In vivo utjecaj imunosupresije u majki za vrijeme trudnoće na imunosni sustav novorođenčadi

When used in pregnancy, immunosuppressants can cross the placental barrier and enter foetal circulation, possibly affecting the immune system of the foetus. This study evaluated the immune function in eight children born by mothers with connective tissue diseases who received immunosuppressants (cyclosporine A or dexamethasone) during pregnancy and in six babies from mothers with similar diseases, but who did not receive any treatment. Judging by the cytokine production of interleukin-2 and interferon-γ in peripheral blood mononuclear cells stimulated by phorbol-myristate-acetate (PMA) and ionomycin, immunosuppressive drugs given for rheumatic disorders during pregnancy do not induce significant immunosuppression in babies.Imunosupresivni lijekovi davani za vrijeme trudnoće mogu proći placentalnu barijeru i ući u cirkulaciju fetusa, s mogućim utjecajem na njegov imunosni sustav. U radu je praćena imunosna funkcija kod osmero djece rođene od majki s bolestima vezivnog tkiva, koje su tretirane za vrijeme trudnoće imunosupresivnim lijekovima (ciklosporin A ili deksametazon) i kod osmero novorođenč adi rođene od majki sa sličnim bolestima, ali koje nisu bile tretirane. Imunosupresivni lijekovi primijenjeni za vrijeme trudnoće kod majki koje boluju od reumatskih bolesti ne izazivaju značajniju imunosupresiju u novorođenčadi praćenu nastajanjem citokina, interleukina 2 i interferona γ_ u perifernim mononuklearnim krvnim stanicama pod djelovanjem forbol-miristat-acetata (PMA) i ionomicina

Anti-inflammatory and immunosuppressive drugs and reproduction

Rheumatic diseases in women of childbearing years may necessitate drug treatment during a pregnancy, to control maternal disease activity and to ensure a successful pregnancy outcome. This survey is based on a consensus workshop of international experts discussing effects of anti-inflammatory, immunosuppressive and biological drugs during pregnancy and lactation. In addition, effects of these drugs on male and female fertility and possible long-term effects on infants exposed to drugs antenatally are discussed where data were available. Recommendations for drug treatment during pregnancy and lactation are given

The Cotton Centromere Contains a Ty3-gypsy-like LTR Retroelement

The centromere is a repeat-rich structure essential for chromosome segregation; with the long-term aim of understanding centromere structure and function, we set out to identify cotton centromere sequences. To isolate centromere-associated sequences from cotton, (Gossypium hirsutum) we surveyed tandem and dispersed repetitive DNA in the genus. Centromere-associated elements in other plants include tandem repeats and, in some cases, centromere-specific retroelements. Examination of cotton genomic survey sequences for tandem repeats yielded sequences that did not localize to the centromere. However, among the repetitive sequences we also identified a gypsy-like LTR retrotransposon (Centromere Retroelement Gossypium, CRG) that localizes to the centromere region of all chromosomes in domestic upland cotton, Gossypium hirsutum, the major commercially grown cotton. The location of the functional centromere was confirmed by immunostaining with antiserum to the centromere-specific histone CENH3, which co-localizes with CRG hybridization on metaphase mitotic chromosomes. G. hirsutum is an allotetraploid composed of A and D genomes and CRG is also present in the centromere regions of other AD cotton species. Furthermore, FISH and genomic dot blot hybridization revealed that CRG is found in D-genome diploid cotton species, but not in A-genome diploid species, indicating that this retroelement may have invaded the A-genome centromeres during allopolyploid formation and amplified during evolutionary history. CRG is also found in other diploid Gossypium species, including B and E2 genome species, but not in the C, E1, F, and G genome species tested. Isolation of this centromere-specific retrotransposon from Gossypium provides a probe for further understanding of centromere structure, and a tool for future engineering of centromere mini-chromosomes in this important crop species

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Dalla "museificazione" alla "rivitalizzazione" del paesaggio: ricerca, tesi, progetti al Politecnico di Milano - From a process of "museification" to the "rivitalization" of the landscape: research, thesis, projects to the Polytechnic of Milan.

I criteri di lettura e ricognizione descritti nell’articolo hanno come obbiettivo la ricostituzione di un territorio “intelligente”. Da un lato l’idea di incentivare il rispetto del territorio promuovendone un’articolata conoscenza secondo differenti livelli di approfondimento così come le tecnologie digitali oggi consentono, dall’altro lato l’idea di un territorio come luogo vitale e attivo, all’interno del quale è necessario incentivare azioni e usi. È solo attraverso l’uso, riportando il territorio alla vita, che viene garantita una vera conservazione e protezione. Ne deriva una drammaturgia del territorio, che come un vasto “piano-sequenza” cinematografico è in grado di mettere a sistema spazialità sovrapposte e compresenti, materiali diversi, dilatazioni temporali, salti percettivi, sui quali il visitatore potrà costruire nuove letture e diversi sistemi di nessi logici

DALLA ‘MUSEIFICAZIONE’ ALLA ‘RIVITALIZZAZIONE’ DEL PAESAGGIO: RICERCA, TESI, PROGETTI AL POLITECNICO DI MILANO PER L’ISOLA DI SPARGI NELL’ARCIPELAGO DI LA MADDALENA

The island of Spargi is an extraordinary example of integration between nature and human activities, in particular if we consider the military settlements that have been realized on the island in the last 200 years. A territory of such complexity requires the development of analysis and investigation tools that must be strongly focused on the direct experience of places, considered as the most important strategy to understand them thoroughly. This means to learn how to read the landscape, literally ‘incorporating’ it through the observer’s experience: through feets, eyes, hands and senses. So to understand its physical and cultural characters more closely and in depth. This is ours way of seeing, a fundamental process to conjugate landscape protection and instances of renewal useful for sustainable use. The idea is to overcome the limits of mere conservation, whether referred to a landscape shaped by nature or by human actions, to encourage a wider vision based upon participatory and proactive processes. It is only through use, that a landscape can remain in life, being preserved and protected. The proposed projects underline with various variations this fundamental aspect, proposing a correct preservation through various types of uses of the island's natural space and of its remains of military batteries

SPAF: Stateless FSA-Based Packet Filters

Abstract-We propose a stateless packet filtering technique based on Finite-State Automata (FSA). FSAs provide a comprehensive framework with well-defined composition operations that enable the generation of stateless filters from high-level specifications and their compilation into efficient executable code without resorting to various opportunistic optimization algorithms. In contrast with most traditional approaches, memory safety and termination can be enforced with minimal run-time overhead even in cyclic filters, thus enabling full parsing of complex protocols and supporting recursive encapsulation relationships. Experimental evidence shows that this approach is viable and improves the state of the art in terms of filter flexibility, performance and scalability without incurring in the most common FSA deficiencies, such as state space explosion