Arsenic in mining environments: evidences from Sardinia (Italy)

In Sardinia, the dispersion of arsenic in the environment appears strictly linked with mineralised bodies and mining activities. Currently, the areas of main concern are the active gold mine at Furtei, and the abandoned Pb- As mine at Baccu Locci. At Furtei, the main sources of arsenic are enargite, and arsenian pyrite; an ongoing monitoring program of water quality in the area around the mine documented so far no major changes with respect to pre-mine conditions, except for the formation of extremely acid, As-rich pit lakes. At Baccu Locci, the main primary source is arsenopyrite; arsenic dispersion is essentially due to the past unwise practice of discarding mine tailings into the nearby creek. Arsenic is slowly released from residual arsenopyrite and temporary secondary mineral traps such as Fe-oxyhydroxides, causing contamination of soils and waters as far as 10 km downstream of the mine

Deficiency in interferon type 1 receptor improves definitive erythropoiesis in Klf1 null mice

A key regulatory gene in definitive erythropoiesis is the transcription factor Krüppel-like factor 1 (Klf1). Klf1 null mice die in utero by day 15.5 (E15.5) due to impaired definitive erythropoiesis and severe anemia. Definitive erythropoiesis takes place in erythroblastic islands in mammals. Erythroblastic islands are formed by a central macrophage (Central Macrophage of Erythroblastic Island, CMEI) surrounded by maturating erythroblasts. Interferon-β (IFN-β) is activated in the fetal liver’s CMEI of Klf1 null mice. The inhibitory effect of IFN-β on erythropoiesis is known and, therefore, we speculated that IFN-β could have contributed to the impairment of definitive erythropoiesis in Klf1 knockout (KO) mice fetal liver. To validate this hypothesis, in this work we determined whether the inactivation of type I interferon receptor (Ifnar1) would ameliorate the phenotype of Klf1 KO mice by improving the lethal anemia. Our results show a prolonged survival of Klf1/Ifnar1 double KO embryos, with an improvement of the definitive erythropoiesis and erythroblast enucleation, together with a longer lifespan of CMEI in the fetal liver and also a restoration of the apoptotic program. Our data indicate that the cytotoxic effect of IFN-β activation in CMEI contribute to the impairment of definitive erythropoiesis associated with Klf1 deprivation

Delta-Globin Gene Expression Is Enhanced in vivo by Interferon Type I

Beta hemoglobinopathies are widely spread monogenic lethal diseases. Delta-globin gene activation has been proposed as a possible approach for curing these pathologies. The therapeutic potential of delta-globin, the non-alpha component of Hemoglobin A2 (α2δ2; HbA2), has been demonstrated in a mouse model of beta thalassemia, while its anti-sickling effect, comparable to that of gamma globin, was established some time ago. Here we show that the delta-globin mRNA level is considerably increased in a Deoxyribonuclease II-alpha knockout mouse model in which type 1 interferon (interferon beta, IFNb) is activated. IFNb activation in the fetal liver improves the delta-globin mRNA level, while the beta-globin mRNA level is significantly reduced. In addition, we show that HbA2 is significantly increased in patients with multiple sclerosis under type 1 interferon treatment. Our results represent a proof of principle that delta-globin expression can be enhanced through the use of molecules. This observation is potentially interesting in view of a pharmacological approach able to increase the HbA2 level

TP-fusion at peak exercise: A novel marker for the recognition of unsuspected long QT syndrome patients

Background and aims: The frequent occurrence of sudden death as the sentinel event in the Long QT Syndrome (LQTS) forces the search for still asymptomatic patients. We tested our hypothesis that complete fusion of the T and P waves (TP-fusion) at peak exercise might be a marker of likely LQTS. Methods: A maximal exercise stress test, off-therapy, was performed by healthy athletes and genotype-positive LQTS patients. TP-fusion had to be complete in all precordial leads except V1. Results: The study population (n=578) included 310 healthy athletes (all with QTc <430 ms) and 268 LQTS patients. To deal only with clear-cut phenotypes, 64 athletes and 70 patients with incomplete TP-fusion were excluded. TP-fusion was present in 2% of controls and in 22% (p<0.001) of the 198 LQTS patients. By limiting the analysis to subjects below age 25 (n=262), the prevalence of TP-fusion increased to 3% in healthy athletes and to 32% in LQTS (p<0.001). TP-fusion depends on the combination of QTc prolongation and fast heart rates; either alone is not sufficient. The appearance of TP-fusion predicted an 88% probability of being affected by LQTS. Importantly, of the 44 LQTS patients with TP-fusion, 24 (55%) had a borderline/normal baseline QTc (<460 ms). Conclusion: TP-fusion, a qualitative trait more easily assessable at peak exercise than QTc prolongation, especially outside referral centres, unmasks a high probability of LQTS, even in subjects with normal baseline QTc. Further clinical assessment and genetic screening allow life-saving prophylactic therapy

Parental ethnic identity and child test scores

We examine the relationship between parental ethnic identity and the test scores of ethnic minority children. We use standard survey measures of the strength of parental identity alongside validated cognitive test scores in a rich British cohort study. We show that children whose mothers report either an adoption or an active rejection of the majority identity tend to score lower in cognitive tests at age 7, compared to those children whose mothers report neutral feelings about the majority identity. We find no consistent differences in test scores according to mothers’ minority identity. Our findings provide no support for education or citizenship policies which promote the adoption of the majority identity or discourage the maintenance of separate identities in ethnic minority communities

