Factors associated with a change in smoking habit during the first COVID-19 lockdown: an Italian cross-sectional study among ever-smokers

Background: The COVID-19 pandemic and the lockdown period lasted from March to May 2020, resulted in a highly stressful situation yielding different negative health consequences, including the worsening of smoking habit. Methods: A web-based cross-sectional study on a convenient sample of 1013 Italian ever smokers aged 18 years or more was conducted. Data were derived from surveys compiled by three different groups of people: subjects belonging to Smoking Cessation Services, Healthcare Providers and Nursing Sciences' students. All institutions were from Northern Italy. The primary outcome self-reported worsening (relapse or increase) or improvement (quit or reduce) of smoking habit during lockdown period. Multiple unconditional (for worsening) and multinomial (for improving) logistic regressions were carried out. Results: Among 962 participants, 56.0% were ex-smokers. Overall, 13.2% of ex-smokers before lockdown reported relapsing and 32.7% of current smokers increasing cigarette intake. Among current smokers before lockdown, 10.1% quit smoking and 13.5% decreased cigarette intake. Out of 7 selected stressors related to COVID-19, four were significantly related to relapse (OR for the highest vs. the lowest tertile ranging between 2.24 and 3.62): fear of being infected and getting sick; fear of dying due to the virus; anxiety in listening to news of the epidemic; sense of powerlessness in protecting oneself from contagion. In addition to these stressors, even the other 3 stressors were related with increasing cigarette intensity (OR ranging between 1.90 and 4.18): sense of powerlessness in protecting loved ones from contagion; fear of losing loved ones due to virus; fear of infecting other. Conclusion: The lockdown during the COVID-19 pandemic was associated with both self-reported relapse or increase smoking habit and also quitting or reduction of it

The universal YrdC/Sua5 family is required for the formation of threonylcarbamoyladenosine in tRNA

Threonylcarbamoyladenosine (t6A) is a universal modification found at position 37 of ANN decoding tRNAs, which imparts a unique structure to the anticodon loop enhancing its binding to ribosomes in vitro. Using a combination of bioinformatic, genetic, structural and biochemical approaches, the universal protein family YrdC/Sua5 (COG0009) was shown to be involved in the biosynthesis of this hypermodified base. Contradictory reports on the essentiality of both the yrdC wild-type gene of Escherichia coli and the SUA5 wild-type gene of Saccharomyces cerevisiae led us to reconstruct null alleles for both genes and prove that yrdC is essential in E. coli, whereas SUA5 is dispensable in yeast but results in severe growth phenotypes. Structural and biochemical analyses revealed that the E. coli YrdC protein binds ATP and preferentially binds RNAThr lacking only the t6A modification. This work lays the foundation for elucidating the function of a protein family found in every sequenced genome to date and understanding the role of t6A in vivo

Endothelial dysfunction in patients with spontaneous venous thromboembolism

Background and Objectives A high incidence of atherosclerotic lesions and cardiovascular events has been reported in patients with spontaneous venous thromboembolism. Endothelial dysfunction is an early marker of atherosclerosis and has predictive value for ischemic events. We have evaluated endothelial function in patients with a history of spontaneous venous thromboembolism.Design and Methods Patients with a history of symptomatic, objectively confirmed, spontaneous venous thromboembolism were included in a case-control study. Exclusion criteria were any known risk factors for cardiovascular diseases, other conditions associated with endothelial dysfunction, estro-progestinic therapy or pregnancy. Controls were age-(±5 years) and sex-matched subjects with the same exclusion criteria but without previous venous thromboembolism. Endothelial function was evaluated by the non-invasive measurement of flow-mediated vasodilation of the brachial artery and of plasma markers of endothelium activation; platelet activation parameters were also measured.Results Twenty-eight cases (8 females; mean age 59±15 years) and 28 controls (8 females; mean age 58±15) were studied. Flow-mediated vasodilation was 3.5±0.6% in cases (95% CIs: 2.2 to 4.8) and 5.7±0.6% (4.2 to 6.8) in controls (p=0.015). Brachial artery blood flow and hyperemic blood flow did not differ between the two groups. Plasma von Willebrand factor and soluble P-selectin levels were significantly higher in patients with venous thromboembolism, while plasma soluble CD40 ligand and urinary 11-dehydro-TxB2 levels were similar in cases and controls.Interpretation and Conclusions Patients with spontaneous venous thromboembolism have endothelial dysfunction, unlike age- and sex- matched controls. This finding suggests that spontaneous venous thromboembolism may be a condition associated with an enhanced risk of atherosclerosis

Projeto de uma planta para manufatura de produtos pecuários a partir do reaproveitamento de resíduos plásticos industriais e fibras vegetais

