Treatment chronic macular edema in Vogt-Koyanagi Harada syndrome with dexamethasone intravitreal implant: description of three case

Purpose: To report our experience with dexamethasone intravitreal implant (Ozurdex, DEX implant) in the chronic cystic macular edema (ME )with Vogt-Koyanagi-Harada (VKH) Syndrome. Method: A retrospective chart review of three patients with (VKH) treated with sustained-release dexamethasone 0.7 mg intravitreal implant was performed.Complete ophthalmic examination included: best corrected visual acuity; ocular tonometry, were also evaluated signs of inflammatory activity of the anterior segment with biomicroscopy slit-lamp, and posterior segment with fundus biomiocrosopy, fundus photography and fluorescein angiography; measurement of macular morphology and thickness, optical with coherence tomography; and tolerability of the implant. Mean follow-up time post-injection was 6 months. All three eyes received 1Ozurdex implants during the follow-up period. The duration of effect of the implant was 4 to 6 months. No serious ocular or systemic adverse events were noted during the follow-up period. Results: In all three eyes, were observed a remarkable decrease ME, in angiographic and OCT , following placement intravitreal DEX implant Conclusions: The DEX implant 0.7 mg may be an effective treatment option for reduction ME in VGT, met the primary efficacy endpoint for improvement in visual acuity (VA) and safety profile was also acceptabl

Automated vehicles and the rethinking of mobility and cities

The project CityMobil2 has carried out a forward-looking exercise to investigate a lternative cybermobility scenarios, including both niche and large-market innovations, and their impacts on European cities and their transport systems. The paper describes the current status of and main trends in automated vehicles, a preliminary vision of the future city with mobility supported mainly by automated vehicles, and freight distribution. The expected positive impacts derive from the development of car sharing, the reduction of space required for parking vehicles, the possibilities for older people or those with disabilities to use cars, the enhancement of safety, and the improvement of efficiency of the transport system

Proteome characterization of a human urothelial cell line resistant to the bladder carcinogen 4-aminobiphenyl

<p>Abstract</p> <p>Background</p> <p>The aromatic amine 4-aminobiphenyl (4-ABP) is an environmental and occupational contaminant known to be a major etiological agent of human bladder cancer. 4-ABP metabolites are able to form DNA adducts that may induce mutations and initiate bladder carcinogenesis. Cells exposed to 4-ABP may develop resistance to the carcinogen. The aim of the present study was to detect and identify proteins whose expression is altered in the bladder carcinoma RT112 sub-lines selected for acquired resistance to 4-ABP, in order to disentangle the mechanisms.</p> <p>Results</p> <p>Differential proteome analysis of cell lysates showed an overall perturbation in cell metabolism and energy pathways in the 4-ABP-resistant human urothelial clones, with over-expression of membrane trafficking proteins such as annexin 2. The resistant clones had altered expression of many proteins linked directly (<it>i.e</it>. lamin A/C, programmed cell death 6 interacting protein) or indirectly (<it>i.e</it>. 94 kDa glucose-regulated protein, fatty acid-binding protein) to decreased apoptosis, suggesting that resistance to 4-ABP might be associated with low apoptotic activity.</p> <p>Conclusion</p> <p>Our data provide evidence that deregulation of apoptosis and membrane trafficking proteins might be strongly implicated in the selection of carcinogen resistant cells. Some of these proteins might have potential as biomarkers of resistance and cancer risk.</p

Occupational Medicine and Hygiene: Applied Research in Italy

The goal of Occupational Medicine and Hygiene is that of ensuring safety, health and well-being at workplaces, mainly assessing and preventing existing occupational risk. Scientific research in this field can provide useful arguments and further evidence upon which effective, efficient and sustainable policies and prevention measures have to be chosen and applied by the occupational physician in work-life. This paper summarizes four original studies, conducted in different professional settings across Italy, focusing critical items, such as stress and violence, biological risk and sleep hygiene. The knowledge obtained can be useful to orientate proper prevention programs aimed at improving workplace health

Predictive Role of Serum Thyroglobulin after Surgery and before Radioactive Iodine Therapy in Patients with Thyroid Carcinoma

