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Background The Italian telephone-based Mini-Mental State Examination (Itel-MMSE), despite being psychometrically sound, has shown relevant ceiling effects, which may negatively impact the interpretation of its scores. In address to overcome such an issue, this study aimed at providing item-level insights on the Itel-MMSE through Item Response Theory (IRT) analyses. Methods Five-hundred and sixty-seven healthy Italian adults (227 males, 340 females; mean age: 51 ± 17 years, range 18–96; mean education: 13.31 ± 4.3 years). A two-parameter logistic IRT model was implemented to assess item discrimination and difficulty of the Itel-MMSE. Construct unidimensionality, statistical independence of items, and model and item fit were tested. Informativity levels were also assessed graphically. Results With respect to the Itel-MMSE total score, ceiling effects were found in 92.7% of participants. Unidimensionality was violated; both model and item fit were poor; a few items showed statistical dependence. Both the whole test and its items proved to be scarcely informative, especially for medium-to-high levels of ability, except for attention and spatial orientation subtests, which consistently yielded the highest discriminative capability. Discussion The Itel-MMSE appears to be most informative in low-performing healthy individuals. However, the present findings should not lead practitioners to aprioristically equate ceiling effects/low informativity to clinical uselessness. Items assessing attention and, to a lesser extent, spatial orientation appear to be the most informative. Supplementary Information The online version contains supplementary material available at 10.1007/s40520-021-02041-4.

Background Telephone-based cognitive screening (TBCS) is crucial to telehealth care of neurological patients, prevention campaigns, and epidemiological studies on cognitive impairment. The Telephone Interview for Cognitive Status (TICS) is one of the most widespread and psychometrically/diagnostically sound TBCS test, with several versions developed worldwide (e.g., with and without a delayed recall item). In Italy, only attempts of adaptation and preliminary evidence of its statistical features have been provided so far. This study thus aimed at (1) developing an Italian version of the TICS and assessing its (2) psychometric and (3) diagnostic properties. Methods A back-translated and culturally adapted version of the TICS was developed. Three-hundred and sixty-five healthy individuals from different regions of Italy (147 males, 216 females; age: 53.2 ± 16 years; education: 13 ± 4.5 years) were administered the TICS and the Italian telephone-based Mini-Mental State Examination (Itel-MMSE). Validity was tested by convergence and at the structure level, whereas reliability as internal consistency, test–retest, and inter-rater. Diagnostic accuracy, item difficulty, and discrimination were also examined. Results The TICS featured a single component and its score converged with that of the Itel-MMSE (rs = .37). Reliability was excellent as inter-rater (ICC = .94), good as test–retest (ICC = .78), and acceptable as internal consistency (Cronbach’s α = .63). Accuracy was high as tested against the Itel-MMSE (AUC = .83) and did not improve when adding the delayed recall. Backward subtraction was the most difficult and discriminative task. Discussion The Italian TICS is a valid, reliable, and diagnostically accurate TBCS test. The original format of the TICS can be thus adopted in both clinical and research settings. Supplementary Information The online version contains supplementary material available at 10.1007/s10072-021-05729-7.

International audience; Different position isomers of furandicarboxylic acid (FDCA) can be obtained from the biomass by a Henkel disproportionation reaction. 2,5- and 2,4-FDCA are obtained in amounts that are large enough to be used for the synthesis of polyethylene furanoate (PEF). The homopolyesters obtained with ethylene glycol (EG) and either 2,5- or 2,4-FDCA have a completely different crystallization behavior, for 2,5-PEF can crystallize whereas 2,4-PEF cannot, even after very long annealing times. The synthesis of random copolyesters with EG and different ratios of 2,5/2,4-FDCA may therefore allow to tune PEF crystallization ability. The partial replacement of 2,5-FDCA by its position isomer could help disrupting crystallinity analogously to what happens when EG is partially replaced by cyclohexane dimethanol (CHDM) in glycolyzed polyethylene terephthalate (PETg). This work investigates the thermal behavior of the homopolyester 2,5-PEF and the microstructural consequences of copolymerization (replacement of small amounts of 2,5-FDCA with 2,4-FDCA). Crystallization is performed in isothermal conditions after cooling down from the molten state, and investigated with both conventional DSC and Fast Scanning Calorimetry (FSC). When the amount of 2,4-FDCA-based repeating units is low (10 and 15 mol %), crystallization still occurs but with an increased induction time. Neither the crystalline nor the rigid amorphous fractions are significantly affected by copolymerization. Due to multiple and complex microstructural reorganizations observed at relatively slow heating rates, conventional DSC is inaccurate and does not provide a reliable microstructural depiction of these polyesters. The use of FSC is recommended, for it allows to obtain a better characterization of the quality and thermal stability of the formed crystals.

