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This research explores a sustainable approach for fabricating high-performance nanodiamond composite (NDC) hard coatings for dry machining. Aiming to address limitations in conventional coatings, such as environmental concerns, restricted film thickness, and compromised performance. The study utilizes Coaxial Arc Plasma Deposition (CAPD), a clean and efficient technique, to deposit thick (10 μm) NDC films directly on WC−Co substrates without chemical etching. Compared to traditional Chemical Vapor Deposition (CVD), CAPD offers significant advantages: lower temperature deposition, faster growth rate, and precise control over film thickness and morphology. The resulting NDC films boast exceptional durability due to their unique nanostructure, diamond nanocrystallites embedded in an amorphous carbon matrix. The addition of Al-interlayers (100–500 nm thickness) optimizes film properties. The optimal interlayer at 100 nm thickness not only mitigates the catalytic effects of Co but also enhances film hardness (50.4–58 GPa), Young's modulus (516–613.75 GPa), and adhesion (13–18.5 N) compared to films without an interlayer. Notably, the 100 nm Al-interlayer triples the deposition rate to 3.3 μm/h, achieving the desired thickness for effective hard coatings. The high density of grain boundaries within the films allows for exceptional stress release, enabling this increased thickness. Furthermore, these grain boundaries and the graphitic phase contribute to the film's superior tribological performance – a low coefficient of friction (0.1) and minimal wear rate (1.5 × 10⁻7 mm³/N⋅m) under dry machining conditions. These findings demonstrate the immense potential of CAPD-deposited NDC films as a sustainable alternative for advanced cutting tools, promoting environmental responsibility, economic viability, and energy efficiency.

The interaction between bubbles and tissues (bone and fat) in ultrasound and the mechanism of drug transport accompanied by bubble collapse were investigated numerically by using the ghost fluid methods with zonal grids. A parameter defined by the ratio of t0 to ts which is proportional to the ratio of bubble radius to wavelength, where t0 is the bubble collapse time and ts is the period of an incident pressure wave, was used to characterize the relationship between the incident pressure waveform and the bubble collapse. It was found that the bubble collapse near a tissue surface was classified into three types by considering the penetration of liquid jet and bubble blobs into the tissues. The transport process of matter (imaginary drug) distributed around the bubble surface was calculated with the bubble collapse. The results showed that the mechanism of matter transport due to bubble collapse was summarized as follows. First, both the shock wave by the liquid jet impact on the bubble surface and the rebound shock wave lead to the depression of the tissue wall, and the matter is transported with the vortex flow due to liquid jet formation. Then, the bubble penetrates into the depression, increasing the amount of matter transported into the tissue. The bubble collapse and the matter transport in the bone wall case were compared with those in the fat wall case. Although the maximum wall pressure was higher in the bone case, the amount of matter transported inside the tissue was higher in the fat case. This was caused by the difference in the acoustic impedance between both tissues: the large acoustic impedance of bone induced the reflection of the incident wave, leading to the superposition of the incident wave and the reflection wave that contributed to the acceleration of bubble collapse. Since the stiffer property of bone suppressed the development of the vortex flow and the bubble growth inside the tissue, a larger circulation existed inside the fat, which contributed to the advection of the matter, resulting in a higher concentration of matter inside the fat than inside the bone.

Abstract Background Neurological symptoms and radiographic abnormalities may remain in a small proportion of patients with metronidazole-induced encephalopathy (MIE). Although experimental animal models of MIE have suggested a Wernicke’s encephalopathy-like pathology, little is known about the histopathological features of MIE. Here we report the first autopsy case of irreversible MIE. Case presentation A 72-year-old Japanese woman with pancreatic neuroendocrine tumour and metastatic tumours in the liver developed intraabdominal bleeding from a hepatic abscess. She was administered metronidazole for 79 days (1.5 g/day), which caused dysarthria followed by hand tremor and altered mental status. Brain magnetic resonance imaging at the time of onset revealed hyperintensities in the deep white matter of the bilateral parietal lobes and splenium of the corpus callosum on diffusion-weighted imaging (DWI) with reduced apparent diffusion coefficient (ADC) values. Despite the improvement of dysarthria and hand tremor, her cognition remained affected even after the withdrawal of metronidazole. She died of pancreatic neuroendocrine tumour at the age of 74 years. Histopathological examinations of the brain confirmed a combination of severe demyelination and moderate axonal degeneration, which corresponded to the regions showing abnormal signal intensities on DWI with reduced ADC values. There were no pathological findings suggestive of Wernicke’s encephalopathy in the brain. Conclusion We have demonstrated the clinical, radiographic and histopathological aspects of irreversible MIE. Hyperintensities on DWI with reduced ADC values in affected regions may indicate a poor clinical prognosis due to irreversible pathological damage.

