December 2016, women from couples presenting for evaluation and eligible for ART were invited to participate. Information on alcohol intake, current smoking and leisure physical activity (PA) during the year before the interview was collected, using a structured questionnaire. We considered the ART outcomes of the cycle immediately following the interview.Primary and secondary outcome measures The primary outcome measure was cumulative pregnancy rate per retrieval. Secondary measures were number of retrieved oocytes, embryo transfer and live birth.Results In 492 women undergoing an ART cycle, 427 (86.8%) underwent embryo transfer, 157 (31.9%) had at least one clinical pregnancy and 121 (24.6%) had live birth. The cumulative pregnancy rate per retrieval was 33.3% (95% CI 28.5% to 38.7%). In women in the third tertile of alcohol intake, adjusted relative risk was 0.97 (95% CI 0.87 to 1.08), 0.90 (95% CI 0.62 to 1.30) and 0.89 (95% CI 0.57 to 1.37) for embryo transfer, clinical pregnancy and live birth, respectively. The corresponding figures in women currently smoking more than 5 cigarettes/day were 1.00 (95% CI 0.88 to 1.16), 0.94 (95% CI 0.60 to 1.48) and 1.14 (95% CI 0.68 to 1.90), and in women with PA ≥5 hours/week were 0.93 (95% CI 0.79 to 1.08), 0.44 (95% CI 0.22 to 0.90) and 0.48 (95% CI 0.22 to 1.05), respectively.Conclusion There were no significant differences in in vitro fertilisation outcomes among women who used alcohol or tobacco in the year prior to treatment. Conservatively, all women should be advised to limit substance abuse. Moreover, our study suggested that maintaining a moderate, but not high, level of PA could be beneficial.

Il laboratorio di italiano L2 è lo spazio didattico che dovrebbe creare un ponte tra ciò che sanno fare gli allievi plurilingui e ciò che devono ancora imparare per potersi muovere con sufficiente autonomia nelle attività di classe. Per definirne la programmazione didattica sarebbe dunque fondamentale una co-progettazione condivisa tra docente di italiano L2 e insegnanti di classe, di modo che i percorsi dedicati all’italiano L2 favoriscano realmente una maggiore partecipazione alle attività in classe, e viceversa le proposte per la classe siano maggiormente accessibili per gli studenti plurilingui. Non è sempre scontato però a scuola avviare questo tipo di collaborazione. Una strada per favorire questo processo può essere quella di lavorare insieme, cominciando a piccoli passi, con la sperimentazione di materiali didattici. Il presente contributo descrive alcune proposte organizzate in modo da costruire un ponte nelle due direzioni, dal laboratorio alla classe e viceversa, permettendo di avviare “prove di progettazione condivisa”, oltre che mettere in dialogo i due spazi educativi complementari e diffondere buone pratiche di educazione linguistica. A bridge between the class and the Italian L2 lab: teaching strategies The Italian L2 lab is the didactic space that should create a bridge between what multilingual students know how to do and what they still need to learn in order to gain sufficient autonomy in class activities. In order to define the lessons, shared co-planning between the L2 Italian teacher and class teachers is fundamental, so that L2 Italian promotes and supports greater participation in class activities, and vice versa the proposals in class are more accessible for multilingual students. However, the idea to establish this type of collaboration it is not always obvious at school. One way to encourage this process can be to work together, starting in small steps, by experimenting with teaching materials. This paper describes some proposals aimed at building a bridge in both directions, from the lab to the classroom and vice versa, allowing for “shared planning”, as well as creating a dialogue between the two complementary educational spaces and spreading good practices for language education.