Idiopathic pulmonary fibrosis (IPF) is a disease characterized by progressive scarring of the lung that involves the pulmonary interstitium. The disease may rapidly progress, leading to respiratory failure, and the long-term survival is poor. There are no accurate biomarkers available so far. Our aim was to evaluate the expression of the B4GALT1 in patients with IPF. Analysis of B4GALT1 gene expression was performed in silico on two gene sets, retrieved from the Gene Expression Omnibus database. Expression of B4GALT1 was then evaluated, both at the mRNA and protein levels, on lung specimens obtained from lung biopsies of 4 IPF patients, on one IPF-derived human primary cell and on 11 cases of IPF associated with cancer. In silico re-analysis demonstrated that the B4GALT1 gene was overexpressed in patients and human cell cultures with IPF (p = 0.03). Network analysis demonstrated that B4GALT1 upregulation was correlated with genes belonging to the EMT pathway (p = 0.01). The overexpression of B4GALT1 was observed, both at mRNA and protein levels, in lung biopsies of our four IPF patients and in the IPF-derived human primary cell, in other fibrotic non-lung tissues, and in IPF associated with cancer. In conclusion, our results indicate that B4GALT1 is overexpressed in IPF and could represent a novel marker of this disease.

This works aims to investigate the effect of the molecular groups found in polyester backbones (type of ring in the acidic subunit and length of the glycolic subunit) on the molecular dynamics. The investigation is done on three furan-based polyesters (PEF, PPF and PBF) as compared to their terephthalic counterparts (PET, PTT, and PBT) after full quenching from the molten state. The segmental molecular dynamics is investigated with MT-DSC, FSC and DRS. It is shown that the cooperativity decreases as the length of the glycolic subunit increases in both furan-based and terephthalic polyesters. No direct correlation between the fragility index and the cooperativity is observed in furan-based polyesters containing glycolic subunits of different lengths. The differences in the isochoric fragilities obtained for the furan-based polyesters and their terephthalic counterparts has been assumed to result from the combination of backbone flexibility and packing efficiency of the macromolecular chains in the amorphous phase.

BackgroundImmune checkpoint inhibitors are still unable to provide clinical benefit to the large majority of non-small cell lung cancer (NSCLC) patients. A deeper characterization of the tumor immune microenvironment (TIME) is expected to shed light on the mechanisms of cancer immune evasion and resistance to immunotherapy. Here, we exploited malignant pleural effusions (MPEs) from lung adenocarcinoma (LUAD) patients as a model system to decipher TIME in metastatic NSCLC.MethodsMononuclear cells from MPEs (PEMC) and peripheral blood (PBMC), cell free pleural fluid and/or plasma were collected from a total of 24 LUAD patients and 12 healthy donors. Bulk-RNA sequencing was performed on total RNA extracted from PEMC and matched PBMC. The DEseq2 Bioconductor package was used to perform differential expression analysis and CIBERSORTx for the regression-based immune deconvolution of bulk gene expression data. Cytokinome analysis of cell-free pleural fluid and plasma samples was performed using a 48-Plex Assay panel. THP-1 monocytic cells were used to assess macrophage polarization. Survival analyses on NSCLC patients were performed using KM Plotter (LUAD, N=672; lung squamous cell carcinoma, N=271).ResultsTranscriptomic analysis of immune cells and cytokinome analysis of soluble factors in the pleural fluid depicted MPEs as a metastatic niche in which all the components required for an effective antitumor response are present, but conscripted in a wound-healing, proinflammatory and tumor-supportive mode. The bioinformatic deconvolution analysis revealed an immune landscape dominated by myeloid subsets with the prevalence of monocytes, protumoral macrophages and activated mast cells. Focusing on macrophages we identified an MPEs-distinctive signature associated with worse clinical outcome in LUAD patients.ConclusionsOur study reports for the first time a wide characterization of MPEs LUAD microenvironment, highlighting the importance of specific components of the myeloid compartment and opens new perspectives for the rational design of new therapies for metastatic NSCLC.