Abstract Immune checkpoint inhibitors (ICIs) treatment can result in endocrine immune-related adverse events (irAEs), including pituitary dysfunction. Quick diagnosis of secondary adrenal insufficiency (AI) is challenging because no universal definition of ICI-induced secondary AI has been agreed. The aim of this study was to clarify the clinical features of ICI-induced secondary AI that can be used for screening in standard clinical practice. This retrospective study was performed using the medical records of patients who received ICIs at Hirosaki University Hospital between 1 September 2014 and 31 January 2021. Longitudinal clinical data of patients who developed AI were analyzed and compared with the data of thyroid irAEs. Regression analysis showed a significant correlation between ICI-induced secondary AI and absolute or relative eosinophil counts at pre-onset of AI, as well as differences or rate of increase in eosinophil counts at baseline and at pre-onset. Absolute eosinophil counts > 198.36/µL or relative eosinophil counts > 5.6% at pre-onset, and a difference of 65.25/µL or a rate of eosinophil count increase of 1.97 between the baseline and at pre-onset showed the best sensitivity and specificity. This is the first report to demonstrate that eosinophil counts can be a predictor of ICI-induced secondary AI.

Radioactive cesium (r-Cs) released from the 2011 Fukushima Daiichi Nuclear Power Plant attaches to vegetation/soil and is collected as municipal solid waste (MSW) for incineration, being concentrated in incineration ash (bottom ash [BA], fly ash [FA], and chelate-treated FA [TFA]). r-Cs in FA and TFA can easily leach upon contact with moisture. It is important to prevent further contamination, as r-Cs has negative effects on ecosystems and the human body. Naturally available clay minerals, considered effective for capturing r-Cs, are a good alternative. Here, we sampled ash from MSW incineration facilities in Fukushima in August 2016 and February 2017. We used energy dispersive X-ray fluorescence spectroscopy and Ge semiconductor detector to determine elemental composition and r-Cs concentration in the samples and conducted leaching tests. We also determined the extent of leaching suppression by zeolite, acidic clay, and vermiculite. Chloride contents and r-Cs leaching rates were higher in FA and TFA than in BA, regardless of the season. Prior direct addition and mixing of clay minerals (5 to 20 wt.%) effectively prevented r-Cs leaching. This study is the first to examine r-Cs leaching inhibition by clay mineral direct addition and mixing to MSW incineration ash.

Balloon pulmonary angioplasty (BPA) has been recognized as an alternative therapeutic approach for patients with inoperative chronic thromboembolic pulmonary hypertension and those with residual pulmonary hypertension after pulmonary endarterectomy. However, the safe and successful treatment rate for a total occlusion lesion (TOL) using BPA is low, mainly because vessels distal to the occlusion are invisible by angiogram. Here, we present the case of a 53-year-old woman with chronic thromboembolic pulmonary hypertension with successfully recanalization of a TOL by use of BPA with the aid of intracardiac echocardiography. The intracardiac echocardiography–assisted wire passage technique may be a promising method for safe and reliable TOL treatment using BPA. Résumé: Il est reconnu que l’angioplastie pulmonaire par ballonnet (APB) est une alternative thérapeutique chez les patients atteints d’hypertension pulmonaire thromboembolique chronique inopérable et chez les patients atteints d’hypertension pulmonaire résiduelle après l’endartériectomie pulmonaire. Toutefois, le taux d’innocuité et de réussite du traitement d’une occlusion totale (OT) à l’aide de l’APB est faible, principalement en raison de l’invisibilité des vaisseaux distaux de l’occlusion à l’angiographie. Dans cet article, nous présentons le cas d’une femme de 53 ans atteinte d’hypertension pulmonaire thromboembolique chez qui la recanalisation de l’OT par l’utilisation de l’APB à l’aide d’une échocardiographie intracardiaque a été réussie. La technique de passage du fil assistée par échocardiographie intracardiaque peut constituer une technique prometteuse pour traiter de façon sûre et fiable l’OT à l’aide de l’APB.

