Possible involvement of overexposure to environmental selenium in the etiology of amyotrophic lateral sclerosis: a short review.

Excess exposure to the metalloid selenium (Se), a trace element with both toxicologicaland nutritional properties, has been implicated in the etiology of a human motor neuron diseaseof unknown origin and extremely severe prognosis, sporadic amyotrophic lateral sclerosis (ALS).This relation has been suggested on the basis of two epidemiologic investigations which found anincreased risk of ALS associated with residence in a seleniferous area or with consumption of drinkingwater with unusually high levels of inorganic hexavalent Se, in South Dakota and in northernItaly respectively. Biological plausibility to a Se-ALS relation is provided by veterinary medicineobservations and toxicological studies, showing that Se, particularly the inorganic forms, has a selectivetoxicity to motor neurons in swine and in cattle. Neurotoxic effects of Se species have also beendemonstrated in laboratory studies and, for the inorganic forms, even at very low concentrations.Selenium has also been shown to affect muscle function in experimental animal models. Overall,these findings from the epidemiologic and the toxicological literature indicate that environmental Se,particularly in its inorganic forms and at unexpectedly low levels of exposure, might be a risk factorfor ALS, suggesting the opportunity to further investigate this issue

Exposure to pesticides and risk of amyotrophic lateral sclerosis: a population-based case-control study

A few epidemiologic studies have suggested an association of agricultural work and pesticidesexposure with a severe degenerative disease of the motor neurons, amyotrophic lateral sclerosis(ALS), though conflicting results have also been provided. We investigated through a populationbasedcase-control study the possible relation between overall occupational exposure to pesticidesand ALS risk in the northern Italy municipality of Reggio Emilia. By administering a questionnaire,we investigated occupational history and leisure-time habits of the 41 ALS patients diagnosed in the1995-2006 period, and of 82 age- and sex-matched randomly sampled population controls. Morecases than controls were found to have been exposed to pesticides for at least six months (31.7% vs13.4%, respectively), in all cases within the occupational environment. In a conditional logistic regressionmodel, we found an excess ALS risk associated with exposure to pesticides, with a relativerisk of 3.6 (95% confidence interval 1.2-10.5). Such association persisted after inclusion in the statisticalanalysis of potential confounders. Despite the limited statistical stability of the risk estimates,these results appear to indicate that occupational exposure to pesticides is a risk factor for ALS,suggesting the need to further investigate this issue

SRtP 2.0 \u2014 The Evolution of the Safe Return to Port Concept

In 2010 IMO (International Maritime Organisation) introduced new rules in SOLAS with the aim of intrinsically increase the safety of passenger ships. This requirement is achieved by providing safe areas for passengers and essential services for allowing ship to Safely Return to Port (SRtP). The entry into force of these rules has changed the way to design passenger ships. In this respect big effort in the research has been done by industry to address design issues related to the impact on failure analysis of the complex interactions among systems. Today the research activity is working to bring operational matters in the design stage. This change of research focus was necessary because human factor and the way to operate the ship itself after a casualty on board may have a big impact in the design of the ship/systems. Also the management of the passengers after a casualty is becoming a major topic for safety. This paper presents the state of the art of Italian knowledge in the field of system engineering applied to passenger ship address to safety improvement and design reliability. An overview of present tools and methodologies will be offered together with future focuses in the research activity

