Glucocorticoid receptors modulate dendritic spine plasticity and inflammation in an animal model of Alzheimer\u2019s disease.

Chronic exposure to high dose of glucocorticoids (GC) is a key risk factor for the development of Alzheimer\u2019s Disease (AD), as recently described by clinical and genetic studies. Furthermore, hyper-activation of glucocorticoids receptors (GR) induces, in brain, alterations comparable to those produced by AD. In a transgenic mice model for AD, GC induces the increasing production of A\u3b240, A\u3b242 and Tau total, the most important and typical hallmarks of this dementia. Two of the key roles of GC in brain are the regulation of dendritic spine turnover and the inflammation state, two phenomena strongly altered in AD. The aim of my project was to investigate the correlation between glucocorticoids and Alzheimer\u2019s Disease. In particular, I focused my attention on how dendritic spine plasticity and microglia activation in CA1 region of hippocampus of 3xTg-AD mice are modified by modulation of glucocorticoid receptor with agonist and antagonist. Using an innovative combined Golgi Cox and immunofluorescence technique, we found that 5 days of treatment with 8mg/kg of dexamethasone, an agonist of GR, was able to vigorously reduce dendritic spine density in CA1 region of 3xTg-AD mice, both at 6 and 10 months of age and induced proliferation and activation of microglia. The activation of microglia could contribute to spine damage. On the contrary, the treatment with 20mg/kg of mifepristone, an antagonist of GR, strongly enhanced dendritic spine density in CA1 region, at both ages, results confirmed also by electron microscopy analyses. Moreover, the antagonist was able to improve the 3xTg-AD mice performance in Y-maze task at 10 months of ages and the proliferation of microglia, but it was not able to reduce the activation of microglia. I speculated that these apparently ambiguous results could be explained by the well-known biphasic behavior of GC in brain, as already observed for spine plasticity and memory. Additionally, in vitro experiments, using immunofluorescence and immunoblotting techniques, revealed that dexamethasone, clearly, induced activation of microglia in vitro, a result never described before. On the contrary, mifepristone promoted both activation and inhibition of microglia inflammatory state, suggesting the existence of a biphasic behavior of GC also on inflammation regulation. In conclusion, my data demonstrates that stress induced by dexamethasone exacerbate AD and promote a more rapid progression of the pathology through a premature reduction of dendritic spine density and enhancement of inflammation. Consequently, the use of antagonist, like mifepristone, could represent a promising therapeutic strategy to delay the onset and slow down the progression of AD. Taking in account the biphasic behavior of GC, the right dose and time of treatment need to be found, in order to obtain the best improvement: the increasing of spine turnover together with the reduction of inflammation and improvement of behavioral performances

SMA applications in an innovative multishot deployment mechanism

An innovative Deployment and Retraction hinge Mechanism (DARM) in the frame of a technological program is examined. The mechanism includes two restraint/release devices, which enable it to be stable in its stowed or deployed position while sustaining all associated loads, and to carry its payload by remote command. The main characteristics of the DARM are as follows: deployment and retraction movements are spring actuated; the available amount of functional sequences is almost unlimited; and no use of electrical motors is made. These features were accomplished by: the application of a special kinematic scheme to the mechanical connection between the spring motor and the swivel head arm; and the use of shape memory alloys (SMA) actuators for both release and spring recharge functions. DARM is thus a mechanism which can find many applications in the general space scenario of in-orbit maintenance and servicing. In such a frame, the DARM typical concept, which has a design close to very simple one-shot deployment mechanisms, has a good chance to replace existing analog machines. Potential items that could be moved by DARM are: booms for satellite instruments; antenna reflector tips; entire antenna reflectors; and solar panels

"Digital Dilatation of Contracted Pylorus."

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Mesenteric-Portal Vein Resection during Pancreatectomy for Pancreatic Cancer

The aim of the present study was to determine the outcome of patients undergoing pancreatic resection with (VR+) or without (VR 12) mesenteric-portal vein resection for pancreatic carcinoma. Between January 1998 and December 2012, 241 patients with pancreatic cancer underwent pancreatic resection: in 64 patients, surgery included venous resection for macroscopic invasion of mesenteric-portal vein axis. Morbidity and mortality did not differ between the two groups (VR+: 29% and 3%; VR 12: 30% and 4.0%, resp.). Radical resection was achieved in 55/64 (78%) in the VR+ group and in 126/177 (71%) in the VR 12 group. Vascular invasion was histologically proven in 44 (69%) of the VR+ group. Survival curves were not statistically different between the two groups. Mean and median survival time were 26 and 15 months, respectively, in VR 12 versus 20 and 14 months, respectively, in VR+ group . In the VR+ group, only histologically proven vascular invasion significantly impacted survival , while, in the VR 12 group, R0 resection and tumor\u2019s grading significantly influenced long-term survival. Vascular resection during pancreatectomy can be performed safely, with acceptable morbidity and mortality. Long-term survival was the same, with or without venous resection. Survival was worse for patients with histologically confirmed vascular infiltration

COMPARISON OF TWO CHICKEN GENOTYPES ORGANICALLY REARED: OXIDATIVE STABILITY AND OTHER QUALITATIVE TRAITS

The effect of genotype on the oxidative stability and other qualitative traits of chicken meat was studied. Two groups of 200 chicks (Ross 205 and Kabir) were reared according to the organic farming system. At 81 d of age 20 birds per group were slaughtered and after refrigeration (24 h at 4°C) of the carcasses, Pectoralis major muscles were excised for analyses.Samples were analysed after 0, 24, 48, 72 and 96 hours of storage at 4°C under continuous fluorescent illumination (2300 lux). The analyses concerned the chemical composition and the shear force (only at time 0) and the progress of several traits as pH, CIELAB values, Thiobarbituric Acid Reactive Substances (TBARS), panel test and fatty acid composition (at 0 and after 96 h). Genotype greatly affected the physico-chemical characteristics and the sensory evaluation. The meat from Ross chickens showed high TBARS values, perhaps due to selection for growth rate that reduced their adaptability to greater space allowance and to poorer environmental conditions; these higher TBARS values were also negatively correlated to lightness and yellowness. The initial level of TBARS affected the oxidative stability of breast meat during storage. The amount of TBARS showed significantly negative relationship with the sensory evaluation; breast meat of Kabir had higher scores for liking when the level of malondialdehyde was less than 2.5 mg kg-1

Systematic review and meta-analysis of surgical drain management after the diagnosis of postoperative pancreatic fistula after pancreaticoduodenectomy: draining-tract-targeted works better than standard management

Drains' role after pancreaticoduodenectomy (PD) is debated by proponents of no drain, draining selected cases, and early drain removal. The aim of the study was to assess the effect of "standard" and "draining-tract-targeted" management of abdominal drains still in situ after diagnosing a postoperative pancreatic fistula (POPF)

Do cultural differences affect the share price puzzle?

We examine the impact of cultural differences on nominal share prices across 63 countries from 2002 to 2018. Using institutional and catering theories, we assess how cultural dimensions—including World Governance Indicators (WGI), legal systems, religious influences, and GLOBE dimensions—affect the spatial heterogeneity of share price levels. Our findings indicate that share prices are higher in countries with common law systems and comprehensive information reporting, as these environments tend to attract institutional investors. Conversely, cultural traits emphasizing altruistic values correspond with lower share prices, reflecting the preferences of individual investors