3,421 research outputs found
METABOLOMIC FINGERPRINTS OF NEONATAL DYSGLYCEMIA IN PRETERM INFANTS
No full textPreterm infants are exposed to glucose fluctuation, including hypo- and hyper-glycemia, as consequence of immaturity of metabolic and hormonal processes regulating glucose homeostasis. Neonatal provision of brain metabolic fuels, including glucose and other metabolites, are thought to be significant determinant of neurodevelopment, though evidence linking neonatal glucose homeostasis to long-term neurodevelopment remains controversial. The aim of this study is to investigate the metabolomic changes associated with neonatal dysglycemia detected with continuous glucose monitoring (CGM) in infants born preterm and their long-term neurodevelopmental effect. This was a monocentric prospective observational study conducted at the Neonatal Intensive Care Unit (NICU) of the University Hospital of Padova. We included preterm infants with birth weight (BW) <1500 g or gestational age (GA) ≤32 weeks, who were started on a continuous glucose sensor within 48 hours of life. Euglycemia is defined as glucose sensor value between 4 and 8 mmol/L; hypoglycemia below 4 mmol/L and hyperglycemia above 8 mmol/L. Glycemic variability (GV) was described as percentage of time spent in each category of glycemia out of total time of monitoring and as coefficient of variation (CV). Targeted metabolomic analysis was applied to plasma samples collected during glucose monitoring and performed on an Acquity Ultra Performance Liquid Chromatography (UPLC) coupled to Mass Spectrometer (MS). Neurodevelopment was assessed at 12 months corrected age (CA) with Bayley Scales of Infant and Toddler Development (BSID) III and gap-overlap (GO) task. Statistical analysis was conducted with non-parametric test using linear regression and univariate analysis. 52 infants were included in the analysis, enrolled between March 2020 and June 2023. Females were 53%, median GA and BW were 29.7 weeks and 1215 g respectively. Targeted metabolomic analysis was performed for 40 patients. Follow-up assessment was available for 43/44 participants. CGM data revealed median time in euglycemic range (TIR) and a CV of 81.8% and 0.19 respectively, negatively correlated with each other (tau b-0.339, p-value<0.001). According to tertile distribution of TIR and CV, we found higher intrauterine growth restriction (IUGR) (0% vs 43%, p-value 0.016) and lower auxological parameter at birth (BW centile 59° vs 17°, p-value 0.015) in those with higher GV. Both extrauterine growth restriction (EUGR) (8% vs 57%, p-value 0.001), and bronchopulmonary dysplasia (BPD) (0% vs 36%, p-value 0.018) prevailed in infants with higher GV. Targeted metabolomic analysis showed higher GV associated with more mobilization of gluconeogenic precursors as lactic acid (421.783 vs 621.894 μM, p-value 0.050) and alanine (365.413 vs 433.433 μM, p-value 0.028), higher level of long chain acylcarnitines as myristoylcarnitine (0.028 vs 0.046 μM, p-value 0.010) and stearoylcarnitine (0.224 vs 0.380 μM, p-value 0.039) and imbalance of metabolites implying in insulin sensitivity as carnosine (12.672 vs 5.328 μM, p-value 0.007), cystathionine (9.452 vs 4.576 μM, p-value 0.016) and DOPA (0.016 vs 0.009 μM, p-value 0.024). GV impaired kynurenine pathway with lower neuroprotective metabolites (p=0.043, tau b=-0.236). Long-term follow up revealed lower performance in communication (BSID III 97 vs 91, p-value 0.016); lower visual attention at GO task was related to GV (tau b 0.389; p-value 0.030). The study demonstrated that GV of preterm infants was influenced by perinatal factors and related to short and long-term clinical outcomes, suggesting GV as a marker of early neonatal health. Targeted metabolomic analysis described the imbalance of several metabolomic pathway involved in alternative energetic substrates and of kynurenine pathway. These findings gave plausibility to the hypothesis of negative influence of neonatal dysglycemia on developing brain
Eloge
No full textOverview of the typology of the encomiastic epigram, from the archaic to the Byzantine period. Silvia Barbantani is author of the section on Greek epigram Rosario Moreno Soldevila is author of the section on the latin epigram
Tumor-induced expansion of regulatory T cells by conversion of CD4(+)CD25(-) lymphocytes is thymus and proliferation independent