O presente trabalho discute o projeto conceitual de um sistema de produção sustentável para manufaturar equipamentos destinados à alimentação e suplementação de bovinos – os produtos são fabricados de materiais compostos végeto-poliméricos obtidos de uma combinação de resíduos de filmes plásticos e fibras vegetais. Este artigo se refere a um projeto de inovação tecnológica do Conselho Nacional de Desenvolvimento Científico e Tecnológico, Programa de Formação de Recursos Humanos em Áreas Estratégicas (CNPq-RHAE). As atividades de pesquisa foram realizadas em parceria entre duas universidades federais brasileiras e um fabricante de embalagens plásticas flexíveis e possibilitou a elaboração de um plano para implantar uma nova unidade de negócios. Por fim, a nova unidade fabril está alinhada com a Política Nacional de Resíduos Sólidos (Lei Federal nº 12.305/2010), permitindo agregar valor aos resíduos para produzir novos produtos pecuários

Reprocessability of PHB in extrusion: ATR-FTIR, tensile tests and thermal studies

Mechanical recycling of biodegradable plastics has to be encouraged, since the consumption of energy and raw materials can be reduced towards a sustainable development in plastics materials. In this study, the evolution of thermal and mechanical properties, as well as structural changes of poly(hydroxybutyrate) (PHB) up to three extrusion cycles were investigated. Results indicated a significant reduction in mechanical properties already at the second extrusion cycle, with a reduction above 50% in the third cycle. An increase in the crystallinity index was observed due to chemicrystallization process during degradation by chain scission. On the other hand, significant changes in the chemical structure or in thermal stability of PHB cannot be detected by Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analyses (TGA), respectively.National Foundation for Science and Technology Development (CNPq)Univ Fed Rio Grande Norte UFRN, Dept Mat Engn DEMat, Natal, RN, BrazilUniv Fed Sao Carlos UFSCar, Dept Mat Engn DEMa, Sao Carlos, SP, BrazilUniv Fed Paraiba UFPB, Dept Mat Engn DEMAT, Joao Pessoa, Paraiba, BrazilUniv Fed Rio Grande Norte UFRN, Dept Chem DQ, Natal, RN, BrazilUniv Fed Sao Paulo UNIFESP, Inst Sci & Technol ICT, Sao Jose Dos Campos, SP, BrazilUniv Fed Sao Paulo UNIFESP, Inst Sci & Technol ICT, Sao Jose Dos Campos, SP, BrazilWeb of Scienc

3D gelatin-chitosan hybrid hydrogels combined with human platelet lysate highly support human mesenchymal stem cell proliferation and osteogenic differentiation

Bone marrow and adipose tissue human mesenchymal stem cells were seeded in highly performing 3D gelatin–chitosan hybrid hydrogels of varying chitosan content in the presence of human platelet lysate and evaluated for their proliferation and osteogenic differentiation. Both bone marrow and adipose tissue human mesenchymal stem cells in gelatin–chitosan hybrid hydrogel 1 (chitosan content 8.1%) or gelatin–chitosan hybrid hydrogel 2 (chitosan 14.9%) showed high levels of viability (80%–90%), and their proliferation and osteogenic differentiation was significantly higher with human platelet lysate compared to fetal bovine serum, particularly in gelatin–chitosan hybrid hydrogel 1. Mineralization was detected early, after 21 days of culture, when human platelet lysate was used in the presence of osteogenic stimuli. Proteomic characterization of human platelet lysate highlighted 59 proteins mainly involved in functions related to cell adhesion, cellular repairing mechanisms, and regulation of cell differentiation. In conclusion, the combination of our gelatin–chitosan hybrid hydrogels with hPL represents a promising strategy for bone regenerative medicine using human mesenchymal stem cells

The new small tyrosine-kinase inhibitor ARQ531 targets acute myeloid leukemia cells by disrupting multiple tumor-addicted programs

Tyrosine kinases have been implicated in promoting tumorigenesis of several human cancers. Exploiting these vulnerabilities has been shown to be an effective anti-tumor strategy as demonstrated for example by the Bruton's tyrosine kinase (BTK) inhibitor, ibrutinib, for treatment of various blood cancers. Here, we characterize a new multiple kinase inhibitor, ARQ531, and evaluate its mechanism of action in preclinical models of acute myeloid leukemia. Treatment with ARQ531, by producing global signaling pathway deregulation, resulted in impaired cell cycle progression and survival in a large panel of leukemia cell lines and patient-derived tumor cells, regardless of the specific genetic background and/or the presence of bone marrow stromal cells. RNA-seq analysis revealed that ARQ531 constrained tumor cell proliferation and survival through Bruton's tyrosine kinase and transcriptional program dysregulation, with proteasome-mediated MYB degradation and depletion of short-lived proteins that are crucial for tumor growth and survival, including ERK, MYC and MCL1. Finally, ARQ531 treatment was effective in a patient-derived leukemia mouse model with significant impairment of tumor progression and survival, at tolerated doses. These data justify the clinical development of ARQ531 as a promising targeted agent for the treatment of patients with acute myeloid leukemia

