Dynamic features of the selective pressure on the human immunodeficiency virus type 1 (HIV-1) gp120 CD4-binding site in a group of long term non progressor (LTNP) subjects.

Abstract The characteristics of intra-host human immunodeficiency virus type 1 (HIV-1) env evolution were evaluated in untreated HIV-1-infected subjects with different patterns of disease progression, including 2 normal progressor [NP], and 5 Long term non-progressor [LTNP] patients. High-resolution phylogenetic analysis of the C2-C5 env gene sequences of the replicating HIV-1 was performed in sequential samples collected over a 3–5 year period; overall, 301 HIV-1 genomic RNA sequences were amplified from plasma samples, cloned, sequenced and analyzed. Firstly, the evolutionary rate was calculated separately in the 3 codon positions. In all LTNPs, the 3rd codon mutation rate was equal or even lower than that observed at the 1st and 2nd positions (p = 0.016), thus suggesting strong ongoing positive selection. A Bayesian approach and a maximum-likelihood (ML) method were used to estimate the rate of virus evolution within each subject and to detect positively selected sites respectively. A great number of N-linked glycosylation sites under positive selection were identified in both NP and LTNP subjects. Viral sequences from 4 of the 5 LTNPs showed extensive positive selective pressure on the CD4-binding site (CD4bs). In addition, localized pressure in the area of the IgG-b12 epitope, a broad neutralizing human monoclonal antibody targeting the CD4bs, was documented in one LTNP subject, using a graphic colour grade 3-dimensional visualization. Overall, the data shown here documenting high selective pressure on the HIV-1 CD4bs of a group of LTNP subjects offers important insights for planning novel strategies for the immune control of HIV-1 infection.</p

Oral Feeding Competences of Healthy Preterm Infants: A Review

Background. With increasing sophistication and technology, survival rates hugely improved among preterm infants admitted to the neonatal intensive care unit. Nutrition and feeding remain a challenge and preterm infants are at high risk of encountering oral feeding difficulties. Objective. To determine what facts may impact on oral feeding readiness and competence and which kind of interventions should enhance oral feeding performance in preterm infants. Search Strategy. MEDILINE database was explored and articles relevant to this topic were collected starting from 2009 up to 2011. Main Results. Increasingly robust alertness prior to and during feeding does positively impact the infant's feeding Skills. The review found that oral and non-oral sensorimotor interventions, provided singly or in combination, shortened the transition time to independent oral feeding in preterm infants and that preterm infants who received a combined oral and sensorimotor intervention demonstrated more advanced nutritive sucking, suck-swallow and swallow-respiration coordination than those who received an oral or sensorimotor intervention singly

Deciphering ascending thoracic aortic aneurysm hemodynamics in relation to biomechanical properties

The degeneration of the arterial wall at the basis of the ascending thoracic aortic aneurysm (ATAA) is a complex multifactorial process, which may lead to clinical complications and, ultimately, death. Individual genetic, biological or hemodynamic factors are inadequate to explain the heterogeneity of ATAA development/progression mechanisms, thus stimulating the analysis of their complex interplay. Here the disruption of the hemodynamic environment in the ATAA is investigated integrating patient-specific computational hemodynamics, CT-based in vivo estimation of local aortic stiffness and advanced fluid mechanics methods of analysis. The final aims are (1) deciphering the ATAA spatiotemporal hemodynamic complexity and its link to near-wall topological features, and (2) identifying the existing links between arterial wall degeneration and hemodynamic insult. Technically, two methodologies are applied to computational hemodynamics data, the wall shear stress (WSS) topological skeleton analysis, and the Complex Networks theory. The same analysis was extended to the healthy aorta. As main findings of the study, we report that: (1) different spatiotemporal heterogeneity characterizes the ATAA and healthy hemodynamics, that markedly reflect on their WSS topological skeleton features; (2) a link (stronger than canonical WSS-based descriptors) emerges between the variation of contraction/expansion action exerted by WSS on the endothelium along the cardiac cycle, and ATAA wall stiffness. The findings of the study suggest the use of advanced methods for a deeper understanding of the hemodynamics disruption in ATAA, and candidate WSS topological skeleton features as promising indicators of local wall degeneration

Chemokines in hyperthyroidism

The term “hyperthyroidism” indicates a condition due to an exaggerate production of thyroid hormone; the most frequent cause is Graves’ disease (GD). We review cytokines and chemokines in hyperthyroidism, with a special focus in GD. In GD, recruited Th1 lymphocytes are responsible for enhanced IFN-γ and TNF-α production, which in turn stimulates Th1 chemokines release from thyrocytes, initiating and perpetuating the autoimmune process. Circulating levels of these chemokines are associated with the active phase of GD. Additional studies are necessary to investigate whether Th1 chemokines could be a novel therapeutic target in this disease

Rubin LSST observing strategies to maximize volume and uniformity coverage of Star Forming Regions in the Galactic Plane

A complete map of the youngest stellar populations of the Milky Way in the era of all-sky surveys, is one of the most challenging goals in modern astrophysics. The characterisation of the youngest stellar component is crucial not only for a global overview of the Milky Way structure, of the Galactic thin disk, and its spiral arms, but also for local studies. In fact, the identification of the star forming regions (SFRs) and the comparison with the environment in which they form are also fundamental to put them in the context of the surrounding giant molecular clouds and to understand still unknown physical mechanisms related to the star and planet formation processes. In 10 yrs of observations, Vera C. Rubin Legacy Survey of Space and Time (Rubin-LSST) will achieve an exquisite photometric depth that will allow us to significantly extend the volume within which we will be able to discover new SFRs and to enlarge the domain of a detailed knowledge of our own Galaxy. We describe here a metrics that estimates the total number of young stars with ages t < 10 Myr and masses >0.3M$_\odot$ that will be detected with the Rubin LSST observations in the gri bands at a 5 {\sigma} magnitude significance. We examine the results of our metrics adopting the most recent simulated Rubin-LSST survey strategies in order to evaluate the impact that different observing strategies might have on our science case.Comment: 11 pages, 5 figures, 1 table; accepted for publication in The Astrophysical Journal Supplement Serie

