Mortality for chronic-degenerative diseases in Tuscany: Ecological study comparing neighboring areas with substantial differences in environmental pollution

Objectives: Environmental pollution is associated with morbidity and mortality for chronic-degenerative diseases. Recent data points out a relationship between proximity to industrial plants and mortality due to neoplasms. The aim of this study has been to compare mortality due to chronic-degenerative diseases in the area of Tuscany (Bassa Val di Cecina), Italy, characterized by the presence of 2 neighboring municipalities similar in terms of size but with substantial differences in industrial activities: Rosignano (the site of chemical, energy production and waste processing industries) and Cecina (with no polluting activity). Material and Methods: Standardized mortality rates for the 2001–2010 decade were calculated; the data of the whole Tuscany was assumed as reference. Environmental levels of pollutants were obtained by databases of the Environmental Protection Agency of Tuscany Region (Agenzia Regionale per la Protezione Ambientale della Toscana – ARPAT). Maximum tolerated pollutant levels set by national laws were assumed as reference. Results: In the whole Bassa Val di Cecina, significantly elevated standardized mortality rates due to mesothelioma, ischemic heart diseases, cerebrovascular diseases and Alzheimer and other degenerative diseases of nervous system were observed. In the municipality of Rosignano, a significant excess of mortality for all these groups of diseases was confirmed. On the contrary, the municipality of Cecina showed only significantly higher mortality rates for ischemic heart diseases. Elevated levels of heavy metals in sea water and of particulate matter which contains particles of diameter ≤ 10 mm (PM10) and ozone in air were detected in Rosignano. Conclusions: This study shows an excess of mortality for chronic-degenerative diseases in the area with elevated concentration of polluting factories. Proximity to industrial plants seems to represent a risk factor for those diseases. Int J Occup Med Environ Health 2017;30(4):641–65

Disclosing Early Excited State Relaxation Events in Prototypical Linear Carbon Chains

One-dimensional (1D) linear nanostructures comprising sp-hybridized carbon atoms, as derivatives of the prototypicalallotropeknown as carbyne, are predicted to possess outstanding mechanical,thermal, and electronic properties. Despite recent advances in theirsynthesis, their chemical and physical properties are still poorlyunderstood. Here, we investigate the photophysics of a prototypicalpolyyne (i.e., 1D chain with alternating single and triple carbonbonds) as the simplest model of finite carbon wire and as a prototypeof sp-carbon-based chains. We perform transient absorptionexperiments with high temporal resolution (<30 fs) on monodispersedhydrogen-capped hexayne H (C C)(6)Hsynthesized by laser ablation in liquid. With the support of computationalstudies based on ground state density functional theory (DFT) andexcited state time-dependent (TD)-DFT calculations, we provide a comprehensivedescription of the excited state relaxation processes at early timesfollowing photoexcitation. We show that the internal conversion froma bright high-energy singlet excited state to a low-lying singletdark state is ultrafast and takes place with a 200 fs time constant,followed by thermalization on the picosecond time scale and decayof the low-energy singlet state with hundreds of picoseconds timeconstant. We also show that the time scale of these processes doesnot depend on the end groups capping the sp-carbonchain. The understanding of the primary photoinduced events in polyynesis of key importance both for fundamental knowledge and for potentialoptoelectronic and light-harvesting applications of low-dimensionalnanostructured carbon-based materials

Preface: BITS2014, the annual meeting of the Italian Society of Bioinformatics

This Preface introduces the content of the BioMed Central journal Supplements related to BITS2014 meeting, held in Rome, Italy, from the 26th to the 28th of February, 2014

