Target-Selective Drug Delivery through Liposomes Labeled with Oligobranched Neurotensin Peptides.

The structure and the in vitro behavior of liposomes filled with the cytotoxic drug doxorubicin (Doxo) and functionalized on the external surface with a branched moiety containing four copies of the 8-13 neurotensin (NT) peptide is reported. The new functionalized liposomes, DOPC-NT(4) Lys(C(18) )(2) , are obtained by co-aggregation of the DOPC phospholipid with a new synthetic amphiphilic molecule, NT(4) Lys(C(18) )(2) , which contains a lysine scaffold derivatized with a lipophilic moiety and a tetrabranched hydrophilic peptide, NT8-13, a neurotensin peptide fragment well known for its ability to mimic the neurotensin peptide in receptor binding ability. Dynamic light scattering measurements indicate a value for the hydrodynamic radius (RH) of 88.3±4.4 nm. The selective internalization and cytotoxicity of DOPC-NT(4) Lys(C(18) )(2) liposomes containing Doxo, as compared to pure DOPC liposomes, were tested in HT29 human colon adenocarcinoma and TE671 human rhabdomyosarcoma cells, both of which express neurotensin receptors. Peptide-functionalized liposomes show a clear advantage in comparison to pure DOPC liposomes with regard to drug internalization in both HT29 and TE671 tumor cells: FACS analysis indicates an increase in fluorescence signal of the NT(4) -liposomes, compared to the DOPC pure analogues, in both cell lines; cytotoxicity of DOPC-NT(4) Lys(C(18) )(2) -Doxo liposomes is increased four-fold with respect to DOPC-Doxo liposomes in both HT29 and TE671 cell lines. These effects could to be ascribed to the higher rate of internalization for DOPC-NT(4) Lys(C(18) )(2) -Doxo liposomes, due to stronger binding driven by a lower dissociation constant of the NT(4) -liposomes that bind the membrane onto a specific protein, in contrast to DOPC liposomes, which approach the plasma membrane unselectively

The Role of Eif6 in Skeletal Muscle Homeostasis Revealed by Endurance Training Co-expression Networks

Regular endurance training improves muscle oxidative capacity and reduces the risk of age-related disorders. Understanding the molecular networks underlying this phenomenon is crucial. Here, by exploiting the power of computational modeling, we show that endurance training induces profound changes in gene regulatory networks linking signaling and selective control of translation to energy metabolism and tissue remodeling. We discovered that knockdown of the mTOR-independent factor Eif6, which we predicted to be a key regulator of this process, affects mitochondrial respiration efficiency, ROS production, and exercise performance. Our work demonstrates the validity of a data-driven approach to understanding muscle homeostasis

Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin

Pathological processes involved in the initiation of rheumatoid synovitis remain unclear. We undertook the present study to identify immune and stromal processes that are present soon after the clinical onset of rheumatoid arthritis ( RA) by assessing a panel of T cell, macrophage, and stromal cell related cytokines and chemokines in the synovial fluid of patients with early synovitis. Synovial fluid was aspirated from inflamed joints of patients with inflammatory arthritis of duration 3 months or less, whose outcomes were subsequently determined by follow up. For comparison, synovial fluid was aspirated from patients with acute crystal arthritis, established RA and osteoarthritis. Rheumatoid factor activity was blocked in the synovial fluid samples, and a panel of 23 cytokines and chemokines measured using a multiplex based system. Patients with early inflammatory arthritis who subsequently developed RA had a distinct but transient synovial fluid cytokine profile. The levels of a range of T cell, macrophage and stromal cell related cytokines ( e. g. IL-2, IL-4, IL-13, IL-17, IL-15, basic fibroblast growth factor and epidermal growth factor) were significantly elevated in these patients within 3 months after symptom onset, as compared with early arthritis patients who did not develop RA. In addition, this profile was no longer present in established RA. In contrast, patients with non-rheumatoid persistent synovitis exhibited elevated levels of interferon-gamma at initiation. Early synovitis destined to develop into RA is thus characterized by a distinct and transient synovial fluid cytokine profile. The cytokines present in the early rheumatoid lesion suggest that this response is likely to influence the microenvironment required for persistent RA