L’identificazione di unità valide e affidabili per l’analisi è un passaggio essenziale per condurre analisi quantitative di dati sul parlato al fine di indagare dimensioni come complessità, accuratezza e fluidità o misurare la frequenza di caratteristiche specifiche del discorso o della grammatica. L’Analysis of Speech Unit (AS-unit), inizialmente proposta da Foster et al. (2000) per l’inglese, ha dimostrato di essere uno strumento utile: si basa su processi di pianificazione psicolinguistica ed è descritta ed esemplificata in dettaglio, il che contribuisce alla sua validità e affidabilità. Il presente articolo illustra l’applicazione di questa unità di produzione del parlato all’italiano L1 e L2. Dopo aver presentato l’unità AS e i suoi vantaggi, vengono discusse le questioni relative alla sua applicazione in generale e all’italiano in particolare. Sulla base di queste osservazioni, ne viene proposta una parziale ridefinizione. The AS-UNIT as a production unit for spoken L1 and L2 Italian. Application problems and possible solutions Identifying valid and reliable units for analysis is an essential step in conducting quantitative analyses of spoken data in order to investigate dimensions such as complexity, accuracy and fluency or to measure the frequency of specific features of discourse or grammar. The Analysis of Speech Unit (AS-unit), initially proposed by Foster et al. (2000) for English, has proven to be a useful tool: it is based on psycholinguistic planning processes and it is described and exemplified in detail, which contributes to its validity and reliability. The present paper illustrates the application of this unit of production to spoken L1 and L2 Italian. After presenting the AS-unit and its advantages, issues concerning its application in general and to Italian in particular are discussed. Based on these remarks, a partial redefinition is proposed.

The transcriptional regulators YAP (Yes-associated protein) and TAZ (transcriptional co-activator with PDZ-binding motif) are the major downstream effectors in the Hippo pathway and are involved in cancer progression through modulation of the activity of TEAD (transcriptional enhanced associate domain) transcription factors. To exploit the advantages of drug repurposing in the search of new drugs, we developed a similar approach for the identification of new hits interfering with TEAD target gene expression. In our study, a 27-member in-house library was assembled, characterized, and screened for its cancer cell growth inhibition effect. In a secondary luciferase-based assay, only seven compounds confirmed their specific involvement in TEAD activity. IA5 bearing a p-quinoid structure reduced the cytoplasmic level of phosphorylated YAP and the YAP–TEAD complex transcriptional activity and reduced cancer cell growth. IA5 is a promising hit compound for TEAD activity modulator development.

Low-cost and simple methods are constantly chased in order to produce less expensive lithium-ion batteries (LIBs) while possibly increasing the energy and power density as well as the volumetric capacity in order to boost a rapid decarbonization of the transport sector. Li alloys and tin-carbon composites are promising candidates as anode materials for LIBs both in terms of capacity and cycle life. In the present paper, electrospinning was employed in the preparation of Sn/SnOx@C composites, where tin and tin oxides were homogeneously dispersed in a carbonaceous matrix of carbon nanofibers. The resulting self-standing and light electrode showed a greatly enhanced performance compared to a conventional electrode based on the same starting materials that are simply mixed to obtain a slurry then deposited on a Cu foil. Fast kinetics were achieved with more than 90% of the reaction that resulted being surface-controlled, and stable capacities of about 300 mAh/g over 500 cycles were obtained at a current density of 0.5 A/g.

L’articolo illustra uno studio esplorativo sulle modalità di produzione dell’atto comunicativo del richiedere nell’interazione di bambini di 8-9 anni, basato su una sperimentazione educativa di ricerca-azione, condotta in Italia nella classe curricolare della scuola primaria. Gli aspetti specifi camente indagati sono i seguenti: le modalità di realizzazione dell’atto comunicativo; la relazione tra atto comunicativo e sequenza interazionale; la capacità dei bambini di rifl ettere sugli usi linguistici. I risultati ottenuti offrono indicazioni per lo sviluppo di materiali didattici appropriati e per la defi nizione di futuri protocolli di ricerca.

Carbon capture is amongst the key emerging technologies for the mitigation of greenhouse gases (GHG) pollution. Several materials as adsorbents for CO2 and other gases are being developed, which often involve using complex and expensive fabrication techniques. In this work, we suggest a sound, easy and cheap route for the production of nitrogen-doped carbon materials for CO2 capture by pyrolysis of electrospun poly(acrylonitrile) (PAN) fibers. PAN fibers are generally processed following specific heat treatments involving up to three steps (to get complete graphitization), one of these being stabilization, during which PAN fibers are oxidized and stretched in the 200–300 °C temperature range. The effect of stabilization temperature on the chemical structure of the carbon nanofibers is investigated herein to ascertain the possible implication of incomplete conversion/condensation of nitrile groups to form pyridine moieties on the CO2 adsorption capacity. The materials were tested in the pure CO2 atmosphere at 20 °C achieving 18.3% of maximum weight increase (equivalent to an uptake of 4.16 mmol g−1), proving the effectiveness of a high stabilization temperature as route for the improvement of CO2 uptake.

