Multifactorial Activation of NLRP3 Inflammasome: Relevance for a Precision Approach to Atherosclerotic Cardiovascular Risk and Disease

Chronic low-grade inflammation, through the specific activation of the NACHT leucine-rich repeat- and PYD-containing (NLRP)3 inflammasome-interleukin (IL)-1\u3b2 pathway, is an important contributor to the development of atherosclerotic cardiovascular disease (ASCVD), being triggered by intracellular cholesterol accumulation within cells. Within this pathological context, this complex pathway is activated by a number of factors, such as unhealthy nutrition, altered gut and oral microbiota, and elevated cholesterol itself. Moreover, evidence from autoinflammatory diseases, like psoriasis and others, which are also associated with higher cardiovascular disease (CVD) risk, suggests that variants of NLRP3 pathway-related genes (like NLRP3 itself, caspase recruitment domain-containing protein (CARD)8, caspase-1 and IL-1\u3b2) may carry gain-of-function mutations leading, in some individuals, to a constitutive pro-inflammatory pattern. Indeed, some reports have recently associated the presence of specific single nucleotide polymorphisms (SNPs) on such genes with greater ASCVD prevalence. Based on these observations, a potential effective strategy in this context may be the identification of carriers of these NLRP3-related SNPs, to generate a genomic score, potentially useful for a better CVD risk prediction, and, possibly, for personalized therapeutic approaches targeted to the NLRP3-IL-1\u3b2 pathway. View Full-Tex

Gli insetti al servizio degli inquirenti

Per molti anni gli insetti che popolavano la superficie e gli orifizi dei cadaveri sono stati considerati solo una presenza poco gradevole del lavoro dei medici legali e delle Forze dell'Ordine coinvolte nelle indagini inerenti a crimini violenti. Ma come gli intriganti romanzi di Deawer e della Cornwell ci hanno insegnato, gli insetti costituiscono dei silenziosi custodi di preziosi informazioni sull'accadimento di fatti a volte inspiegabili. Tuttavia mentre le varie branche delle scienze criminalistiche (la biologia, la balistica, la chimica, ecc.) hanno avuto nel tempo una crescita esponenziale, affinando tecniche e metodologie, lo studio degli insetti associati alla scena criminis è stato, nel nostro Paese per molto tempo sottovalutato o addirittura ignorato. L'Entomologia Forense è un ramo della zoologia dedicata allo studio degli insetti e di altri artropodi, dal cui esame è possibile ricavare elementi decisivi per la persecuzione di un reato. Negli ultimi anni tale disciplina ha visto crescere l'interesse da parte degli scienziati forensi, dei Medici Legali e delle Forze dell'Ordine, soprattutto in Europa e negli USA, dove esistono figure professionali specialistiche che affiancano la magistratura inquirente nella risoluzione di casi di morti sospette ed altri reati accomunati dalla presenza di insetti. Purtroppo in Italia solo da pochi anni si è sviluppato l'interesse verso la materia e ancora oggi gli entomologi forensi non lavorano sistematicamente accanto agli organi di Giustizia. Lo scopo del presente lavoro è una disamina delle potenzialità dell'Entomologia Forense e delle relative applicazioni come strumento spesso determinante per la risoluzione di intriganti e complessi casi giudiziari

Lifelong exposure to air pollution and cognitive development in young children: the UK Millennium Cohort Study