Violence against women, Espírito Santo, Brazil

OBJETIVO Estimar a prevalência e os fatores associados às violências psicológica, física e sexual nas mulheres vítimas de violência perpetrada pelo parceiro íntimo atendidas nos serviços de atenção primária. MÉTODOS Estudo transversal, realizado em 26 unidades de saúde do município de Vitória, no Espírito Santo, de março a setembro de 2014. Foram entrevistadas 991 usuárias de 20 a 59 anos. Para classificar as violências psicológica, física e sexual foi utilizado o instrumento da Organização Mundial de Saúde sobre violência contra a mulher e um questionário foi elaborado para investigar as características sociodemográficas, comportamentais e de história familiar e de vida da mulher. As análises estatísticas utilizadas foram: regressão de Poisson, teste exato de Fisher e Qui-quadrado. RESULTADOS As prevalências observadas foram: psicológica 25,3% (IC95% 22,6–28,2); física 9,9% (IC95% 8,1–11,9) e sexual 5,7% (IC95% 4,3–7,3). A violência psicológica manteve-se associada à escolaridade, situação conjugal, histórico materno de violência por parceiro íntimo, violência sexual na infância e ter feito uso de drogas, enquanto a agressão física esteve relacionada à idade, escolaridade, situação conjugal e a história materna de violência por parceiro íntimo. A violência sexual foi mais frequente nas mulheres de menor renda e que sofreram abuso sexual na infância. CONCLUSÕES As violências psicológica, física e sexual apresentaram alta magnitude entre as mulheres usuárias dos serviços de atenção primária de saúde. Fatores sociodemográficos, comportamentais e experiências pessoal e materna de violência influenciam a ocorrência do fenômeno.OBJECTIVE To estimate the prevalence and factors associated with psychological, physical and sexual violence in women victims of intimate partner violence assisted in the primary care services. METHODS This is a cross-sectional study, conducted in 26 health units in Vitória, State of Espírito Santo, from March to September 2014. We interviewed 991 women aged 20-59 years. To classify the psychological, physical and sexual violence, the World Health Organization instrument on violence against women was used and a questionnaire to investigate the sociodemographic, behavioral characteristics, and the women’s family and life history was developed. The statistical analyzes used were Poisson regression, Fisher’s exact test and Chi-square. RESULTS The prevalence we observed were psychological 25.3% (95%CI 22.6–28.2); physical 9.9% (95%CI 8.1–11.9) and sexual 5.7% (95%CI 4.3–7.3). Psychological violence remained associated with education, marital status, maternal history of intimate partner violence, sexual violence in childhood and drug use, while physical assault was related to age, education, marital status and maternal history of intimate partner violence. Sexual violence occurred the most among women with low income, and victims of sexual violence in childhood. CONCLUSIONS Psychological, physical and sexual violence showed highly frequency among women assisted by primary care services. Sociodemographic and behavioral factors, personal experiences, and maternal violence influence the phenomenon

Resources and tools for rare disease variant interpretation

Collectively, rare genetic disorders affect a substantial portion of the world’s population. In most cases, those affected face difficulties in receiving a clinical diagnosis and genetic characterization. The understanding of the molecular mechanisms of these diseases and the development of therapeutic treatments for patients are also challenging. However, the application of recent advancements in genome sequencing/analysis technologies and computer-aided tools for predicting phenotype-genotype associations can bring significant benefits to this field. In this review, we highlight the most relevant online resources and computational tools for genome interpretation that can enhance the diagnosis, clinical management, and development of treatments for rare disorders. Our focus is on resources for interpreting single nucleotide variants. Additionally, we present use cases for interpreting genetic variants in clinical settings and review the limitations of these results and prediction tools. Finally, we have compiled a curated set of core resources and tools for analyzing rare disease genomes. Such resources and tools can be utilized to develop standardized protocols that will enhance the accuracy and effectiveness of rare disease diagnosis

Applying an Empirical Hydropathic Forcefield in Refinement May Improve Low-Resolution Protein X-Ray Crystal Structures

BACKGROUND: The quality of X-ray crystallographic models for biomacromolecules refined from data obtained at high-resolution is assured by the data itself. However, at low-resolution, >3.0 Å, additional information is supplied by a forcefield coupled with an associated refinement protocol. These resulting structures are often of lower quality and thus unsuitable for downstream activities like structure-based drug discovery. METHODOLOGY: An X-ray crystallography refinement protocol that enhances standard methodology by incorporating energy terms from the HINT (Hydropathic INTeractions) empirical forcefield is described. This protocol was tested by refining synthetic low-resolution structural data derived from 25 diverse high-resolution structures, and referencing the resulting models to these structures. The models were also evaluated with global structural quality metrics, e.g., Ramachandran score and MolProbity clashscore. Three additional structures, for which only low-resolution data are available, were also re-refined with this methodology. RESULTS: The enhanced refinement protocol is most beneficial for reflection data at resolutions of 3.0 Å or worse. At the low-resolution limit, ≥4.0 Å, the new protocol generated models with Cα positions that have RMSDs that are 0.18 Å more similar to the reference high-resolution structure, Ramachandran scores improved by 13%, and clashscores improved by 51%, all in comparison to models generated with the standard refinement protocol. The hydropathic forcefield terms are at least as effective as Coulombic electrostatic terms in maintaining polar interaction networks, and significantly more effective in maintaining hydrophobic networks, as synthetic resolution is decremented. Even at resolutions ≥4.0 Å, these latter networks are generally native-like, as measured with a hydropathic interactions scoring tool