Background: Sub-clinical cognitive efficiency deficits of a dysexecutive nature are moderately prevalent in healthy older adults and negatively affect their functional outcomes. To screen for such dysfunctions, the Frontal Assessment Battery (FAB) provided promising evidence, although its diagnostic properties have not been tested to date. This study thus aimed at exploring the performance on the FAB of a large sample of Italian healthy adults and comparing it in individuals aged < 75 years vs. ≥ 75 years. Methods: Four hundred and seventy-five healthy adults (169 males, 306 females, age: 61.1 ± 15.1; education 11.7 ± 4.6) were administered the FAB and the Montreal Cognitive Assessment (MoCA). Sensitivity, specificity, positive and negative predictive values and likelihood ratios were computed through receiver-operating characteristics analyses by addressing an above- vs. below-cutoff performance on the MoCA as the state variable (as including measures of executive functioning). Results: The FAB overall showed good accuracy (AUC = 0.71–0.76), although higher for healthy older adults. A trend towards higher specificity (64.4–80.3%) than sensitivity (61.1–77.8%) was found, despite these metrics being comparable in healthy older adults. Negative predictive values (0.98–0.99) were systematically higher than positive predictive values (0.05–0.24), whereas consistent post-test probabilities were detected (positive likelihood ratios: 2.19–3.35; negative likelihood ratios: 0.28–0.48). Discussion: The FAB is an accurate test for the first-level assessment of dysexecutive-related global cognitive inefficiency in the general population, despite being moderately conservative as far as both its pre- and post-test features are concerned. Its diagnostic value is more informative for individuals aged ≥ 75 years.

Background Up to 50% of motor neuron disease (MND) patients show neuropsychological deficits which negatively affect prognosis and care. However, disability-related logistical issues and uneven geographical coverage of healthcare services may prevent MND patients from accessing neuropsychological evaluations. This study thus aimed to standardize for the Italian population the ALS Cognitive Behavioral Screen-Phone Version (ALS-CBS™-PhV), an MND-specific, telephone-based screening for frontotemporal dysfunction. Methods The cognitive section of the ALS-CBS™-PhV, the Italian telephone-based Mini-Mental State Examination (Itel-MMSE), and the Telephone Interview for Cognitive Status (TICS) was administered to 359 healthy individuals (143 males, 216 females; age, 52.7 ± 15.8; education, 13.1 ± 4.4). Norms were derived through equivalent scores. Validity, factorial structure, reliability, diagnostic accuracy, and item difficulty and discrimination were examined. Statistical equivalence between the telephone-based and in-person versions was tested. Results ALS-CBS™-PhV measures were predicted by age and education. The ALS-CBS™-PhV reflected a mono-component structure, converged with Itel-MMSE and TICS scores (rs = .23–.51) and was equivalent to its in-person format (t = .37; p = .72). Good internal (Cronbach’s α = .61), test–retest (ICC = .69), and inter-rater (ICC = .96) reliability was detected. High accuracy was found when tested against both the Itel-MMSE and the TICS (AUC = .82–89). Backward digit span items were the most discriminative. Discussion The ALS-CBS™-PhV is a statistically solid screening test for frontotemporal disorders featuring MND. Its standardization allows for (1) improvements in tele-healthcare for MND patients, (2) epidemiological applications, and (3) effective assessments in decentralized clinical trials. The ALS-CBS™-PhV can be also suitable for assessing bedridden and visually impaired patients with motor disorders.