Compliance with Tuberculosis Screening in Irregular Immigrants

Tuberculosis (TB) is a serious public health problem in many regions of the world, especially in the poorest areas. For this reason, screening for active and latent forms must be considered when dealing with high-risk groups such as irregular immigrants in Western countries. We conducted a retrospective cohort study by recruiting subjects aged 6515 years who underwent a tuberculin skin test at a dedicated National Health Service Centre in a northern Italian province between 1 January 2012 and 31 December 2013. These participants were followed up until 31 December 2016. We aimed at evaluating an experimental protocol for active and latent tuberculosis screening, focusing on patient compliance, feasibility, and capability to detect clinical forms of the disease. We enrolled 368 irregular immigrants, i.e., immigrants not having a valid residence permit and who were therefore not entitled to choose a general practitioner. In total, 90.22% of these completed all the steps for the screening of active TB, while 87.33% also undertook screening for the latent form of the disease. Homelessness, self-reported prostitution, female sex, and employment status adversely affected compliance. Chronic alcohol consumption was associated with increased risk of no beginning or interruption of the procedures. All of the five patients with active TB successfully completed the treatment. Overall, adherence to the screening program was high compared to other studies in immigrants, possibly owing to organizational factors such as the availability of cultural mediators, the network between the different health services, the presence of dedicated nursing staff and a free-of-charge service. In addition, selected vulnerable subgroups should be targeted using tailored screening and follow-up programs

Importance of Tests for the Complete Lorentz Structure of the t --> W+ b vertex at Hadron Colliders

The most general Lorentz-invariant decay-density-matrix for $t\to W^{+}b\to (l^{+}\nu)b$, or for $t\to W^{+}b\to (j_{\bar d}j_u)b$, is expressed in terms of eight helicity parameters. The parameters are physically defined in terms of partial-width-intensities for polarized-final-states in $t\to W^{+}b$ decay. The parameters are the partial width, the $b$ quark's chirality parameter $\xi$, the $W^+$ polarimetry parameter $\sigma$, a "pre-SSB" test parameter $\zeta$, and four $W_{L}$-$W_{T}$ interference parameters $\eta$, $\eta^{'}$, $\omega$, $\omega^{'}$ which test for $\tilde T_{FS}$ violation. They can be used to test for non-CKM-type CP violation, anomalous $\Gamma_{L,T}$'s, top weak magnetism, weak electricity, and second-class currents. By stage-two spin-correlation techniques, percent level statistical uncertainites are typical for measurements at the Tevatron, and several mill level uncertainites are typical at the LHC.Comment: Minor clarifications. Expression for r_{+-} corrected. 19 pages LaTex + Tables + 1 Figur

Proteasome system dysregulation and treatment resistance mechanisms in major depressive disorder

Several studies have demonstrated that allelic variants related to inflammation and the immune system may increase the risk for major depressive disorder (MDD) and reduce patient responsiveness to antidepressant treatment. Proteasomes are fundamental complexes that contribute to the regulation of T-cell function. Only one study has shown a putative role of proteasomal PSMA7, PSMD9 and PSMD13 genes in the susceptibility to an antidepressant response, and sparse data are available regarding the potential alterations in proteasome expression in psychiatric disorders such as MDD. The aim of this study was to clarify the role of these genes in the mechanisms underlying the response/resistance to MDD treatment. We performed a case-control association study on 621 MDD patients, of whom 390 were classified as treatment-resistant depression (TRD), and we collected peripheral blood cells and fibroblasts for mRNA expression analyses. The analyses showed that subjects carrying the homozygous GG genotype of PSMD13 rs3817629 had a twofold greater risk of developing TRD and exhibited a lower PSMD13 mRNA level in fibroblasts than subjects carrying the A allele. In addition, we found a positive association between PSMD9 rs1043307 and the presence of anxiety disorders in comorbidity with MDD, although this result was not significant following correction for multiple comparisons. In conclusion, by confirming the involvement of PSMD13 in the MDD treatment response, our data corroborate the hypothesis that the dysregulation of the complex responsible for the degradation of intracellular proteins and potentially controlling autoimmunity- and immune tolerance–related processes may be involved in several phenotypes, including the TRD

Supplementation with ribonucleotide-based ingredient (Ribodiet®) lessens oxidative stress, brain inflammation, and amyloid pathology in a murine model of Alzheimer