No full textThe CD25(-) and CD25(+) CD4 T-lymphocyte compartments are tightly regulated. We show here that tumors break such balance, increasing the number of CD4(+)CD25(+) T cells in draining lymph node and spleen but not contralateral node of tumor-bearing mice. Tumor injection in thymectomized and CD25-depleted mice shows that CD4(+)CD25(+) T-cell expansion occurs even in the absence of the thymus and independently from proliferation of preexisting CD25(+) T cells. These newly generated cells are bona fide regulatory T cells (T reg) in terms of Foxp3 expression and suppression of CD3-stimulated or allogeneic effector cell proliferation. Transfer of congenic Thy1.1 CD4(+)CD25(-) T cells, from mice treated or not with vinblastine, into tumor-bearing or tumor-free mice and analysis of recovered donor lymphocytes indicate that conversion is the main mechanism for acquiring the expression of CD25 and Foxp3 through a process that does not require proliferation. Although conversion of CD4(+)CD25(-) T cells for generation of T regs has been described as a natural process that maintains peripheral T-reg population, this process is used by the tumor for immune escape. The prompt recovery of T regs from monoclonal antibody-mediated CD25 depletion in tumor-bearing mice suggests attempts able to inactivate rather than deplete them when treating existing tumors
Immunosuppression for interstitial lung disease in systemic sclerosis
No full textThe efficacy of immunosuppressors in the treatment of systemic sclerosis-interstitial lung disease is still matter of controversy. In this review we will analyse the evidence that immunosuppressors, despite not being able to reverse fibrotic changes, may help in slowing disease progression. Induction treatment with cyclophosphamide should be started as soon as possible in patients at risk for progression. Mycophenolate mofetil and rituximab have to be considered in patients who are unable to tolerate cyclophosphamide. After remission, maintenance treatment with mycophenolate mofetil or azathioprine should be started in order to preserve the benefits achieved during the induction treatment
Avascular bone necrosis: An underestimated complication of systemic sclerosis
No full textAvascular bone necrosis: An underestimated complication of systemic sclerosi
The National Labour Policies in the context of the Europe 2020 strategy and of the European Economic Governance
No full textThe National Labour Policies in the context of the Europe 2020 strategy and of the European Economic Governance, by Silvia Borelli
The author presents the main priorities of the Europe 2020 strategy and the different steps of the European Semester of the European Economic Governance. The system of the European measures to solve the economic crisis is completed by the analysis of the “Six Pack”, the EuroPlus Pact and the Treaty on Stability, Coordination and Governance. The author clarifies how the European Employment Strategy has been fully absorbed by the European Economic Governance. After considering some of the new European economic framework’s consequences on Member States’ labour policies and on social dialogue, the author focuses on the recent review of Italian labour policies, performed by European Commission as part of the European Semester
Lavorare per la rivoluzione. Un'impresa commerciale tra Italia e Cina
No full textThe volume collects the biographical testimony of Fabio Matteini who, starting from the ’60s, undertook an import activity of Chinese handcra products with the aim of supporting the political and cultural initiative of the Edizioni Oriente of Milan, the main center for the spread of Maoism in Italy. The testimony is accompanied by a prefatory essay by Gilda Zazzara on Matteini work culture and by a selection of photographs taken by the author during the years of the Cultural Revolution, chosen and introduced by Silvia Calamandrei
Very early and early diagnosis of systemic sclerosis
No full textSystemic sclerosis (SSc) is easily diagnosed when the disease is evolved to skin fibrosis with obliterative vasculopathy and internal organs involvement. In the very early/early phase of SSc, the diagnosis remains very difficult because of the lack of validated diagnostic criteria. Actually, the American College of Rheumatology (ACR) and LeRoy classification criteria are not sufficiently sensitive to enable very early/early diagnosis of the disease, limiting the possibility of a precocious treatment. Therefore, in many cases, treatment is delayed for several years following the onset of Raynaud‘s phenomenon (RP) and even after the onset of the first non-RP symptom. For this reason, the very early/early diagnosis of SSc is today of pivotal importance. Recently, RP, puffy fingers turning into sclerodactyly and antinuclear antibody (ANA) positivity are considered the three red flags for the suspicion of a very early SSc. Further signs such as positivity of other specific autoantibodies and/or videocapillaroscopy pattern may allow very early diagnosis of SSc. This may allow follow-up of the patient and start the appropriate therapeutic regimen to arrest the disease progression when an organ involvement is detected. The time gap between the onset of signs and the diagnosis can be considered the ‘window of opportunity‘ where the disease may be stopped before skin and internal organs are irreversibly damaged. Therefore, the main topic discussed in this chapter will be ‘why we need to distinguish between a very early and an early diagnosis of SSc‘
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