Introduction: Thyroidectomy followed by radioactive iodine therapy (RAI) is the treatment of choice for differentiated thyroid carcinoma (DTC). Serum thyroglobulin (Tg) measurement has proved to be useful for predicting persistent and/or recurrent disease during follow-up of DTC patients. In our study, we evaluated the risk of disease recurrence in patients with papillary thyroid carcinoma (PTC), who were treated with thyroidectomy and RAI, by measuring serum Tg at different time-points: at least 40 days after surgery, in euthyroidism with TSH &lt; 1.5 and usually 30 days before RAI (Tg−30), on the day of RAI (Tg0), and seven days after RAI (Tg+7). Methods: One hundred and twenty-nine patients with PTC were enrolled in this retrospective study. All patients were treated with 131I for thyroid remnant ablation. Disease relapse (nodal disease or distant disease) during at least 36 months follow-up was evaluated by serum measurements of Tg, TSH, AbTg at different time points and by imaging techniques (neck ultrasonography, 131I-whole body scan (WBS) after Thyrogen® stimulation). Typically, patients were assessed at 3, 6, 12, 18, 24, and 36 months after RAI. We classified patients in five groups: (i) those who developed nodal disease (ND), (ii) those who developed distant disease (DD), (iii) those with biochemical indeterminate response and minimal residual thyroid tissue (R), (iv) those with no evidence of structural or biochemical disease + intermediate ATA risk (NED-I), and (v) those with no evidence of structural or biochemical disease + low ATA risk (NED-L). ROC curves for Tg were generated to find potential discriminating cutoffs of Tg values in all patients’ groups. Results: A total of 15 out of 129 patients (11.63%) developed nodal disease and 5 (3.88%) distant metastases, during the follow-up. We found that Tg−30 (with suppressed TSH) has the same sensitivity and specificity than Tg0 (with stimulated TSH), and it is slightly better than Tg+7, which can be influenced by the size of the residual thyroid tissue. Conclusion: Serum Tg−30 value, measured in euthyroidism 30 days before RAI, is a reliable prognostic factor to predict future nodal or distant disease, thus allowing to plan the most appropriate therapy and follow-up

Light-Triggered Trafficking to the Cell Nucleus of a Cationic Polyamidoamine Functionalized with Ruthenium Complexes

Strategies for endosomal escape and access to the cell nucleus are highly sought for nanocarriers to deliver their load efficiently following endocytosis. In this work, we have studied the uptake and intracellular trafficking of a polycationic polyamidoamine endowed with a luminescent Ru complex, Ru-PhenAN, that shows unique trafficking to the cell nucleus. Live cell imaging confirmed the capacity of this polymer to access the nucleus, excluding artefacts due to cell fixation, and clarified that the mechanism of escape is light-triggered and relies on the presence of the Ru complexes and their capacity to absorb light and act as photosensitizers for singlet oxygen production. These results open up the possibility to use polyamidoamineruthenium complexes for targeted light-triggered delivery of genetic material or drugs to the cytosol and nucleus

Star-Related Lipid Transfer Protein 10 (STARD10): A Novel Key Player in Alcohol-Induced Breast Cancer Progression