Prediction of early recurrent thromboembolic event and major bleeding in patients with acute stroke and atrial fibrillation by a risk stratification schema: the ALESSA score study

Background and Purposes—This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation. Methods—The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00–1.11) and severe atrial enlargement (hazard ratio, 2.05; 95% confidence interval, 1.08–2.87) were predictors for ischemic outcome events (stroke, transient ischemic attack, and systemic embolism) at 90 days from acute stroke. Small lesions (≤1.5 cm) were inversely correlated with both major bleeding (hazard ratio, 0.39; P=0.03) and ischemic outcome events (hazard ratio, 0.55; 95% confidence interval, 0.30–1.00). We assigned to age ≥80 years 2 points and between 70 and 79 years 1 point; ischemic index lesion >1.5 cm, 1 point; severe atrial enlargement, 1 point (ALESSA score). A logistic regression with the receiver-operating characteristic graph procedure (C statistic) showed an area under the curve of 0.697 (0.632–0.763; P=0.0001) for ischemic outcome events and 0.585 (0.493–0.678; P=0.10) for major bleedings. Results—The validation cohort consisted of 994 patients included in prospective series between April 2014 and June 2016. Logistic regression with the receiver-operating characteristic graph procedure showed an area under the curve of 0.646 (0.529–0.763; P=0.009) for ischemic outcome events and 0.407 (0.275–0.540; P=0.14) for hemorrhagic outcome events. Conclusions—In acute stroke patients with atrial fibrillation, high ALESSA scores were associated with a high risk of ischemic events but not of major bleedings

Impact of Host Genes and Strand Selection on miRNA and miRNA* Expression

Dysregulation of miRNAs expression plays a critical role in the pathogenesis of genetic, multifactorial disorders and in human cancers. We exploited sequence, genomic and expression information to investigate two main aspects of post-transcriptional regulation in miRNA biogenesis, namely strand selection regulation and expression relationships between intragenic miRNAs and host genes. We considered miRNAs expression profiles, measured in five sizeable microarray datasets, including samples from different normal cell types and tissues, as well as different tumours and disease states. First, the study of expression profiles of “sister” miRNA pairs (miRNA/miRNA*, 5′ and 3′ strands of the same hairpin precursor) showed that the strand selection is highly regulated since it shows tissue-/cell-/condition-specific modulation. We used information about the direction and the strength of the strand selection bias to perform an unsupervised cluster analysis for the sample classification evidencing that is able to distinguish among different tissues, and sometimes between normal and malignant cells. Then, considering a minimum expression threshold, in few miRNA pairs only one mature miRNA is always present in all considered cell types, whereas the majority of pairs were concurrently expressed in some cell types and alternatively in others. In a significant fraction of concurrently expressed pairs, the major and the minor forms found at comparable levels may contribute to post-transcriptional gene silencing, possibly in a coordinate way. In the second part of the study, the behaved tendency to co-expression of intragenic miRNAs and their “host” mRNA genes was confuted by expression profiles examination, suggesting that the expression profile of a given host gene can hardly be a good estimator of co-transcribed miRNA(s) for post-transcriptional regulatory networks inference. Our results point out the regulatory importance of post-transcriptional phases of miRNAs biogenesis, reinforcing the role of such layer of miRNA biogenesis in miRNA-based regulation of cell activities

Timing of initiation of oral anticoagulants in patients with acute ischemic stroke and atrial fibrillation comparing posterior and anterior circulation strokes

Background: The aim of this study in patients with acute posterior ischemic stroke (PS) and atrial fibrillation (AF) were to evaluate the risks of recurrent ischemic event and severe bleeding and these risks in relation with oral anticoagulant therapy (OAT) and its timing. Methods: Patients with PS were prospectively included; the outcome events of these patients were compared with those of patients with anterior stroke (AS) which were taken from previous registries. The primary outcome was the composite of: stroke recurrence, TIA, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding occurring within 90 days from acute stroke. Results: A total of 2,470 patients were available for the analysis: 473 (19.1%) with PS and 1,997 (80.9%) AS. Over 90 days, 213 (8.6%) primary outcome events were recorded: 175 (8.7%) in patients with AS and 38 (8.0%) in those with PS. In patients who initiated OAT within 2 days, the primary outcome occurred in 5 out of 95 patients (5.3%) with PS compared to 21 out of 373 patients (4.3%) with AS (OR 1.07; 95% CI 0.39-2.94). In patients who initiated OAT between days 3 and 7, the primary outcome occurred in 3 out of 103 patients (2.9%) with PS compared to 26 out of 490 patients (5.3%) with AS (OR 0.54; 95% CI 0.16-1.80). Conclusions: Patients with posterior or anterior stroke and AF appear to have similar risks of ischemic or hemorrhagic events at 90 days with no difference concerning the timing of initiation of OAT