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Abstract: Fe48-at.%Al alloy were implanted with 50 keV H+ ions to the fluence of 3×1016 and 1×1018/cm2 at room temperature. Positron annihilation Doppler broadening and lifetime measurements for these alloys have been carried out using slow positron beam apparatus with an energy range of 0.2 to 30.2 keV. The positron annihilation S-parameter decreased by H+ ion irradiation. Also the positron lifetimes for hydrogen deposited region in the alloy decreased by the irradiation. These results show that implanted H atoms were trapped by vacancy type defects. [Copyright &y& Elsevier]

In internal parasitism, the respiration strategy within the host's body is as essential as evading attack from the host's immune system. Tachinid flies are parasitoids of terrestrial arthropods, mostly insects, during their larval stage. To obtain oxygen while living in the host body, they build a cylindrical structure known as the respiratory funnel at the aperture opened by the tachinid larva on the host integument or trachea. These funnels can be divided morphologically into sheath and cone types. Previous research on sheath-type funnels revealed that they are derived from the encapsulating substance produced by the host's immune system. In contrast, the cone-type funnels cover part of the body of the larval tachinid and may be constructed independently from the host immune system. To determine the mechanisms of cone-type funnel formation, histological observations were carried out on Gymnosoma rotundatum (L.) (Diptera: Tachinidae), which possesses this type of funnel. The respiratory funnel of G. rotundatum was found to be derived from the tube-shaped faeces wrapped with the peritrophic membrane and excreted by the fly larva, not from host tissue or haemocytes. Additionally, secretory glands putatively involved in the funnel formation were discovered around the larval anal plate of G. rotundatum . A comparison of funnel types within Tachinidae revealed that Phasiinae and Dexiinae have cone-type funnels, which may be created by the same mechanism as in G. rotundatum . These new findings suggest that funnel formation that does not use the host immune system is relevant to tachinid phylogeny.

A nondestructive detection method for internal Li-metal plating in lithium-ion batteries is essential to improve their lifetime. Here, we demonstrate a direct Li-metal detection technology that focuses on electromagnetic behaviour. Through an interdisciplinary approach combining the ionic behaviour of electrochemical reactions at the negative electrode and the electromagnetic behaviour of electrons based on Maxwell's equations, we find that internal Li-metal plating can be detected by the decrease in real part of the impedance at high-frequency. This finding enables simpler diagnostics when compared to data-driven analysis because we can correlate a direct response from the electronic behaviour to the metallic material property rather changes in the ionic behaviour. We test this response using commercial Li-ion batteries subject to extremely fast charging conditions to induce Li-metal plating. From this, we develop a battery sensor that detects and monitors the cycle-by-cycle growth of Li-metal plating. This work not only contributes to advancing future Li-ion battery development but may also serve as a tool for Li-metal plating monitoring in real-field applications to increase the useable lifetime of Li-ion batteries and to prevent detrimental Li-metal plating., (© 2023. The Author(s).)

Prior to 2020, healthcare professionals in the United States already had high rate of burnout. Since 2020, the COVID-19 pandemic created an urgent need for public health measures to effectively mitigate its negative health impacts. Despite these measures including vaccination, masking, handwashing, and physical distancing, people continue to be affected by post-COVID conditions (PCC) or newly acquired infections. Promoting one's well-being and self-care, especially the methods that promote one's relaxation and immune functions will serve as valuable tools among all healthcare practitioners and educators. For example, Kanpumasatsu, a skin rubdown using a dry towel, is simple to instruct, safe, and a cost-containing self-care approach that has the potential to promote relaxation and improve one's immune functions. At the present moment, the evidence is limited and the mechanism of how kanpumasatsu improves immune functions has not been clearly documented. However, this author postulates this superficial massage causes the skin to stretch and enhances the lymphatic flow beneath the skin in a mechanism similar to that of lymphatic drainage massage. While the limited evidence of the health benefits of kanpumasatsu is available today, there is a potential for creating and enhancing instructional resources, conducting research and practice through awareness of kanpumasatsu among interprofessional educators and practitioners as a pilot self-care program to prevent burnout., (© 2023 Elsevier Inc. All rights reserved.)

We present a case report of transient global amnesia (TGA) after vaccinating the third dose of coronavirus disease-19 (COVID-19). A 65-year-old Japanese woman presented with TGA after her third vaccination, which spontaneously resolved. This article aims to facilitate the clinicians' understanding that TGA could occur after the COVID-19 vaccination in the COVID-19 global outbreak., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Katsuki et al.)

