“Načrt Kopra izdelan po naročilu presvetlega gospoda Bernarda Malipiera Podestata in Kapitana; Prvega avgusta 1619; narisal Giacomo Fino”Načrt Kopra Giacoma Fina iz leta 1619 ponazarja mesto znotraj ...obzidja.
Repeated cycles of infections, caused mainly by Pseudomonas aeruginosa, combined with a robust host immune response and tissue injury, determine the course and outcome of cystic fibrosis (CF) lung ...disease. As the disease progresses, P. aeruginosa adapts to the host modifying dramatically its phenotype; however, it remains unclear whether and how bacterial adaptive variants and their persistence influence the pathogenesis and disease development. Using in vitro and murine models of infection, we showed that P. aeruginosa CF-adaptive variants shaped the innate immune response favoring their persistence. Next, we refined a murine model of chronic pneumonia extending P. aeruginosa infection up to three months. In this model, including CFTR-deficient mice, we unveil that the P. aeruginosa persistence lead to CF hallmarks of airway remodelling and fibrosis, including epithelial hyperplasia and structure degeneration, goblet cell metaplasia, collagen deposition, elastin degradation and several additional markers of tissue damage. This murine model of P. aeruginosa chronic infection, reproducing CF lung pathology, will be instrumental to identify novel molecular targets and test newly tailored molecules inhibiting chronic inflammation and tissue damage processes in pre-clinical studies.
Abstract
Background
High-mobility group box 1 protein (HMGB1) is an ubiquitous nuclear protein that once released in the extracellular space acts as a Damage Associated Molecular Pattern and promotes ...inflammation. HMGB1 is significantly elevated during
Pseudomonas aeruginosa
infections and has a clinical relevance in respiratory diseases such as Cystic Fibrosis (CF). Salicylates are HMGB1 inhibitors. To address pharmacological inhibition of HMGB1 with small molecules, we explored the therapeutic potential of pamoic acid (PAM), a salicylate with limited ability to cross epithelial barriers.
Methods
PAM binding to HMGB1 and CXCL12 was tested by Nuclear Magnetic Resonance Spectroscopy using chemical shift perturbation methods, and inhibition of HMGB1·CXCL12-dependent chemotaxis was investigated by cell migration experiments. Aerosol delivery of PAM, with single or repeated administrations, was tested in murine models of acute and chronic
P. aeruginosa
pulmonary infection in C57Bl/6NCrlBR mice. PAM efficacy was evaluated by read-outs including weight loss, bacterial load and inflammatory response in lung and bronco-alveolar lavage fluid.
Results
Our data and three-dimensional models show that PAM is a direct ligand of both HMGB1 and CXCL12. We also showed that PAM is able to interfere with heterocomplex formation and the related chemotaxis in vitro. Importantly, PAM treatment by aerosol was effective in reducing acute and chronic airway murine inflammation and damage induced by
P. aeruginosa
. The results indicated that PAM reduces leukocyte recruitment in the airways, in particular neutrophils, suggesting an impaired in vivo chemotaxis. This was associated with decreased myeloperoxidase and neutrophil elastase levels. Modestly increased bacterial burdens were recorded with single administration of PAM in acute infection; however, repeated administration in chronic infection did not affect bacterial burdens, indicating that the interference of PAM with the immune system has a limited risk of pulmonary exacerbation.
Conclusions
This work established the efficacy of treating inflammation in chronic respiratory diseases, including bacterial infections, by topical delivery in the lung of PAM, an inhibitor of HMGB1.
Purpose:
To report a successful revascularization case using the Rotarex™S atherothrombectomy system in a recent iliac limb thrombosis, and chronic hypogastric stent obstruction after previous ...aortoiliac aneurysm endovascular repair (EVAR).
Case Report:
A 72-year-old patient was treated for recent right iliac limb thrombosis and left iliac branch chronic hypogastric stent occlusion, 5 years after EVAR. A total endovascular approach, using both upper extremity and femoral vascular access, was settled with 2 Rotarex™S (6Fr and 10Fr) devices. The Rotarex™S catheters removed most of the intraluminal material, allowing additional endografts and bare metal stents to be deployed to support a new healthy lumen surface.
Conclusion:
The total endovascular approach provided by the Rotarex™S device appears to be safe and effective in treating aortoiliac endografts occlusions, both in subacute and chronic phases. Larger studies could highlight differences and eventual advantages compared with more traditional solutions.
The high metabolic flexibility and biodiversity of microalgae make them promising systems for the production of chemicals and high-value metabolites to be utilized in various industrial applications. ...Currently, microalgae are primarily cultivated in phototrophic processes or in fermenters using glucose as substrate. However, such configurations are often too costly for the majority of potential applications and require improvements. The use of acetate as substrate to enhance biomass productivity and reduce cost and environmental impacts is a promising solution. In a future bio-based economy, acetate can serve as an excellent intermediate to link many industrial facilities, as it can be synthesized using different technologies from renewable resources as CO
2
and waste. This work provides a detailed description of acetate synthesis processes alternative to the conventional methanol carbonylation, including the pros and cons of each: aerobic and anaerobic fermentations; thermochemical treatments; C1 gas fermentation; microbial electrosynthesis and artificial photosynthesis. Additionally, the utilization of acetate as substrate for microalgae growth in mixotrophic and heterotrophic conditions is reviewed, covering key metabolic and engineering aspects (strains, yields, growth rate, inhibition, productivity, process configuration). These aspects serve as guidelines for a rationale design of an algal cultivation process based on acetate as a carbon source. Finally, the review critically assesses the state of the art of coupling of acetate-rich streams with algal biomass production, highlighting the pros and cons and addressing the main knowledge gaps to be filled through future research.
