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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 Metastases are the major cause of cancer-related morbidity and mortality. By the time cancer cells detach from their primary site to eventually spread to distant sites, they need to acquire the ability to survive in non-adherent conditions and to proliferate within a new microenvironment in spite of stressing conditions that may severely constrain the metastatic process. In this study, we gained insight into the molecular mechanisms allowing cancer cells to survive and proliferate in an anchorage-independent manner, regardless of both tumor-intrinsic variables and nutrient culture conditions. Methods 3D spheroids derived from lung adenocarcinoma (LUAD) and breast cancer cells were cultured in either nutrient-rich or -restricted culture conditions. A multi-omics approach, including transcriptomics, proteomics, and metabolomics, was used to explore the molecular changes underlying the transition from 2 to 3D cultures. Small interfering RNA-mediated loss of function assays were used to validate the role of the identified differentially expressed genes and proteins in H460 and HCC827 LUAD as well as in MCF7 and T47D breast cancer cell lines. Results We found that the transition from 2 to 3D cultures of H460 and MCF7 cells is associated with significant changes in the expression of genes and proteins involved in metabolic reprogramming. In particular, we observed that 3D tumor spheroid growth implies the overexpression of ALDOC and ENO2 glycolytic enzymes concomitant with the enhanced consumption of glucose and fructose and the enhanced production of lactate. Transfection with siRNA against both ALDOC and ENO2 determined a significant reduction in lactate production, viability and size of 3D tumor spheroids produced by H460, HCC827, MCF7, and T47D cell lines. Conclusions Our results show that anchorage-independent survival and growth of cancer cells are supported by changes in genes and proteins that drive glucose metabolism towards an enhanced lactate production. Notably, this finding is valid for all lung and breast cancer cell lines we have analyzed in different nutrient environmental conditions. broader Validation of this mechanism in other cancer cells of different origin will be necessary to broaden the role of ALDOC and ENO2 to other tumor types. Future in vivo studies will be necessary to assess the role of ALDOC and ENO2 in cancer metastasis.

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.

Chemotherapy-induced alopecia (CIA), although generally reversible, is felt as extremely distressing by patients with breast cancer. A certified medical device (Capelli Naturali a ContattoThe present study aimed to evaluate the impact of the CNCA pilot study was carried out on 21 patients affected by CIA due to recurrent breast cancer. A mixed quantitative/qualitative method was used, including administering a questionnaire and a focus group.Based on the Body Image Scale, body image perception improved after 3 and 6 months using the device in the 20 patients who answered the questionnaire. No significant change over time emerged for the six dimensions investigated by the Italian version of the Psychological Well-Being Scale. The thematic analysis of the focus groups showed six themes: definition of the prosthetic device, acceptance of the proposal, experience with the conventional wig, strengths, weaknesses, economic issues.Compared to the previous experience of CIA and the standard wig, the use of the CNC

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.

Summary Composites made of a thermoplastic matrix reinforced by bamboo fibers were obtained by extrusion and injection methods. It was found that the lignin of the bamboo fibers protects them from thermal exposure and prevents their degradation. As a consequence, in spite of the relatively high processing temperatures required for polymer melting, it is possible to obtain composite materials with acceptable properties for specific low-tech applications.

This study explores the self-organized activities undertaken across Web 2.0 and social media services by individual PhD researchers in their doctoral journey. It aims to add to the emergent body of knowledge reporting the doctoral students' experience in the digital venues for scholarly purposes. This chapter is based upon an international and multi-method research carried out to canvass the variety of social media practices characterizing the PhD researchers' digital engagement. The findings offer a detailed and unprecedented repertoire of individual experiments in taming social media to scholarly tasks. The results suggest that complex negotiations occur between technology and practice, where the tension between the need for supporting existing tasks and the attempt for expanding opportunities for personal development is always at work and prefigures an approach to digital engagement always on the move. Furthermore, the research sparks questions about any institution-led initiatives to support the sort of ‘do-it-yourself' PhD emerging from the participants' narratives.

AIM The aim of the present study is to report our series of incidental thyroid carcinomas in the last 15 years and their follow-up, discussing therapeutics indications and surgical choices. PATIENTS AND METHODS We have considered 1793 patients operated on Surgical Sciences Department of "Sapienza" University of Rome from January 1, 2001 to December 31, 2015. The study was conducted on 83 totally thyroidectomized patients with a real incidental thyroid carcinoma, by clinical, laboratory and instrumental controls. Whole-body scan was the most important test in postoperative evaluation. RESULTS In our series, the incidence of incidental carcinomas was 4.62%. Compared to the total number of cancer patients, the percentage is 21,9%. In 15.66% of cases there was multifocality and in 7.23% also bilaterality. Regarding the histological type, in all cases they were papillary carcinoma. The size of the neoplastic lesions ranged from a minimum of 3 to a maximum of 10 mm. Whole-body scan revealed lymph node metastasis in 57.69% of patients. DISCUSSION Comparing these data with our previous studies we have seen a significant increase in incidence of incidental thyroid carcinomas over the years. Our therapeutical choice is total thyroidectomy and complection thyroidectomy after lobectomy, because of a relevant percentage of multifocality and/or bilaterality of these tumors. Many Authors on the contrary prefer a more conservative approach invoking the good prognosis of these tumors. The 57.69% of lymph node metastasis at postoperative whole-body scan comfort us in our setting. CONCLUSION Incidental thyroid carcinomas are not uncommon. We consider only tumors until 1 cm in diameter. Multifocality and bilaterality are often present such as occult lymph node metastasis. Our therapeutical choice is total thyroidectomy in order to conduct a proper follow-up.