In this study, the effects of charge/discharge cycling on the thermal stability of LiNi 0.8 Co 0.1 Mn 0.1 O 2 , a high-Ni cathode material, are systematically investigated. X-ray diffraction measurements show that there is almost no change in the bulk structure of the cathode after cycling. However, X-ray absorption fine structure measurements indicate that Ni in the surface layer is reduced and stable rock-salt structures are formed. Differential scanning calorimetry (DSC) measurements show that the heat generation at the lowest temperature, which can trigger thermal runaway in batteries that use high-Ni cathodes, decreases significantly with the formation of rock-salt structures on the active material surface. This finding indicates that the rock-salt layer on the surface enhances the thermal stability of a high-Ni cathode. The change in the total heat generation with degradation, indicated by DSC measurements, is similar to that in the K-edge of Ni (i.e., the Ni valency), suggesting a strong correlation between the heat generation and crystal structure changes during cycling.

Cerebral aneurysm and mother artery assessment after clipping is essential to evaluate aneurysm remnant, regrowth, and clip slippage. Usually, cerebral angiography and contrast-enhanced computed tomography angiography (CTA) are used for the evaluation, but they have the side effect of contrast medium and are time-consuming. Time-of-flight magnetic resonance angiography (TOF-MRA) is a non-invasive and fast modality, but clip-induced artifacts limit the signal near the metal clip. Recent ultrashort echo time (UTE)-MRA reduces metal artifacts but its availability is still low worldwide. Therefore, we developed a modified TOF-MRA sequence, named short TE-MRA, using Optima MR 360 1.5T Advance (GE Healthcare Life Sciences, Buckinghamshire, UK). It could describe the artery near the clip using general MRA equipment without recent UTE-MRA technology. We present a subarachnoid hemorrhage patient who underwent short TE-MRA about a year after clipping for the aneurysms at the bilateral internal carotid arteries. Short TE-MRA described the left internal carotid, middle cerebral, and anterior cerebral arteries. The right middle and anterior cerebral arteries were described, but the right internal carotid artery was not. Normal TOF-MRA could not describe them. Without recent UTE-MRA technology, short TE-MRA might be an alternative method for evaluating the artery near the clip. Short TE-MRA can be performed by general MRA equipment with a little time, so it may be helpful until UTE-MRA is widely used. Further research is needed on whether short TE-MRA can describe the aneurysm remnant, regrowth, and clip slippage up to the clinically useful level., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Higo et al.)

Transient ischemia produces postischemic tingling sensation. Ischemia also produces nerve conduction block that may modulate spinal neural circuits. In the present study, reduced mechanical thresholds for hindpaw-withdrawal reflex were found in mice after transient hindpaw ischemia, which was produced by a high pressure applied around the hindpaw for 30 min. The reduction in the threshold was blocked by spinal application of LY354740, a specific agonist of group II metabotropic glutamate receptors. Neural activities in the spinal cord and the primary somatosensory cortex (S1) were investigated using activity-dependent changes in endogenous fluorescence derived from mitochondrial flavoproteins. Ischemic treatment induced potentiation of the ipsilateral spinal and contralateral S1 responses to hindpaw stimulation. Both types of potentiation were blocked by spinal application of LY354740. The contralateral S1 responses, abolished by lesioning the ipsilateral dorsal column, reappeared after ischemic treatment, indicating that postischemic tingling sensation reflects a sensory modality shift from tactile sensation to nociception in the spinal cord. Changes in neural responses were investigated during ischemic treatment in the contralateral spinal cord and the ipsilateral S1. Potentiation already appeared during ischemic treatment for 30 min. The present findings suggest that the postischemic potentiation shares spinal mechanisms, at least in part, with neuropathic pain.

Mice navigate nearby space using their vision and whiskers, and young mice learn to integrate these heterogeneous inputs in perceptual space. We found that cortical responses were depressed in the primary visual cortex of young mice after wearing a monocular prism. This depression was uniformly observed in the primary visual cortex and was eliminated by whisker trimming or lesions in the posterior parietal cortex. Compensatory visual map shifts of responses elicited via the eye that had worn the prism were also observed. As a result, cortical responses elicited via each eye were clearly separated when a visual stimulus was placed in front of the mice. A comparison of response areas before and after prism wearing indicated that the map shifts were produced by depression with spatial eccentricity. Visual map shifts based on whisker-guided cues may serve as a model for investigating the cellular and molecular mechanisms underlying higher sensory integration in the mammalian brain., (Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.)

