First Results of the “Carbonaceous Aerosol in Rome and Environs (CARE)” Experiment: Beyond Current Standards for PM10

In February 2017 the “Carbonaceous Aerosol in Rome and Environs (CARE)” experiment was carried out in downtown Rome to address the following specific questions: what is the color, size, composition, and toxicity of the carbonaceous aerosol in the Mediterranean urban background area of Rome? The motivation of this experiment is the lack of understanding of what aerosol types are responsible for the severe risks to human health posed by particulate matter (PM) pollution, and how carbonaceous aerosols influence radiative balance. Physicochemical properties of the carbonaceous aerosol were characterised, and relevant toxicological variables assessed. The aerosol characterisation includes: (i) measurements with high time resolution (min to 1–2 h) at a fixed location of black carbon (eBC), elemental carbon (EC), organic carbon (OC), particle number size distribution (0.008–10 μ m), major non refractory PM1 components, elemental composition, wavelength-dependent optical properties, and atmospheric turbulence; (ii) 24-h measurements of PM10 and PM2.5 mass concentration, water soluble OC and brown carbon (BrC), and levoglucosan; (iii) mobile measurements of eBC and size distribution around the study area, with computational fluid dynamics modeling; (iv) characterisation of road dust emissions and their EC and OC content. The toxicological assessment includes: (i) preliminary evaluation of the potential impact of ultrafine particles on lung epithelia cells (cultured at the air liquid interface and directly exposed to particles); (ii) assessment of the oxidative stress induced by carbonaceous aerosols; (iii) assessment of particle size dependent number doses deposited in different regions of the human body; (iv) PAHs biomonitoring (from the participants into the mobile measurements). The first experimental results of the CARE experiment are presented in this paper. The objective here is to provide baseline levels of carbonaceous aerosols for Rome, and to address future research directions. First, we found that BC and EC mass concentration in Rome are larger than those measured in similar urban areas across Europe (the urban background mass concentration of eBC in Rome in winter being on average 2.6 ± 2.5 μ g · m − 3 , mean eBC at the peak level hour being 5.2 (95% CI = 5.0–5.5) μ g · m − 3 ). Then, we discussed significant variations of carbonaceous aerosol properties occurring with time scales of minutes, and questioned on the data averaging period used in current air quality standard for PM 10 (24-h). Third, we showed that the oxidative potential induced by aerosol depends on particle size and composition, the effects of toxicity being higher with lower mass concentrations and smaller particle size. Albeit this is a preliminary analysis, findings reinforce the need for an urgent update of existing air quality standards for PM 10 and PM 2.5 with regard to particle composition and size distribution, and data averaging period. Our results reinforce existing concerns about the toxicity of carbonaceous aerosols, support the existing evidence indicating that particle size distribution and composition may play a role in the generation of this toxicity, and remark the need to consider a shorter averaging period (<1 h) in these new standards

Gestão de resíduos de equipamentos eletroeletrônicos em municípios do Estado de São Paulo: caracterização e propostas de diretrizes / Waste Electrical and Electronic Equipment management in municipalities in the state of São Paulo: characterization and improvement points

Nas últimas décadas, em um contexto de crescimento populacional e transformação dos padrões de produção e consumo, é possível observar a ascensão do mercado digital e das tecnologias da informação. Visto que o uso de metais pesados é comum na indústria eletroeletrônica, o descarte irregular ou o tratamento inadequado de seus resíduos podem representar riscos, tanto ao meio ambiente quanto para a saúde humana. Os resíduos de equipamentos elétricos e eletrônicos (REEE) são resultantes de equipamentos dotados de circuitos ou componentes elétricos e uma fonte de alimentação ou bateria. De acordo com o levantamento do “Observatorio mundial de los resíduos eletrônicos 2020”, o Brasil é o país que mais gera REEE na América do Sul, com uma média de geração anual superior à média mundial, no ano de 2020.A Política Nacional de Resíduos Sólidos (PNRS), instituída pela Lei Federal nº 12.305/2010 trouxe em seus princípios a responsabilidade compartilhada pelo ciclo de vida dos produtos. Além disso, a logística reversa advém como um instrumento que propicia o encaminhamento dos resíduos sólidos ao setor empresarial, para o seu reaproveitamento ou destinação final adequada. No ano de 2019 foi firmado o Acordo Setorial que definiu as diretrizes para a estruturação e operacionalização do sistema de logística reversa de produtos eletrônicos de uso doméstico em todo o país, e em 2020 foi publicado o Decreto n º 10.240/2020 que reforça a necessidade de implementação da logística reversa para produtos eletroeletrônicos. Diante disso, esse artigo tem como objetivo caracterizar o gerenciamento de resíduos eletroeletrônicos em alguns municípios do Estado de São Paulo. Para tanto, foi realizada uma pesquisa de caráter quali-quantitativo, a partir de dados coletados em uma pesquisa que compreendeu um questionário pré-estruturado com 155 questões acerca do gerenciamento de resíduos sólidos. Outros dados foram coletados através da base de dados do IBGE Cidades (Instituto Brasileiro de Geografia e Estatística). Foi utilizada uma correlação Pearson para avaliar a relação entre os dados quantitativos, e para os dados qualitativos, foi elaborada uma matriz comparativa entre aspectos, boas práticas e marcos legais pertinentes. Com isso, foi possível caracterizar a gestão dos REEE e, então, propor algumas diretrizes para melhorias no âmbito da administração pública