Background: Ethanol abuse promotes breast cancer development, metastasis and recurrence stimulating mammary tumorigenesis by mechanisms that remain unclear. Normally, 35% of breast cancer is Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2)-positive that predisposes to poor prognosis and relapse, while ethanol drinking leads to invasion of their ERBB2 positive cells triggering the phosphorylation status of mitogen-activated protein kinase. StAR-related lipid transfer protein 10 (STARD10) is a lipid transporter of phosphatidylcholine (PC) and phosphatidylethanolamine (PE); changes on membrane composition of PC and PE occur before the morphological tumorigenic events. Interestingly, STARD10 has been described to be highly expressed in 35–40% of ERBB2-positive breast cancers. In this study, we demonstrate that ethanol administration promotes STARD10 and ERBB2 expression that is significantly associated with increased cell malignancy and aggressiveness. Material and methods: We investigated the effect of ethanol on STARD10-ERBB2 cross-talk in breast cancer cells, MMTV-neu transgenic mice and in clinical ERBB2-positive breast cancer specimens with Western Blotting and Real-time PCR. We also examined the effects of their knockdown and overexpression on transient transfected breast cancer cells using promoter activity, MTT, cell migration, calcium and membrane fluidity assays in vitro. Results: Ethanol administration induces STARD10 and ERBB2 expression in vitro and in vivo. ERBB2 overexpression causes an increase in STARD10 expression, while overexpression of ERBB2’s downstream targets, p65, c-MYC, c-FOS or c-JUN induces STARD10 promoter activity, correlative of enhanced ERBB2 function. Ethanol and STARD10-mediated cellular membrane fluidity and intracellular calcium concentration impact ERBB2 signaling pathway as evaluated by enhanced p65 nuclear translocation and binding to both ERBB2 and STARD10 promoters. Conclusion: Our finding proved that STARD10 and ERBB2 positively regulate each other’s expression and function. Taken together, our data demonstrate that ethanol can modulate ERBB2’s function in breast cancer via a novel interplay with STARD10

HIV-1 tat protein enters dysfunctional endothelial cells via integrins and renders them permissive to virus replication

Previous work has shown that the Tat protein of Human Immunodeficiency Virus (HIV)-1 is released by acutely infected cells in a biologically active form and enters dendritic cells upon the binding of its arginine-glycine-aspartic acid (RGD) domain to the α5β1, αvβ3, and αvβ5 integrins. The up-regulation/activation of these integrins occurs in endothelial cells exposed to inflammatory cytokines that are increased in HIV-infected individuals, leading to endothelial cell dysfunction. Here, we show that inflammatory cytokine-activated endothelial cells selectively bind and rapidly take up nano-micromolar concentrations of Tat, as determined by flow cytometry. Protein oxidation and low temperatures reduce Tat entry, suggesting a conformation- and energy-dependent process. Consistently, Tat entry is competed out by RGD-Tat peptides or integrin natural ligands, and it is blocked by anti-α5β1, -αvβ3, and -αvβ5 antibodies. Moreover, modelling-docking calculations identify a low-energy Tat-αvβ3 integrin complex in which Tat makes contacts with both the αv and β3 chains. It is noteworthy that internalized Tat induces HIV replication in inflammatory cytokine-treated, but not untreated, endothelial cells. Thus, endothelial cell dysfunction driven by inflammatory cytokines renders the vascular system a target of Tat, which makes endothelial cells permissive to HIV replication, adding a further layer of complexity to functionally cure and/or eradicate HIV infection

SARS-CoV-2 infection predicts larger infarct volume in patients with acute ischemic stroke

Background and purpose: Acute ischemic stroke (AIS) is a fearful complication of Coronavirus Disease-2019 (COVID-19). Aims of this study were to compare clinical/radiological characteristics, endothelial and coagulation dysfunction between acute ischemic stroke (AIS) patients with and without COVID-19 and to investigate if and how the SARS-CoV-2 spike protein (SP) was implicated in triggering platelet activation. Methods: We enrolled AIS patients with COVID-19 within 12 h from onset and compared them with an age- and sex-matched cohort of AIS controls without COVID-19. Neuroimaging studies were performed within 24 h. Blood samples were collected in a subset of 10 patients. Results: Of 39 AIS patients, 22 had COVID-19 and 17 did not. Admission levels of Factor VIII and von Willebrand factor antigen were significantly higher in COVID-19 patients and positively correlated with the infarct volume. In multivariate linear regression analyses, COVID-19 was an independent predictor of infarct volume (B 20.318, Beta 0.576, 95%CI 6.077-34.559; p = 0.011). SP was found in serum of 2 of the 10 examined COVID-19 patients. Platelets from healthy donors showed a similar degree of procoagulant activation induced by COVID-19 and non-COVID-19 patients' sera. The anti-SP and anti-FcγRIIA blocking antibodies had no effect in modulating platelet activity in both groups. Conclusions: SARS-CoV-2 infection seems to play a major role in endothelium activation and infarct volume extension during AIS