Effects of Proton Radiation on Behavior in a Mouse Model of Alzheimer’s Disease

Astronauts venturing outside Earth’s magnetosphere risk exposure to charged particle radiation that has been shown to cause neurological deficits in rodents via oxidative stress, neuroinflammation, altered neurogenesis, and synaptic changes. Since these responses are similar to those observed in age-related neurodegenerative diseases, we hypothesized that individuals with a propensity toward developing Alzheimer’s disease (AD) would be more adversely affected by such exposure. To test this hypothesis, we exposed young double transgenic APP/PSEN1 mice (a commercially available strain engineered to develop AD-like neuropathology) and their wild-type (non-transgenic) counterparts to low doses of 150 MeV proton particle radiation and assessed the effects on hippocampus-dependent behaviors. Spatial learning ability, a sensitive behavioral marker of hippocampal damage, was assessed using the water maze and Barnes maze 3 and 6 months after irradiation. Transgenic mice performed worse than wild-type mice on both behavioral measures, and wild-type mice exposed to 0.5 Gy performed worse than the 0 Gy wild-type mice at 6 months post-irradiation. However, radiation doses up to 1 Gy had no effect on transgenic spatial learning performance. These findings suggest that low doses of proton radiation cause deficits in normal individuals, but may not exacerbate or accelerate learning and memory deficits in individuals predisposed toward age-related neurological disease

Neuropsychological Effects of Pomegranate Supplementation Following Ischemic Stroke

Polyphenols are compounds found in fruits and vegetables that have antioxidant and anti-inflammatory properties. Mounting evidence suggests that dietary polyphenol intake can reduce the detrimental effects of various disease processes, and pomegranates have frequently been examined because of their particularly high polyphenol content. Since stroke induces both oxidative stress and inflammation and is currently the leading cause of long-term disability in the U.S., we sought to determine whether dietary supplementation with polyphenols could enhance cognitive recovery in individuals who had suffered an ischemic stroke. We administered polyphenols via 2 POMx pills containing polyphenols derived from pomegranates equivalent to the content of approximately 8 ounces of pomegranate juice, or placebo pills (capsules containing no polyphenol ingredients), every day for one week to inpatients who were in the acute post-stroke phase. Neuropsychological testing pre- and post-treatment was used to determine whether there were any changes in cognitive functioning as a result of pomegranate supplementation. Results trended toward subtle improvements in cognitive abilities in pomegranate-treated subjects compared to placebo-controlled subjects. Findings from this randomized, placebo-controlled, double-blind clinical trial suggest that pomegranate polyphenols may be effective at enhancing the recovery of cognitive functioning after ischemic stroke, although studies with larger sample sizes and longer treatment durations are needed to make any conclusions regarding these potential effects

Rapid Bidirectional Switching of Synaptic NMDA Receptors

SummarySynaptic NMDA-type glutamate receptors (NMDARs) play important roles in synaptic plasticity, brain development, and pathology. In the last few years, the view of NMDARs as relatively fixed components of the postsynaptic density has changed. A number of studies have now shown that both the number of receptors and their subunit compositions can be altered. During development, the synaptic NMDARs subunit composition changes, switching from predominance of NR2B-containing to NR2A-containing receptors, but little is known about the mechanisms involved in this developmental process. Here, we report that, depending on the pattern of NMDAR activation, the subunit composition of synaptic NMDARs is under extremely rapid, bidirectional control at neonatal synapses. This switching, which is at least as rapid as that seen with AMPARs, will have immediate and dramatic consequences on the integrative capacity of the synapse

Per poter dare qualità alla ragione: una fntasia di colori ed una sinfonia di suoni.

Dare qualità alla ragione è una risposta laica alla ansia ed alle angosce della modernità che ha rinunciato a vane promesse religiose (riprese talvolta desacralizzandole, con nuovi, ma sempre vuoti, vestiti ideologici) e maggiormente della post-modernità che non crede più neppure ad indefiniti ed inesistenti fini teleologici. Lo strutturalismo (mutuato da ricerche antropologiche) si presenta come un linguaggio aspro, ma sincero, per rappresentare la complessità della realtà, nella parzialità di ogni rappresentazione. Pressoché in parallelo, si presenta il contributo sociologico e politico, della Scuola di Francoforte neomarxista, a partire dalla critica marxiana al fallace marxismo ortodosso sovietico ed alla vacua società dei consumi occidentale. Sempre in parallelo, il falsificazionismo rappresenta un punto di arrivo di una ricerca filosofica che, dalla filosofia della scienza, si estende alla critica delle dottrine politiche, per sostenere idee di libertà e giustizia. Allora dare qualità alla ragione non è un problema banale, di fronte ai moltissimi fallimenti della storia, passata e recente. Per questo, è necessario concepire, mettere in atto e sostenere, sempre in modo critico e molto responsabile, soluzioni parziali, per tempi limitati e spazi ristretti, sapendo che solo lo incontro, il dialogo e la accoglienza, con altre soluzioni parziali, permetteranno di costruire una rete mirabile di piccole intese, per quanto precarie, fragili e provvisorie. La identità soft tra vero, bene e bello, dove i primi due sono di incerta natura e definizione, mentre il terzo si rifà semplicemente alla educazione civica ed un galateo minimo, senza richiamare falsi assoluti, porta a ricercare la ricchezza e la gioia di una fantasia di colori ed una sinfonia di suoni. Pertanto clemenza, verso gli altri, e temperanza, con se stessi, sono le piccole doti richieste

