Impaired Spatial Reorientation in the 3xTg-AD Mouse Model of Alzheimer's Disease.

In early Alzheimer's disease (AD) spatial navigation is impaired; however, the precise cause of this impairment is unclear. Recent evidence suggests that getting lost is one of the first impairments to emerge in AD. It is possible that getting lost represents a failure to use distal cues to get oriented in space. Therefore, we set out to look for impaired use of distal cues for spatial orientation in a mouse model of amyloidosis (3xTg-AD). To do this, we trained mice to shuttle to the end of a track and back to an enclosed start box to receive a water reward. Then, mice were trained to stop in an unmarked reward zone to receive a brain stimulation reward. The time required to remain in the zone for a reward was increased across training, and the track was positioned in a random start location for each trial. We found that 6-month female, but not 3-month female, 6-month male, or 12-month male, 3xTg-AD mice were impaired. 6-month male and female mice had only intracellular pathology and male mice had less pathology, particularly in the dorsal hippocampus. Thus, AD may cause spatial disorientation as a result of impaired use of landmarks

Invasive pneumococcal disease in tuscany region, Italy, 2016–2017: Integrating multiple data sources to investigate underreporting

Invasive pneumococcal disease (IPD) is a vaccine-preventable disease characterized by the presence of Streptococcus pneumoniae in normally sterile sites. Since 2007, Italy has implemented an IPD national surveillance system (IPD-NSS). This system suffers from high rates of underreporting. To estimate the level of underreporting of IPD in 2016–2017 in Tuscany (Italy), we integrated data from IPD-NSS and two other regional data sources, i.e., Tuscany regional microbiological surveillance (Microbiological Surveillance and Antibiotic Resistance in Tuscany, SMART) and hospitalization discharge records (HDRs). We collected (1) notifications to IPD-NSS, (2) SMART records positive for S. pneumoniae from normally sterile sites, and (3) hospitalization records with IPD-related International Classification of Diseases, Ninth Revision, Clinical Modification (ICD9) codes in discharge diagnoses. We performed data linkage of the three sources to obtain a combined surveillance system (CSS). Using the CSS, we calculated the completeness of the three sources and performed a three-source log-linear capture–recapture analysis to estimate total IPD underreporting. In total, 127 IPD cases were identified from IPD-NSS, 320 were identified from SMART, and 658 were identified from HDRs. After data linkage, a total of 904 unique cases were detected. The average yearly CSS notification rate was 12.1/100,000 inhabitants. Completeness was 14.0% for IPD-NSS, 35.4% for SMART, and 72.8% for HDRs. The capture–recapture analysis suggested a total estimate of 3419 cases of IPD (95% confidence interval (CI): 1364–5474), corresponding to an underreporting rate of 73.7% (95% CI: 34.0–83.6) for CSS. This study shows substantial underreporting in the Tuscany IPD surveillance system. Integration of available data sources may be a useful approach to complement notification-based surveillance and provide decision-makers with better information to plan effective control strategies against IPD

Tamoxifen reduces plasma homocysteine levels in healthy women.

Treatment with tamoxifen is associated with reduced incidence of myocardial infarction. As plasma homocysteine is an independent risk factor for cardiovascular disease, we studied the effects of tamoxifen on plasma homocysteine in 66 healthy women participating in the Italian prevention trial of breast cancer who were randomized in a double-blind manner to tamoxifen 20 mg day(-1) or placebo for 5 years. They were aged between 35 and 70 years, had undergone previous hysterectomy for non-malignant conditions and had no contraindications to the use of tamoxifen. Plasma levels of total homocysteine (tHcy) were measured at randomization and after 2 and 6 months. The mean +/- s.d. plasma levels of tHcy were 7.59 +/- 1.71 micromol l(-1), 7.25 +/- 1.61 and 7.09 +/- 1.33 in the tamoxifen group and 8.07 +/- 2.06, 7.93 +/- 1.77 and 8.12 +/- 2.04 in the placebo group at 0, 2 and 6 months (P = 0.008 for the between-group difference over time). The higher the baseline tHcy level, the greater was the lowering effect of tamoxifen. No statistically significant effect of age, body mass index or smoking habit on baseline tHcy levels and its variation over time was found. In conclusion, tamoxifen (20 mg day(-1) for 6 months) decreased plasma tHcy levels in healthy women. This effect may contribute to its protective effect on myocardial infarction

A Neural Approach to Active Estimation of Nonlinear Systems

Abstract-In this paper, we consider the problem of actively identifying the state of a stochastic dynamic system over a finite horizon. We formalize this Problem as a Stochastic Optimal Control one, in which the minimization of a suitable uncertainty measure is performed. To this end, the use of the Renyi Entropy is proposed and motivated. A neural control scheme, based on the application of the Extended Ritz Method and on the use of a Gaussian Sum Filter, is then presented. Simulation results show the effectiveness of the approach