Background/Aims: FSH receptor (FSHR) Ala307Thr and Asn680Ser and LHβ chain (LHB) Trp28Arg and Ile35Thr polymorphisms affect the response to pharmacological ovarian stimulation with r-FSH in women undergoing assisted reproductive treatment (ART). Here, we evaluated the expression level of selected genes involved in follicle maturation and the possible onset of apoptosis in cumulus cells of patients with single and double FSHR and LHB polymorphisms, as potential markers of oocyte competence. Methods: Cumulus cells from 36 stimulated patients were collected and SNP genotyping performed by PCR. Gene expression was evaluated through real-time PCR, and apoptosis estimated via TUNEL assay, and cleaved caspase-3 and pAKT immunostaining. Results: The cumulative data show significant correlations indicating that the genetic alteration of FSHR and/or LHB genes may lead to perturbations of the signaling network programmed to granulosa cell survival and follicle development. Notably, when double heterozygotes were compared to the rest of the patients, a higher level of apoptosis in terms of both DNA fragmentation index and amount of active caspase-3 was observed in cumulus cells. Conclusions: These results may help to define personalized stimulation protocols in ART programs, to increase the success rate of ICSI procedures in accordance with the polymorphic condition of the individual patient.

L’attenzione allo sviluppo delle competenze linguistiche in italiano L1 e L2 è un tema quanto mai attuale nella scuola di oggi. Chi si occupa di educazione linguistica è spesso insoddisfatto del livello di competenza d’uso dei propri apprendenti, italiani e non. Poiché gli approcci tradizionali basati sull’insegnamento di lessico e grammatica non sempre garantiscono lo sviluppo delle abilità d’uso della lingua italiana, diventa essenziale trovare nuove strade per far spazio in classe anche a interventi mirati allo sviluppo della competenza pragmatica, ossia di tutte quelle abilità che mettono gli apprendenti nelle condizioni di usare in modo adeguato la lingua nelle diverse situazioni. Il presente articolo illustra il progetto di formazione e ricerca-azione Oggi facciamo pragmatica, un primo tentativo di dare risposta a questo bisogno educativo nella scuola primaria, accompagnando i docenti di area linguistica nella riflessione sull’importanza della competenza d’uso della lingua, nell’elaborazione e nella sperimentazione di materiali didattici per il suo insegnamento in classe. Doing pragmatics: a teacher training course and an educational research project for primary school The development of linguistic competence in Italian L1 and L2 is a highly discussed topic in mainstream education today. Teachers who work in the field of linguistic education are often unsatisfied with their students’ ability to use language in different contexts. As traditional approaches based on lexis and grammar teaching do not always guarantee a good level of language performance, in mainstream classrooms it is essential to explore new ways to foster the development of pragmatic competence, namely all those abilities which enable learners to use language appropriately in different situational contexts. This paper presents the teacher training course and educational research project Doing pragmatics, a first attempt to address this educational need in primary school, guiding teachers through the analyses of the importance of pragmatic competence, the preparation and the use of original teaching materials tailored to their teaching context.

There is currently no effective long-term treatment for ovarian cancer (OC) resistant to poly-chemotherapy regimens based on platinum drugs. Preclinical and clinical studies have demonstrated a strong association between development of Pt-drug resistance and increased thymidylate synthase (hTS) expression, and the consequent cross-resistance to the hTS inhibitors 5-fluorouracil (5-FU) and raltitrexed (RTX). In the present work, we propose a new tool to combat drug resistance. We propose to treat OC cell lines, both Pt-sensitive and -resistant, with dual combinations of one of the four chemotherapeutic agents that are widely used in the clinic, and the new peptide, hTS inhibitor, [D-Gln4]LR. This binds hTS allosterically and, unlike classical inhibitors that bind at the catalytic pocket, causes cell growth inhibition without inducing hTS overexpression. The dual drug combinations showed schedule-dependent synergistic antiproliferative and apoptotic effects. We observed that the simultaneous treatment or 24h pre-treatment of OC cells with the peptide followed by either agent produced synergistic effects even in resistant cells. Similar synergistic or antagonistic effects were obtained by delivering the peptide into OC cells either by means of a commercial delivery system (SAINT-PhD) or by pH sensitive PEGylated liposomes. Relative to non-PEGylated liposomes, the latter had been previously characterized and found to allow macrophage escape, thus increasing their chance to reach the tumour tissue. The transition from the SAINT-PhD delivery system to the engineered liposomes represents an advancement towards a more drug-like delivery system and a further step towards the use of peptides for in vivo studies. Overall, the results suggest that the association of standard drugs, such as cDDP and/or 5-FU and/or RTX, with the novel peptidic TS inhibitor encapsulated into PEGylated pH-sensitive liposomes can represent a promising strategy for fighting resistance to cDDP and anti-hTS drugs.