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Significance Chronic obstructive pulmonary disease (COPD) is an inflammatory disease characterized by limitation of expiratory airflow. Cellular and molecular pathways involved in disease pathogenesis are not completely defined. Our study reveals that metabolism and immune response cooperate in COPD pathogenesis and progression. COPD subjects with different disease stages showed progressive increase of systemic leptin, an adipose tissue-derived proinflammatory molecule, that, at high concentrations, impaired the capacity of T cells to engage in glycolysis and to generate regulatory T cells. Thus, the loss of these immunoregulatory circuits during COPD determined the hyperactivation of effector T cells that amplified inflammation, leading to progressive decline of lung function. Understanding these immunometabolic mechanisms can have important implications for monitoring COPD progression and for disease treatment., Chronic obstructive pulmonary disease (COPD) is an inflammatory condition associated with abnormal immune responses, leading to airflow obstruction. Lungs of COPD subjects show accumulation of proinflammatory T helper (Th) 1 and Th17 cells resembling that of autoreactive immune responses. As regulatory T (Treg) cells play a central role in the control of autoimmune responses and their generation and function are controlled by the adipocytokine leptin, we herein investigated the association among systemic leptin overproduction, reduced engagement of glycolysis in T cells, and reduced peripheral frequency of Treg cells in different COPD stages. These phenomena were also associated with an impaired capacity to generate inducible Treg (iTreg) cells from conventional T (Tconv) cells. At the molecular level, we found that leptin inhibited the expression of forkhead-boxP3 (FoxP3) and its splicing variants containing the exon 2 (FoxP3-E2) that correlated inversely with inflammation and weakened lung function during COPD progression. Our data reveal that the immunometabolic pathomechanism leading to COPD progression is characterized by leptin overproduction, a decline in the expression of FoxP3 splicing forms, and an impairment in Treg cell generation and function. These results have potential implications for better understanding the autoimmune-like nature of COPD and the pathogenic events leading to lung damage.

Reduced bone mineral density (BMD) is a well-known complication in childhood acute lymphoblastic leukemia (ALL) survivors; the optimal method to assess BMD is still debated. We studied BMD by quantitative ultrasound (QUS) in 72 ALL survivors, and evaluated any correlation with cumulative doses of steroids and cytotoxic agents. Mean age at diagnosis was 61±45 months, while mean age at QUS was 318.3±129.6 months; mean period of follow-up was 41.2±37.8 months. Mean amplitude-dependent speed of sound z-score was -1.22±1.19. Ten survivors (13.8%) presented a z-score below -2 SD. A negative correlation was found between amplitude-dependent speed of sound z-score and age at diagnosis (P=0.01). A positive correlation was observed with length of follow-up (P=0.01). No correlation was found with cytotoxic drugs. This study represents the largest cohort of childhood ALL survivors studied by QUS. Our results suggest that QUS for its characteristics of being radiation free may be an effective option to assess BMD in pediatric age. In addition, our data outline the importance to improve the awareness about the specific expression of this complication in the pediatric age, concerning the major determinants of bone impairment, which are the disease itself and the phase of bone growth when the disease occurs.

This work consists in investigating the influence of the structural changes induced by annealing, such as the presence of a rigid amorphous fraction (RAF) and crosslinking, on the mechanical properties of polyphenylene sulfide (PPS) and the fracture mechanical behavior (particularly tenacity) of a Carbon/PPS laminated composite. The first part of the study aimed at obtaining PPS samples with different amounts of RAF, and in determining the conditions potentially favoring crosslinking. The results obtained on the matrix alone encouraged to transpose the mechanisms associated with the structural changes in PPS to the polymer phase in C/PPS laminated composites with woven-fibers reinforcement. The laminates have a [(+/-45°)]7 stacking sequence, whose overall mechanical response is controlled by the PPS matrix. The ultimate axial strength is little influenced (about 10% increase) by different annealing conditions with respect to as-received state. The optimum annealing conditions (230 °C under air for 576 h) contribute to the improvement of the axial stiffness (doubled compared to the as-received state). At the same time, the critical translaminar toughness (at initiation) is significantly increased (about 20%) and the translaminar failure is associated with a slower crack propagation.

Background The availability of fine-grained, culture-specific psychometric outcomes can favor the interpretation of scores of the Montreal Cognitive Assessment (MoCA), the most frequently used instrument to screen for mild cognitive dysfunctions in both instrumental and non-instrumental domains. This study thus aimed at providing: (i) updated, region-specific norms for the Italian MoCA, by also (ii) comparing them to pre-existing ones with higher geographical coverage; (iii) information on sensitivity and discriminative capability at the item level. Methods Five hundred and seventy nine healthy individuals from Northern Italy (208 males, 371 females; age: 63.4 ± 15, 21–96; education: 11.3 ± 4.6, 1–25) were administered the MoCA. Item Response Theory (IRT) was adopted to assess item difficulty and discrimination. Normative values were derived by means of the Equivalent Scores (ESs) method, applied to the MoCA and its sub-scales. Average ESs were also computed. Agreement with previous ESs classification was assessed via Cohen’s k. Results Age and education significantly predicted all MoCA measures except for Orientation, which was related to age only. No sex differences were detected when tested along with age and education. Substantial disagreements with previous ESs classifications were detected. Several items proved to be scarcely sensitive, especially the place item from Orientation and the letter detection task. Memory items showed high discriminative capability, along with certain items assessing executive functions and orientation. Discussion Item-level information herewith provided for the Italian MoCA can help interpret its scores by Italian practitioners. Italian practitioners should consider an adaptive use of region-specific norms for the MoCA.

