Down syndrome (DS) is a genetic pathology characterized by intellectual disability and brain hypotrophy. Widespread neurogenesis impairment characterizes the fetal and neonatal DS brain, strongly ...suggesting that this defect may be a major determinant of mental retardation. Our goal was to establish, in a mouse model for DS, whether early pharmacotherapy improves neurogenesis and cognitive behavior. Neonate Ts65Dn mice were treated from postnatal day (P) 3 to P15 with fluoxetine, an antidepressant that inhibits serotonin (5-HT) reuptake and increases proliferation in the adult Ts65Dn mouse (Clark et al., 2006). On P15, they received a BrdU injection and were killed after either 2 h or 1 month. Results showed that P15 Ts65Dn mice had notably defective proliferation in the hippocampal dentate gyrus, subventricular zone, striatum, and neocortex and that proliferation was completely rescued by fluoxetine. In the hippocampus of untreated P15 Ts65Dn mice, we found normal 5-HT levels but a lower expression of 5-HT1A receptors and brain-derived neurotrophic factor (BDNF). In Ts65Dn mice, fluoxetine treatment restored the expression of 5-HT1A receptors and BDNF. One month after cessation of treatment, there were more surviving cells in the dentate gyrus of Ts65Dn mice, more cells with a neuronal phenotype, more proliferating precursors, and more granule cells. These animals were tested for contextual fear conditioning, a hippocampus-dependent memory task, and exhibited a complete recovery of memory performance. Results show that early pharmacotherapy with a drug usable by humans can correct neurogenesis and behavioral impairment in a model for DS.
At 250-300 degree C and 30-50 bar, a continuous-flow (CF) transesterification of different dialkyl and alkylene carbonates (dimethyl-, diethyl-, dibenzyl-, and propylene carbonate, respectively) with ...two glycerol derived acetals (glycerol formal and solketal) was investigated without any catalyst. An unprecedented result was obtained; not only the desired process occurred, but also the formation of the corresponding mono-transesterification products took place with an excellent selectivity (up to 98%) in all cases. Under isothermal conditions, a study on the effect of pressure allowed us to optimize the conversion of acetals (up to 95%) for the reactions of dimethyl- and diethyl-carbonate (DMC and DEC, respectively). This proved that an abrupt progress of the reaction occurred for very small increments of pressure. For example, at 250 degree C, the thermal transesterification of DMC with glycerol formal showed a sharp increase of the conversion from 1-2% at 30 bar to similar to 85% at 37 bar. The lower the temperature, the lower the pressure interval at which the onset of the reaction is achieved. The absence of catalysts allowed us to run CF-reactions virtually indefinitely and with a very high productivity (up to 68 mg min super(-1)) compared to the capacity (1 mL) of the used CF-reactor. Products of the transesterification of DMC and DEC were isolated in good-to-almost quantitative yields. In the case of heavier carbonates, steric reasons were responsible for the considerably lower reactivity of propylene carbonate (PC) with respect to DMC and DEC, while the transesterification of dibenzyl carbonate (DBnC, solid at room temperature) with glycerol formal required the presence of acetone as an additional solvent/carrier. Although the reactions of both PC and DBnC were not optimized, results offered a proof-of-concept on the extension of thermal transesterification processes to higher homologues of linear and alkylene carbonates.
High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard of care for patients with relapsed Hodgkin's lymphoma (HL). However, there is currently little ...information on the predictors of outcome for patients whose disease recurs after ASCT.
Five hundred and eleven adult patients with relapsed HL after ASCT from EBMT-GITMO databases were reviewed.
Treatments administered following ASCT failure included conventional chemotherapy and/or radiotherapy in 294 (64%) patients, second ASCT in 35 (8%), and alloSCT in 133 (29%). After a median follow-up of 49 months, overall survival (OS) was 32% at 5 years. Independent risk factors for OS were early relapse (<6 months) after ASCT, stage IV, bulky disease, poor performance status (PS), and age ≥50 years at relapse. For patients with no risk factors OS at 5 years was 62% compared with 37% and 12% for those having 1 and ≥2 factors, respectively. This score was also predictive for outcome in each group of rescue treatment after ASCT failure.
