Ketones Prevent Oxidative Impairment of Hippocampal Synaptic Integrity through K\u3csub\u3eATP\u3c/sub\u3e Channels

Dietary and metabolic therapies are increasingly being considered for a variety of neurological disorders, based in part on growing evidence for the neuroprotective properties of the ketogenic diet (KD) and ketones. Earlier, we demonstrated that ketones afford hippocampal synaptic protection against exogenous oxidative stress, but the mechanisms underlying these actions remain unclear. Recent studies have shown that ketones may modulate neuronal firing through interactions with ATP-sensitive potassium (KATP) channels. Here, we used a combination of electrophysiological, pharmacological, and biochemical assays to determine whether hippocampal synaptic protection by ketones is a consequence of KATP channel activation. Ketones dose-dependently reversed oxidative impairment of hippocampal synaptic integrity, neuronal viability, and bioenergetic capacity, and this action was mirrored by the KATP channel activator diazoxide. Inhibition of KATP channels reversed ketone-evoked hippocampal protection, and genetic ablation of the inwardly rectifying K+ channel subunit Kir6.2, a critical component of KATP channels, partially negated the synaptic protection afforded by ketones. This partial protection was completely reversed by co-application of the KATP blocker, 5-hydoxydecanoate (5HD). We conclude that, under conditions of oxidative injury, ketones induce synaptic protection in part through activation of KATP channels

Feasibility of low-dose CT with model-based iterative image reconstruction in follow-up of patients with testicular cancer.

Purpose: We examine the performance of pure model-based iterative reconstruction with reduced-dose CT in follow-up of patients with early-stage testicular cancer. Methods: Sixteen patients (mean age 35.6 ± 7.4 years) with stage I or II testicular cancer underwent conventional dose (CD) and low-dose (LD) CT acquisition during CT surveillance. LD data was reconstructed with model-based iterative reconstruction (LD–MBIR). Datasets were objectively and subjectively analysed at 8 anatomical levels. Two blinded clinical reads were compared to gold-standard assessment for diagnostic accuracy. Results: Mean radiation dose reduction of 67.1% was recorded. Mean dose measurements for LD–MBIR were: thorax – 66 ± 11 mGy cm (DLP), 1.0 ± 0.2 mSv (ED), 2.0 ± 0.4 mGy (SSDE); abdominopelvic – 128 ± 38 mGy cm (DLP), 1.9 ± 0.6 mSv (ED), 3.0 ± 0.6 mGy (SSDE). Objective noise and signal-to-noise ratio values were comparable between the CD and LD–MBIR images. LD–MBIR images were superior (p < 0.001) with regard to subjective noise, streak artefact, 2-plane contrast resolution, 2-plane spatial resolution and diagnostic acceptability. All patients were correctly categorised as positive, indeterminate or negative for metastatic disease by 2 readers on LD–MBIR and CD datasets. Conclusions: MBIR facilitated a 67% reduction in radiation dose whilst producing images that were comparable or superior to conventional dose studies without loss of diagnostic utility

Synthesis and styrene copolymerization of novel alkoxy ring-substituted isobutyl phenylcyanoacrylates

Novel alkoxy ring-substituted isobutyl phenylcyanoacrylates, RPhCH=C(CN)CO2CH2CH(CH3)2 (where R is 2-methoxy, 3-methoxy, 4-methoxy, 2-ethoxy, 3-ethoxy, 4-ethoxy, 4-propoxy, 4-butoxy, 4-hexyloxy) were prepared and copolymerized with styrene. The acrylates were synthesized by the piperidine catalyzed Knoevenagel condensation of ring-substituted benzaldehydes and isobutyl cyanoacetate and characterized by CHN elemental analysis, IR, 1H- and 13C-NMR. All the acrylates were copolymerized with styrene in solution with radical initiation (ABCN) at 70C. The composition of the copolymers was calculated from nitrogen analysis, and the structures were analyzed by IR, 1H and 13C-NMR. Thermal properties of the copolymers are characterized by DSC and TGA. Decomposition of the copolymers in nitrogen occurred in two steps, first in the 200-500ºC range with residue (1.8-3.3% wt.), which then decomposed in the 500-800ºC range