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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.

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.

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.

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.

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

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.

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.

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.

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.

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.

Objectives The aim of the study was to investigate the in vivo effect of abacavir (ABC) on platelet oxidative stress. Methods We performed a randomized pilot study including 39 HIV-1-infected patients, 17 on zidovudine/lamivudine (ZDV/3TC) and 22 on tenofovir/emtricitabine (TDF/FTC). Ten patients on ZDV/3TC and eight patients on TDF/FTC were randomly allocated to switching the nucleoside backbone to ABC/3TC. At baseline and after 6 months, platelet oxidative stress was assessed by platelet NADPH oxidase 2 (NOX2)-derived peptide (sNOX2-dp), a marker of NOX2 activation, and platelet prostaglandin F2α (8-iso-PGF2α). Platelet activation was measured by soluble CD40L (sCD40L). Results At baseline, no differences between ZDV/3TC or TDF/FTC recipients were found. After 6 months, patients switching from ZDV/3TC showed a decrease of sNOX2-dp (from 20.9±5.7 to 12.5±3.8 pg/ml, p=0.002) and 8-iso-PGF2α (from 154.3±41.9 to 122.9±28.0 pmol/l, p=0.025). No effects on platelet oxidative stress biomarkers were observed in subjects from TDF/FTC, who showed a significant increase in blood glucose (p=0.043) and total cholesterol (p=0.027). ABC showed no effect on sCD40L levels in both groups. Conclusions ABC reduced platelet sNOX2-dp and 8-iso-PGF2α in HIV-1 subjects switching from ZDV/3TC but not in those from TDF/FTC after 6 months. No changes in platelet activation were found in both groups.

The recrudescence of syphilis is leading to the development of new serological tests. The goal of this study was to compare the performance of the more recent Elecsys Syphilis assay, the Electro Chemiluminescence Immunoassay (ECLIA), with the former Architect Syphilis TP assay, the Chemiluminescent Microparticle Immunoassay (CMIA), for the detection of antibodies against Treponema pallidum in blood donors. Serum samples of 5543 voluntary blood donors were screened in parallel with two tests. All repeatedly reactive (RR) samples by one or both assays were further analysed for confirmation by immmunoblot INNO-LIA and TPHA. Of 32 RR samples by CMIA, 21 were confirmed positive; of 21 RR samples by ECLIA, 20 were confirmed positive. The sensitivities of CMIA and ECLIA were 100% and 95.24% (95% CI = 85.71-100), respectively, not significant (p > 0.05). The specificity and predictive positive value (PPV) of CMIA were 99.86% (95% CI = 99.74-99.94) and 72.41%, respectively, while the specificity and PPV of ECLIA were both 100%, being statistically significant (p = 0.01 for both). The overall agreement was 99.80% and the Cohen's kappa coefficients was 0.79. In conclusion, the recent Elecsys Syphilis assay could represent another reliable assay for blood donor screening.

Background: Although overt hyperthyroidism is a well known cause of bone loss, systemic effects of subclinical hyperthyroidism (SH) are still a matter of debate. Objective: The aim of this cross-sectional study was to evaluate the effect of endogenous SH on bone in relation to the menopausal status. Methods: Bone mass and turnover were assessed in a group of 60 patients with endogenous SH due to multinodular goitre; 30 of them were premenopausal and 30 early postmenopausal (mean age, 40.9±7.3 and 57.7±6.75, respectively). Sixty healthy women matched for age-, BMI- and menopausal status served as controls. Three different skeletal sites were evaluated using two different techniques: lumbar spine and femoral neck were assessed by DEXA whereas the proximal phalanges were evaluated by quantitative ultrasonometry (QUS), measuring the amplitude-dependent speed of sound (Ad-SoS). Serum osteocalcin and urinary deoxypyridinoline (DPD) were also determined as markers of bone turnover. Results: A significant decrease was found in femoral BMD (P