Association between the ACCN1 Gene and Multiple Sclerosis in Central East Sardinia

Multiple genome screens have been performed to identify regions in linkage or association with Multiple Sclerosis (MS, OMIM 126200), but little overlap has been found among them. This may be, in part, due to a low statistical power to detect small genetic effects and to genetic heterogeneity within and among the studied populations. Motivated by these considerations, we studied a very special population, namely that of Niloro, Sardinia, Italy. This is an isolated, old, and genetically homogeneous population with high prevalence of MS. Our study sample includes both nuclear families and unrelated cases and controls. A multi-stage study design was adopted. In the first stage, microsatellites were typed in the 17q11.2 region, previously independently found to be in linkage with MS. One significant association was found at microsatellite D17S798. Next, a bioinformatic screening of the region surrounding this marker highlighted an interesting candidate MS susceptibility gene: the Amiloride-sensitive Cation Channel Neuronal 1 (ACCN1) gene. In the second stage of the study, we resequenced the exons and the 3′ untranslated (UTR) region of ACCN1, and investigated the MS association of Single Nucleotide Polymorphisms (SNPs) identified in that region. For this purpose, we developed a method of analysis where complete, phase-solved, posterior-weighted haplotype assignments are imputed for each study individual from incomplete, multi-locus, genotyping data. The imputed assignments provide an input to a number of proposed procedures for testing association at a microsatellite level or of a sequence of SNPs. These include a Mantel-Haenszel type test based on expected frequencies of pseudocase/pseudocontrol haplotypes, as well as permutation based tests, including a combination of permutation and weighted logistic regression analysis. Application of these methods allowed us to find a significant association between MS and the SNP rs28936 located in the 3′ UTR segment of ACCN1 with p=0.0004 (p=0.002, after adjusting for multiple testing). This result is in tune with several recent experimental findings which suggest that ACCN1 may play an important role in the pathogenesis of MS

Social and Behavioral Rhythms is Related to the Perception of Quality of Life in Old Adults

Introduction: The purpose is to verify in old adults if social and behavioral rhythms (SBRs) are correlated with a positive perception of the quality of life (QoL). Social and behavioral rhythms and related circadian biorhythms are known as central points in the pathophysiology of bipolar disorders. A secondary aim is to see if a similar relationship can be found in Major Depressive Disorder (MDD) in old adults. Sample: 141 people aged ≥65 years (58.9% Female). Methods: Each subject was evaluated using the Social and Behavioral Rhythms Scale (in which higher scores show more dysfunctional SRBs); SF-12 for QoL and a screening tool for depressive symptoms. They underwent a medical evaluation and blood level assays including cholesterol and triglycerides. The medical diagnoses including MDD were taken into account. Results: The Social and Behavioral Rhythms Scale score correlated inversely with SF-12 score (p<0.001) and positively with PHQ9 (p<0.0001). People with MDD had a higher score on social rhythms than controls without (p<0.01). The study highlighted, for the first time, that social and behavioral rhythms have a role in old adults living in the community. Conclusion: Further longitudinal studies with a sufficient number of individuals will be required to confirm these data and clarify causal links of the association

Moderate exercise improves cognitive function in healthy elderly people: Results of a randomized controlled trial

BACKGROUND: Physical activity in the elderly is recommended by international guidelines to protect against cognitive decline and functional impairment. OBJECTIVE: This Randomized Controlled Trial (RCT) was set up to verify whether medium-intensity physical activity in elderly people living in the community is effective in improving cognitive performance. DESIGN: RCT with parallel and balanced large groups. SETTING: Academic university hospital and Olympic gyms. SUBJECTS: People aged 65 years old and older of both genders living at home holding a medical certificate for suitability in non-competitive physical activity. METHODS: Participants were randomized to a 12-week, 3 sessions per week moderate physical activity program or to a control condition focused on cultural and recreational activities in groups of the same size and timing as the active intervention group. The active phase integrated a mixture of aerobic and anaerobic exercises, including drills of “life movements”, strength and balance. The primary outcome was: any change in Addenbrooke's Cognitive Examination Revised (ACE-R) and its subscales. RESULTS: At the end of the trial, 52 people completed the active intervention, and 53 people completed the control condition. People in the active intervention improved on the ACE-R (ANOVA: F(1;102)=4.32, p=0.040), and also showed better performances on the memory (F(1;102)=5.40 p=0.022) and visual-space skills subscales of the ACE-R (F(1;102)=4.09 p=0.046). CONCLUSION: A moderate-intensity exercise administered for a relatively short period of 12 weeks is capable of improving cognitive performance in a sample of elderly people who live independently in their homes. Clinical Trials Registration No: NCT0385811

Simulating the Impact on the Local Economy of Alternative Management Scenarios for Natural Areas

This working paper estimates the impact on the local economy of the High Garda Natural Park of alternative management scenarios for the West Garda Regional Forest. The local economy is specialized in tourist services and strongly linked to the tourist presence and their level of expenditure. We wish to investigate the effects of the participative management strategy, which takes into account users preferences and the non-participative strategy, using the SAM multiplier analysis. The local SAM has been constructed considering three sectors: agriculture, tourism and a third aggregate sector including all the other activities. The resident population has been divided into two categories: residents employed in the tourist sector and the remaining resident population. The SAM analysis shows that the accounting representation of the local economy is meaningful and that the participative program, if chosen by the central regional management, would be the most desirable program also at the local level