Early relapse, stage IV, bulky disease, poor PS, and age ≥50 years at ASCT failure are relevant factors for outcome that may help to understand the results of different therapeutic approaches.
In systemic sclerosis (SSc) reduced capillary density decreases blood flow and leads to tissue ischaemia and fingertip ulcers. Nail fold videocapillaroscopy (NVC) is a diagnostic and follow-up ...parameter useful to evaluate the severity, activity and the stage of SSc microvascular damage. Autologous haemopoietic stem cell transplantation (HSCT) is a new treatment for patients with severe diffuse cutaneous systemic sclerosis (dcSSc) refractory to conventional therapies. We aimed to evaluate the improvement of microvasculature after HSCT using NVC.
A total of 16 patients with severe dcSSc with a "late" videocapillaroscopy pattern underwent an immunesuppressive treatment: 6 were treated with HSCT and 10 with monthly pulse cyclophosphamide (CYC) 1 g for 6 months and then orally with 50 mg/day for further 6 months. NVC was performed before and after 3 months from the beginning of each treatment and then repeated every 3 months.
In all patients, before HSCT NVC showed large avascular areas and ramified capillaries and vascular architectural disorganisation ("late" pattern). At 3 months after HSCT, the NVC pattern changed from "late" into "active", showing frequent giant capillaries (>6/mm) and haemorrhages, absence of avascular areas and angiogenesis phenomena; 1 year after HSCT, microvascular abnormalities were still in the "active" pattern. In patients treated with CYC, no NVC modifications were observed during 24 months of follow-up and the pattern always remained "late".
These results indicate that HSCT with a high dose CYC regimen may foster vascular remodelling, while CYC at lower doses and with a chronic regimen does not influence the microvasculature.
The Health and Safety Executive (HSE) indicator tool is one of the most commonly used tools for assessing the risk of work-related stress. Few studies, however, have investigated whether and how its ...scales are related to psychological distress or other work-related health outcomes.
To investigate the relationship between the HSE indicator tool, psychological distress, as measured by the General Health Questionnaire (GHQ)-12, and work ability, assessed by the Work Ability Index (WAI).
All the employees of a mid-sized bank in Italy were asked to fill in an anonymous cross-sectional questionnaire. The questionnaire was structured in four sections: the first one comprised socio-demographic questions and the other three corresponded, respectively, to the Italian translations of the GHQ-12, the HSE and the WAI questionnaires.
Four hundred and thirteen employees completed the questionnaire. The response rate was 99%. Controlling for age and gender, the indicator subscales were negatively associated with the adopted measures of psychological distress and work ability. The GHQ score was also highly correlated with the WAI score and able to explain ≈ 47% of its variance. The only subscale that was still significantly associated with the WAI after removing the effect of psychological distress was 'control'.
The study presents new evidence for the validity of the HSE indicator tool to estimate the risk of work-related stress and suggests that most but not all the effects of psychosocial conditions on work ability might be mediated by the level of psychological distress induced by these conditions.
Data on the association of resistin levels with markers of insulin resistance are highly contrasting in humans and very few studies about its role in inflammation are available. This study ...investigates associations between serum resistin levels and markers of insulin resistance, inflammation (C-reactive protein (CRP)) and of oxidative stress (nytrotirosine (NT)).
A randomly collected sample of 300 men from a population-based cohort was analysed, separated into two groups according to body mass index (BMI) and waist values.
Correlations between resistin and BMI, waist, triglyceride, uric acid, fasting glucose, insulin and Homeostasis Model Assessment (HOMA) values were significant in subjects with normal BMI, but not in overweight/obese subjects. In a multiple regression model, after multiple adjustments and exclusion of diabetic patients, only fasting glucose remained significantly associated with resistin levels. Otherwise, resistin is associated to CRP levels in all individuals, after multiple adjustments and exclusion of diabetic patients (in normal BMI beta=0.82; 95% CI 0.21, 1.42; in overweight/obese beta=0.43; 95% CI 0.10, 0.76). In the same model, resistin values are negatively related to NT levels in normal weight individuals (beta=-1.61; 95% CI -0.77-2.45).