Exploring novel arterio-venous graft designs to reduce vascular access failure risk

Although arterio-venous grafts (AVGs) are the second best option as permanent vascular access for hemodialysis, this solution is still affected by a relevant failure rate associated with neointimal hyperplasia (IH), mainly located at the venous anastomosis, where abnormal hemodynamics occurs. In this study we use computational fluid dynamics (CFD) to investigate the impact of six innovative AVG designs on reducing the IH risk at the distal anastomosis in AVGs. Findings from simulations clearly show that using a helical shaped flow divider located in the venous side of the graft could assure a reduced hemodynamic risk of failure at the distal anastomosis, with a clinically irrelevant increase in pressure drop over the graft

Effectiveness and acceptability of psycho-education group intervention for people hospitalized in psychiatric wards and nurses

Objective: To assess effectiveness and acceptability of a Psycho-education Group Intervention (PGI) on a sample of patients admitted to a Psychiatric Inpatient Unit (PIU) and on ward nurses. Methods: Case-control study. PGI was delivered according to the model of Vendittelli and colleagues (2008). Male and female patients aged 18-70 were eligible. Cases attended the PGI, while controls did not. A 5-item ad hoc Likert-scale was used to record ward atmosphere. The Italian version of the Simple Feedback Question Form for people attending Cognitive Behaviour Therapy Group (SFQF-CBTG) was administered to each patient before discharge. The primary outcome was readmission rate after 6 months from discharge, secondary outcomes were ratings of ward atmosphere by nurses and feed-back from people hospitalized. All Statistics were performed with STATA 13.1. Results: Fifty-two patients were enrolled, 17 cases and 35 controls. No significant differences emerged in the primary outcome, though compulsory readmissions were noticeable only among controls. Ratings of ward atmosphere in relation to group activities did not differ. Seventeen SFQF-CBTG were filled in. Most cases reported at discharge to have found the group "helpful", stating that "they would attend it in the future again", and "group topics were not difficult". Conclusions: No evidence emerged in favour or against effectiveness of the PGI for patients and ward nurses, though the intervention was rated as acceptable and feasible

Immune and inflammatory cells in thyroid cancer microenvironment

A hallmark of cancer is the ability of tumor cells to avoid immune destruction. Activated immune cells in tumor microenvironment (TME) secrete proinflammatory cytokines and chemokines which foster the proliferation of tumor cells. Specific antigens expressed by cancer cells are recognized by the main actors of immune response that are involved in their elimination (immunosurveillance). By the recruitment of immunosuppressive cells, decreasing the tumor immunogenicity, or through other immunosuppressive mechanisms, tumors can impair the host immune cells within the TME and escape their surveillance. Within the TME, cells of the innate (e.g., macrophages, mast cells, neutrophils) and the adaptive (e.g., lymphocytes) immune responses are interconnected with epithelial cancer cells, fibroblasts, and endothelial cells via cytokines, chemokines, and adipocytokines. The molecular pattern of cytokines and chemokines has a key role and could explain the involvement of the immune system in tumor initiation and progression. Thyroid cancer-related inflammation is an important target for diagnostic procedures and novel therapeutic strategies. Anticancer immunotherapy, especially immune checkpoint inhibitors, unleashes the immune system and activates cytotoxic lymphocytes to kill cancer cells. A better knowledge of the molecular and immunological characteristics of TME will allow novel and more effective immunotherapeutic strategies in advanced thyroid cancer

Immunomodulation of CXCL10 secretion by hepatitis C virus: Could CXCL10 be a prognostic marker of chronic hepatitis C?

Chemokine (C-X-C motif) ligand (CXCL)10 and other CXCR3 chemokines are involved in the pathogenesis of acute and \u201cchronic hepatitis C virus (HCV) infection\u201d (CHC). Here, we review the scientific literature about HCV and CXCL10. The combination of circulating CXCL10 and single nucleotide polymorphisms (SNPs) in IL-28B can identify patients with acute HCV infection most likely to undergo spontaneous HCV clearance and those in need of early antiviral therapy. In CHC, the HCV and intrahepatic interferon- (IFN-) \u3b3 drive a raised CXCL10 expression by sinusoidal endothelium and hepatocytes, thereby inducing the recruitment of CXCR3-expressing T cells into the liver; thus, CXCL10 plays an important role in the development of necroinflammation and fibrosis. Increased CXCL10 was significantly associated with the presence of active vasculitis in HCV-associated cryoglobulinemia, or with autoimmune thyroiditis in CHC. Pretreatment CXCL10 levels are predictive of early virological response and sustained virological response (SVR) to IFN-\u3b1 and ribavirin and may be useful in the evaluation of candidates for therapy. The occurrence of SNPs adjacent to IL-28B (rs12979860, rs12980275, and rs8099917), and CXCL10 below 150 pg/mL, independently predicted the first phase viral decline and rapid virological response, which in turn independently predicted SVR. Directly acting antiviral agents-mediated clearance of HCV is associated with the loss of intrahepatic immune activation by IFN-\u3b1, associated by decreased levels of CXCL10. In conclusion, CXCL10 is an important marker of HCV clearance and successful therapy in CHC patients. Whether CXCL10 is a novel therapeutic target in CHC will be evaluated