Mid-term durability of branches has already been established, and BF-branched and fenestrated endovascular repair has shown comparable results with open repair in the treatment of thoracoabdominal ...aortic aneurysms (TAAAs). Nevertheless, target vessel instability remains the most frequent adverse event after complex endovascular aortic repair. Type III endoleaks from directional branches have been reported with a low incidence, but risk factors for this complication have not been investigated yet.
This was a dual-center observational retrospective cohort study. Data were collected prospectively for each patient treated with branched endovascular repair between April 2008 and December 2019. The primary outcome was to assess potential risk factors for branch disconnection and fracture. A logistic regression analysis was performed, including preoperative and postoperative measurements as well as intraoperative details. A Cox regression hazard analysis was performed to evaluate the influence of preoperative aneurysm diameter and target vessel angulation on the outcome during follow-up.
Two hundred ninety-five target visceral vessels (TVVs) in 91 patients were considered suitable for cannulation. Technical success was 96.9% (286/295 TVVs). The median follow-up was 32.5 months (interquartile range, 14.2-50.1 months). Twelve type III endoleaks from directional branches were detected (4.2%; 5 bridging stent graft fractures and 7 disconnections). Five type III endoleaks involved the celiac trunk (one fracture and four disconnections), five the superior mesenteric artery (four fractures and one disconnection), and two the renal arteries (both disconnections). The median time to type III endoleak was 22.2 months (interquartile range, 10.9-37.6 months). Preoperative TAAA diameter (P = .028), preoperative TVV angulation (P = .037), the use of a BeGraft stent graft as bridging stent graft (P = .001), and different stent types on the same vessel (P = .048) were associated with type III endoleak at univariable analysis. Using a BeGraft stent graft (P = .010) was the only significant factor predisposing to type III endoleak at multiple logistic regression. The Cox regression analysis showed a two-fold increased risk for type III endoleak for every 10-mm increase in preoperative TAAA diameter (hazard ratio, 2.00; 95% confidence interval, 1.08-3.72; P = .028) and a 1.5 increased risk every 12° increase of preoperative TVV angulation (hazard ratio, 1.47; 95% confidence interval, 1.02-2.10; P = .037).
Type III endoleaks from directional branches are a non-negligible complication after branched endovascular repair, with a relevant incidence. They tended to be clustered on specific patients, and aneurysm diameter and TVV angulation are strictly associated with the outcome. Different stent types on the same vessel should be avoided whenever possible. An intensified follow-up should be adopted for patients with large aneurysms, implanted with first-generation BeGraft, or who have been already diagnosed with type III endoleaks.
In Italy the fertility rate is very low, and an increasing number of patients are infertile and require treatments. The Italian Law concerning the safety of patient care, and the professional ...liability of health professionals, indicates that health professionals must comply with the recommendations set out in the guidelines developed by public and private bodies and institutions, as well as scientific societies and technical-scientific associations of the health professions, except for specific cases. Unfortunately, no guideline for the diagnosis and the management of infertility is currently available in Italy. In 2019, the Italian Society of Human Reproduction pointed out the need to produce Italian guidelines and subsequently approved the establishment of a multidisciplinary and multiprofessional working group (MMWG) to develop such a guideline. The MMWG was representative of 5 scientific societies, one national federation of professional orders, 3 citizens' and patients' associations, 5 professions (including lawyer, biologist, doctor, midwife, and psychologist), and 3 medical specialties (including medical genetics, obstetrics and gynecology, and urology). The MMWG chose to adapt a high-quality guideline to the Italian context instead of developing one from scratch. Using the Italian version of the Appraisal of Guidelines for Research and Evaluation II scoring system, the National Institute of Clinical Excellence guidelines were selected and adapted to the Italian context. The document was improved upon by incorporating comments and suggestions where needed. This study presents the process of adaptation and discusses the pros and cons of the often-neglected choice of adapting rather than developing new guidelines.
Affective Dependence (AD) is a problematic model of the love relationship that is becoming increasingly prevalent and evident in the context of couple relationships. Similarly, the phenomenon is ...being observed with growing frequency in daily clinical practice, making it increasingly necessary to identify treatment guidelines that can help clinicians in dealing with AD, while waiting for the literature to reach a consensus on its definition and nosographic profile. The main objective of this work is to explore the existing evidence of effectiveness regarding feasible treatments for Affective Dependence through a scoping review of the international literature carried out using the main scientific databases and following the PRISMA-ScR (PRISMA Extension for Scoping Reviews) guidelines. Seven studies were included in this review, and the results show that several pharmaceuticals, as well as different types of individual and group therapies, are proposed as treatment plans for AD. However, there is a lack of clinical trials that can verify the efficacy of the AD treatments reported so far in the literature. Some reflections that may help to distinguish a “healthy” addiction from a dysfunctional or markedly pathological one are considered alongside potential prevention perspectives.
The emergency represented by the COVID-19 pandemic represents a new challenge for clinicians who deal with autoimmune diseases because of patients undergoing immunosuppressive therapy. Few cases of ...Multiple Sclerosis (MS) patients receiving ocrelizumab who contracted COVID-19 with a benign course have recently been published.
We present the case of a MS patient with mild COVID-19 who developed SARS-CoV-2 specific IgA without IgG ten weeks after infection. Patients on B-cell depleting drugs have a reduced antibody immune response to viral neoantigens. A relative sparing of mucosal-associated lymphoid tissues (MALT) could be responsible for IgA response in our patient.
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