Clinical correlates of “pure” essential tremor: the TITAN study

BackgroundTo date, there are no large studies delineating the clinical correlates of “pure” essential tremor (ET) according to its new definition.MethodsFrom the ITAlian tremor Network (TITAN) database, we extracted data from patients with a diagnosis of “pure” ET and excluded those with other tremor classifications, including ET-plus, focal, and task-specific tremor, which were formerly considered parts of the ET spectrum.ResultsOut of 653 subjects recruited in the TITAN study by January 2022, the data of 208 (31.8%) “pure” ET patients (86M/122F) were analyzed. The distribution of age at onset was found to be bimodal. The proportion of familial cases by the age-at-onset class of 20 years showed significant differences, with sporadic cases representing the large majority of the class with an age at onset above 60 years. Patients with a positive family history of tremor had a younger onset and were more likely to have leg involvement than sporadic patients despite a similar disease duration. Early-onset and late-onset cases were different in terms of tremor distribution at onset and tremor severity, likely as a function of longer disease duration, yet without differences in terms of quality of life, which suggests a relatively benign progression. Treatment patterns and outcomes revealed that up to 40% of the sample was unsatisfied with the current pharmacological options.DiscussionThe findings reported in the study provide new insights, especially with regard to a possible inversed sex distribution, and to the genetic backgrounds of “pure” ET, given that familial cases were evenly distributed across age-at-onset classes of 20 years. Deep clinical profiling of “pure” ET, for instance, according to age at onset, might increase the clinical value of this syndrome in identifying pathogenetic hypotheses and therapeutic strategies

Theoretical analyses of the expansion of gene families implicated in dominant diseases

Les familles de gènes impliqués dans le cancer et autres maladies génétiques se sont beaucoup élargies via deux Duplications Globales de Génome (DGG) qui ont eu lieu à l'origine des vertébrés. La rétention des copies de ces gènes implique une susceptibilité plus grande aux maladies génétiques et constitue une énigme du point de vue de l'évolution. Dans cette thèse, nous avons généralisé des modèles classiques de génétique des populations pour révéler le mécanisme non-adaptatif qui a conduit à cette conservation de gènes potentiellement délétères chez les vertébrés. Nous avons résolu un modèle déterministe haploïde, nous avons étendu ce modèle à des génomes diploïdes et nous avons analysé les effets de taille finie des populations et de la sélection positive par une approche stochastique. Les résultats montrent, en accord avec les données génomiques du cancer chez l'homme, que les copies DGG susceptibles aux mutations délétères dominantes sont conservées indirectement via la sélection de purification dans les espèces post-DGG, qui présentent nécessairement une incompatibilité de ploïdie avec la population pre-DGG. Les résultats obtenus en étendant des méthodes avancées d'inférence bayésienne, quantifiant les effets causaux directs, soutiennent l'hypothèse d'une influence directe de la susceptibilité aux mutations délétères dominantes sur la rétention des copies DGG. Ces résultats révèlent le mécanisme d'évolution non-adaptatif responsable de la rétention de gènes DGG susceptibles aux mutations délétères dominantes et notre extension de méthodes d'inférence bayesienne ouvre la voie à la quantification des relations causales directes dans un large ensemble de problématiques.Gene families implicated in cancer and other genetic diseases have been greatly expanded through two rounds of whole-genome duplication (WGD) that occurred at the onset of jawed vertebrates. However, such gene duplicates are expected to lead to an enhanced susceptibility to genetic diseases, and thus their retention represents an evolutionary puzzle from a natural selection perspective. In this thesis, we have expanded classical population genetics models to reveal the non-adaptive mechanism through which such potentially deleterious ohnologs (WGD-duplicated genes) were retained in the vertebrate genomes. We have solved a deterministic haploid model, we have considered extensions to diploid genotypes, and we have analyzed population size effects and the impact of positive selection through a stochastic approach. The results demonstrate, consistently with available human cancer genome data, that ohnologs prone to dominant deleterious mutations are indirectly selected through purifying selection in post-WGD species, arisen through the ploidy incompatibility between post-WGD individuals and the rest of the pre-WGD population. Extending advanced Bayesian inference methods to quantify direct and indirect causal effects, we have found further supporting evidences for the direct role of the gene susceptibility to deleterious mutations on ohnolog retention. Our findings rationalize the evolutionary mechanism responsible for the expansion of ohnologs prone to dominant deleterious mutations, highlighting the role of WGD-induced speciation. Our extension of Bayesian inference methods paves the way for the identification of direct causal relationships in a huge variety of problems