Background Deficits of executive functioning (EF) are frequently found in neurological disorders. The Frontal Assessment Battery (FAB) is one of the most widespread and psychometrically robust EF screeners in clinical settings. However, in Italy, FAB norms date back to 15 years ago; moreover, its validity against “EF-loaded” global cognitive screeners (e.g., the Montreal Cognitive Assessment, MoCA) has yet to be tested. This study thus aimed at (a) providing updated normative data for the Italian FAB and (b) assessing its convergent validity with the MoCA. Methods Four-hundred and seventy-five healthy Italian native speakers (306 females, 169 males; mean age: 61.08 ± 15.1; mean education: 11.67 ± 4.57) were administered by the MoCA and the FAB. FAB items were divided into three subscales: FAB-1 (linguistically mediated EF), FAB-2 (planning), and FAB-3 (inhibition). Regression-based norms were derived (equivalent scores) for all FAB measures. Results Age and education were predictive of all FAB measures, whereas no gender differences were detected. The FAB and its sub-scales were related to MoCA measures—the strongest associations being found with MoCA total and MoCA-EF scores. FAB sub-scales were both internally related and associated with FAB total scores. Discussion The FAB proved to have convergent validity with both global cognitive and EF measures in healthy individuals. The present study provides updated normative data for the FAB and its sub-scales in an Italian population sample, and thus supports an adaptive usage of this EF screener.

Background: There is an increasing need for objective and standardized assessment of testamentary capacity (TC) in dementia. A new instrument, the Testamentary Capacity Assessment Tool (TCAT), has been recently developed; however, the lack of validation and normative data regarding this cognitive screening test has limited its adoption in forensic and clinical settings. The present study collects normative data for the TCAT and assesses its convergent validity with standardized cognitive tests and the capacity to define what a ‘testament’ is. Methods: The study involved 323 neurologically healthy adults (123 males, 200 females) of different ages (31–93 years) and different educational levels (4–25 years). The TCAT was administered along with the Beck Depression Inventory-II (BDI-II), the Montreal Cognitive Assessment (MoCA), the Mini-Mental State Examination (MMSE), the Frontal Assessment Battery (FAB) and the Testament Definition Scale (TDS). Results: Multiple regression analyses revealed a significant effect for gender, age and education on TCAT scores. Correlation analyses showed significant associations between the TCAT and the MMSE, MoCA, FAB and BDI-II. A positive correlation between the TCAT and TDS was also found, proving good convergent validity of the TCAT with respect to TC. Finally, cut-off scores and Equivalent Scores (ES) were computed. Discussion: The present study provides normative data for using the TCAT as an adjuvant cognitive screening test in the neuropsychological evaluation of TC. Our findings shall be of interest for the adoption of the TCAT also in clinical practice, since it evaluates cognitive functions (e.g., autobiographic memory, Theory of Mind) not measured by traditional screening tests.

Klinefelter syndrome (KS) is a genetic anomaly involving the presence of one or more supernumerary X chromosomes in male individuals. In the cognitive profile of these individuals, strengths are found in nonverbal abilities, whereas weaknesses are observed in executive function, language, and academic performance. Our study is based on a comparison between eight children diagnosed with KS (47,XXY) (age range: 9-13 years; IQ range: 80-123), with no delay in language development, and eight typically developing (TD) controls. We explored a range of high-level language competencies and Theory of Mind (ToM) in addition to basic language competency. High-level language competencies were assessed by a battery that measures pragmatic language skills and a metaphor comprehension test (MCT). To assess ToM, we administered the corresponding subtest of the NEPSY II. Basic language competence was assessed by the NEPSY II Comprehension of Instructions subtest. Although basic language performance did not differentiate the individuals with KS from the TD controls, relevant differences appeared in some of the high-level language competencies as well as in the ToM task. All tasks in which the individuals with KS performed less well were characterized by complex inferential processes. Some possible clinical and educational implications are discussed.

