Multi-centre evaluation of variation in cumulative dose assessment in reirradiation scenarios.

Background And Purpose: Safe reirradiation relies on assessment of cumulative doses to organs at risk (OARs) across multiple treatments. Different clinical pathways can result in inconsistent estimates. Here, we quantified the consistency of cumulative dose to OARs across multi-centre clinical pathways.

STING-Dependent Signaling in Microglia or Peripheral Immune Cells Orchestrates the Early Inflammatory Response and Influences Brain Injury Outcome.

While originally identified as an antiviral pathway, recent work has implicated that cyclic GMP-AMP-synthase-Stimulator of Interferon Genes (cGAS-STING) signaling is playing a critical role in the neuroinflammatory response to traumatic brain injury (TBI). STING activation results in a robust inflammatory response characterized by the production of inflammatory cytokines called interferons, as well as hundreds of interferon stimulated genes (ISGs). Global knock-out (KO) mice inhibiting this pathway display neuroprotection with evidence that this pathway is active days after injury; yet, the early neuroinflammatory events stimulated by STING signaling remain understudied.

Atypical Neurogenesis, Astrogliosis, and Excessive Hilar Interneuron Loss Are Associated with the Development of Post-Traumatic Epilepsy.

Background: Traumatic brain injury (TBI) remains a significant risk factor for post-traumatic epilepsy (PTE). The pathophysiological mechanisms underlying the injury-induced epileptogenesis are under investigation. The dentate gyrus-a structure that is highly susceptible to injury-has been implicated in the evolution of seizure development.

Amide-to-ester substitution as a stable alternative to N-methylation for increasing membrane permeability in cyclic peptides.

Naturally occurring peptides with high membrane permeability often have ester bonds on their backbones. However, the impact of amide-to-ester substitutions on the membrane permeability of peptides has not been directly evaluated. Here we report the effect of amide-to-ester substitutions on the membrane permeability and conformational ensemble of cyclic peptides related to membrane permeation.

The role of STING signaling in central nervous system infection and neuroinflammatory disease.

The cyclic guanosine monophosphate-adenosine monophosphate (GMP-AMP) synthase-Stimulator of Interferon Genes (cGAS-STING) pathway is a critical innate immune mechanism for detecting the presence of double-stranded DNA (dsDNA) and prompting a robust immune response. Canonical cGAS-STING activation occurs when cGAS, a predominantly cytosolic pattern recognition receptor, binds microbial DNA to promote STING activation. Upon STING activation, transcription factors enter the nucleus to cause the production of Type I interferons, inflammatory cytokines whose primary function is to prime the host for viral infection by producing a number of antiviral interferon-stimulated genes.

Monocyte proinflammatory phenotypic control by ephrin type A receptor 4 mediates neural tissue damage.

Circulating monocytes have emerged as key regulators of the neuroinflammatory milieu in a number of neuropathological disorders. Ephrin type A receptor 4 (Epha4) receptor tyrosine kinase, a prominent axon guidance molecule, has recently been implicated in the regulation of neuroinflammation. Using a mouse model of brain injury and a GFP BM chimeric approach, we found neuroprotection and a lack of significant motor deficits marked by reduced monocyte/macrophage cortical infiltration and an increased number of arginase-1+ cells in the absence of BM-derived Epha4.

Conditional Deletion of EphA4 on Cx3cr1-Expressing Microglia Fails to Influence Histopathological Outcome and Blood Brain Barrier Disruption Following Brain Injury.

Erythropoietin-producing human hepatocellular receptors play a major role in central nervous system injury. Preclinical and clinical studies revealed the upregulation of erythropoietin-producing human hepatocellular A4 (EphA4) receptors in the brain after acute traumatic brain injury. We have previously reported that Cx3cr1-expressing cells in the peri-lesion show high levels of EphA4 after the induction of controlled cortical impact (CCI) injury in mice.

Geometrically Diverse Lariat Peptide Scaffolds Reveal an Untapped Chemical Space of High Membrane Permeability.

Constrained, membrane-permeable peptides offer the possibility of engaging challenging intracellular targets. Structure-permeability relationships have been extensively studied in cyclic peptides whose backbones are cyclized from head to tail, like the membrane permeable and orally bioavailable natural product cyclosporine A. In contrast, the physicochemical properties of lariat peptides, which are cyclized from one of the termini onto a side chain, have received little attention.

Abrogation of atypical neurogenesis and vascular-derived EphA4 prevents repeated mild TBI-induced learning and memory impairments.

Brain injury resulting from repeated mild traumatic insult is associated with cognitive dysfunction and other chronic co-morbidities. The current study tested the effects of aberrant neurogenesis in a mouse model of repeated mild traumatic brain injury (rmTBI). Using Barnes Maze analysis, we found a significant reduction in spatial learning and memory at 24 days post-rmTBI compared to repeated sham (rSham) injury.