Effect of raloxifene on IGF-I and IGFBP-3 in postmenopausal women with breast cancer

The effect on the IGF system of 60 mg and 600 mg daily of raloxifene administered for 2 weeks prior to surgery was investigated in 37 postmenopausal women with breast cancer. Raloxifene significantly decreased insulin-like growth factor (IGF-I) as compared to placebo (P < 0.05) with no dose–response relationship. No significant change was observed in IGFBP-3, while the IGF-I/IGFBP-3 molar ratio was decreased by treatment, with a statistically significant effect only for the higher dose. Given that high plasma levels of IGF-I have been suggested as a risk factor for breast cancer, these findings provide further support for the potential activity of raloxifene in breast cancer prevention. © 2001 Cancer Research Campaign http://www.bjcancer.co

Serum oncostatin M at baseline predicts mucosal healing in Crohn's disease patients treated with infliximab

Background: Oncostatin M is upregulated in Crohn's disease inflamed intestinal mucosa, and has been suggested as a promising biomarker to predict responsiveness to anti-TNF therapy in patients with inflammatory bowel diseases. Aim: To evaluate the suitability of serum oncostatin M as a predictive marker of response to infliximab in Crohn's disease. Methods: We included patients treated with infliximab monotherapy. All patients underwent colonoscopy at week 54 to evaluate mucosal healing. Serum oncostatin M and faecal calprotectin were measured at baseline and after 14&nbsp;weeks of treatment. Mann-Whitney test was used to evaluate correlation of oncostatin M and faecal calprotectin at baseline and week 14 with mucosal healing at week 54. Their accuracy in predicting mucosal healing was assessed by area under the curve (AUC). Results: In a cohort of 45 included patients, 27 displayed mucosal healing. At both baseline and week 14, oncostatin M levels were significantly lower in patients with mucosal healing than in patients not achieving this endpoint (P&nbsp;&lt;&nbsp;0.001). Faecal calprotectin levels at week 14 were lower also in responders than nonresponders (P&nbsp;&lt;&nbsp;0.001). Oncostatin M values at baseline and week 14 were significantly associated (Spearman correlation&nbsp;=&nbsp;0.92, P&nbsp;&lt;&nbsp;0.001). The diagnostic accuracy of oncostatin M at baseline in predicting mucosal healing (AUC&nbsp;=&nbsp;0.91) was greater than faecal calprotectin (AUC&nbsp;=&nbsp;0.51, P&nbsp;&lt;&nbsp;0.001). Conclusion: These results suggest that oncostatin M can predict the outcome of infliximab treatment. Compared with faecal calprotectin, the predictive capability of oncostatin M was appreciable at baseline, thus indicating oncostatin M as a promising biomarker for driving therapeutic choices in Crohn's disease

Epigenome-wide association study reveals decreased average methylation levels years before breast cancer diagnosis

Interest in the potential of DNA methylation in peripheral blood as a biomarker of cancer risk is increasing. We aimed to assess whether epigenome-wide DNA methylation measured in peripheral blood samples obtained before onset of the disease is associated with increased risk of breast cancer. We report on three independent prospective nested case-control studies from the European Prospective Investigation into Cancer and Nutrition (EPIC-Italy; n = 162 matched case-control pairs), the Norwegian Women and Cancer study (NOWAC; n = 168 matched pairs), and the Breakthrough Generations Study (BGS; n = 548 matched pairs). We used the Illumina 450k array to measure methylation in the EPIC and NOWAC cohorts. Whole-genome bisulphite sequencing (WGBS) was performed on the BGS cohort using pooled DNA samples, combined to reach 50× coverage across ~16 million CpG sites in the genome including 450k array CpG sites. Mean β values over all probes were calculated as a measurement for epigenome-wide methylation

Remote Working and Home Learning: How the Italian Academic Population Dealt with Changes Due to the COVID-19 Pandemic Lockdown

The COVID-19 pandemic introduced changes in people's lives that affected their mental health. Our study aimed to explore the level of psychological distress in the academic population during the lockdown period and investigate its association with the new working or studying conditions. The study sample included 9364 students and 2159 employees from five Italian universities from the study IO CONTO 2020. We applied linear regression models to investigate the association between home learning or remote working conditions and psychological distress, separately for students and employees. Psychological distress was assessed using the Hospital Anxiety and Depression Scale (HADS). In both students and employees, higher levels of distress were significantly associated with study/work-family conflicts, concerns about their future careers, and inadequacy of equipment; in employees, higher levels of distress were significantly associated with a lack of clarity on work objectives. Our results are in line with previous research on the impact of spaces and equipment in remote working/studying from home. Moreover, the study contributes to deepening the association between well-being and telework-family conflict, which in the literature is still equivocal. Practical implications require academic governance to promote sustainable environments both in remote and hybrid work conditions, by referring to a specific management by objectives approach