HIV-1 patients show increased platelet activation, but the mechanisms involved are not completely clarified. We speculated that HIV-1 might induce in vivo platelet activation by enhancing platelet NOX2-related oxidative stress.We measured soluble CD40 Ligand (sCD40L), a systemic marker of platelet activation, in 36 HIV-1 patients under effective combined antiretroviral therapy (cART) and in 10 naïve HIV-1 subjects. As control, 20 healthy subjects (HS) were included. Platelet oxidative stress was measured by platelet NOX2-derived peptide (sNOX2-dp), p47(phox) translocation to platelet membrane and platelet prostaglandin F2α (8-iso-PGF2α).sCD40L was increased both in HIV-1 naïve and cART patients compared to HS (p0.001). Platelet sNOX2-dp and 8-iso-PGF2α were significantly higher in HIV-1 naïve subjects compared to those on cART and to HS, and both were mutually correlated (R = 0.734, p0.001). A stepwise multivariable linear regression analysis showed that platelet sNOX2-dp (β: 0.803, p0.001), HIV-1 infection (β: 0.146, p = 0.014) and age (β: 0.166, p = 0.001) were independently associated to sCD40L levels.HIV-1 infection is associated with increased platelet oxidative stress, which was related to the activation of NOX2. The independent association between platelet NOX2 activation and plasma levels of sCD40L suggest that in vivo platelet activation may be dependent upon platelet oxidative stress.

Bone complications after allogeneic stem cell transplant (alloSCT) include osteoporosis, fractures, and osteonecrosis. We investigated bone abnormalities in long-term survivors after busulfan cyclophosphamide-conditioning regimen, followed by human leukocyte antigen-identical sibling SCT. Bone density was measured by dual-energy x-ray absorptiometry at lumbar spine (LS) and femoral neck (FN) and phalangeal osteosonogrammetry (OSG) in 41 patients 1–10 yr after allo-SCT. Using colony-forming units-fibroblast (CFU-F) assay, we analyzed the repopulating capacity of clonogenic fibroblast progenitors belonging to the osteogenic stromal lineage. LS and FN bone mineral density (BMD) and phalangeal densitometric values were significantly reduced, compared with 188 healthy controls (P < 0.001). Decrease in T-score less than 1 SD was documented in 29% and 52% of patients at the LS and FN, respectively. OSG detected densitometric values with a Tscore less than 1 SD in 68% of transplanted patients. The patients examined within the first 3 yr after transplant showed low BMD, which remained stable at FN and improved at LS. Phalangeal densitometry was low up to 10 yr after transplant. CFU-F was found permanently depressed and unable to give rise to a confluent stroma. Low serum osteocalcin levels were present throughout the whole follow-up period. A significant correlation was found between densitometric values detected by both techniques and CFU-F growth in vitro. Osteonecrosis was associated with lower FN BMD, and phalangeal densitometry correlated inversely with duration of amenorrhea and chronic graft vs. host disease requiring long-lasting steroid therapy. In conclusion, dual-energy x-ray absorptiometry and phalangeal OSG may provide complementary information on bone density after allo-SCT. Prolonged severe impairment of femoral BMD and phalangeal densitometry suggest that bone loss may persist for many years after transplant. Inability to regenerate a normal number of osteoblastic precursors in the stromal stem cell compartment may in part account for severe long-lasting posttransplant decrease in bone mass. (J Clin Endocrinol Metab 87: 5058 –5065, 2002)

Hypoxia regulates the inflammatory-antiinflammatory balance by the receptor for advanced glycation end products (RAGE), a versatile sensor of damage-associated molecular patterns. The multiligand nature of RAGE places this receptor in the midst of chronic inflammatory diseases.To characterize the impact of the hypoxia-RAGE pathway on pathogenic airway inflammation preventing effective pathogen clearance in cystic fibrosis (CF) and elucidate the potential role of this danger signal in pathogenesis and therapy of lung inflammation.We used in vivo and in vitro models to study the impact of hypoxia on RAGE expression and activity in human and murine CF, the nature of the RAGE ligand, and the impact of RAGE on lung inflammation and antimicrobial resistance in fungal and bacterial pneumonia.Sustained expression of RAGE and its ligand S100B was observed in murine lung and human epithelial cells and exerted a proximal role in promoting inflammation in murine and human CF, as revealed by functional studies and analysis of the genetic variability of AGER in patients with CF. Both hypoxia and infections contributed to the sustained activation of the S100B-RAGE pathway, being RAGE up-regulated by hypoxia and S100B by infection by Toll-like receptors. Inhibiting the RAGE pathway in vivo with soluble (s) RAGE reduced pathogen load and inflammation in experimental CF, whereas sRAGE production was defective in patients with CF.A causal link between hyperactivation of RAGE and inflammation in CF has been observed, such that targeting pathogenic inflammation alleviated inflammation in CF and measurement of sRAGE levels could be a useful biomarker for RAGE-dependent inflammation in patients with CF.

