Impaired Sleep-Dependent Memory Consolidation in Pediatric Narcolepsy Type 1.

Study Objectives: Disrupted nighttime sleep (DNS) is common in pediatric Narcolepsy type 1, yet its cognitive impact is unknown. As N2 sleep spindles are necessary for sleep-dependent memory consolidation, we hypothesized that Narcolepsy Type 1 impairs memory consolidation via N2 sleep fragmentation and N2 sleep spindle alterations.

Methods: We trained 28 pediatric Narcolepsy Type 1 participants and 27 healthy controls (HC) on a spatial declarative memory task before a nocturnal in-lab polysomnogram and then gave them a cued recall test upon awakening in the morning.

Characterizing disrupted nighttime sleep and associated functional outcomes in youth with narcolepsy type 1.

Study Objectives: Disrupted nighttime sleep (DNS) and sleep instability are common in children and adolescents with Narcolepsy Type 1 (NT1), but optimal objective sleep measures have not been determined. We compared self-reported and objective sleep measures between young people with NT1 and healthy controls (HC) and test the hypotheses that the Wake/N1 Index is the best objective measure of perceived nocturnal wakings vs. other DNS measures reported in the literature and is associated with daytime functional problems.

Stereotactic body radiation therapy (SBRT) for prostate cancer: Improving treatment delivery efficiency and accuracy.

Purpose: In stereotactic body radiation therapy (SBRT) for prostate cancer, intrafraction motion is an important source of treatment uncertainty as it could not be completely smoothed through fractionation. Herein, we compared different arrangements and beam qualities for extreme hypofractionated treatments to minimize beam delivery time and so intrafractional errors.

Methods: A retrospective dataset of 11 patients was used.

A CT deep learning reconstruction algorithm: Image quality evaluation for brain protocol at decreasing dose indexes in comparison with FBP and statistical iterative reconstruction algorithms.

Purpose: To characterise the impact of Precise Image (PI) deep learning reconstruction algorithm on image quality, compared to filtered back-projection (FBP) and iDose iterative reconstruction for brain computed tomography (CT) phantom images.

Methods: Catphan-600 phantom was acquired with an Incisive CT scanner using a dedicated brain protocol, at six different dose levels (volume computed tomography dose index (CTDI): 7/14/29/49/56/67 mGy). Images were reconstructed using FBP, levels 2/5 of iDose, and PI algorithm (Sharper/Sharp/Standard/Smooth/Smoother).

Assessing the Spontaneous Spread of Climate-Adapted Woody Plants in an Extensively Maintained Collection Garden.

Climate change may strongly modify the habitat conditions for many woody plant species. Some species could disappear from their natural habitats and become endangered, while others could adapt well to the changed environmental conditions and continue to survive successfully or even proliferate more easily. A similar process can occur within the artificial urban environment as the hitherto popularly planted urban trees may suffer from the extremities of the urban climate.

Dosimetric characterization of a mobile accelerator dedicated for intraoperative radiation therapy: Monte Carlo simulations and experimental validation.

Purpose: This Technical Note validates previously published data about the dosimetry of the electron beams produced by a mobile accelerator dedicated for intraoperative radiation therapy (IORT). The evaluation of the directional response of a PTW microDiamond detector is presented together with a detailed analysis of the output factors (OFs) for bevelled applicators.

Methods: The OFs of the 6, 8, 10 and 12 MeV electron beams produced by a light intraoperative accelerator (LIAC, SIT, Italy) were measured in a commercial water phantom using the microDiamond.

Rapid Identification of Potential Drug Candidates from Multi-Million Compounds' Repositories. Combination of 2D Similarity Search with 3D Ligand/Structure Based Methods and In Vitro Screening.

Rapid in silico selection of target focused libraries from commercial repositories is an attractive and cost-effective approach in early drug discovery. If structures of active compounds are available, rapid 2D similarity search can be performed on multimillion compounds' databases. This approach can be combined with physico-chemical parameter and diversity filtering, bioisosteric replacements, and fragment-based approaches for performing a first round biological screening.

Prostaglandin E a postulated mediator of neurovascular coupling, at low concentrations dilates whereas at higher concentrations constricts human cerebral parenchymal arterioles.

There is considerable controversy regarding the vasoactive action of prostaglandin E (PGE). On the one hand, indirect evidence implicates that astrocytic release of PGE contributes to neurovascular coupling responses mediating functional hyperemia in the brain. On the other hand, overproduction of PGE was also reported to contribute to cerebral vasospasm associated with subarachnoid hemorrhage.

Design and Selection of Novel C1s Inhibitors by In Silico and In Vitro Approaches.

The complement system is associated with various diseases such as inflammation or auto-immune diseases. Complement-targeted drugs could provide novel therapeutic intervention against the above diseases. C1s, a serine protease, plays an important role in the CS and could be an attractive target since it blocks the system at an early stage of the complement cascade.

Improving Post-Operative Outcomes in Aged and Diabetic Obese Mice.

Due to their small size, high metabolic rate, and large surface to volume ratio, mice are a challenge to work with surgically and pre-operatively. Working with mice that are more susceptible to anesthetic agents, aged, or obese (e.g.