Background. Evidence about the impact of air pollution on cognitive development of children has been growing but remains inconclusive. Objectives. To investigate the association of air pollution exposure and the cognitive development of children in the UK Millennium Cohort Study. Methods. Longitudinal study of a nationally representative sample of 13,058-14,614 singleton births, 2000-2002, analysed at age 3, 5 and 7 years for associations between exposure from birth to selected air pollutants and cognitive scores for: School Readiness, Naming Vocabulary (age 3 and 5), Picture Similarity, Pattern Construction (age 5 and 7), Number Skills and Word Reading. Multivariable regression models took account of design stratum, clustering and sampling and attrition weights with adjustment for major risk factors, including age, gender, ethnicity, region, household income, parents' education, language, siblings and second-hand tobacco smoke. Results: In fully adjusted models, no associations were observed between pollutant exposures and cognitive scores at age 3. At age 5, particulate matter (PM2.5, PM10), nitrogen dioxide (NO2), sulphur dioxide (SO2) and carbon monoxide (CO) were associated with lower scores for Naming Vocabulary but no other outcome except for SO2 and Picture Similarity. At age 7, PM2.5, PM10 and NO2 were associated with lower scores for Pattern Construction, SO2 with lower Number Skills and SO2 and ozone with poorer Word Reading scores, but PM2.5, PM10 and NO2 were associated with higher Word Reading scores. Adverse effects of air pollutants represented a deficit of up to around 4 percentile points in Naming Vocabulary at age 5 for an interquartile range increase in pollutant concentration, which is smaller than the impact of various social determinants of cognitive development. Conclusions: In a study of multiple pollutants and outcomes, we found mixed evidence from this UK-wide cohort study for association between lifetime exposure to neighbourhood air pollutants and cognitive development to age 7 years

SIGLA - Sistema Integrato per il Monitoraggio e Gestione di Lagune ed Ambiente, sotto-azione CARLA Parte I : CARatterizzazione chimica e chimico-fisica e qualità acque LAguna di Cabras e Golfo di Oristano

È stata effettuata una prima caratterizzazione chimica e chimico-fisica della colonna d’acqua nella Laguna di Cabras tramite l’analisi di dati raccolti in precedenti indagini. Tali studi sono stati completati con campionamenti di acqua e misure in situ delle variabili idrologiche nella laguna e nel golfo di Oristano. Su questo set di dati sono state effettuate le analisi per individuare le relazioni tra le variabili misurate e per studiare le variabilità stagionali delle caratteristiche chimico-fisiche della colonna d’acqua. Lo studio ha permesso la compilazione di un protocollo metodologico di indagine e di monitoraggio dello stato trofico e di salute di ambienti lagunari costieri. I dati più recenti hanno mostrato come rispetto alle medie storiche, si sia avuto un aumento della temperatura e una diminuzione della salinità. Quest’ultima viene associata ad un limitato scambio tra la laguna ed il mare. I valori di ossigeno e pH non sono indicativi di un elevato stress ambientale, infatti non sono state rilevate condizioni di ipossia o anossia, e valori di pH superiori alla norma. Tuttavia in precedenti campionamenti nell’estate 2002 sono stati descritti al fondo valori ipossici. Tali valori hanno indicato come la laguna sia periodicamente soggetta a crisi anossiche. Il netto calo di nutrienti rispetto agli anni ottanta-novanta è associato ad una diminuzione degli input d’acqua dolce nel periodo monitorato. Inoltre non è trascurabile l’influenza degli scambi tra sedimento e colonna d’acqua. In conclusione, dagli studi condotti si può dedurre come nello specifico, nella Laguna di Cabras, lo stato trofico del sistema sia principalmente condizionato dagli input d’acqua dolce, e come questi condizionino anche gli scambi con il golfo. In aggiunta, data la diminuzione degli input di acqua dolce nel periodo monitorato e vista la relazione positiva tra volumi e nutrienti in entrata, il loro abbattimento in entrata tramite depurazione delle acque sembra essere un valido strumento di mitigazione e di recupero

Autoradiographic Study of the Turnover of Chromatin-Associated Phospholipids in Vicia Faba L.