Purpose Human leukocyte antigen (HLA)-G is a non-classic major histocompatibility complex HLA class I molecule. HLA-G may have tolerogenic properties which are linked to epigenetic-sensitive pathways. There is a correlation of sHLA-G levels and graft acceptance in transplantation studies. There are previous data on correlation of sHLA-G with graft rejection as well as with viral infections such as hepatitis C virus (HCV) in kidney transplanted patients. Here, we report the sHLA-G expression in patients on the waiting list for kidney transplantation, with and without anti-HCV compared to a control group. Methods Serum of 67 patients on the waiting list for kidney transplantation (n = 43 with anti-HCV and n = 24 without anti-HCV) was analyzed. Among these patients, n = 39 were on the waiting list for the first transplantation, while n = 28 were patients who returned in the list. The control group included n = 23 blood donors with anti-HCV (n = 13) and without anti-HCV (n = 10). Results The expression of sHLA-G was significantly lower in the control group (39.6 ± 34.1 U/ml) compared to both - patients on the waiting list for the first transplantation (62.5 ± 42.4 U/ml, p=0.031) and patients who returned in the list (76.7 ± 53.9 U/ml, p=0.006). No significant differences were observed in all anti-HCV positive groups. A positive linear correlation between sHLA-G and TNF-α, and patient age was observed. Conclusions Serum sHLA-G values were significantly increased in both - patients on the waiting list for the first transplantation and patients who returned in the list, as compared to control group. Our findings confirm the key tolerogenic role of sHLA-G levels as epigenetic-related marker for measuring the state of kidney allograft acceptance.

Among all the emergent biobased polymers, poly(ethylene 2,5-furandicarboxylate) (2,5-PEF) seems to be particularly interesting for packaging applications. This work is focused on the investigation of the relaxation dynamics and the macromolecular mobility in totally amorphous 2,5-PEF as well as in the less studied poly(ethylene 2,4-furandicarboxylate) (2,4-PEF). Both biopolymers were investigated by differential scanning calorimetry and dielectric relaxation spectroscopy in a large range of temperatures and frequencies. The main parameters describing the relaxation dynamics and the molecular mobility in 2,5-PEF and 2,4-PEF, such as the glass transition temperature, the temperature dependence of the α and β relaxation times, the fragility index, and the apparent activation energy of the secondary relaxation, were determined and discussed. 2,5-PEF showed a higher value of the dielectric strength as compared to 2,4-PEF and other well-known polyesters, such as poly(ethylene terephthalate), which was confirmed by molecular dynamics simulations. According to the Angell's classification of glass-forming liquids, amorphous PEFs behave as stronger glass-formers in comparison with other polyesters, which may be correlated to the packing efficiency of the macromolecular chains and therefore to the free volume and the barrier properties.

Recent works highlighted how interesting are the properties of furan-based polyesters. Most of the attention has been focused on the homopolyester obtained with 2,5-furandicarboxylic acid and ethylene glycol, but other possibilities exist, which could help in tuning the final properties by carefully selecting the nature and proportion of the initial building blocks. This work reports the synthesis and properties (thermal stability, activation energy for thermal decomposition, glass transition temperature, and aptitude to crystallize) of three series of polyesters obtained by combining various amounts of two isomers of furandicarboxylic acid with different linear aliphatic diols, such as ethylene glycol, 1,3-propanediol, and 1,4-butanediol. This approach provided homopolymers and copolymers with high molecular weights, good thermal stability, broad processing windows, and a thermal behavior that can be tuned both in terms of glass transition temperature and crystallinity. In most cases, the mixtures of 2,5- A nd 2,4-isomers obtained during the Henkel disproportionation reaction can be directly used to synthetize furan-based copolyesters with good properties without the downstream processing typically performed to separate the isomers prior to polymerization, which may considerably reduce the time and costs for biomass valorization.