Avulsion of spinal nerve roots in the brachial plexus (BP) can be repaired by crossing nerve transfer via a nerve graft to connect injured nerve ends to the BP contralateral to the lesioned side. Sensory recovery in these patients suggests that the contralateral primary somatosensory cortex (S1) is activated by afferent inputs that bypassed to the contralateral BP. To confirm this hypothesis, the present study visualized cortical activity after crossing nerve transfer in mice through the use of transcranial flavoprotein fluorescence imaging. In naïve mice, vibratory stimuli applied to the forepaw elicited localized fluorescence responses in the S1 contralateral to the stimulated side, with almost no activity in the ipsilateral S1. Four weeks after crossing nerve transfer, forepaw stimulation in the injured and repaired side resulted in cortical responses only in the S1 ipsilateral to the stimulated side. At eight weeks after crossing nerve transfer, forepaw stimulation resulted in S1 cortical responses of both hemispheres. These cortical responses were abolished by cutting the nerve graft used for repair. Exposure of the ipsilateral S1 to blue laser light suppressed cortical responses in the ipsilateral S1, as well as in the contralateral S1, suggesting that ipsilateral responses propagated to the contralateral S1 via cortico-cortical pathways. Direct high-frequency stimulation of the ipsilateral S1 in combination with forepaw stimulation acutely induced S1 bilateral cortical representation of the forepaw area in naïve mice. Cortical responses in the contralateral S1 after crossing nerve transfer were reduced in cortex-restricted heterotypic GluN1 (NMDAR1) knockout mice. Functional bilateral cortical representation was not clearly observed in genetically manipulated mice with impaired cortico-cortical pathways between S1 of both hemispheres. Taken together, these findings strongly suggest that activity-dependent potentiation of cortico-cortical pathways has a critical role for sensory recovery in patients after crossing nerve transfer.

We investigated nociceptive cortical responses using transcranial flavoprotein fluorescence imaging in anesthetized mice with capsaicin-induced allodynia. Tactile stimuli applied to the hindpaw produced fluorescence increases in the contralateral somatosensory cortex of naïve mice. Lesioning of the ipsilateral dorsal column in the spinal cord abolished most of the cortical responses. However, the responses to the same tactile stimuli appeared again after capsaicin was injected into the hindpaw. The capsaicin treatment reduced the thresholds of the hindpaw withdrawal responses. These findings strongly suggest that the responses to tactile stimuli in the lesioned mice after capsaicin injection represented nociceptive cortical responses., (Copyright © 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)

Human vitamin D3 hydroxylase (CYP24) catalyzes the inactivation of 1alpha,25-dihydroxyvitamin D3 (calcitriol), which exerts antiproliferative effects. CYP24 has been reported to be overexpressed in various cancers in which microRNA levels are dysregulated. In silico analysis identified a potential miR-125b recognition element (MRE125b) in the 3'-untranslated region of human CYP24 mRNA. We investigated whether CYP24 is regulated by miR-125b. In luciferase assays using a reporter plasmid containing MRE125b, transfection of the antisense oligonucleotide (AsO) for miR-125b increased the reporter activity in KGN cells, and transfection of precursor miR-125b decreased the reporter activity in MCF-7 cells. The endogenous CYP24 protein level was also increased by AsO for miR-125b in KGN cells and was decreased by precursor miR-125b in MCF-7 cells. These results suggested that human CYP24 is regulated by miR-125b. Immunohistochemical analysis revealed that the CYP24 protein levels in human breast cancer were higher than in adjacent normal tissues, without an accompanying CYP24 mRNA increase. On the other hand, the expression levels of miR-125b in cancer tissues were significantly (P < 0.0005) lower than those in normal tissues. It is noteworthy that the CYP24 protein levels in cancer tissues were inversely associated with the cancer/normal ratios of the miR-125b levels, indicating that the decreased miR-125b levels in breast cancer tissues would be one of the causes of the high CYP24 protein expression. In conclusion, this study clearly demonstrates that miR-125b post-transcriptionally regulates the CYP24, which serves as a possible mechanism for the high CYP24 expression in cancer tissues.

Most of the biological effects of 1alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) are elicited by the binding to vitamin D receptor (VDR), which regulates gene expression. Earlier studies reported no correlation between the VDR protein and mRNA levels, suggesting the involvement of posttranscriptional regulation. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression through translational repression or mRNA degradation. A potential miR-125b recognition element (MRE125b) was identified in the 3'-untranslated region of human VDR mRNA. We investigated whether VDR is regulated by miR-125b. In luciferase assays using a plasmid containing the MRE125b, the antisense oligonucleotide for miR-125b significantly increased (130% of control) the reporter activity in KGN cells, whereas the precursor for miR-125b significantly decreased (40% of control) the reporter activity in MCF-7 cells, suggesting that miR-125b functionally recognized the MRE125b. By electrophoretic mobility shift assays, it was demonstrated that the overexpression of miR-125b significantly decreased the endogenous VDR protein level in MCF-7 cells to 40% of control. 1,25(OH)(2)D(3) drastically induced the CYP24 mRNA level in MCF-7 cells, but the induction was markedly attenuated by the overexpression of miR-125b. In addition, the antiproliferative effects of 1,25(OH)(2)D(3) in MCF-7 cells were significantly abolished by the overexpression of miR-125b. These results suggest that the endogenous VDR level was repressed by miR-125b. In conclusion, we found that miR-125b posttranscriptionally regulated human VDR. Since the miR-125b level is known to be downregulated in cancer, such a decrease may result in the upregulation of VDR in cancer and augmentation of the antitumor effects of 1,25(OH)(2)D(3)., (2009 UICC)