SAERMA: Stacked Autoencoder Rule Mining Algorithm for the Interpretation of Epistatic Interactions in GWAS for Extreme Obesity

One of the most important challenges in the analysis of high-throughput genetic data is the development of efficient computational methods to identify statistically significant Single Nucleotide Polymorphisms (SNPs). Genome-wide association studies (GWAS) use single-locus analysis where each SNP is independently tested for association with phenotypes. The limitation with this approach, however, is its inability to explain genetic variation in complex diseases. Alternative approaches are required to model the intricate relationships between SNPs. Our proposed approach extends GWAS by combining deep learning stacked autoencoders (SAEs) and association rule mining (ARM) to identify epistatic interactions between SNPs. Following traditional GWAS quality control and association analysis, the most significant SNPs are selected and used in the subsequent analysis to investigate epistasis. SAERMA controls the classification results produced in the final fully connected multi-layer feedforward artificial neural network (MLP) by manipulating the interestingness measures, support and confidence, in the rule generation process. The best classification results were achieved with 204 SNPs compressed to 100 units (77% AUC, 77% SE, 68% SP, 53% Gini, logloss=0.58, and MSE=0.20), although it was possible to achieve 73% AUC (77% SE, 63% SP, 45% Gini, logloss=0.62, and MSE=0.21) with 50 hidden units - both supported by close model interpretation

Catheter inversion during cavotricuspid isthmus catheter ablation: the new shaft visualization catheter reduces fluoroscopy use

Aims: Catheter ablation (CA) is the choice therapy of cavotricuspid isthmus (CTI) atrial flutter. The aim of this study was to describe our approach to improve the CTI ablation using a zero-fluoroscopy (ZF). The procedural difficulties could be related to anatomical characteristics of the CTI. Methods: One hundred eighty-eight patients that performed CA of CTI were retrospectively and consecutively evaluated between 2017 and 2019. The studied population was divided into two groups. Eighty-eight patients who were undergone CA using ablation catheter without shaft visualization catheter (NSV) were Group 1. One hundred patients were undergone CA using ablation catheter with a shaft visualization (SV); they were Group 2. The catheter was looped at the Eustachian ridge after 200 seconds of radiofrequencies (RF) without elimination of local electrogram. Results: A conduction line block of CTI was obtained in all patients of Group 2 using a ZF approach. In 16 patients of Group 1, the catheter inversion was obtained using fluoroscopy to avoid damages during its loop. In Group 2, a complete CTI block was obtained with a catheter inversion approach in ten patients without fluoroscopy, visualizing the shaft and the tip of the ablation catheter on the electroanatomic (EAM) map. In the overall population studied the use of SV had a linear correlation with the ZF approach (r =.629; P <.001). The duration of RF was lower in Group 2 than in Group 1 (Group 1: 27.8 ± 6.3 vs Group 2: 15.6 ± 7.2 minutes; P <.01). The procedure time between two groups was lower in Group 2 than in Group 1 (Group 1: 58.4 ± 22.4 vs Group 2: 42.2 ± 15.7 minutes; P <.01). No differences between two groups were documented regarding success and complications. Conclusions: The visualization of the shaft's catheter on the EAM permitted the catheter inversion safely in order to overcome some complex CTI anatomy and obtain bidirectional block. The SV reduced procedure time, RF applications and fluoroscopy exposition during CTI ablation. © 2021 The Author

Platelet aggregation is affected by nitrosothiols in patients with chronic hepatitis: in vivo and in vitro studies

AIM: To investigate the relationship among the number of platelets and plasma levels of S-nitrosothiols (S-NO), nitrite, total non-protein SH (NPSH), glutathione (GSH), cysteine (CYS), malondialdehyde (MDA), 4-hydroxininenal (4HNE), tumor necrosis factor-alpha (TNFalpha) and interleukin (IL)-6 in patients with chronic hepatitis C (CH). METHODS: In vitro the aggregation of platelets derived from controls and CH patients was evaluated before and after the addition of adenosine diphosphate (ADP) and collagen, both in basal conditions and after incubation with nitrosoglutathione (GSNO). RESULTS: In vivo, S-NO plasma levels increased significantly in CH patients and they were significantly directly correlated with platelet numbers. Patients with platelet counts 150000/microL. In vitro, the ADP and collagen aggregation time was increased in platelets from patients and not from controls; in addition, platelets from CH patients but not from controls also showed a latency time after exposure to collagen