The human SLC1A5 commonly known as ASCT2 is a sodium-dependent neutral amino acid antiporter involved in transmembrane traffic of glutamine that is exchanged through the cell membrane with smaller amino acids such as serine or threonine. Due to the strong overexpression in human cancers, ASCT2 is widely studied for its relevance to human health. Of special interest are the aspects related to the regulation of its function. The role of cholesterol as a modulator of the transport activity has been studied using a combined strategy of computational and experimental approaches. The effect of cholesterol on the Na ex + -[3H]glutamineex/glutaminein antiport in proteoliposomes has been evaluated by adding cholesteryl hemisuccinate. A strong stimulation of transport activity was observed in the presence of 75 μg cholesteryl hemisuccinate per mg total lipids. The presence of cholesterol did not influence the proteoliposome volume, in a wide range of tested concentration, excluding that the stimulation could be due to effects on the vesicles. cholesteryl hemisuccinate, indeed, improved the incorporation of the protein into the phospholipid bilayer to some extent and increased about three times the Vmax of transport without affecting the Km for glutamine. Docking of cholesterol into the hASCT2 trimer was performed. Six poses were obtained some of which overlapped the hypothetical cholesterol molecules observed in the available 3D structures. Additional poses were docked close to CARC/CRAC motifs (Cholesterol Recognition/interaction Amino acid Consensus sequence). To test the direct binding of cholesterol to the protein, a strategy based on the specific targeting of tryptophan and cysteine residues located in the neighborhood of cholesterol poses was employed. On the one hand, cholesterol binding was impaired by modification of tryptophan residues by the Koshland's reagent. On the other hand, the presence of cholesterol impaired the interaction of thiol reagents with the protein. Altogether, these results confirmed that cholesterol molecules interacted with the protein in correspondence of the poses predicted by the docking analysis.

BACKGROUND: In epileptic patients with motor disability, it's difficult to disentangle the effects of antiepileptic drugs (AEDs) on bone health from those provoked by impaired mobility. The aim of this study was to evaluate the effects of AEDs on bone mineral status by phalangeal quantitative ultrasound (QUS), a no-radiation and non-invasive method, in pediatric patients with motor impairment and epilepsy. METHODS: We enrolled 56 patients (31 females, 25 males) with epilepsy and motor impairment and 24 children with only motor disability (13 females, 11 males). Patients were stratified by Gross Motor Function Classification System Scale (GMFCS) in 4 groups: group A1 with epilepsy and mild motor impairment (GMFCS levels I-II), group A2 with only mild motor impairment, group B1 with epilepsy and severe motor impairment (GMFCS levels III-V), group B2 with only severe motor impairment. The bone mineral status was evaluated by QUS and amplitude-dependent speed of sound (AD-SoS) Z-score was calculated for each patient. RESULTS: The four groups showed no significant differences in age, gender and 25- hydroxyvitamin D levels. The group B1 had a statistically lower amplitude-dependent speed of sound Z-score as compared to group A2 (p

Poly(ethylene 2,5-furandicarboxylate) (2,5-PEF) is one of the most credible biobased alternative to poly (ethylene terephthalate) (PET). The Henkel disproportionation reaction that leads to furandicarboxylic acid (FDCA) provides three position isomers: 2,5-FDCA (obtained with the highest yield), 2,4-FDCA (so far considered as a by-product), and 3,4-FDCA (traces). The copolymerization of the two main isomers of FDCA with a diol, e.g. ethylene glycol (EG), is an interesting approach to obtain a family of furan-based biopolymers with adjusted physical properties. This work investigates the molecular mobility of three copolymers obtained with EG and ratios of 2,5-FDCA and 2,4-FDCA ensuring the complete disruption of crystallization (90:10, 85:15 and 50:50 mol % of 2,5:2,4 FDCA), as compared to the homopolymers 2,5-PEF and 2,4-PEF. The molecular mobility was investigated by cross-comparing the results obtained by Modulated-Temperature Differential Scanning Calorimetry (MT-DSC), Dielectric Relaxation Spectroscopy (DRS) and Thermo-Stimulated Depolarization Currents (TSDC), with the aim of evaluating the local and segmental molecular mobilities, their activation energies, as well as the temperature dependence of the relaxation time and of the cooperatively rearranging regions at the glass transition. The furan ring in 2,5-FDCA (2,5-PEF) has a rotation axis that is less linear compared to the benzene ring in terephthalic acid (PET), with consequences on the ring-flipping mechanisms. 2,5-FDCA and 2,4-FDCA differ by the position of the carbonyl groups on the furan ring, which adds asymmetry to non-linearity. The incorporation of 2,4-FDCA-based units into a polymer backbone mainly constituted of 2,5-FDCA-based repeating units is responsible for longer relaxation times associated with the local β relaxation processes, no striking effects on the kinetic fragility index m, no obvious effects on cooperativity (a slightly increase in the cooperativity length is observed in the liquid state), no effects on the activation energy for the segmental α relaxation in the liquid state, and a decrease in the activation energy in the glassy state.