How do university researchers consider attributes such as ‘digital’ and ‘open’ as regards to their research practices? This article reports a small–scale interview project carried out at the University of Milan, aiming to probe whether and to what extent actual digital research practices are affecting cultures of sharing in different subject areas and are prompting emergent approaches such as open publishing, open data, open education and open boundary between academia and society. Most of the 14 interviewed researchers seem not to see any clear benefit to move to further technological means or new open practices and call for institutional support and rules. However, a few profiles of ‘digital, networked and open’ researchers stand out and show both a self–legitimating approach to new modes of knowledge production and distribution and a particular sensitiveness towards values and perspectives driven by ‘openness’ in digital networks.

This chapter stems from the need to focus on the inherent interplay of faculty and student engagement while studying the impact of social media in higher education teaching and learning. The discussion is specifically concerned with the role and affordances of microblogging in the rethinking of the teacher/student relationship and in blurring the boundaries of academic contexts. The chapter examines an early experimentation of Twitter use to foster and monitor participation by the master students enrolled in a Human Resources Management class in an Italian university. The pilot is discussed referring to lessons learned from a range of accounted empirical cases and relevant studies on microblogging for teaching and learning in academia. A special focus addresses both a revised notion of academic scholarship and engagement, prompted by emergent profiles of networked faculty, and debates about the multiple ways of conceptualizing student engagement in the current academic cultures and contexts, being challenged by an increasingly complex digital landscape and by a varied typology of learners coming to university. As conclusion, issues related to the range of alignments to be taken into account when adopting social networking services in a higher education context are suggested as cues for an ongoing discussion.

Background Calcium (Ca2+) and vitamin D (VitD) play an important role in child health. We evaluated the daily intake of Ca2+ and VitD in healthy children. Moreover, we demonstrate the efficacy of Ca2+ and VitD supplementation. Methods Daily Ca2 + and VitD intake was evaluated in consecutive healthy children through a validated questionnaire. Subjects with 2+ and VitD were invited to participate in a prospective randomized trial with 2 groups of nutritional intervention: Group 1, dietary counseling aiming to optimize daily Ca2+ and VitD intake plus administration of a commercially available Ca2 + and VitD supplementation product; Group 2, dietary counseling alone. At the enrollment (T0) and after 4 months (T1) serum 25(OH) Vitamin D levels were assessed. Results We evaluated 150 healthy children (male 50%, mean age 10 years); at baseline a low VitD intake was observed in all subjects (median 0.79 μg/die, IQR 1.78; range 0.01-5.02); this condition was associated with Ca2+ intake Conclusions Adequate Ca2+ and VitD intakes are difficult to obtain through dietary counseling alone in pediatric subjects. Oral supplementation with of Ca2+ and VitD is a reliable strategy to prevent this condition. Trial registration The study was registered in Clinical Trials Protocol Registration System (ID number: NCT01638494).

This chapter reports selected findings from a small-scale, exploratory study aiming to provide a snapshot of actual modes of uptaking new digital tools for research purposes. The study consists in an interview project, carried out in a large Italian university and constituted by semi-structured interviews to 14 senior, young, and doctoral researchers, working in humanities, social sciences, medicine, and physics subject areas. Whereas the most popular attitude is a pragmatic and efficiency-driven approach in selecting and using old and new tools, a few isolated profiles of digital scholars emerge, championing the construction of their digital identity along with networked modes of knowledge production and distribution, despite the lack of legitimation of their own research context.

Osteoporosis (OP) is a skeletal disorder characterized by compromised bone strength that predisposes to an increased risk of fracture. The prevalence of OP in the general population is very high as established in several studies, and OP represents one of the possible aspects of bone involvement in arthritis. In psoriatic arthritis this involvement is particularly complex because it affects not only mechanisms of bone loss but also of bone formation. We will discuss these aspects and the available epidemiological data.

In HIV-1 infected patients, increase of liver enzymes may be mainly due to viral coinfections, alcohol intake, hepatotoxic drugs or autoimmune diseases. Three cases of aminotransferase elevation occurred during a phase of uncontrolled viral replication combined with a severe immunodeficiency and resolved by an effective HAART are described, focusing on the etio-pathogenetic role possibly played by HIV-1 infection.

