Catholic University of the Sacred Heart

About: Catholic University of the Sacred Heart is a education organization based out in Milan, Lombardia, Italy. It is known for research contribution in the topics: Population & Medicine. The organization has 13592 authors who have published 31048 publications receiving 853961 citations.

Dopamine neuronal loss contributes to memory and reward dysfunction in a model of Alzheimer’s disease

Abstract: Alterations of the dopaminergic (DAergic) system are frequently reported in Alzheimer's disease (AD) patients and are commonly linked to cognitive and non-cognitive symptoms. However, the cause of DAergic system dysfunction in AD remains to be elucidated. We investigated alterations of the midbrain DAergic system in the Tg2576 mouse model of AD, overexpressing a mutated human amyloid precursor protein (APPswe). Here, we found an age-dependent DAergic neuron loss in the ventral tegmental area (VTA) at pre-plaque stages, although substantia nigra pars compacta (SNpc) DAergic neurons were intact. The selective VTA DAergic neuron degeneration results in lower DA outflow in the hippocampus and nucleus accumbens (NAc) shell. The progression of DAergic cell death correlates with impairments in CA1 synaptic plasticity, memory performance and food reward processing. We conclude that in this mouse model of AD, degeneration of VTA DAergic neurons at pre-plaque stages contributes to memory deficits and dysfunction of reward processing.

Aspirin plus warfarin compared to aspirin alone after acute coronary syndromes: an updated and comprehensive meta-analysis of 25,307 patients.

Abstract: Aims In patients recovering from acute coronary syndromes (ACS) the role of oral anticoagulation (and its intensity) in addition to aspirin remains controversial. We conducted a specific meta-analysis of randomized trials comparing aspirin plus warfarin (AþW) with aspirin alone in such patients. Methods and results MEDLINE and Cochrane databases yielded 14 (of 148 potentially relevant) articles enrolling 25 307 patients. Follow-up ranged from 3 months to 5 years. Irrespective of International normalized ratio (INR), AþW did not significantly affect the risk of major adverse events (MAE: all cause death, non-fatal myocardial infarction, and non-fatal thrombo-embolic stroke) when compared with aspirin alone [OR 0.96 (0.90–1.03), P ¼ 0.30], but increased the risk of major bleeds (MB): OR 1.77 (1.47–2.13), P , 0.00001. However, in studies with INR of 2–3, AþW was associated with a significant reduction of MAE [OR 0.73 (0.63–0.84), P , 0.0001, number needed to treat to avoid one MAE ¼ 33], albeit at an increased risk of MB [OR 2.32 (1.63–3.29), P , 0.00001; number needed to harm by causing one MB ¼ 100]. In both analyses, intracranial bleeding was not significantly increased by AþW when compared with aspirin alone. Conclusion For patients recovering from ACS, a combined strategy of AþW at INR values of 2–3 doubles the risk of MB, but is nonetheless superior to aspirin alone in preventing MAE. Whether this combined regimen is also superior to a ‘double’ anti-platelet strategy or to newer evolving treatments warrants further investigation.

Alteration in cellular fatty acid composition as a response to salt, acid, oxidative and thermal stresses in Lactobacillus helveticus.

Abstract: The fundamental question in this study is concerned with whether the increase of unsaturated fatty acids in the cell membrane is a general response of certain thermotolerant strains or species when exposed to superoptimal temperatures, and in combination with other stresses, especially oxidative stress. A strain of Lactobacillus helveticus, a species widely used as a starter in the dairy industry and able to tolerate high temperature and NaCl concentrations as well as acidic conditions, was chosen for this study. Cells of strain CNBL 1156, grown in its natural medium (i.e. milk whey), were exposed for 100 min to sublethal combinations of temperature, NaCl, H2O2 and pH, modulated according to a Central Composite Design. The fatty acid composition of cell lipid extract was identified by GC/MS. Polynomial equations, able to describe the individual interactive and quadratic effects of the independent variables on cell fatty acid composition, were obtained. The results and the mathematical models relative to the individual fatty acids indirectly suggest that desaturase activation or hyperinduction play an important role in the response to heat stress. In fact, the relative proportions of oleic, linoleic and palmitic acids increased with temperature in a range between 38 and 54 °C. The fatty acid profiles included vernolic acid (up to 37% of total fatty acids), an epoxide of linoleic acid not previously reported in microbial cells. In particular, this epoxide was present in cells exposed to low pH in combination with high temperatures and oxidative stress. In conclusion, these results provide experimental support to the hypothesis that the increase of an oxygen-consuming desaturase system, with a consequent increase in fatty acid desaturation, is a cellular response to environmental stresses able to protect the cells of this anaerobic micro-organism from toxic oxygen species and high temperatures.

Clinical impact of thrombectomy in acute ST-elevation myocardial infarction: an individual patient-data pooled analysis of 11 trials

Abstract: Aims Thrombectomy in patients with ST-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) is associated to better myocardial reperfusion. However, no single trial was adequately powered to asses the impact of thrombectomy on long-term clinical outcome and to identify patients at higher benefit. Thus, we sought to assess these issues in a collaborative individual patient-data pooled analysis of randomized studies (study acronym: ATTEMPT, number of registration: NCT00766740). Methods and results Individual data of 2686 patients enrolled in 11 trials entered the pooled analysis. Primary endpoint of the study was all-cause mortality. Major adverse cardiac events (MACE) were considered as the occurrence of all-cause death and/or target lesion/vessel revascularization and/or myocardial infarction (MI). Subgroups analysis was planned according to type of thrombectomy device (manual or non-manual), diabetic status, IIb/IIIa-inhibitor therapy, ischaemic time, infarct-related artery, pre-PCI TIMI flow. Clinical follow-up was available in 2674 (99.6%) patients at a median of 365 days. Kaplan–Meier analysis showed that allocation to thrombectomy was associated with significantly lower all-cause mortality ( P = 0.049). Thrombectomy was also associated with significantly reduced MACE ( P = 0.011) and death + MI rate during the follow-up ( P = 0.015). Subgroups analysis showed that thrombectomy is associated to improved survival in patients treated with IIb/IIIa-inhibitors ( P = 0.045) and that the survival benefit is confined to patients treated in manual thrombectomy trials ( P = 0.011). Conclusion The present large pooled analysis of randomized trials suggests that thrombectomy (in particular manual thrombectomy) significantly improves the clinical outcome in patients with STEMI undergoing mechanical reperfusion and that its effect may be additional to that of IIb/IIIa-inhibitors.