Restoring Conjunctival Tolerance by Topical Nuclear Factor–κB Inhibitors Reduces Preservative-Facilitated Allergic Conjunctivitis in Mice

Purpose.: To evaluate the role of nuclear factor–κB (NF-κB) activation in eye drop preservative toxicity and the effect of topical NF-κB inhibitors on preservative-facilitated allergic conjunctivitis. Methods.: Balb/c mice were instilled ovalbumin (OVA) combined with benzalkonium chloride (BAK) and/or NF-κB inhibitors in both eyes. After immunization, T-cell responses and antigen-induced ocular inflammation were evaluated. Nuclear factor–κB activation and associated inflammatory changes also were assessed in murine eyes and in an epithelial cell line after BAK exposure. Results.: Benzalkonium chloride promoted allergic inflammation and leukocyte infiltration of the conjunctiva. Topical NF-κB inhibitors blocked the disruptive effect of BAK on conjunctival immunological tolerance and ameliorated subsequent ocular allergic reactions. In line with these findings, BAK induced NF-κB activation and the secretion of IL-6 and granulocyte-monocyte colony-stimulating factor in an epithelial cell line and in the conjunctiva of instilled mice. In addition, BAK favored major histocompatibility complex (MHC) II expression in cultured epithelial cells in an NF-κB–dependent fashion after interaction with T cells. Conclusions.: Benzalkonium chloride triggers conjunctival epithelial NF-κB activation, which seems to mediate some of its immune side effects, such as proinflammatory cytokine release and increased MHC II expression. Breakdown of conjunctival tolerance by BAK favors allergic inflammation, and this effect can be prevented in mice by topical NF-κB inhibitors. These results suggest a new pharmacological target for preservative toxicity and highlight the importance of conjunctival tolerance in ocular surface homeostasis.Fil: Guzman, Mauricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Sabbione, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Gabelloni, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Vanzulli, Silvia. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Trevani, Analía Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Giordano, Mirta Nilda. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Galletti, Jeremías Gastón. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentin

Libertà vigilata. Una critica del paternalismo libertario

L’economia comportamentale ha ormai svelato i limiti della nostra capacità di giudizio e di scelta: ci illudiamo di essere razionali ma in realtà siamo pigri e inefficienti. Se la nostra razionalità è limitata e siamo destinati a prendere decisioni controproducenti nei settori più importanti della vita (salute, lavoro, pensione, investimenti finanziari), è necessario rivedere gli strumenti politici di governo dei cittadini. Senza interferire con la libertà di scelta degli individui, ufficiali pubblici e soggetti privati possono disegnare ambienti (architetture della scelta) che sfruttano i difetti cognitivi e volitivi delle persone per “spingerle gentilmente” verso scelte che promuovono in modo più efficace i loro stessi interessi. È questo il cuore della teoria del nudge e della proposta del “paternalismo libertario” di Richard Thaler e Cass Sunstein, che aspirano a tenere insieme democrazia, liberalismo e promozione attiva del benessere, in modo da assicurare l’esercizio dell’autonomia come condizione imprescindibile della vita democratica, con una minima pretesa di regolare i comportamenti individuali dall’alto. Interrogandosi sulla coerenza concettuale e normativa del nudge paternalistico, questo libro intende ricostruire la letteratura critica sul paternalismo libertario analizzandolo, da un lato, come una forma di naturalismo metodologico, e, dall’altro, come una tecnica di regolazione i cui requisiti etici, meta-etici, giuridici e politici sono da confrontare con il liberalismo di J.S. Mill, l’utilitarismo di J. Bentham e la riflessione sul neoliberalismo di M. Foucault

Antisense to Epstein Barr virus-encoded LMP1 does not affect the transcription of viral and cellular proliferation-related genes, but induces phenotypic effects on EBV-transformed B lymphocytes

It is generally accepted that Epstein-Barr virus (EBV) latent genes EBNA-2, EBNA-3A, -3C, EBNA-LP and LMP1 are essential for growth transformation and immortalization of B lymphocytes. Among these genes, LMP1 plays a key role in the survival and dissemination of the infected B cells by inducing anti-apoptotic genes and surface expression of several activation antigens and adhesion molecules. We have previously shown that antisense oligodeoxynucleotides directed to LMP1 mRNA, effectively suppress LMP1 gene expression and substantially reduce B95.8 cell proliferation. In this study, we have used antisense LMP1 oligomers to investigate whether LMP1 suppression might influence the expression of latent EBV genes with oncogenic potential, anti-apoptotic genes, or affect the phenotype of EBV-infected B95.8 cells. Our data show that LMP1 suppression does not affect the transcription of EBNA-2, EBNA-3A, -3B and -3C genes, or that of bcl-2 and mcl-1 anti-apoptotic genes. In contrast, consistent modifications in the expression of CD39, CD54, CD23, CD11 and CD10 molecules were observed in B95.8 cells after treatment with antisense LMP1. Our findings support the possibility for using LMP1 antisense oligomers as therapeutics in EBV-associated tumors