Intravenous immunoglobulins (IVIGs) are generally used as replacement therapy for humoral immunodeficiencies. In consideration of their immune-modulating properties, they are also employed as "immune-modulating/anti-inflammatory" treatment in different clinical conditions. In HIV-1 infection, an increased incidence of autoimmune and auto-inflammatory manifestations has been described, probably as a consequence of the chronic immune activation associated with the disease. The initial use in the treatment of bacterial infections in children with HIV/AIDS has been replaced by the treatment, in combination with antiretroviral therapy, of these autoimmune/inflammatory conditions. We review the results obtained with IVIGs therapy in these HIV-1-associated clinical manifestations.

Several studies have been published on discovering involvement of PARs receptors in a number of disease states, including cancer and inflammation of the cardiovascular, respiratory, musculoskeletal, gastrointestinal and nervous systems. This mini-review will focus on recent advances in the synthesis of PAR ligands highlighting their therapeutic potential in the treatment of various inflammatory diseases.

BACKGROUND Inflammatory cytokines in bone marrow may impair hematolymphopoiesis in human immunodeficiency virus (HIV)-infected subjects who do not experience reconstitution of CD4(+) T cells despite suppression of virus replication while receiving highly active antiretroviral therapy (HAART) (immunological nonresponders). METHODS Bone marrow samples from 12 immunological nonresponders receiving HAART were studied and compared with samples from 11 immunological responders. The mean CD4(+) T cell count (+/- standard deviation) was 174 +/- 68 cells/mm(3) and plasma HIV RNA levels had been

OBJECTIVE: To evaluate whether long-term l-thyroxine therapy in young adults with congenital hypothyroidism may affect bone mineral density (BMD). DESIGN: Thirty-seven subjects with congenital hypothyroidism, detected by neonatal screening and longitudinally followed from the time of diagnosis and treatment (26+/-4 days) up to the age of 17.8+/-1.0 years, were studied. METHODS: Spinal (L2-L4) BMD, measured by dual-energy X-ray densitometry, and bone quality, measured as amplitude-dependent speed of sound (Ad-SoS) by quantitative ultrasound, were evaluated. RESULTS: Z-score mean values (+/-s.d.) of BMD (-0.3+/-0.7) and Ad-SoS (-0.7+/-1. 1) were slightly below the average but within the normal range. Ad-SoS resulted in a z-score below -1 in 38% of patients as compared with BMD which resulted in a z-score below -1 in only 13.5% of subject. No significant differences were observed between males (BMD, -0.3+/-0.7; Ad-SoS, -0.9+/-1.0) and females (BMD, -0.3+/-0.7; Ad-SoS, -0.5+/-1.2) or when dividing patients on the basis of aetiological defects; ectopic gland (BMD, -0.3+/-0.6; Ad-SoS, -0.8+/-0.9), athyreosis (BMD, -0.3+/-0.9; Ad-SoS, -0.8+/-1.0) and eutopic gland (BMD, -0.3+/-0.8; Ad-SoS, -0.4+/-1.3). No significant relationships were observed between BMD or Ad-SoS z-score and hormonal status or l-thyroxine dosages at the time of the study or during the pubertal period. CONCLUSIONS: The careful monitoring of serum thyroid-stimulating hormone and adjustment of l-thyroxine dosage avoided the significant deleterious effects of prolonged l-thyroxine replacement therapy on bone tissue in adolescents and young adults with congenital hypothyroidism treated from the neonatal period.

The influence of duration of diabetes and metabolic control on phalangeal quantitative ultrasound (QUS) was evaluated in a group of children and adolescents with type 1 diabetes. Eighty-six patients (mean age 11.9 years; mean duration 4.3 years) were studied. Daily calcium intake was assessed by means of a questionnaire. Amplitude-dependent speed of sound (AD-SoS) was measured at the phalanxes of the non-dominant hand and expressed as a z-score. Linear and multivariate correlations with duration of diabetes and, short term and long term metabolic control were sought. AD-SoS z-score was −0.43±1.4 (95% CI, −0.73; −0.13). Nine subjects had values below −2S.D. Daily calcium intake was 1042±456 mg/day; 47 subjects (54.6%) were below the recommended levels. A negative correlation was found between AD-SoS z-score and duration (r, −0.33, P=0.002) or metabolic control (HbA1c-last year r, −0.32, P=0.002; HbA1c-whole duration, r, −0.40; P=0.003). Negative AD-SoS z-scores depended significantly and directly on duration and quality of metabolic control, even when controlled for calcium intake. In conclusion, the architectural organization of bone was impaired in 10.5% patients. Duration of diabetes and poor metabolic control were the main determinants affecting AD-SoS. QUS may be a useful tool in the screening of bone disturbance in young patients with diabetes. Optimization of metabolic control is required to prevent osteoporosis.