Analyses théoriques de l'expansion des familles de gènes impliqués dans des maladies dominantes

Gene families implicated in cancer and other genetic diseases have been greatly expanded through two rounds of whole-genome duplication (WGD) that occurred at the onset of jawed vertebrates. However, such gene duplicates are expected to lead to an enhanced susceptibility to genetic diseases, and thus their retention represents an evolutionary puzzle from a natural selection perspective. In this thesis, we have expanded classical population genetics models to reveal the non-adaptive mechanism through which such potentially deleterious ohnologs (WGD-duplicated genes) were retained in the vertebrate genomes. We have solved a deterministic haploid model, we have considered extensions to diploid genotypes, and we have analyzed population size effects and the impact of positive selection through a stochastic approach. The results demonstrate, consistently with available human cancer genome data, that ohnologs prone to dominant deleterious mutations are indirectly selected through purifying selection in post-WGD species, arisen through the ploidy incompatibility between post-WGD individuals and the rest of the pre-WGD population. Extending advanced Bayesian inference methods to quantify direct and indirect causal effects, we have found further supporting evidences for the direct role of the gene susceptibility to deleterious mutations on ohnolog retention. Our findings rationalize the evolutionary mechanism responsible for the expansion of ohnologs prone to dominant deleterious mutations, highlighting the role of WGD-induced speciation. Our extension of Bayesian inference methods paves the way for the identification of direct causal relationships in a huge variety of problems.Les familles de gènes impliqués dans le cancer et autres maladies génétiques se sont beaucoup élargies via deux Duplications Globales de Génome (DGG) qui ont eu lieu à l'origine des vertébrés. La rétention des copies de ces gènes implique une susceptibilité plus grande aux maladies génétiques et constitue une énigme du point de vue de l'évolution. Dans cette thèse, nous avons généralisé des modèles classiques de génétique des populations pour révéler le mécanisme non-adaptatif qui a conduit à cette conservation de gènes potentiellement délétères chez les vertébrés. Nous avons résolu un modèle déterministe haploïde, nous avons étendu ce modèle à des génomes diploïdes et nous avons analysé les effets de taille finie des populations et de la sélection positive par une approche stochastique. Les résultats montrent, en accord avec les données génomiques du cancer chez l'homme, que les copies DGG susceptibles aux mutations délétères dominantes sont conservées indirectement via la sélection de purification dans les espèces post-DGG, qui présentent nécessairement une incompatibilité de ploïdie avec la population pre-DGG. Les résultats obtenus en étendant des méthodes avancées d'inférence bayésienne, quantifiant les effets causaux directs, soutiennent l'hypothèse d'une influence directe de la susceptibilité aux mutations délétères dominantes sur la rétention des copies DGG. Ces résultats révèlent le mécanisme d'évolution non-adaptatif responsable de la rétention de gènes DGG susceptibles aux mutations délétères dominantes et notre extension de méthodes d'inférence bayesienne ouvre la voie à la quantification des relations causales directes dans un large ensemble de problématiques