The equilibrium enthalpy of melting ΔHm0 [J·g−1] is an extrapolated thermodynamic quantity attributed to crystallizable macromolecules and widely used to characterize polymers in their semi-crystalline state, for it allows estimating the degree of crystallinity by direct comparison with the enthalpy of melting obtained from differential scanning calorimetry. ΔHm0 is typically obtained by cross-comparing the results obtained by at least two techniques. This work proposes a simplified experimental protocol to determine ΔHm0 by the use of Fast Scanning Calorimetry (FSC). This approach applies to any crystallizable polymer for which a specific microstructure can be obtained (i.e. a two-phase semi-crystalline microstructure with a negligible amount of rigid amorphous fraction) and that can also be quenched to its fully amorphous state. Such a two-phase microstructure can be obtained on nanoscale samples through an annealing process performed in situ on the FSC sensor at crystallization temperatures as close as possible to the melting temperature. The enthalpy of melting is then evaluated from the two-phase model for different crystallization times (i.e. different crystallinities) and the ΔHm0 is obtained by extrapolating the data to the 100% crystalline state. This procedure was applied on samples whose ΔHm0 values are already available in the literature, but also on more recent biobased polyesters whose thermal properties are still under investigations.

Serological assays are still considered the most useful tests in the diagnosis of syphilis. Since no single serological assay is able to provide a satisfactory result, in our laboratory we have evaluated the usefulness of a commercially-available immunoblot to diagnose syphilis infection among blood donors. From October 2012 to June 2013, 4572 blood donors were screened for syphilis with an automated chemiluminescent microparticle immunoassay (CMIA). To confirm the presence of treponemal antibodies, CMIA-reactive sera were tested by standard Treponema pallidum haemagglutination assay (TPHA). In addition, an alternative confirmatory test – the immunoblot INNO-LIA assay was introduced in our laboratory. Since two additional positives among CMIA-reactive-TPHA-negative samples were found, we concluded that the INNO-LIA immunoblot allowed a better detection of syphilis compared to TPHA. A confirmatory strategy based on the use of two treponemal assays could meet the screening requirements for blood donors as well as in our centre.

A growing body of evidence indicates that effective medical treatment depends on personalized care. However, to focus on the person, to consider the other as a “person”, requires a special commitment, which corresponds to our expectations and it is mandatory for an effective medical approach, but it is not spontaneous and it does not hold automatically. The entire discussion on humanization of medicine relates to this question. At present, we are observing a cultural shift which risks destroying some essential aspects of the medical profession that contribute to high-quality health care. How to overcome this cultural shift which substantially impairs a personalized approach? Starting from a question posed by an editorial of the Journal and describing our teaching experience, we analyze recent Literature to contribute to this discussion.

The molecular dynamics of the constrained and unconstrained mobile amorphous fractions in semi-crystalline polylactide (PLA) was investigated in the presence of both flow-induced crystalline structures and spherulites by fast scanning calorimetry (FSC) through cooperativity and physical aging concepts. First, the shear rate conditions leading to flow-induced crystallization were characterized by examining the relaxation of shear-induced precursors. At a temperature of 150 °C, the critical relaxation time is so long that cooling down the sheared melt to the crystallization temperature does not affect significantly the precursors. Therefore, highly oriented structures develop. The arrangement of the crystalline fraction, either in flow-induced crystalline structures or spherulites, has no influence on the molecular dynamics of the mobile amorphous fraction, whereas the crystallinity degree was proved to play a significant role. Two kinds of molecular dynamics were distinguished, respectively associated to the α and secondary relaxations. The molecular dynamics related to the α relaxation of the mobile amorphous fraction was investigated in terms of cooperativity: a clear dependence on the coupling and the confinement by the crystals was observed, because a classic decrease of the cooperativity length was found when comparing amorphous to semi-crystalline PLA. On the contrary, the molecular dynamics related to the secondary relaxations of the mobile amorphous fraction was not modified by the presence of the crystals, as observed from close physical aging investigations below the glass transition. The different length-scale of the α and secondary relaxations seems to be the reason why the crystalline environment influences the macromolecular motions rather than the molecular or local motions.