Improving the Patency of Jugular Vein Catheters in Sprague-Dawley Rats by Using an Antiseptic Nitrocellulose Coating.

Preclinical studies in animals often require frequent blood sampling over prolonged periods. A preferred method in rats is the implantation of a polyurethane catheter into the jugular vein, with heparinized glycerol as a lock solution. However, analysis of various biologic compounds (for example, microRNA) precludes the use of heparin.

The CD47-SIRPα signaling axis as an innate immune checkpoint in cancer.

Immune checkpoint inhibitors, including those targeting CTLA-4/B7 and the PD-1/PD-L1 inhibitory pathways, are now available for clinical use in cancer patients, with other interesting checkpoint inhibitors being currently in development. Most of these have the purpose to promote adaptive T cell-mediated immunity against cancer. Here, we review another checkpoint acting to potentiate the activity of innate immune cells towards cancer.

Epigenetic contribution of the myosin light chain kinase gene to the risk for acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a devastating clinical syndrome with a considerable case fatality rate (∼30%-40%). Health disparities exist with African descent (AD) subjects exhibiting greater mortality than European descent (ED) individuals. Myosin light chain kinase is encoded by MYLK, whose genetic variants are implicated in ARDS pathogenesis and may influence ARDS mortality.

Immunoreceptors on neutrophils.

Neutrophils play a critical role in the host defense against infection, and they are able to perform a variety of effector mechanisms for this purpose. However, there are also a number of pathological conditions, including autoimmunity and cancer, in which the activities of neutrophils can be harmful to the host. Thus the activities of neutrophils need to be tightly controlled.

Trichuris suis induces human non-classical patrolling monocytes via the mannose receptor and PKC: implications for multiple sclerosis.

Introduction: The inverse correlation between prevalence of auto-immune disorders like the chronic neuro-inflammatory disease multiple sclerosis (MS) and the occurrence of helminth (worm) infections, suggests that the helminth-trained immune system is protective against auto-immunity. As monocytes are regarded as crucial players in the pathogenesis of auto-immune diseases, we explored the hypothesis that these innate effector cells are prime targets for helminths to exert their immunomodulatory effects.

Results: Here we show that soluble products of the porcine nematode Trichuris suis (TsSP) are potent in changing the phenotype and function of human monocytes by skewing classical monocytes into anti-inflammatory patrolling cells, which exhibit reduced trans-endothelial migration capacity in an in vitro model of the blood-brain barrier.

SCAN database: facilitating integrative analyses of cytosine modification and expression QTL.

Functional annotation of genetic variants including single nucleotide polymorphisms (SNPs) and copy number variations (CNV) promises to greatly improve our understanding of human complex traits. Previous transcriptomic studies involving individuals from different global populations have investigated the genetic architecture of gene expression variation by mapping expression quantitative trait loci (eQTL). Functional interpretation of genome-wide association studies (GWAS) has identified enrichment of eQTL in top signals from GWAS of human complex traits.

Thrombocytosis of Liver Metastasis from Colorectal Cancer as Predictive Factor.

There is increasing evidence that thrombocytosis is associated with tumor invasion and metastasis formation. It was shown in several solid tumor types that thrombocytosis prognosticates cancer progression. The aim of this study was to evaluate preoperative thrombocytosis as a potential prognostic biomarker in isolated metastases, in patients with liver metastasis of colorectal cancer (mCRC).

Dectin-1 deficiency does not affect atherosclerosis development in mice.

Objective: Recent data suggest the involvement of dectin-1 in atherosclerosis through regulation of local reactive oxygen species production. The aim of the current study was to assess the effect of dectin-1 deficiency on atherosclerotic plaque development.

Methods: Using immunohistochemistry dectin-1 expression was observed on foamy macrophages in atherosclerotic lesions in mice.

PKCδ is dispensible for oxLDL uptake and foam cell formation by human and murine macrophages.

Aims: Uptake of oxidized lipoprotein particles (oxLDL) and foam cell formation by macrophages is one of the first steps in the development of atherosclerosis. Recently, protein kinase C δ (PKCδ) has been implicated as a regulator of oxLDL uptake and foam cell formation via down-regulation of PKCβ and scavenger receptors CD36 and SR-A expression. Here, we describe studies in which we have re-evaluated the role of PKCδ in oxLDL uptake and foam cell formation.

Quantitative characterization of the activation steps of mannan-binding lectin (MBL)-associated serine proteases (MASPs) points to the central role of MASP-1 in the initiation of the complement lectin pathway.

Mannan-binding lectin (MBL)-associated serine proteases, MASP-1 and MASP-2, have been thought to autoactivate when MBL/ficolin·MASP complexes bind to pathogens triggering the complement lectin pathway. Autoactivation of MASPs occurs in two steps: 1) zymogen autoactivation, when one proenzyme cleaves another proenzyme molecule of the same protease, and 2) autocatalytic activation, when the activated protease cleaves its own zymogen. Using recombinant catalytic fragments, we demonstrated that a stable proenzyme MASP-1 variant (R448Q) cleaved the inactive, catalytic site Ser-to-Ala variant (S646A).