We present the case of a 22-year-old man who was diagnosed with tonsillitis and treated with antibiotics. Although the symptoms subsided, 1 week later, he presented with weakness in the lower limbs and was hospitalized. The weakness in the lower limbs worsened; he developed difficulty speaking and was transferred to our hospital. Laboratory tests showed a white blood cell count of 10,600/μL (24% atypical lymphocytes). Positive results were obtained for immunoglobulin M (IgM) antibody against Epstein-Barr virus (EBV) viral capsid antigen. EBV-deoxyribonucleic acid quantification in blood yielded positive results. Magnetic resonance imaging (MRI) revealed a hyperintensity in the spinal cord at the Th11 level of the lower spine on T2-weighted imaging (T2WI). In addition, T2WI and fluid-attenuated inversion recovery imaging showed hyperintense lesions on the right cerebral peduncle, bilateral thalami, posterior leg of the left internal capsule, and right corona radiata. We diagnosed acute disseminated encephalomyelitis (ADEM) with EBV and initiated steroid pulse therapy. Symptoms, along with the lesions seen on MRI, subsequently ameliorated. This case suggests that ADEM can be difficult to diagnose, but careful diagnosis is crucial since appropriate treatment is necessary to improve the symptoms.

Abstract Background Recent preclinical data suggest that androgen receptor (AR) signaling plays a significant role in subsets of breast cancer. Clinical trials testing AR-targeting therapies in breast cancer have been conducted. Assessment of AR-signal in breast cancer tissue maybe useful for treatment selections. Prostate specific antigen (PSA) is the product of an androgen-responsive gene. Serum PSA (sPSA) can be detected in women by a highly sensitive assay although the concentration is much lower than that observed in males. We investigated if sPSA reflects tumor biology, including AR signaling in breast cancer patients. Methods In this study, 132 healthy controls and 144 breast cancer patients were enrolled. sPSA was evaluated by the chemiluminescent enzyme immunoassay (CLEIA) method. Correlations between sPSA and the various clinicopathological factors were analyzed. Results In post-menopausal state, sPSA detection rate was significantly higher in breast cancer patients compared with controls (27.4% vs 11.3%: p = 0.0090), but not in the whole cohort (29.2% vs 25.8%: p = 0.5265) or pre-menopausal subgroup (37.0% vs 42.6%: p = 0.6231). In post-menopausal breast cancer cases, higher sPSA value was associated with clinic-pathological factors including the expression of AR protein in primary legion. In a correlation analysis of quantitative data limited to post-menopausal metastatic breast cancer (MBC), sPSA was positively, albeit weakly correlated with clinic-pathological features including serum testosterone levels and AR positivity. Conclusions Our data suggest that sPSA may reflect tumor biological properties including AR activity in post-menopausal breast cancer.

Background/Aims: The association of diastolic blood pressure (DBP) with incidence of chronic kidney disease (CKD) in the general population is not well examined. Methods: Using national health check-up database from 2008 to 2011 in the general Japanese population aged 39–74 years, we evaluated the association between DBP and incidence of CKD 2 years later in 127,954 participants without CKD. DBP was categorized by every 5 mm Hg from the lowest (100 mm Hg) and was further stratified into those with and without antihypertensive medications (BP meds). We calculated the OR for estimating adjusted risk of incident CKD using logistic regression model. Results: Participants were 62% female and 25.9% with BP meds, mean age of 76 years with estimated glomerular filtration rate of 78.2 ± 13.4 and DBP of 76 ± 11 mm Hg. Two years later, 12,379 (9.7%) developed CKD. Compared to DBP 60–64 mm Hg without BP meds as reference, multivariate analysis showed no difference in CKD risk at any DBP category among those without BP meds. However, in those with BP meds, risk increased according to lower DBP from 95 to 60 mm Hg (p for trend 0.05) with OR 1.51 (95% CI 1.14–1.99) in DBP