Buccal health in Family Health Strategy in the city of São Paulo: the patient's perceptions

O presente trabalho trata da recente inserção da saúde bucal no Programa Saúde da Família (PSF) identificando as opiniões, percepções e necessidades dos usuários adultos da UBS Vila Espanhola, município de São Paulo. Para sua realização foi feita uma pesquisa qualitativa, composta pelas seguintes etapas: observação sistemática das atividades da equipe de saúde bucal da UBS e entrevista com os usuários adultos, maiores de 18 anos, que tiveram algum tipo de atendimento odontológico na UBS nos últimos 6 meses. Na fase de análise optou-se pela técnica de análise de conteúdo de Bardin. Percebeu-se que a inserção do PSF aumentou o acesso da população estudada na região da UBS, o que trouxe maior demanda por serviços especializados em odontologia. Contudo, os usuários não estavam conseguindo utilizar esses serviços de atenção secundária em saúde bucal. Algumas insatisfações foram detectadas: a constante troca de dentistas na equipe, comprometendo o vínculo, assim como os critérios e prioridades nos atendimentos. A inserção da saúde bucal no PSF trouxe alguns avanços, porém precisa ser constantemente reavaliada para realmente conseguir atingir suas principais propostas, como a integralidade da atenção, a equidade, entre outras.This work is about the insertion of oral health in the Family Health Program - PSF identifying opinions, perceptions and necessities of the adult's patients from Vila Espanhola UBS (Health Basic Unity), São Paulo city, in relation to dental health and the service of attention to buccal health offered by the PSF. The methodology was qualitative research made of the following steps: systematic observation of the activities done by the buccal health team of the UBS, and interview with the adult patients, older than 18, that had any kind of attention in the past six months. In the analyses phase, we opted by the content analysis of Bardin. It was noticed that the insertion of PSF increased the access of the studied population in the UBS region, which increase brought a bigger demand by specialized oral services. The patients are not being able to have access to those secondary attentions in buccal health. Some dissatisfaction were detected: the constant changing of the dentists in the team - compromising the link, lack of patients' autonomy in relation to their own oral health, as the way how it is applied the equity principle to prioritize the cares. Then, the insertion of buccal health in the PSF brought some advances, however it needs to be reevaluated to really reach its main proposals as integrality of attention, equity among others needs

Atmospheric deposition of organic matter at a remote site in the central Mediterranean Sea: implications for the marine ecosystem

Abstract. Atmospheric fluxes of dissolved organic matter (DOM) were studied for the first time on the island of Lampedusa, a remote site in the central Mediterranean Sea (Med Sea), between 19 March 2015 and 1 April 2017. The main goals of this study were to quantify total atmospheric deposition of DOM in this area and to evaluate the impact of Saharan dust deposition on DOM dynamics in the surface waters of the Mediterranean Sea. Our data show high variability in DOM deposition rates without a clear seasonality and a dissolved organic carbon (DOC) input from the atmosphere of 120.7 mmol DOC m−2 yr−1. Over the entire time series, the average dissolved organic phosphorus (DOP) and dissolved organic nitrogen (DON) contributions to the total dissolved pools were 40 % and 26 %, respectively. The data on atmospheric elemental ratios also show that each deposition event is characterized by a specific elemental ratio, suggesting a high variability in DOM composition and the presence of multiple sources. This study indicates that the organic substances transported by Saharan dust on Lampedusa mainly come from a natural sea spray and that Saharan dust can be an important carrier of organic substances even though the load of DOC associated with dust is highly variable. Our estimates suggest that atmospheric input has a larger impact on the Med Sea than on the global ocean. Further, DOC fluxes from the atmosphere to the Med Sea can be up to 6 times larger than total river input. Longer time series combined with modeling would greatly improve our understanding of the response of DOM dynamics in the Med Sea to the change in aerosol deposition pattern due to the effect of climate change

Dissecting histone deacetylase role in pulmonary arterial smooth muscle cell proliferation and migration