ON OUTLIER DETECTION IN A PHOTOGRAMMETRIC MOBILE MAPPING DATASET

Various types of technology are used for Terrestrial Mobile Mapping (TMM) such as IMU, cameras, odometers, laser scanner etc., which are integrated in order to determine the attitude and the position of the vehicle in use, especially in the absence of GNSS signal i.e. in an urban canyon. The aim of this study is to use only photogrammetric measurements obtained with a low cost camera (with a reduced focal length and small frames) located on the vehicle, in order to improve the quality of TMM solution in the absence of a GNSS signal. It is essential to have good quality frames in order to solve this problem. In fact it is generally quite easy to extract a large number of common points between the frames (the so-called 'tie points'), but this does not necessarily imply the goodness of the matching quality, which might be uncorrected due to the presence of obstacles that may occlude the camera sight. The Authors used two different methods for solving the problem of the presence of outliers: RANSAC and the Forward Search. In this article the Authors show the results obtainable with good quality frames (frames without occlusions) and under difficult conditions that simulate better reality

Cost-effectiveness analysis of alectinib versus crizotinib in first-line treatment of anaplastic lymphoma kinase-positive advanced non-small cell lung cancer:

In the randomized, active-controlled, multicenter Phase III open-label ALEX trial, alectinib showed superior efficacy and lower toxicity compared with crizotinib in the primary treatment of anaplastic lymphoma kinase-positive non-small cell lung cancer (ALK-positive NSCLC). The aim of this economic evaluation was to assess the cost-utility of alectinib versus crizotinib from the perspective of the Italian National Health Service (INHS). A partitioned survival model with three health states (progression-free, post-progression, and death) was used. The clinical data (progression-free survival, overall survival and time to progression) was based on the ALEX trial. Utility values were derived from EQ-5D scores evaluated in the ALEX trial and literature. Costs included drug treatments, progression-free, post-progression and supportive care. Direct medical costs and benefits (quality-adjusted life-years, QALYs) were discounted at a 3.0% annual rate. Uncertainty was assessed using deterministic and probabilistic sensitivity analyses. Treatment with alectinib versus crizotinib led to a gain of 2.82 life-years, 1.86 QALYs, and incremental costs of €58,276, resulting in an incremental cost-utility ratio of €31,353 per QALY. The deterministic analysis showed that the most critical parameters in the model were the cost of post-progression and utility scores. From the probabilistic sensitivity analysis, alectinib had a 64.5% probability of being cost-effective at a willingness-to-pay threshold of €40,000 per QALY. Compared with crizotinib, alectinib increased the length of the progression-free state and the QALYs. The incremental overall cost increase was reflective of longer treatment durations in the progression-free state. Compared with crizotinib, alectinib can be considered a valid cost-utility option in the treatment of naive patients with ALK-positive NSCLC

Alexithymia and psychological distress affect perceived quality of life in patients with type 2 diabetes mellitus

Backgrounds: Psychological factors may affect patients' ability to cope with chronic illness, which occur with a high incidence as they represent age related disorder. Anxiety, depression and alexithymia could specifically interfere with compliance and adherence leading to predictable consequences and predicting morbidity and mortality independently of several confounders. The present work aims at investigating the relationship between alexithymia and affective dimension such as anxiety and depression levels, and health related quality of life in T2DM patients. Particularly, alexithymia was analyzed in its three main facets and time since diagnosis was considered with also metabolic control. Methods: Forty seven patients with T2DM were consecutively enrolled and assessed with a gold standard interview and with a psycho-diagnostic evaluation. Clinical psychological exploration consisted of HAM-A, BECK-II, SF-36 and TAS-20 administration. Statistical analysis was performed using IBM SPSS statistical version 25. Data were analyzed anonymously. Results: 47 participants showed moderate depressive symptoms as confirmed by the mean BDI-II and HAMA-A score (15.14 ± 8.95 and 24.31 ± 6.95, respectively), suggesting a high prevalence of anxiety in the enrolled subjects. It was observed a lower perceived QoL as resulted by the MCS and PCS mean values (37.68 ± 9.41 and 39.31 ± 12.29, respectively) and TAS-20 highlighted considerable mean values of 60.53 ± 7.93 in the recruited participants with a prevalence in EOT values (27.51± 4.27), in comparison with mean DID and DDF values (17.26 ± 5.52 and 15.48 ± 3.84, respectively). Conclusions: Our study may suggest a predictive role of alexithymia in patients with T2DM. Moreover, lower PCS and MCS, revealing worst perceived QoL were associated to both higher anxiety and disease duration