Brain hemodynamic intermediate phenotype links Vitamin B12 to cognitive profile of healthy and mild cognitive impaired subjects

Vitamin B12, folate, and homocysteine are implicated in pivotal neurodegenerative mechanisms and partake in elders' mental decline. Findings on the association between vitamin-related biochemistry and cognitive abilities suggest that the structural and functional properties of the brain may represent an intermediate biomarker linking vitamin concentrations to cognition. Despite this, no previous study directly investigated whether vitamin B12, folate, and homocysteine levels are sufficient to explain individual neuropsychological profiles or, alternatively, whether the activity of brain regions modulated by these compounds better predicts cognition in elders. Here, we measured the relationship between vitamin blood concentrations, scores at seventeen neuropsychological tests, and brain activity of sixty-five elders spanning from normal to Mild Cognitive Impairment. We then evaluated whether task-related brain responses represent an intermediate phenotype, providing a better prediction of subjects' neuropsychological scores, as compared to the one obtained considering blood biochemistry only. We found that the hemodynamic activity of the right dorsal anterior cingulate cortex was positively associated (p value < 0 05 cluster corrected) with vitamin B12 concentrations, suggesting that elders with higher B12 levels had a more pronounced recruitment of this salience network region. Crucially, the activity of this area significantly predicted subjects' visual search and attention abilities (p value = 0 0023), whereas B12 levels per se failed to do so. Our results demonstrate that the relationship between blood biochemistry and elders' cognitive abilities is revealed when brain activity is included into the equation, thus highlighting the role of brain imaging as intermediate phenotype.Vitamin B12, folate, and homocysteine are implicated in pivotal neurodegenerative mechanisms and partake in elders' mental decline. Findings on the association between vitamin-related biochemistry and cognitive abilities suggest that the structural and functional properties of the brain may represent an intermediate biomarker linking vitamin concentrations to cognition. Despite this, no previous study directly investigated whether vitamin B12, folate, and homocysteine levels are sufficient to explain individual neuropsychological profiles or, alternatively, whether the activity of brain regions modulated by these compounds better predicts cognition in elders. Here, we measured the relationship between vitamin blood concentrations, scores at seventeen neuropsychological tests, and brain activity of sixty-five elders spanning from normal to Mild Cognitive Impairment. We then evaluated whether task-related brain responses represent an intermediate phenotype, providing a better prediction of subjects' neuropsychological scores, as compared to the one obtained considering blood biochemistry only. We found that the hemodynamic activity of the right dorsal anterior cingulate cortex was positively associated (p value < 0 05 cluster corrected) with vitamin B12 concentrations, suggesting that elders with higher B12 levels had a more pronounced recruitment of this salience network region. Crucially, the activity of this area significantly predicted subjects' visual search and attention abilities (p value = 0 0023), whereas B12 levels per se failed to do so. Our results demonstrate that the relationship between blood biochemistry and elders' cognitive abilities is revealed when brain activity is included into the equation, thus highlighting the role of brain imaging as intermediate phenotype

Randomized trial on the effects of a combined physical/cognitive training in aged MCI subjects: the Train the Brain study

Age-related cognitive impairment and dementia are an increasing societal burden. Epidemiological studies indicate that lifestyle factors, e.g. physical, cognitive and social activities, correlate with reduced dementia risk; moreover, positive effects on cognition of physical/cognitive training have been found in cognitively unimpaired elders. Less is known about effectiveness and action mechanisms of physical/cognitive training in elders already suffering from Mild Cognitive Impairment (MCI), a population at high risk for dementia. We assessed in 113 MCI subjects aged 65-89 years, the efficacy of combined physical-cognitive training on cognitive decline, Gray Matter (GM) volume loss and Cerebral Blood Flow (CBF) in hippocampus and parahippocampal areas, and on brain-blood-oxygenation-level-dependent (BOLD) activity elicited by a cognitive task, measured by ADAS-Cog scale, Magnetic Resonance Imaging (MRI), Arterial Spin Labeling (ASL) and fMRI, respectively, before and after 7 months of training vs. usual life. Cognitive status significantly decreased in MCI-no training and significantly increased in MCI-training subjects; training increased parahippocampal CBF, but no effect on GM volume loss was evident; BOLD activity increase, indicative of neural efficiency decline, was found only in MCI-no training subjects. These results show that a non pharmacological, multicomponent intervention improves cognitive status and indicators of brain health in MCI subjects