Magnetic nanoparticles: a strategy to target the choroidal layer in the posterior segment of the eye

Despite the higher rate of blindness due to population aging, minimally invasive and selective drug delivery to the eye still remains an open challenge, especially in the posterior segment. The retina, the retinal pigment epithelium (RPE) and the choroid are posterior segment cell layers, which may be affected by several diseases. In particular, damages to the choroid are associated with poor prognosis in the most severe pathologies. A drug delivery approach, able to target the choroid, is still missing. Recently, we demonstrated that intravitreally injected magnetic nanoparticles (MNP) are able to rapidly and persistently localise within the RPE in an autonomous manner. In this work we functionalised the MNP surface with the vascular endothelial growth factor, a bioactive molecule capable of transcytosis from the RPE towards more posterior layers. Such functionalisation successfully addressed the MNPs to the choroid, while MNP functionalised with a control polypeptide (poly-L-lysine) showed the same localisation pattern of the naked MNP particles. These data suggest that the combination of MNP with different bioactive molecules could represent a powerful strategy for cell-specific targeting of the eye posterior segment

General Health, Psychological Well-Being and Distress of Youth Immigrants in Italy

In seeking to ease the rehabilitation of refugees there has generally been a failure to take account of the complexity of the refugees’ experience of suffering and loss. In this their psychological and emotional well-being as well as the social and economic aspects of the question have frequently been of only peripheral concern, and the response to the psychological impact of violence has been primarily focused on the concept of Post-Traumatic Stress Disorder (PTSD). This approach assumes a pathological response to stress that is both universal across different cultures and centred on the potential of pathologizing coping strategies that might be essential not only for survival but also for psychological well-being

Approaches to Identify Pregnancy Failure in Buffalo Cows

Simple SummaryEmbryonic mortality and pregnancy failures still represent a major issue in domestic livestock production, particularly in dairy cattle. Despite the presence of extensive work in this research area, there is still no effective, accurate and practical method able to determine timing and viability of embryo specifically during early gestation. Indeed, technologies and techniques for predicting pregnancy success must continue to be developed. The aim of this work was to find the best strategy to diagnose pregnancy failures in buffalo cows in order to improve farm reproductive management. Among the methods compared in this study (ultrasonography, progesterone, PAGs), pregnancy-associated glycoproteins (PAGs) seem to be the best marker for predicting embryonic mortality between 25 and 40 days of gestation to be utilized as a diagnostic tool to improve reproductive management in buffalo farms.The aim of this work was to find the best strategy to diagnose pregnancy failures in buffalo. A total of 109 animals belonging to a buffalo herd subjected to a synchronization and artificial insemination (AI) program were enrolled in this study. Blood samples were collected at days 0, 14, 25, 28 and 40 after AI for the determination of progesterone (P4) and pregnancy-associated glycoproteins (PAGs) by the radioimmunoassay (RIA) method. Transrectal ultrasonography was performed on day 25, 28 and 40 after AI to monitor pregnancy. The animals included in the data analysis were assigned ex post in pregnant (n = 50) and mortality (n = 12) groups. By ultrasonography, the predictive sign of mortality was the heartbeat. At day 25, the PAGs concentration was significant in predicting embryonic mortality with respect to ultrasonography and P4, at the cut-off of 1.1 ng/mL. At day 28, either PAGs, at a cut-off of 2.2 ng/mL, or ultrasonography, with no detection of heartbeat, were highly predictive of embryonic mortality. PAGs were the best marker (p < 0.05) for predicting embryonic mortality between 25 and 40 days of gestation in buffalo. Its utilization as a diagnostic tool can influence management decisions in order to improve farm reproductive management

Interferon-Tau in Maternal Peripheral Blood and Its Relationship with Progesterone and Pregnancy-Associated Glycoproteins in the Early Phases of Gestation in Water Buffalo

The aim of this study was to investigate the interferon tau (IFNt) concentration in the peripheral maternal blood during the early phase of pregnancy in buffalo cows and improve the knowledge on the physiological importance of circulating IFNt, evaluating the possible interaction with pregnancy-associated glycoproteins (PAGs) and progesterone (P4). Blood samples were taken from buffalo cows on day 0 (day of AI), 7, 14, 18, 28, and 40 post insemination for the IFNt, PAG, and P4 analysis and to determine the IFNt mRNA expression. The animals were categorized ex post into Pregnant, Non-pregnant and Embryo mortality groups. The interferon value was influenced by group (p = 0.003), being always higher in pregnant buffalo cows than in non-pregnant ones, while the embryo mortality group showed intermediate values between those for pregnant and non-pregnant animals. The mRNA expression of IFNt was not influenced by groups or any time points. The regression analysis that included IFNt as the independent variable showed that PAGs, from day 18 (p < 0.01), and P4, from day 28 (p < 0.05), were positively associated with IFNt values. The close associations among IFNt, PAGs and P4 demonstrate that all three molecules work together for fetal–placental well-being and pregnancy support. Unfortunately, the great individual variability in circulating IFNt makes this analysis unsuitable for early pregnancy diagnosis

Neonatal isolated coronary artery dilatation: to treat (and how) or not to treat, that’s the question!

