64 research outputs found

    Activin A circulating levels in patients with bone metastasis from breast or prostate cancer

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    Recent studies have highlighted that Activin A, a member of the transforming growth factor-beta (TGF-beta) superfamily, may be involved in the regulation of osteoblastic activity and in osteoclast differentiation. Therefore, we have investigated the clinical significance of its circulating levels in patients with bone metastasis. Activin A serum concentrations were determined, by a commercially available enzyme-linked immunosorbent assay kit, in 72 patients with breast cancer (BC) or prostatic cancer (PC) with (BM+) or without (BM-) bone metastases, in 15 female patients with age-related osteoporosis (OP), in 20 patients with benign prostatic hypertrophy (BPH) and in 48 registered healthy blood donors (HS) of both sex (25 female and 23 male). Activin A serum concentrations were significantly increased in BC or PC patients as compared to OP (P < 0.0001) or BPH (P = 0.045), respectively, or to sex matched HS (P < 0.0001). Additionally, these levels resulted more elevated in PC patients as compared to BC patients (P = 0.032). Interestingly, Activin A was significantly higher in BM+ patients than in BM- patients (BC, P = 0.047; PC, P = 0.016). In BC patients, a significant correlation was observed only between Activin A and number of bone metastases (P = 0.0065) while, in PC patients, Activin A levels were strongly correlated with the Gleason score (P = 0.011) or PSA levels (P = 0.0001) and, to a lessen extent, with the number of bone metastases (P = 0.056). Receiver operating characteristic curve (ROC) analysis showed a fair diagnostic accuracy of Activin A to discriminate between BM+ and BM- patients (BC: AUC = 0.71 +/- 0.09, P = 0.03; PC: AUC = 0.73 +/- 0.081, P = 0.005). These findings indicate that Activin A may be implicated in the pathogenesis of bone metastasis. Therefore, this cytokine may be considered a novel potential target for a more selective therapeutic approach in the treatment of skeletal metastasis and may be also useful as additional biochemical marker of metastatic bone disease

    Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

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    A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons

    A survey by indicators on housing conditions in a city of Lazio, Italy

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    Introduction. To test the applicability, in a little town of central Italy, of an indicator set proposed by WHO to assess housing stock condition and wellbeing of its inhabitants. Methods. The indicator set created by WHO to evaluate housing conditions (LARES project) concerns affordability, accessibility, crowding, extremes of indoor air temperature, dampness and mould growth, household hygiene, housing safety and accidents, crime and fear of crime indicators. It was tested in Veroli (FR), a little town of Lazio, Italy. After a territory’s analysis, a questionnaire, formulated to obtain data for indicator values calculation, was administered to 310 voluntary subjects, corresponding to 17% of town’s residents, living in 98 different houses. At the same time, a visual inspection of the building was carried out to collect data about the dwelling’s quality, physical condition and technical equipments. Results. We obtained he necessary data for value calculation for all the proposed indicators except affordability and extremes of indoor air temperature, because this kind of information was not available at local level. Although available space is inadequate for only 1% of inhabitants (less than 14 m2 per person), overcrowding index (number of rooms available per person) is 16%, suggesting that spaces are not well distributed or are without adequate divisions. 94% of houses showed physical environmental barriers (such as narrow doors, staircase without lift, height differences within dwelling) and 39% of households included at least one person with functional limitations. 45% of houses presented mould and humidity inconvenience and/or presence of moulds on the walls. For 20% of houses water furniture was irregular. Discussion and conclusions. Study by indicators is a brief and effective analysis method to evaluate housing condition. It should represent an advantageous way for local Authorities which aim to extend on a large scale this analysis, to quantify urban decline and to identify intervention areas requesting priority. Nevertheless, this tool is not completely applicable in little towns where disaggregated data and adequate information systems are not existing

    Atrial Fibrillation and Stroke

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    Atrial fibrillation (AF) represents a major cause of morbidity and mortality in adults, especially for its strong association with thromboembolism and stroke. In this chapter, we aim to provide an overview on this cardiac arrhythmia, addressing several important questions. Particularly, we faced the possible mechanisms leading to an increased risk of embolism in AF, emphasizing how Virchow’s triad for thrombogenesis is unable to fully explain this risk. Disentangling the risk of stroke caused by AF and by other associated vascular conditions is extremely challenging, and risk stratification of patients with AF into those at high and low risk of thromboembolism has become a crucial determinant of optimal antithrombotic prophylaxis. Moreover, we discuss the typical clinical and radiological characteristics of cardioembolic strokes, addressing acute, time-dependent reperfusional therapies in case of ischemic stroke. The role of anticoagulation in AF is also fully analyzed; the benefit of oral anticoagulation generally outweighs the risk of bleeding in AF patients, and a variety of scoring systems have been developed to improve clinical decision-making when initiating anticoagulation. With their predictable pharmacokinetic profiles, wide therapeutic windows, fewer drug–drug and drug-food interactions, and the non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) have changed the landscape of thromboprophylaxis for AF patients, offering the opportunity to use effective anticoagulants without the need for intensive therapeutic drug monitoring

    Isolation of microrganisms involved in endodontic infection

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    In endodontic infections a lot of different microrganisms can be time inside dentinal tubules to support such infections. Most of these are Gram negative anaerobes bacteria able to induce an immune response that is the apparent cause of periapical lesion, but also Gram positive facultative aerobic species and fungi of the genus Candida.They play an important role in pain but also in bone periapical resorption. Therefore, the exact knowledge and the subsequent elimination of the microrganisms involved by the system of root canals, although difficult to achieve completely, is essential for the resolution of apical periodontitis
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