In recent decades, increasing attention has been paid to the influence of diet on reproductive health. Carbohydrates in diet affect glucose metabolism and multiple evidences showed the key role of insulin sensitivity in regulating female fertility. We designed a prospective cohort study to investigate the relation between dietary carbohydrate intake, glycemic load (GL) and the outcomes of assisted reproduction. A population of 494 female partners of couples referring to an Italian Fertility Center and eligible for in vitro fertilization (IVF) were enrolled in the study. On the day of the oocyte retrieval, information on their diet was obtained using a validated food frequency questionnaire (FFQ). We calculated the relative risk and 95% confidence interval of embryo transfer, clinical pregnancy and live birth according to the following dietary exposures: GL, glycemic index (GI) as well as the daily carbohydrate and fiber intake. A multiple regression model was used to account for the confounders. After adjusting for age, college degree, body mass index (BMI), leisure physical activity and previous assisted reproduction techniques (ART) cycles, no significant association was observed between the considered dietary exposures and the IVF outcomes. The roles of GL, carbohydrate intake and GI were assessed in strata of the cause of infertility and body mass index and no relation emerged in this further analysis. We found no clear association between the dietary carbohydrate quantity and quality and IVF outcomes in a cohort of infertile Italian women.

Proteomics and bioinformatics are a useful combined technology for the characterization of protein expression level and modulation associated with the response to a drug and with its mechanism of action. The folate pathway represents an important target in the anticancer drugs therapy. In the present study, a discovery proteomics approach was applied to tissue samples collected from ovarian cancer patients who relapsed after the first-line carboplatin-based chemotherapy and were treated with pemetrexed (PMX), a known folate pathway targeting drug. The aim of the work is to identify the proteomic profile that can be associated to the response to the PMX treatment in pre-treatement tissue. Statistical metrics of the experimental Mass Spectrometry (MS) data were combined with a knowledge-based approach that included bioinformatics and a literature review through ProteinQuest™ tool, to design a protein set of reference (PSR). The PSR provides feedback for the consistency of MS proteomic data because it includes known validated proteins. A panel of 24 proteins with levels that were significantly different in pre-treatment samples of patients who responded to the therapy vs. the non-responder ones, was identified. The differences of the identified proteins were explained for the patients with different outcomes and the known PMX targets were further validated. The protein panel herein identified is ready for further validation in retrospective clinical trials using a targeted proteomic approach. This study may have a general relevant impact on biomarker application for cancer patients therapy selection.

Human thymidylate synthase (hTS) is pivotal for cell survival and proliferation, indeed it provides the only synthetic source of dTMP, required for DNA biosynthesis. hTS represents a validated target for anticancer chemotherapy. However, active site-targeting drugs towards hTS have limitations connected to the onset of resistance. Thus, new strategies have to be applied to effectively target hTS without inducing resistance in cancer cells. Here, we report the generation and the functional and structural characterization of a new hTS interface variant in which Arg175 is replaced by a cysteine. Arg175 is located at the interface of the hTS obligate homodimer and protrudes inside the active site of the partner subunit, in which it provides a fundamental contribution for substrate binding. Indeed, the R175C variant results catalytically inactive. The introduction of a cysteine at the dimer interface is functional for development of new hTS inhibitors through innovative strategies, such as the tethering approach. Structural analysis, performed through X-ray crystallography, has revealed that a cofactor derivative is entrapped inside the catalytic cavity of the hTS R175C variant. The peculiar binding mode of the cofactor analogue suggests new clues exploitable for the design of new hTS inhibitors.