Objective: The relationship between Osteoarthritis (OA) and Osteoporosis (OP) is not well defined due to lacking in longitudinal data, mainly regarding correlations between biochemical factors and OA incidence. Aim of this paper was to investigate the predictive value for OA incidence of bone mass variations and of selected biochemical markers in healthy women participating in a population-based longitudinal study carried out in Naples (Italy). Subjects and Methods: High completion rate (85.2%) and statistically adequate sample size were obtained: 139 women (45 to 79 years of age) were examined and follow up visit was performed after two years (24±2 months), following the same protocol. Patients underwent medical examination, questionnaire, anthropometric measurements, blood sampling and urine collection. Bone mineral density (BMD) measurement was performed by dual energy X-ray absorptiometry (DEXA) at the lumbar spine (L1-L4) and femoral neck. Radiographs of dorsal and lumbar spine in lateral view were performed at basal and at 24 months visits; a team of three experts scored radiographs using Kellegren and Lawrence grading. Results: The score was calculated for two individual radiographic features (narrowing of the joint space, presence of osteophytes) and as a global score. Results show a relevant percentage, 23% up, of subjects presenting both OA and OP. In the cross-sectional study the presence of osteophytosis correlates with anthropometric variables and PTH levels. In the longitudinal study results show a correlation between serum vitamin D and delta score for osteophytosis (β=0.02 p

BACKGROUND AND AIMS: Bone mineral density (BMD) is one of the main determinants in the pathogenesis of fractures. However, data on factors predicting longitudinal variations in BMD are still limited and incomplete. Such data would be of great importance in order to better focus prevention strategies in both the clinical setting and at the population level. The aim of the study was to investigate the predictive value of both serological and questionnaire variables for bone mass variations in healthy women participating in a population-based longitudinal study carried out in Napoli, Italy. METHODS: High completion rate (85.2%) and adequate sample size were obtained: 139 women (45 to 79 years of age) were examined at study entry and then again after two years (24 +/- 2 months) following the same protocol. They underwent medical examination, questionnaire, anthropometric measurements, blood sampling and urine collection. BMD was measured by dual energy X-ray absorptiometry (DEXA) at the lumbar spine (L1-L4) and femoral neck. Data analysis included calculation of the percent variation in BMD in the 2-year period. Longitudinal data underwent stepwise analysis for a global evaluation of mutual interactions between independent variables. RESULTS AND CONCLUSIONS: Our findings indicate that dietary and serum calcium, and serum 25(OH)vitamin D are the only independent determinants of BMD variations at the lumbar and femoral level, respectively. While the pharmacological significance of calcium and vitamin D in the therapy of established osteoporosis is still controversial, the present longitudinal data evidence their role as essential nutrients in determining the natural history of BMD variations.

Aim: To analyze whether bone mineral density (BMD) and bone resorption status are influenced by long-term metabolic control and duration of disease in adolescents with long-standing type 1 diabetes mellitus. Methods: Twenty-seven adolescents (age 13.1 ± 1.7 years, duration of diabetes 6.9 ± 3.0 years) were studied. The BMD, expressed as z score, was measured at the lumbar spine (L1–L4) using dual-energy X-ray absorptiometry, while the urinary excretion of total deoxypiridinoline (Dpyd), a marker of bone resorption, was measured by immunoassay and was corrected by creatinine (Cr). Linear and multivariate correlations between lumbar BMD z score or Dpyd/Cr excretion and age and disease variables [short-term (Hb A1clatest) or long-term (Hb A1cwholeduration) metabolic control, duration, ‘diabetes impact index’ (mean Hb A1cwholeduration x duration of disease in months)] were sought. Results: In diabetic subjects the mean BMD z score was –0.44 ± (SD) 1.02 (95% CI: –0.03; –0.84), and the Dpyd/Cr excretion was not increased. A negative correlation was found between lumbar BMD z score and age (r –0.59; p = 0.001), duration (r –0.39; p = 0.04), and the diabetes impact index (r –0.4; p = 0.04). The Dpyd/Cr ratio correlated negatively with age (r –0.40; p = 0.04) and positively with height velocity (r 0.42; p = 0.04). By using multiple linear regression, age showed a significant inverse correlation with lumbar BMD z score (β = –0.39; p = 0.0005). A negative correlation was found between lumbar BMD z score and Hb A1cwholeduration (β = –0.40; p = 0.02) or diabetes impact index (β = –0.001; p = 0.01). Conclusions: Poor metabolic control may expose adolescents with long-standing type 1 diabetes to the risk of developing osteopenia in adult age. Optimization of metabolic control in growing diabetic children may prevent osteoporosis in later life.