HBV still represents a global risk factor in transfusion medicine. The residual risk of HBV is not limited to pre-seroconversion window period but it extends to donors with occult HBV infection (OBI) characterized by the presence of HBV DNA in liver and by the absence of the virus surface antigen. Each country developed an appropriate blood screening policy according to local HBV prevalence, yields of infectious units per different screening methods and cost-effectiveness. We underline the need of maintaining a high level of attention for OBI carrier identification in all blood banks worldwide where the screening procedures are generally based on a combination of both serological markers and nucleic acid amplification test. In this context, markers such as hepatitis B surface antibodies and hepatitis B core antibodies (anti-HBc) might be useful, although the use of this latter is highly debated and still controversial. Our aim is to give an overview on the relevant diagnostic approaches for the routine screening for HBV focusing on the feasibility of anti-HBc testing as precautionary measure in preventing OBI transmission worldwide. In our tailored algorithm, the loss of about 1% of ‘anti-HBc only' donors, does not significantly affect the blood supply while improving recipient safety.

Summary Chitosan was prepared from shells of locally available fresh water prawns with variation of sodium hydroxide concentration and reaction time. The biopolymer was melt-mixed with a commercially available biodegradable polymer, the poly(butylene adipate-co-terephthalate) (PBAT). The chitosan and blend films were characterized by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The glass transition temperature (Tg) and melting point of the materials remained unchanged implying complete incompatibility of the blend components. Kinetic study showed that activation energy of the degradation process, i.e., thermal stability of the blends, decreased with increasing chitosan content in the blends. As the thermal properties of all the samples were found to be identical, it can be concluded that there was no effect of the added chitosan on the crystallization and melting behavior of the PBAT. These findings support the notion of the absence of interactions among the blend components. The rate of biodegradation was found to be higher in blends compared to pure PBAT polymer.

In most cases, a three-phase model consisting of crystalline domains surrounded by rigid amorphous areas dispersed in the mobile amorphous phase is required and eventually sufficient to accurately describe the microstructure of semicrystalline polymers. This work shows that the microstructure developed by poly(hydroxybutyrate-co-hydroxyvalerate) by cold crystallization is better described by a complex two-phase model in which the boundaries of the crystalline domains and the surrounding amorphous environment form a “continuum of mobility”. This concept can be extended to a wide range of semicrystalline polymers. When the crystalline and the amorphous phases are strongly coupled, the rigid and mobile amorphous fractions are hardly fractionated, and the whole noncrystalline phase should be rather depicted as continuum with a broad distribution of the relaxation times associated with the glass transition. Such a depiction of the amorphous phase allows taking into account any modification of the mobility land...

A new set of 5-(2-(pyrrolidin-1-yl)acetamido)- N -butyl-2-(substituted)benzamide and 5-(2-(piperidin-1-yl)acetamido)- N -butyl-2-(substituted) benzamide derivatives were synthesized in which as structural features the 2-(1-pyrrolidinyl)- or 2-(1-piperidyl)acetylamino group or a diphenylether moiety are associated to a benzamide scaffold. Their binding affinity for human PrP C and inhibition of its conversion into PrP Sc were determined in vitro; moreover, the antiprion activity was assayed by inhibition of PrP Sc accumulation in scrapie-infected mouse neuroblastoma cells (ScN2a) and scrapie mouse brain (SMB) cells. The results clearly indicate the benzamide derivatives as attractive lead compounds for the development of potential therapeutic agents against prion disease.

See editorial on page 284. BACKGROUND & AIMS: The presence of celiac diseaseassociated autoantibodies (antiendomysium and antitissue transglutaminase [anti-TG2]) with normal jejunal mucosa indicate potential celiac disease. We performed a prospective, 3-year cohort study to determine the natural history of potential celiac disease in children. METHODS: The study included 106 children with potential celiac disease, based on serology analysis and normal duodenal architecture. All but 2 carried the HLA-DQ2 and/or DQ8 haplotype. In all children, every 6 months, growth, nutritional parameters, celiac disease serology, and autoimmunity were investigated. In biopsies, intraepithelial-, CD3-, and lamina propria CD25-positive cells were counted; duodenal deposits of anti-TG2 immunoglobulin A were detected. Biopsy analysis was repeated after 2 years on patients with persistent positive serology and/or symptoms. RESULTS: Celiac disease was detected primarily in firstdegree relatives and patients with autoimmune disorders (40.6%). A gluten-free diet was prescribed to 20/106 patients because of symptoms, which were relieved in only 11. Eightynine of the 106 patients entered the follow-up study, with normal daily consumption of gluten. During the follow-up antibodies disappeared in 14.6% and fluctuated in 32.6%. Villous atrophy was observed in 12/39 patients (30.8%) who underwent a repeat biopsy. CONCLUSIONS: Most children with potential celiac disease remain healthy. After 3 years, approximately 33% of patients develop villous atrophy. Intestinal deposits of anti-TG2 IgA identify children at risk for villous atrophy.