Thymidylate synthase (TS) is an enzyme of paramount importance as it provides the only de novo source of deoxy-thymidine monophosphate (dTMP). dTMP, essential for DNA synthesis, is produced by the TS-catalyzed reductive methylation of 2′-deoxyuridine-5′-monophosphate (dUMP) using N5,N10-methylenetetrahydrofolate (mTHF) as a cofactor. TS is ubiquitous and a validated drug target. TS enzymes from different organisms differ in sequence and structure, but are all obligate homodimers. The structural and mechanistic differences between the human and bacterial enzymes are exploitable to obtain selective inhibitors of bacterial TSs that can enrich the currently available therapeutic tools against bacterial infections. Enterococcus faecalis is a pathogen fully dependent on TS for dTMP synthesis. In this study, we present four new crystal structures of Enterococcus faecalis and human TSs in complex with either the substrate dUMP or the inhibitor FdUMP. The results provide new clues about the half-site reactivity of Enterococcus faecalis TS and the mechanisms underlying the conformational changes occurring in the two enzymes. We also identify relevant differences in cofactor and inhibitor binding between Enterococcus faecalis and human TS that can guide the design of selective inhibitors against bacterial TSs.

In response to the letter of Pace and Multani, in general, we cannot disagree with their considerations about the use of odds ratios, risk ratios, and rate ratios. [...]

Caffeine intake, a frequent lifestyle exposure, has a number of biological effects. We designed a cohort study to investigate the relation between lifestyle and assisted reproduction technique (ART) outcomes. From September 2014 to December 2016, 339 subfertile couples referring to an Italian fertility clinic and eligible for ART procedures were enrolled in our study. Sociodemographic characteristics, smoking, and usual alcohol and caffeine consumption in the year prior to ART were recorded. The mean age of participants was 36.6 ± 3.6 years in women and 39.4 ± 5.2 years in men. After oocytes retrieval, 293 (86.4%) underwent implantation, 110 (32.4%) achieved clinical pregnancy, and 82 (24.2%) live birth. Maternal age was the main determinant of ART outcome. In a model including women’s age and college degree, smoking habits, calorie and alcohol intake for both partners, previous ART cycles, and partner’s caffeine intake, we did not observe any association between caffeine intake and ART outcome. Using the first tertile of caffeine intake by women as a reference, the adjusted rate ratio (ARR) for live birth was 1.09 (95% confidence interval (CI) 0.79–1.50) in the second and 0.99 (95% CI 0.71–1.40) in the third tertiles. In conclusion, a moderate caffeine intake by women and men in the year prior to the ART procedure was not associated with negative ART outcomes.

This work introduces a new method for inserting a Lithium reference electrode into commercially available 18650-type cells in order to obtain electrode potentials during cell operation. The proposed method is simple and requires limited equipment. Furthermore, electrical performance is significantly better and the cell capacity and resistance can be recorded for longer durations when compared to some of the previously used methods. Electrical performance of this new third electrode method is characterized and compared to 18650 cells with no reference electrode inserted. The capacity retention of the modified cell is more than 98% in the first 20 cycles. Harvested electrodes from a disassembled cell were also used to make coin cells that was proven to be a rather critical approach to get electrode potentials and capacities. This is an initial study that shows three-electrode performances of a commercial 18650-type cell, which suggests it could be used for understanding electrode behavior throughout a cell lifetime and for manufacturing instrumented cells.

Long cycle performance is a crucial requirement in energy storage devices. New formulations and/or improvement of “conventional” materials have been investigated in order to achieve this target. Here we explore the performance of a novel type of carbon nanospheres (CNSs) with three heteroatom co-doped (nitrogen, phosphorous and sulfur) and high specific surface area as anode materials for lithium ion batteries. The CNSs were obtained from carbonization of highly-crosslinked organo (phosphazene) nanospheres (OPZs) of 300 nm diameter. The OPZs were synthesized via a single and facile step of polycondensation reaction between hexachlorocyclotriphosphazene (HCCP) and 4,4′-sulphonyldiphenol (BPS). The X-ray Photoelectron Spectroscopy (XPS) analysis showed a high heteroatom-doping content in the structure of CNSs while the textural evaluation from the N2 sorption isotherms revealed the presence of micro- and mesopores and a high specific surface area of 875 m2/g. The CNSs anode showed remarkable stability and coulombic efficiency in a long charge–discharge cycling up to 1000 cycles at 1C rate, delivering about 130 mA·h·g−1. This study represents a step toward smart engineering of inexpensive materials with practical applications for energy devices.