Objective: To evaluate the effects of genetic polymorphisms of drug metabolizing enzymes on the pharmacokinetics of cyclophosphamide and its active metabolite, 4-hydroxycyclophosphamide, and on the pharmacodynamics., Experimental Design: One hundred and three Japanese patients with malignant lymphoma or breast cancer treated with cyclophosphamide (500-750 mg/m) participated in this study. The plasma concentrations of cyclophosphamide and 4-hydroxycyclophosphamide were determined by high-performance liquid chromatography, and pharmacokinetic parameters were calculated. The genotypes of CYP2B6, CYP2C19, CYP3A4, CYP3A5, ALDH1A1, GST genes were determined by allele-specific polymerase chain reaction or polymerase chain reaction-restriction-fragment length polymorphism., Results: A large interindividual difference (54-fold) was observed in the area under the curve ratio of 4-hydroxycyclophosphamide/cyclophosphamide calculated as the metabolic index. We first proved that leukocytopenia and neutropenia were significantly (P<0.01) related to the area under the curve of 4-hydroxycyclophosphamide. We found that the homozygotes of CYP2B6*6 (Q172H and K262R) showed significantly (P<0.05) higher clearance and shorter half-life of cyclophosphamide than heterozygotes and homozygotes of CYP2B6*1. The small sample size, however, limited the impact. On the other hand, it was clearly demonstrated that the patients possessing the single nucleotide polymorphisms of the CYP2B6 gene, g.-2320T>C, g.-750T>C (5'-flanking region), g.15582C>T (intron 3), or g.18492T>C (intron 5), had significantly lower area under the curve ratios of 4-hydroxycyclophosphamide/cyclophosphamide, indicating a decreased cyclophosphamide 4-hydroxylation. Of particular importance was the finding that leukocytopenia was significantly related to the single nucleotide polymorphisms g.-2320T>C, g.-750T>C, and g.18492T>C in CYP2B6 gene, which are highly linked. No relationship was observed between the pharmacokinetics of cyclophosphamide or 4-hydroxycyclophosphamide and genetic polymorphisms of the other enzymes., Conclusions: We clarified that the single nucleotide polymorphisms in the promoter region or introns in the CYP2B6 affect the potency of cyclophosphamide activation to 4-hydroxycyclophosphamide. This information would be valuable for predicting adverse reactions and the clinical efficacy of cyclophosphamide.

Estrogen receptor alpha (ERalpha) is a ligand-inducible transcription factor that mediates the biological effects of estrogens and antiestrogens. Many point mutations in the human ERalpha gene have been reported to be associated with breast cancer, endometrial cancer, and psychiatric diseases. However, functional analyses for most mutants with amino acid changes are still lacking. In the present study, to investigate the effects of point mutations on the function, gel-shift assays and luciferase assays were performed for eight kinds of mutated ERalpha proteins, including a single nucleotide change of C207G (N69K), G478T (G160C), T887C (L296P), A908G (K303R), C926T (S309F), A1058T (E353V), A1186G (M396V), and G1231deletion (411fsX7). The mutated ERalpha expression plasmids were constructed by site-directed mutagenesis. With gel-shift assays using in vitro translated ERalpha proteins, binding to the consensus estrogen response element (ERE) was observed for the mutated ERalpha proteins except ERalpha (G160C) and ERalpha (411fsX7), the binding of which was comparable with that of the wild type. Western blot analyses showed that ERalpha (G160C) could not be efficiently translated with the in vitro transcription/translation system and that ERalpha (411fsX7) produced a truncated protein. To investigate the transactivation potency, wild-type or mutated ERalpha expression plasmids were co-transfected with pGL3-3EREc38 reporter plasmid into human breast adenocarcinoma MDA-MB-435 cells. The concentration-response curves (10pM-100nM E2) of the mutant ERalpha proteins except ERalpha (E353V) and ERalpha (411fsX7) were similar to that of wild-type ERalpha. However, at a low level of E2 (100pM), the mutants ERalpha (N69K), ERalpha (L296P), ERalpha (S309F), and ERalpha (M396V) showed a significant decrease of transactivation compared with that of the wild-type ERalpha. The mutants ERalpha (E353V) and ERalpha (411fsX7) did not show responsiveness to E2 and antiestrogens, 4-hydroxytamoxifen (4OHT) and ICI 182,780. The mutant ERalpha (S309F) showed decreased responsiveness for the antiestrogenicity of 4OHT. In conclusion, we found that some of the naturally occurring human ERalpha mutants with amino acid changes may have an altered responsiveness to estrogen and antiestrogens.