On the retention of gene duplicates prone to dominant deleterious mutations

Recent studies have shown that gene families from different functional categories have been preferentially expanded either by small scale duplication (SSD) or by whole-genome duplication (WGD). In particular, gene families prone to dominant deleterious mutations and implicated in cancers and other genetic diseases in human have been greatly expanded through two rounds of WGD dating back from early vertebrates. Here, we strengthen this intriguing observation, showing that human oncogenes involved in different primary tumors have retained many WGD duplicates compared to other human genes. In order to rationalize this evolutionary outcome, we propose a consistent population genetics model to analyze the retention of SSD and WGD duplicates taking into account their propensity to acquire dominant deleterious mutations. We solve a deterministic haploid model including initial duplicated loci, their retention through sub-functionalization or their neutral loss-of-function or deleterious gain-of-function at one locus. Extensions to diploid genotypes are presented and population size effects are analyzed using stochastic simulations. The only difference between the SSD and WGD scenarios is the initial number of individuals with duplicated loci. While SSD duplicates need to spread through the entire population from a single individual to reach fixation, WGD duplicates are de facto fixed in the small initial post-WGD population arising through the ploidy incompatibility between post-WGD individuals and the rest of the pre-WGD population. WGD duplicates prone to dominant deleterious mutations are then shown to be indirectly selected through purifying selection in post-WGD species, whereas SSD duplicates typically require positive selection. These results highlight the long-term evolution mechanisms behind the surprising accumulation of WGD duplicates prone to dominant deleterious mutations and are shown to be consistent with cancer genome data on the prevalence of human oncogenes with WGD duplicates

Dyskinesia, cardiac arrhythmia and partial seizure associated with paliperidone overdose: a case report

Paliperidone is a new atypical antipsychotic agent. There are few literature reports of paliperidone overdoses and we report a case of these. A 32-year-old man was admitted to Emergency Department for occurrence of opisthotonus, muscular spasms and rigidity. Twenty hours before, he had an ingestion of 168 mg of paliperidone. He had hypotension and tachycardia. The dystonic reaction completely resolved within a few minutes after diazepam. Nine hours after admission, he sudden showed a right hemisoma partial seizure. The peculiar interest of our case is that three different and rare symptoms occurred in successive times after overdose. Some symptoms occurred after several hours following overdose. Oral paliperidone is available as an osmotic release delivery system that results in a gradual rise in plasma concentrations. According to this limited experience in which delayed onset of toxicity has been observed, it may be prudent to recommend prolonged observation after overdose of paliperidone

STUDY OF THE PROTECTIVE ACTIVITY OF NEW SWEET CHERRY CULTIVARS IN NEURON-LIKE SH-SY5Y CELLS

Neurodegenerative diseases, such as Alzheimer\u2019s and Parkinson\u2019s diseases, are caused by the progressive death of neurons in different regions of the nervous system. Their etiology is multifactorial with oxidative stress as one of the most impacting factors. The brain, due to its high oxygen consumption and high lipid content, is highly vulnerable to the effects of reactive oxygen species. The increase in the generation of free radicals damages the cellular biomolecules and induces necrosis or apoptosis. Sweet cherry fruits are a nutritionally dense food rich in anthocyanins, quercetin, hydroxycinnamates, potassium, fiber, vitamin C, and carotenoids. In the present study, we investigated the antioxidant activity of different sweet cherries (Prunus avium L.), obtained through a natural breeding program at the University of Bologna, in neuron-like SH-SY5Y cells differentiated with retinoic acid. The phytochemical pattern of five different cherry extracts has been characterized by HPLC-DAD/FL analysis. To study the protective effects of the extracts, SH-SY5Y cells were treated with different concentrations of the extracts for 24 h before H2O2 exposure. All the extracts, except one, were able to significantly increase cell viability and decrease ROS levels in respect to cells exposed to H2O2 as measured by MTT and DCFH-DA assays, respectively. Three of the five extracts significantly increased GSH levels in respect to H2O2 exposed cells as measured by monochlorobimane assay. The same extracts that significantly reduced ROS production were also able to up-regulate some important phase II antioxidant enzymes, such as GR and NQO1, as measured by RT-PCR. Our findings support the idea that these new sweet cherries can be considered a new functional food with a high antioxidant and neuroprotective effect and these effects seem to be related to the specific phenolic pattern of the different cherry extracts. This work was supported by MIUR-PRIN 2015 (No. 20152HKF3Z)