We describe the clinical presentation of a newborn, who received diagnosis of diffuse right coronary artery dilatation and a high origin of the same vessel, in the absence of intrauterine hypoxia or other identifiable causes of coronary artery ectasia. The relevance of the case is in the complex aetiology of congenital heart malformation. In addition, we also highlight the difficult therapeutic management of these patients, in lack of guidelines for newborn population

Echocardiographic nomograms for chamber diameters and areas in Caucasian children

BACKGROUND: Although a quantitative evaluation of cardiac chamber dimensions in pediatric echocardiography is often important, nomograms for these structures are limited. The aim of this study was to establish reliable echocardiographic nomograms of cardiac chamber diameters and areas in a wide population of children. METHODS: A total of 1,091 Caucasian Italian healthy children (age range, 0 days to 17 years; 44.8% female) with body surface areas (BSAs) ranging from 0.12 to 1.8 m(2) were prospectively enrolled. Twenty-two two-dimensional and M-mode measurements of atrial and ventricular chamber diameters and areas were performed. Models using linear, logarithmic, exponential, and square-root relationships were tested. Heteroscedasticity was tested by the White test and the Breusch-Pagan test. Age, weight, height, and BSA, calculated by the Haycock formula, were used as the independent variables in different analyses to predict the mean value of each echocardiographic measurement. The influence of various confounders, including gender, type of delivery, prematurity, and interobserver variability, was also evaluated. Structured Z scores were then computed. RESULTS: The Haycock formula provided the best fit and was used when presenting data as predicted values (mean ? 2 SDs) for a given BSA and within equations relating echocardiographic measurements to BSA. Confounders were not included in the final models, because they did not show significant effects for most of the measurements. CONCLUSIONS: Echocardiographic reference values are presented for chamber area and diameters, derived from a large population of healthy children. These data partly cover a gap in actual pediatric echocardiographic nomograms. Further studies are required to reinforce these data, as well as to evaluate other parameters and ethnicities

Left Ventricular Function, Epicardial Adipose Tissue, and Carotid Intima-Media Thickness in Children and Adolescents With Vertical HIV Infection.

BACKGROUND: Life expectancy of HIV patients has increased considerably as a result of antiretroviral therapy (ART), and cardiovascular (CV) disease has emerged as an important late concern. People with HIV infection could have an impaired systolic function; however data on diastolic function and markers of CV risk, such as epicardial adipose tissue (EAT) and intima-media thickness (IMT), are lacking. Aim of this study is to evaluate left ventricular function, EAT, and IMT in children and adolescents with vertically acquired HIV infection. METHODS: We enrolled 29 subjects on ART (13, 45% men; median age of 13.0, and interquartile range 9-18), and 29 age-matched controls. All patients and controls underwent echocardiographic evaluation, with study of the systolic and diastolic function and measurement of the EAT, and a carotid ultrasound study for IMT measurement. RESULTS: Comparing HIV-infected patients to healthy controls, we found a statistically significant increase of EAT and IMT (mean ± SD) (EAT: 3.16 ± 1.05 vs 1.24 ± 0.61 mm; P < 0.0001. IMT: 0.77 ± 0.15 vs 0.51 ± 0.11 mm; P < 0.0001), and a significant reduction of ejection fraction, evaluated with the biplane Simpson method (mean ± SD) (58.5% ± 6.66% vs 66% ± 4.24%; P = 0.029). These results are not related with age, gender, degree of lipodystrophy, dyslipidemia, hyperinsulinism, and ART duration or the use of single antiretroviral classes. CONCLUSIONS: Vertically infected HIV children and adolescents show an increased thickness of EAT and IMT, expression of potentially increased CV risk. They also show an impaired systolic function

Nuclear Inositides and Inositide-Dependent Signaling Pathways in Myelodysplastic Syndromes

Myelodysplastic syndromes (MDS) are a heterogeneous group of hematological malignancies characterized by peripheral blood cytopenia and abnormal myeloproliferation, as well as a variable risk of evolution into acute myeloid leukemia (AML). The nucleus is a highly organized organelle with several distinct domains where nuclear inositides localize to mediate essential cellular events. Nuclear inositides play a critical role in the modulation of erythropoiesis or myelopoiesis. Here, we briefly review the nuclear structure, the localization of inositides and their metabolic enzymes in subnuclear compartments, and the molecular aspects of nuclear inositides in MDS

Prognostic immune markers identifying patients with severe COVID-19 who respond to tocilizumab

Introduction: A growing number of evidences suggest that the combination of hyperinflammation, dysregulated T and B cell response and cytokine storm play a major role in the immunopathogenesis of severe COVID-19. IL-6 is one of the main pro-inflammatory cytokines and its levels are increased during SARS-CoV-2 infection. Several observational and randomized studies demonstrated that tocilizumab, an IL-6R blocker, improves survival in critically ill patients both in infectious disease and intensive care units. However, despite transforming the treatment options for COVID-19, IL-6R inhibition is still ineffective in a fraction of patients. Methods: In the present study, we investigated the impact of two doses of tocilizumab in patients with severe COVID-19 who responded or not to the treatment by analyzing a panel of cytokines, chemokines and other soluble factors, along with the composition of peripheral immune cells, paying a particular attention to T and B lymphocytes. Results: We observed that, in comparison with non-responders, those who responded to tocilizumab had different levels of several cytokines and different T and B cells proportions before starting therapy. Moreover, in these patients, tocilizumab was further able to modify the landscape of the aforementioned soluble molecules and cellular markers. Conclusions: We found that tocilizumab has pleiotropic effects and that clinical response to this drug remain heterogenous. Our data suggest that it is possible to identify patients who will respond to treatment and that the administration of tocilizumab is able to restore the immune balance through the re-establishment of different cell populations affected by SARS-COV-2 infection, highlighting the importance of temporal examination of the pathological features from the diagnosis