The melatonin metabolite N1‐acetyl‐5‐methoxykynuramine facilitates long‐term object memory in young and aging mice

Melatonin (MEL) has been reported to enhance cognitive processes, making it a potential treatment for cognitive decline. However, the role of MEL’s metabolites, N1‐acetyl‐N2‐formyl‐5‐methoxykynuramine (AFMK) and N1‐acetyl‐5‐methoxykynuramine (AMK), in these effects are unknown. The current study directly investigated the acute effects of systemic MEL, AFMK, and AMK on novel object recognition. We also analyzed MEL, AFMK, and AMK levels in hippocampus and temporal lobe containing the perirhinal cortex following systemic MEL and AMK treatment. AMK administered post‐training had a more potent effect on object memory than MEL and AFMK. AMK was also able to rescue age‐associated declines in memory impairments when object memory was tested up to 4 days following training. Results from administering AMK at varying times around the training trial and the metabolism time course in brain tissue suggest that AMK’s memory‐enhancing effects reflect memory consolidation. Furthermore, inhibiting the MEL‐to‐AMK metabolic pathway disrupted object memory at 24 hours post‐training, suggesting that endogenous AMK might play an important role in long‐term memory formation. This is the first study to report that AMK facilitates long‐term object memory performance in mice, and that MEL crosses the blood‐brain barrier and is immediately converted to AMK in brain tissue. Overall, these results support AMK as a potential therapeutic agent to improve or prevent memory decline.     

Cutting efficiency of diamond burs operated with electric high‐speed dental handpiece on zirconia

Zirconia‐based dental restorations are becoming used more commonly. However, limited attention has been given to the difficulties experienced, concerning cutting, in removing the restorations when needed. The aim of the present study was to compare the cutting efficiency of diamond burs, operated using an electric high‐speed dental handpiece, on zirconia (Zir) with those on lithium disilicate glass–ceramic (LD) and leucite glass–ceramic (L). In addition, evaluation of the cutting efficiency of diamond burs on Zir of different thicknesses was performed. Specimens of Zir were prepared with thicknesses of 0.5, 1.0, 2.0, and 4.0 mm, and specimens of LD and L were prepared with a thickness of 1.0 mm. Cutting tests were performed using diamond burs with super coarse (SC) and coarse (C) grains. The handpiece was operated at 150,000 rpm with a cutting force of 0.9 N. The results demonstrated that cutting of Zir took about 1.5‐ and 7‐fold longer than cutting of LD and L, respectively. The SC grains showed significantly higher cutting efficiency on Zir than the C grains. However, when the thickness of Zir increased, the cutting depth was significantly decreased. As it is suggested that cutting of zirconia is time consuming, this should be taken into consideration in advance when working with zirconia restorations.     

Antennae sense heat stress to inhibit mating and promote escaping in Drosophila females

Environmental stress is a major factor that affects courtship behavior and evolutionary fitness. Although mature virgin females of Drosophila melanogaster usually accept a courting male to mate, they may not mate under stressful conditions. Above the temperature optimal for mating (20–25?°C), copulation success of D. melanogaster declines with increasing temperature although we observed vigorous courtship attempts by males, and no copulation takes place at temperatures over 36?°C. We attempted to identify the sensory pathway for detecting heat threat that drives a female to escape rather than to engage in mating that detects hot temperature and suppresses courtship behavior. We found that the artificial activation of warmth-sensitive neurons (‘hot cells’) in the antennal arista of females completely abrogates female copulation success even at permissive temperatures below 32?°C. Moreover, mutational loss of the GR28b.d thermoreceptor protein caused females to copulate even at 36?°C. These results indicate that antennal hot cells provide the input channel for detecting the high ambient temperature in the control of virgin female mating under stressful conditions.     

Diffusion abnormalities of the corpus callosum in patients receiving bevacizumab for malignant brain tumors: suspected treatment toxicity

Bevacizumab has been reported to cause diffusion restriction in the tumor bed of patients with malignant gliomas. This study evaluated prolonged diffusion restriction, in the corpus callosum (CC), of patients with malignant brain tumors treated with bevacizumab. We retrospectively reviewed our database of patients treated with bevacizumab for malignant brain tumors looking for those with restricted diffusion in the CC. CC ADC ratio measurements were obtained prior to and following treatment. Correlation was made with biopsy (n = 3) and MR perfusion (n = 7) and PET (n = 4). The temporal evolution of these changes relative to therapy was examined with mixed effects regression analysis. Nine patients (eight malignant gliomas, one malignant meningioma) out of 146 patients were found to have developed areas of diffusion restriction in the CC. These areas tended to enlarge and coalesce over serial MRIs and persisted for up to 22 months. Hypoperfusion was demonstrated in MR perfusion in 7/7. PET was hypometabolic in all 4. Biopsy of the CC showed no tumor in 3/3. ADC ratio measurements indicated a significant overall effect of time (F(16,60) = 11.2; p < 0.0001), consistent with persistent diffusion restriction over the measured time periods. Bevacizumab causes prolonged diffusion restriction in the CC. The negative MR perfusion, FDG PET and histopathology suggest this is a toxicity of bevacizumab and not active tumor. Awareness of these changes can assist in patient care.