The medical field is becoming the sphere of a quite peculiar confrontation, a sort of test of tension between two different approaches: on one side self-referencing, the concept that the whole set of knowledge and capabilities generated by medical science establishes self-sufficiency of our field; on the other, the quest to broaden our concept of reason overcoming this self-imposed limitation of reason. At stake is the need to overcome the dissatisfaction and the crisis our field is currently going through. This article will go over some aspects of what we believe to be a paradigm of a much general and crucial cultural problem.

Background Despite recent evidence, the role of uric acid as a causal factor in the pathogenesis and progression of kidney disease remains controversial, partly because of the inclusion in epidemiologic studies of patients with hypertension, diabetes, and/or proteinuria. Study Design Prospective observational cohort. Setting & Participants 900 healthy normotensive adult blood donors (153 women, 747 men) evaluated at baseline and after 5 years. Predictor Serum uric acid level. Outcomes Decrease in estimated glomerular filtration rate (eGFR) >10 mL/min/1.73 m 2 , computed using the Modification of Diet in Renal Disease (MDRD) Study equation, with secondary analyses examining similar decreases using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Cockcroft-Gault equations. Results During a median follow-up of 59 months, eGFR decreased from 97 ± 16 to 88 ± 14 mL/min/1.73 m 2 . Higher serum uric acid levels were associated with a greater likelihood of eGFR decrease in both women and men (HR, 1.13 [95% CI, 1.04-1.39] per each 1-mg/dL increase in uric acid level); in multivariable analyses adjusting for age, sex, body mass index, blood glucose level, total cholesterol level, mean blood pressure, urine albumin-creatinine ratio, and serum triglyceride level, the association remained highly significant (HR, 1.28 [95% CI, 1.12-1.48]). Results were similar using different estimating equations and when the association was examined in sex-specific subgroups. Limitations Analyses were based on a single baseline uric acid measurement. Women are underrepresented. Conclusions In healthy normotensive individuals, serum uric acid level is an independent risk factor for decreased kidney function.

N'-cyanoisonicotinamidine derivatives, linked to an arylpiperazine moiety, were prepared to identify highly selective and potent 5-HT(1A) ligands as potential pharmacological tools in studies of wide spread psychiatric disorders. The combination of structural elements (heterocyclic nucleus, alkyl chain and 4-substituted piperazine) known to be critical in order to have affinity on 5-HT(1A) receptor and the proper selection of substituents led to compounds with high specificity and affinity towards serotoninergic receptors. In binding studies, several molecules showed affinity in nanomolar and subnanomolar range at 5-HT(1A) and moderate to no affinity for other relevant receptors (5-HT(2A), 5-HT(2C), D(1), D(2), alpha(1) and alpha(2)). N'-cyano-N-(3-(4-(pyridin-2-yl)piperazin-1-yl)propyl)isonicotinamidine (4o) with K(i)=0.038 nM, was the most active and selective derivative for the 5-HT(1A) receptor with respect to other serotoninergic, dopaminergic and adrenergic receptors.

Bone loss, described in individual groups of patients with Type 1 diabetes (T1D), autoimmune thyroid disease (ATD) or celiac disease (CD) is usually viewed as a complication of these diseases. There is increasing evidence that alterations in the immune system may directly affect bone mass. Clustering of autoimmune diseases in the same individual might predispose to higher risk of osteopenia due to imbalance in immune regulation. The aim of this study was to evaluate bone involvement in clusters of the most common autoimmune diseases (T1D, ATD and CD) in children. The study was performed at a tertiary care center for the care of pediatric diabetes. One-hundred-two patients with T1D alone or associated with ATD and/or CD were studied; 13 patients had cluster of three autoimmune diseases. Amplitude-dependent speed of sound (AD-SoS) was measured by phalangeal quantitative ultrasound and expressed as standard deviation score (SDS). AD-SoS SDS < -2 was considered indicative of osteopenia. Osteopenia was equally distributed among children with T1D alone (8.1%), T1D associated with ATD (7.7%) or CD (10.3%), while it was 53.8% in patients presenting with three autoimmune diseases. Poor compliance to gluten-free diet increased osteopenia to 18.8% in patients with T1D and CD and 80% in patients with three autoimmune disorders. No difference among groups was found with regard to gluco-metabolic control, calcium metabolism, thyroid function. In conclusion bone impairment in multiple autoimmune diseases might be considered not only a complication due to endocrine or nutritional mechanisms, but also a consequence of an immunoregulatory imbalance. Alterations of homeostatic mechanisms might explain an imbalance of osteoclast activity leading to osteopenia.