Using a neural network to predict deviations in mean heart dose during the treatment of left-sided deep inspiration breath hold patients.

Purpose: We investigated if a neural network could be used to predict the change in mean heart dose when a patient's heart deviates from its planned position during radiotherapy treatment.

Methods: Predictions were made based on parameters available at the time of treatment planning. The dose prescription, deep inspiration breath-hold (DIBH) amplitude, heart volume, lung volume, V90% and mean heart dose were used to predict the increase in dose to the heart when a shift towards the treatment field was undertaken.

Lactobacillus rescues postnatal neurobehavioral and microglial dysfunction in a model of maternal microbiome dysbiosis.

Increasing reports of pregnancy events leading to maternal microbiome dysbiosis (MMD) show strong correlates with atypical neurodevelopmental outcomes. However, the mechanism(s) driving microbiome-mediated behavioral dysfunction in offspring remain understudied. Here, we demonstrate the presence of a novel gut commensal bacterium strain, Lactobacillus murinus HU-1, was sufficient to rescue behavioral deficits and brain region-specific microglial activationobserved in MMD-reared murine offspring.

A Manganese Pre-Catalyst: Mild Reduction of Amides, Ketones, Aldehydes, and Esters.

A new (N-phosphinoamidinate)manganese complex is shown to be a useful pre-catalyst for the hydrosilative reduction of carbonyl compounds, and in most cases at room temperature. The Mn-catalyzed reduction of tertiary amides to tertiary amines, with a useful scope, is demonstrated for the first time by use of this catalyst, and is competitive with the most effective transition-metal catalysts known for such transformations. Ketones, aldehydes, and esters were also successfully reduced under mild conditions by using this new Mn catalyst.

Dehydrogenative B-H/C(sp )-H Benzylic Borylation within the Coordination Sphere of Platinum(II).

The first examples of stoichiometric dehydrogenative B-H/C(sp )-H benzylic borylation reactions, which are of relevance to catalytic methylarene (di)borylation, are reported. These unusual transformations involving a (κ -P,N)Pt(η -benzyl) complex, and either pinacolborane or catecholborane, proceed cleanly at room temperature. Density functional calculations suggest that borylation occurs via successive σ-bond metathesis steps, whereby a Pt -H intermediate engages in C(sp )-H bond activation-induced dehydrogenation.

Synthesis and Reactivity of a Neutral, Three-Coordinate Platinum(II) Complex Featuring Terminal Amido Ligation.

A crystallographically characterized three-coordinate, formally 14 electron Pt(II) complex 1 featuring terminal amido ligation is reported. Computational analysis revealed relatively weak π donation from the amide lone pair to platinum and supports a 14-electron assignment for 1. Stoichiometric reactivity studies confirmed the viability of net O-H and C-H addition across, as well as isonitrile insertion into, the terminal platinum-amido linkage of 1.

Automatic extraction of property norm-like data from large text corpora.

Traditional methods for deriving property-based representations of concepts from text have focused on either extracting only a subset of possible relation types, such as hyponymy/hypernymy (e.g., car is-a vehicle) or meronymy/metonymy (e.

(1S*,2R*,3S*,4R*,5R*)-5-Tetra-decyloxy-methyl-7-oxabicyclo-[2.2.1]heptane-2,3-dicarb-oxy-lic anhydride.

In the title compound, C23H38O5, the oxabicyclo-[2.2.1]heptane-2,3-dicarb-oxy-lic anhydride unit has a normal geometry and the tetra-decoxymethyl side chain is fully extended.

A method for the prediction of late organ-at-risk toxicity after radiotherapy of the prostate using equivalent uniform dose.

Purpose: To evaluate the predictive value of equivalent uniform doses (EUD) for late bladder and rectal toxicity after high-dose three-dimensional conformal radiation therapy (3D-CRT) to the prostate.

Materials And Methods: Using the method developed by Kutcher et al., EUDs for whole bladder and rectum were calculated from the dose-volume histograms of 180 patients with localized prostate cancer treated to 70-74 Gy with 3D-CRT.

A randomised comparison of two brachytherapy devices for the treatment of uterine cervical carcinoma.

Two brachytherapy applicators commonly used in the treatment of uterine cervical carcinoma, the Henschke shielded and Fletcher-Suit-Declos, were randomly and prospectively compared in vivo in 20 patients. Based on two-dimensional planning and the ICRU-38 bladder and rectal reference points, an advantage for the shielded Henschke applicator was demonstrated.

A dosimetric intercomparison of brachytherapy facilities in Ireland, Scotland and the North of England.

Background And Purpose: A dosimetric intercomparison of brachytherapy remote afterloading units in Ireland, Scotland and the North of England has been carried out involving 9 radiotherapy centres, and sampling 5 HDR and 6 LDR units.

Materials And Methods: Absolute calibrations have been performed in air on both HDR and LDR sources. The results are expressed in terms of a ratio of local to calibrated value.