Abstract Background The pathobiology of rheumatoid arthritis (RA) is similar to that of periodontitis in that proinflammatory cytokines play an important pathologic role. There is evidence to suggest that inhibitors of tumor necrosis factor (TNF) and interleukin-6 (IL-6) receptor for the treatment of RA ameliorated periodontal inflammation. However, no study has evaluated the effect of tofacitinib, an oral Janus kinase inhibitor for the treatment of RA, on periodontitis. Case presentation The present report cases are 51- and 43-year-old non-smoking women with RA who demonstrated localized moderate chronic periodontitis. Both cases showed improvement in the periodontal inflammatory condition after 3 months of tofacitinib therapy, although the teeth count and supragingival bacterial plaque level were relatively unchanged. Improvements were also observed in the serum levels of IL-6 in both cases as well as in the serum levels of TNF-α and anti-cyclic citrullinated peptide immunoglobulin G in one case and of rheumatoid factor and matrix metalloproteinase-3 in the other case. Patients who received tofacitinib exhibited an inconsistent clinical response, likely due to the low disease activity of RA at the start of the administration. Conclusions These are the first reported cases in which tofacitinib may have a beneficial effect on periodontitis. However, more research is required to understand the relationship between periodontitis and tofacitinib therapy.

Background: Graft-versus host disease (GVHD) is a complication of stem cell transplantation associated with significant morbidity and mortality. Non-specific immune-suppression, the mainstay of treatment, may result in immune-surveillance dysfunction and disease recurrence. Methods: We created humanised mice model for chronic GVHD (cGVHD) by injecting cord blood (CB)-derived human CD34+CD38−CD45RA− haematopoietic stem/progenitor cells (HSPCs) into hIL-6 transgenic NOD/SCID/Il2rgKO (NSG) newborns, and compared GVHD progression with NSG newborns receiving CB CD34− cells mimicking acute GVHD. We characterised human immune cell subsets, target organ infiltration, T-cell repertoire (TCR) and transcriptome in the humanised mice. Findings: In cGVHD humanised mice, we found activation of T cells in the spleen, lung, liver, and skin, activation of macrophages in lung and liver, and loss of appendages in skin, obstruction of bronchioles in lung and portal fibrosis in liver recapitulating cGVHD. Acute GVHD humanised mice showed activation of T cells with skewed TCR repertoire without significant macrophage activation. Interpretation: Using humanised mouse models, we demonstrated distinct immune mechanisms contributing acute and chronic GVHD. In cGVHD model, co-activation of human HSPC-derived macrophages and T cells educated in the recipient thymus contributed to delayed onset, multi-organ disease. In acute GVHD model, mature human T cells contained in the graft resulted in rapid disease progression. These humanised mouse models may facilitate future development of new molecular medicine targeting GVHD. Keywords: Acute GVHD, Chronic GVHD, IL-6, Humanised mouse

Rett syndrome (RTT) is a neurodevelopmental disorder with X-linked dominant inheritance caused mainly by mutations in the methyl-CpG-binding protein 2 (MECP2) gene. The effects of various Mecp2 mutations have been extensively assessed in mouse models, but none adequately mimic the symptoms and pathological changes of RTT. In this study, we assessed the effects of Mecp2 gene deletion on female rats (Mecp2+/−) and found severe impairments in social behavior [at 8 weeks (w), 12 w, and 23 w of age], motor function [at 16 w and 26 w], and spatial cognition [at 29 w] as well as lower plasma insulin-like growth factor (but not brain-derived neurotrophic factor) and markedly reduced acetylcholine (30%–50%) in multiple brain regions compared to female Mecp2+/+ rats [at 29 w]. Alternatively, changes in brain monoamine levels were relatively small, in contrast to reports on mouse Mecp2 mutants. Female Mecp2-deficient rats express phenotypes resembling RTT and so may provide a robust model for future research on RTT pathobiology and treatment.