Are periodontitis and psoriasis associated? A pre-clinical murine model

Aim: To investigate the bidirectional influence between periodontitis and psoriasis, using the respective experimental models of ligature- and imiquimod-induced diseases on murine models. Materials and Methods: Thirty-two C57/BL6J mice were randomly allocated to four experimental groups: control (P- Pso-), ligature-induced periodontitis (P+ Pso-), imiquimod-induced psoriasis (P- Pso+) and periodontitis and psoriasis (P+ Pso+). Samples (maxilla, dorsal skin and blood) were harvested immediately after death. Measures of periodontitis (distance between the cemento-enamel junction and alveolar bone crest [CEJ-ABC] and the number of osteoclasts) and psoriasis (epidermal thickness and infiltrate cell [/0.03mm(2)]) severity as well as systemic inflammation (IL-6, IL-17A, TNF-alpha) were collected. Results: The P+ Pso+ group exhibited the most severe experimental periodontitis and psoriasis, with the highest values of CEJ-ABC, number of osteoclasts, epidermal thickness and infiltrate cells in the dorsal skin, as well as the highest blood cytokine concentration. The P+ Pso- group presented with higher cell infiltrate (/0.03mm(2)) compared to the control group (p <.05), while the P- Pso+ group showed substantially higher alveolar bone loss (CEJ-ABC) than the control group (p <.05). Conclusions: Experimental periodontitis may initiate and maintain psoriasiform skin inflammation and, vice versa, experimental psoriasis may contribute to the onset of periodontitis. In a combined model of the diseases, we propose a bidirectional association between periodontitis and psoriasis via systemic inflammation

2018 Top Trends in Academic Libraries

Every other year, the ACRL Research Planning and Review Committee produces a document on top trends in higher education as they relate to academic librarianship. Topics in this edition of ACRL Top Trends will be familiar to some readers who will hopefully learn of new materials to expand their knowledge. Other readers will be made aware of trends that are outside of their experience. This is the nature of trends in our current technological and educational environments: change is continual, but it affects different libraries at different rates. The 2018 top trends share several overarching themes, including the impact of market forces, technology, and the political environment on libraries

Detection of oesophageal course during left atrial catheter ablation

Background: Oesophageal changes and injuries were recorded after atrial fibrillation(AF) ablation procedures. The reduction of power in the posterior left atrial(LA) wall(closest to the oesophagus) and the monitoring of temperature in the oesophagus(OE) reduced oesophageal injuries. The intracardiac-echocardiography(ICE) with a Cartosound module provides two-dimensional imaging (2D) to assess detailed cardiac anatomy and its relationship with the OE. The aim of this study was to highlight the safety and feasibility of 3D-reconstruction of the oesophageal course in left atrial catheter ablation(CA) procedures without OE temperature probe or quadripolar catheter to guide ICE OE reconstruction. Methods: 180 patients(PT) underwent left atrial ablation. AF ablation were 125(69.5%); incisional left atrial tachycardias(IAFL) were 37(20.6%); left atrial tachycardias(LAT) were 19(10.6%). The LA and pulmonary vein anatomies were rendered by traditional electroanatomic mapping(EAM) and merged with an ICE anatomic map. In 109 PT ICE imaging was used to create a geometry of the OE(group A). A quadripolar catheter was used in 71 PT to show OE course associated to ICE(group B). Results: Ablation energy delivery was performed outside the broadest OE anatomy borders. The duration of procedures was longer in group B vs group A Fluoroscopy time was lower in Group A than Group B(Group A 7 ± 3.2 vs 19.2 ± 2.4 min; p < 0.01). Conclusions: OE monitoring with ICE is safe and feasible. Oesophageal anatomy is complex and variable. Many PT will have a broad oesophageal boundary, which increases the risk of untoward thermal injury during posterior LA ablation. ICE with 3D construction of the OE enhances border detection of the OE, and as such, should decrease the risk of oesophageal injury by improving avoidance strategies without intra-oesophageal catheter visualization