Serum resistin is weakly associated with metabolic abnormalities in subjects with normal BMI, while in overweight/obese patients this correlation is not significant, perhaps due to the higher fat content in these subjects. Serum resistin is directly correlated with CRP and inversely to NT. An intriguing hypothesis, which needs to be tested, is that resistin is secreted in response to a chronic low-grade inflammation, and has antioxidant properties.
Background: Over recent years numerous patients with severe forms of multiple sclerosis (MS) refractory to conventional therapies have been treated with intense immunosuppression followed by ...autologous haematopoietic stem cell transplantation (AHSCT). The clinical outcome and the toxicity of AHSCT can be diverse, depending on the various types of conditioning protocols and on the disease phase.
Objectives: To report the Italian experience on all the consecutive patients with MS treated with AHSCT with an intermediate intensity conditioning regimen, named BEAM/ATG, in the period from 1996 to 2008.
Methods: Clinical and magnetic resonance imaging outcomes of 74 patients were collected after a median follow-up period of 48.3 (range = 0.8–126) months.
Results: Two patients (2.7%) died from transplant-related causes. After 5 years, 66% of patients remained stable or improved. Among patients with a follow-up longer than 1 year, eight out of 25 subjects with a relapsing–remitting course (31%) had a 6–12 months confirmed Expanded Disability Status Scale improvement > 1 point after AHSCT as compared with one out of 36 (3%) patients with a secondary progressive disease course (p = 0.009). Among the 18 cases with a follow-up longer than 7 years, eight (44%) remained stable or had a sustained improvement while 10 (56%), after an initial period of stabilization or improvement with median duration of 3.5 years, showed a slow disability progression.
Conclusions: This study shows that AHSCT with a BEAM/ATG conditioning regimen has a sustained effect in suppressing disease progression in aggressive MS cases unresponsive to conventional therapies. It can also cause a sustained clinical improvement, especially if treated subjects are still in the relapsing–remitting phase of the disease.
Land use influences the abundance and diversity of soil arthropods. The evaluation of the impact of different management strategies on soil quality is increasingly sought, and the determination of ...community structures of edaphic fauna can represent an efficient tool. In the area of Langhe (Piedmont, Italy), eight vineyards characterized for physical and chemical properties (soil texture, soil pH, total organic carbon, total nitrogen, calcium carbonate) were selected. We evaluated the effect of two types of crop management, organic and integrated pest management (IPM), on abundance and biodiversity of microarthropods living at the soil surface. Soil sampling was carried out in winter 2011 and spring 2012. All specimens were counted and determined up to the order level. The biodiversity analysis was performed using ecological indexes (taxa richness, dominance, Shannon–Wiener, Buzas and Gibson's evenness, Margalef, equitability, Berger–Parker), and the biological soil quality was assessed with the BSQ-ar index. The mesofauna abundance was affected by both the type of management and sampling time. On the whole, a higher abundance was in organic vineyards (N = 1981) than in IPM ones (N = 1062). The analysis performed by ecological indexes showed quite a high level of biodiversity in this environment, particularly in May 2012. Furthermore, the BSQ-ar values registered were similar to those obtained in preserved soils.
Several guidelines have been published about management of chronic GvHD (cGvHD), but the clinical practice still remains demanding. The Gruppo Italiano Trapianto di Midollo Osseo (GITMO) has planned ...a prospective observational study on cGvHD, supported by a dedicated software, including the updated recommendations. In view of this study, two surveys have been conducted, focusing the management of cGvHD and ancillary therapy in cGvHD, to address the current 'real life' situation. The two surveys were sent to all 57 GITMO centers, performing allografting in Italy; the response rate was 57% and 66% of the interviewed centers, respectively. The first survey showed a great disparity especially regarding steroid-refractory cGvHD, although extracorporeal photo-apheresis resulted as the most indicated treatment in this setting. Another challenging issue was the strategy for tapering steroid: our survey showed a great variance, and this disagreement could be a real bias in evaluating outcomes in prospective studies. As for the second survey, the results suggest that the ancillary treatments are not standardized in many centers. All responding centers reported a strong need to standardize management of cGvHD and to participate in prospective trials. Before starting observational and/or interventional studies, a detailed knowledge of current practice should be encouraged.
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