Pulmonary Arterial Hypertension (PAH) is a rare and devasting condition characterized by elevated pulmonary vascular resistance and pulmonary artery pressure leading to right-heart failure and premature death. Pathologic alterations in proliferation, migration and survival of all cell types composing the vascular tissue play a key role in the occlusion of the vascular lumen. In the current study, we initially investigated the action of selective class I and class II HDAC inhibitors on the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) after exposure to Platelet Derived Growth Factor (PDGF). Class I HDAC inhibitors were able to counteract the hyperproliferative response to PDGF, reducing both proliferation and migration in PASMCs, while class II were ineffective. Selective silencing with siRNAs targeted against different HDACs revealed a major role of class I, and within this class, of HDAC1 in mediating PDGF-induced Akt Phosphorylation and Cyclin D1 (CycD1) expression. These results from these combinatorial approaches were further confirmed by the ability of a specific HDAC1 inhibitor to antagonize the PDGF action. The finding that HDAC1 is a major conductor of PDGF-induced patterning in PAH-PASMCs prompts the development of novel selective inhibitors of this member of class I HDACs as a potential tool to control lung vascular homeostasis in PAH

Colorimetric analysis of painting materials using polymer-supported polydiacetylene films

Polydiacetylenes, exhibiting different headgroups, distinguish among different painting materials

A new bio-based organogel for the removal of wax coating from indoor bronze surfaces

Abstract In this research, we propose an advanced system for the cleaning of wax-based coatings applied on indoor bronzes. To this aim we developed a new kind of eco-friendly gel based on PHB (poly-3-hydroxybutyrate) used as thickening agent, biodiesel (BD) and dimethyl carbonate (DMC). BD is a mixture of methyl esters obtained from palm oil, which acts as cleaning agent while DMC was added as additional solvent to partially solubilize PHB and forming a gelly phase. For the first time a PHB-based gel obtained by mixing two solvents with different proprieties was proposed, expanding the range of possible formulations, that can be used according to the specific restoration purpose. After the preliminary characterization of chemical and physical properties of the gel, an ad hoc analytical protocol was implemented to evaluate both the cleaning efficiency and the release of residues on the treated surfaces. Standard samples were prepared following ancient recipes and submitted to spectroscopic and chromatographic analysis before and after the cleaning procedures. Finally, the performances of PHB-DMC/BD gel were assessed on a real case of study presenting a wax-based coating: the Pulpito della passione attributed to Donatello and dated back to 1460. In situ analysis demonstrated the high cleaning efficiency of the proposed systems also for the removal of aged coatings

Ductal ligation timing and neonatal outcomes: a 12-year bicentric comparison.

Funder: Alma Mater Studiorum - Università di BolognaPatent ductus arteriosus (PDA) is common among extremely preterm infants. In selected cases, surgical PDA ligation may be required. The timing for PDA ligation may depend upon a variety of factors, with potential clinical implications. We aimed to investigate the impact of different surgical PDA managements on ligation timing and neonatal outcomes. Inborn infants < 32 weeks of gestation and < 1500 g admitted at two tertiary Neonatal Intensive Care Units that underwent PDA ligation between 2007 and 2018 were enrolled in this retrospective cohort study and split into the following groups based on their surgical management: on-site bedside PDA ligation (ONS) vs. referral to an off-site pediatric cardiac surgery (OFS). Neonatal characteristics, surgical timing, and clinical outcomes of the enrolled infants were compared between the groups. Multivariate analysis was performed to evaluate the impact of PDA ligation timing on significantly different outcomes. Seventy-eight neonates (ONS, n = 39; OFS, n = 39) were included. Infants in the ONS group underwent PDA ligation significantly earlier than those in the OFS group (median age 12 vs. 36 days, p < 0.001) with no increase in postoperative mortality and complications. The multivariate analysis revealed a significant association between PDA ligation timing, late-onset sepsis prevalence (OR 1.045, 0.032), and oxygen need at discharge (OR 1.037, p = 0.025).Conclusions: Compared with off-site surgery, on-site bedside ligation allows an earlier surgical closure of PDA, with no apparent increase in mortality or complications. Earlier PDA ligation may contribute to reduced rates of late-onset sepsis and post-discharge home oxygen therapy, with possible cost-benefit implications. What is known: • Ineffective or contraindicated pharmacological closure of a hemodynamically significant PDA may require a surgical ligation. • Available literature comparing the effect of early vs. late PDA ligation on the main neonatal morbidities has yield contrasting results. What is new: • The availability of a cardiac surgery service performing bedside PDA ligation allows an earlier intervention compared to patient referral to an off-site center, with no difference in postoperative mortality and complications compared to off-site surgery. • Earlier PDA ligation was associated with a lower prevalence of late-onset sepsis and of oxygen need at discharge, with possible cost-benefit implications