In clinical practice, patients with a range of signs and symptoms suggestive of connective tissue disease, but who do not fulfil the classification criteria for a defined disease are often found. This condition is defined as “Undifferentiated Connective Tissue Disease” (UCTD). Most of the authors consider UCTD as a distinct clinical entity, generally stable during follow-up. Despite this, no mutual agreement regarding criteria for its diagnosis has been reached. The clinical, serological, therapeutical and evolutional patterns of 41 patients initially diagnosed as having early UCTD during a 3-year follow-up are described in this study. At the end of the observational period, 21% of the enrolled patients, followed throughout the follow-up, demonstrated clinical evolution to a defined connective tissue disease (CTD), whereas 52% of the observed subjects maintained an undifferentiated profile with variable clinical findings and presenting a generally stable disease over time. The remaining patients showed clinical improvement or complete regression of the symptoms associated with normalization of the inflammatory indexes. The role of therapy in these different clinical courses is discussed.

Abstract To determine whether abnormal casual blood pressure (BP) is associated with left ventricular (LV) abnormalities in children, 190 6- to 11-year-old children (77 girls, 113 boys) were studied at a school site in Naples, Italy, by limited echocardiography and bioelectric impedance to calculate fat-free body mass (FFM). Single-visit BP measurements (defined as casual BP) were high (based on the Italian tables of BP) in 34 children (18%; 9 girls, 25 boys; 133±8/81±10 mm Hg) and obesity was present in 44 (23%; 15 girls, 29 boys). Sex- and age-independent risk of high casual BP value was 2.9-fold (odds ratio) greater in obese than in normal-weight children (95% confidence interval, 1.3 to 6.5; P 2.7 or FFM) was higher and relative wall thickness increased in children with high casual BP (all P P P P r =−.62, SEE=3.8% and r =−.32, SEE=2.4% in normal children). Shortening as a percentage of predicted from wall stress was increased in children with high casual BP at the endocardial level ( P

BackgroundThe optimal therapeutic strategies for patients presenting with advanced disease at HIV-1 diagnosis are as yet incompletely defined.MethodsAll patients presenting at two outpatient clinics in 2000-2009 with an AIDS-defining clinical condition or a CD4+ T cell count < 200/μL at HIV-1 diagnosis were analyzed for the presence of combined immunovirological response, defined by the concomitant presence of an absolute number of CD4+ T cells > 200 cells/μL and a plasma HIV-1 RNA copy number < 50/mL after 12 months of HAART.ResultsAmong 102 evaluable patients, first-line regimens were protease inhibitors [PI]-based in 78 cases (77%) and efavirenz-based in 24 cases (23%). The overall response rate was 65% (95% CI: 55-74), with no differences by gender, age, nationality, route of transmission, hepatitis virus coinfections, presence of AIDS-defining clinical events, baseline HIV-1 viral load, or type of regimen (response rates with PI-based and efavirenz-based therapy: 63% and 71%, respectively, p = 0.474). Response rate was significantly better with higher baseline CD4+ T cell counts (78% with CD4+ ≥ 100/μL, compared to 50% with CD4+ < 100/μL; odds ratio: 3.5; 95% CI: 1.49-8.23, p = 0.003). Median time on first-line antiretroviral therapy was 24 months (interquartile range: 12-48). Switch to a second line treatment occurred in 57% of patients, mainly for simplification (57%), and was significantly more common with PI-based regimens [adjusted hazard ratios (AHR) with respect to efavirenz-based regimens: 3.88 for unboosted PIs (95% CI: 1.40-10.7, p = 0.009) and 4.21 for ritonavir-boosted PI (95%CI 1.7-10.4, p = 0.002)] and in older subjects (≥ 50 years) (AHR: 1.83; 95% CI: 1.02-3.31, p = 0.044). Overall mortality was low (3% after a median follow up of 48 months).ConclusionsOur data indicate that a favorable immunovirological response is possible in the majority of naive patients presenting at HIV-1 diagnosis with AIDS or low CD4+ T cell counts, and confirm that starting HAART with a more compromised immune system may be associated with a delayed and sometimes partial immune recovery. Simpler regimens may be preferable in this particular population.