SUMMARYAutoradiographic data from labelling studies on the incorporation of [14C] ethanolamine into nuclear phospholipids of meristem cells from roots of Vicia faba indicated the presence of a continuous labelling pattern for the nuclear membrane throughout the cell cycle. In contrast, a periodic labelling pattern was observed in chromatin of interphase nuclei which closely paralleled the synthesis pattern for DNA. This corroborated biochemical data from previously published studies of hepatocyte nuclear membranes and chromatin

New data on distribution of amphibians and reptiles in the Aral Sea Basin and surrounding areas of Kazakhstan. Part I. The Green Toads of Bufo viridis complex (Amphibia: Anura)

First the data on distribution of the toads of Bufo viridis complex are presented for Aral Sea Basin and surrounding areas of Southern and Western Kazakhstan. Karyological analysis revealed a presence of diploid toad populations in the valley of the middle and low flows of Syr-Darya River; in the northern coast of Aral Sea and the desert areas between the last and Irgyz-Turgay Basin; in the northern part of Karatau Range. The only tetraploid population was discovered in the central part of Karatau Range

A guide to medication adherence in depression

Depression is a common mental health disorder that affects at least 350 million people worldwide and exerts a negative effect upon a person’s physical, mental and social functions, and it is associated with an increased risk of premature death. The treatment of depression involves the use of antidepressants and selective serotonin inhibitors are currently the first line of treatment. In particular, fluoxetine is safe and effective in the treatment the disorder. It is one of the few antidepressants licensed for use in children under the age of 18 years in the UK. Fluoxetine is associated with fewer dose adjustments compared to other SSRIs and this simplifies therapy and may improve outcomes. However, fluoxetine induces a number of side effects like, nausea, insomnia, sexual dysfunction and its interaction with monoamine oxidase inhibitors can cause the serotonin syndrome

Concurrent validity of an Estimator of Weekly Alcohol Consumption (EWAC) based on the Extended AUDIT

Background and Aims: The 3-question Alcohol Use Disorders Identification Test (AUDIT-C) is frequently used in healthcare for screening and brief advice about levels of alcohol consumption. AUDIT-C scores (0–12) provide feedback as categories of risk rather than estimates of actual alcohol intake, an important metric for behaviour change. The study aimed to (a) develop a continuous metric from the Extended AUDIT-C expressed in United Kingdom (UK) units (8g pure ethanol), offering equivalent accuracy, and providing a direct estimator of weekly alcohol consumption (EWAC) and (b) evaluate the EWAC’s bias and error using the Graduated-Frequency (GF) questionnaire as a reference standard of alcohol consumption. Design: Cross-sectional diagnostic study based on a nationally-representative survey. Settings: Community-dwelling households in England. Participants: 22,404 household residents aged 16 years reporting drinking alcohol at least occasionally. Measurements: Computer-assisted personal interviews consisting of (a) AUDIT questionnaire with extended response items (the ‘Extended AUDIT’) and (b) GF. Primary outcomes were: mean deviation <1 UK unit (metric of bias); root mean squared deviation <2 UK units (metric of total error) between EWAC and GF. The secondary outcome was the receiver operating characteristic area under the curve for predicting alcohol consumption in excess of 14 and 35 UK units. Findings: EWAC had a positive bias of 0.2 UK units [95% confidence interval: 0.08, 0.4] compared with GF. Deviations were skewed: while the mean error was ±11 UK units/week [9.5, 11.9], in half of participants the deviation between EWAC and GF was between 0 and ±2.1 UK units/week. EWAC predicted consumption in excess of 14 UK units/week with a significantly greater area under the curve (0.918 [0.914, 0.923]) than AUDIT-C (0.870 [0.864, 0.876]) or the full AUDIT (0.854 [0.847, 0.860]). Conclusions: A new estimator of weekly alcohol consumption (EWAC), which uses answers to the Extended Alcohol Use Disorders Identification Test (Extended AUDIT-C), meets the targeted bias tolerance. It is superior in accuracy to AUDIT-C and the full AUDIT when predicting consumption thresholds, making it a reliable complement to the Extended AUDIT-C for health promotion interventions