Abstract Alzheimer's disease (AD) is the most common type of dementia worldwide, characterized by the deposition of neurofibrillary tangles and amyloid-β (Aβ) peptides in the brain. Additionally, increasing evidence demonstrates that a neuroinflammatory state and oxidative stress, iron-dependent, play a crucial role in the onset and disease progression. Besides conventional therapies, the use of natural-based products represents a future medical option for AD treatment and/or prevention. We, therefore, evaluated the effects of a ribonucleotides-based ingredient (Ribodiet®) in a non-genetic mouse model of AD. To this aim, mice were injected intracerebroventricularly (i.c.v.) with Aβ1–42 peptide (3 µg/3 μl) and after with Ribodiet® (0.1–10 mg/mouse) orally (p.o.) 3 times weekly for 21 days following the induction of experimental AD. The mnemonic and cognitive decline was then evaluated, and, successively, we have assessed ex vivo the modulation of different cyto-chemokines on mice brain homogenates. Finally, the level of GFAP, S100β, and iron-related metabolic proteins were monitored as markers of reactive gliosis, neuro-inflammation, and oxidative stress. Results indicate that Ribodiet® lessens oxidative stress, brain inflammation, and amyloid pathology via modulation of iron-related metabolic proteins paving the way for its rationale use for the treatment of AD and other age-related diseases

The relation between amyotrophic lateral sclerosis and inorganic selenium in drinking water: a population-based case-control study

<p>Abstract</p> <p>Background</p> <p>A community in northern Italy was previously reported to have an excess incidence of amyotrophic lateral sclerosis among residents exposed to high levels of inorganic selenium in their drinking water.</p> <p>Methods</p> <p>To assess the extent to which such association persisted in the decade following its initial observation, we conducted a population-based case-control study encompassing forty-one newly-diagnosed cases of amyotrophic lateral sclerosis and eighty-two age- and sex-matched controls. We measured long-term intake of inorganic selenium along with other potentially neurotoxic trace elements.</p> <p>Results</p> <p>We found that consumption of drinking water containing ≥ 1 μg/l of inorganic selenium was associated with a relative risk for amyotrophic lateral sclerosis of 5.4 (95% confidence interval 1.1-26) after adjustment for confounding factors. Greater amounts of cumulative inorganic selenium intake were associated with progressively increasing effects, with a relative risk of 2.1 (95% confidence interval 0.5-9.1) for intermediate levels of cumulative intake and 6.4 (95% confidence interval 1.3-31) for high intake.</p> <p>Conclusion</p> <p>Based on these results, coupled with other epidemiologic data and with findings from animal studies that show specific toxicity of the trace element on motor neurons, we hypothesize that dietary intake of inorganic selenium through drinking water increases the risk for amyotrophic lateral sclerosis.</p

Comparison of HPV-positive triage strategies combining extended genotyping with cytology or p16/ki67 dual staining in the Italian NTCC2 study

Background Each high-risk HPV genotype has different oncogenic potential, and the risk of CIN3+ varies according to genotype. We evaluated the performance of different strategies of HPV-positivity triage combining cytology, p16/ki67 dual staining (DS), and extended genotyping. Methods Samples from 3180 consecutive women from the NTCC2 study (NCT01837693) positive for HPV DNA at primary screening, were retrospectively analyzed by the BD Onclarity HPV Assay, which allows extended genotyping. Genotypes were divided into three groups based on the risk of CIN3+. HPV DNA-positive women were followed up for 24 months or to clearance. Findings Combining the three groups of genotypes with cytology or DS results we identify a group of women who need immediate colposcopy (PPV for CIN3+ from 7.8 to 20.1%), a group that can be referred to 1-year HPV retesting (PPV in those HPV-positive at retesting from 2.2 to 3.8), and a group with a very low 24-month CIN3+ risk, i.e. 0.4%, composed by women cytology or DS negative and positive for HPV 56/59/66 or 35/39/68 or negative with the Onclarity test, who can be referred to 3-year retesting. Interpretation Among the baseline HPV DNA positive/cytology or DS negative women, the extended genotyping allows to stratify for risk of CIN3+, and to identify a group of women with a risk of CIN3+ so low in the next 24 months that they could be referred to a new screening round after 3 years