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Aims: Although right ventricular (RV) dysfunction is associated with adverse outcomes in tricuspid regurgitation (TR), the potential role of right atrial (RA) function is unknown. We aimed to investigate the relationship between RA function and clinical outcomes in patients with significant TR., Methods: This retrospective study included 169 outpatients with moderate or severe TR due to left-sided heart diseases who underwent transthoracic echocardiography between June 2020 and April 2023 (average age, 75 ± 10 years; male, 40%). Patients with atrial fibrillation were excluded from this study due to the inaccuracy of the evaluation using 2D speckle-tracking echocardiography. RA function was compared between patients with and without events, which were defined as all-cause mortality or hospitalization due to heart failure. RA function was calculated as RA global longitudinal strain (RAGLS) with the 2D speckle-tracking echocardiography., Results: During a median follow-up of 13 months, 19 patients had events (all-cause mortality: 14 cases, hospitalization due to heart failure: 5 cases). RAGLS was lower in patients with events than in those without events (13% ± 10% vs. 18% ± 9%, P = 0.02). When the patients were categorized into two groups [low RAGLS ≤ 16.2% vs. high RAGLS > 16.2%, high RA volume index (RAVI) ≥ 50 mL/m 2 vs. low RAVI < 50 mL/m 2 ], Kaplan-Meier curves showed that patients with low RAGLS had higher event rates than those with high RAGLS (log-rank test, P = 0.003). Patients with high RAVI had higher event rates than those with low RAVI (log-rank test, P < 0.001). In the multivariate Cox regression analysis, low RAGLS (≤16.2%) was significantly associated with events in a model that included RV dysfunction (RV fractional area change ≤ 35%) or high RAVI (≥50 mL/m 2 ) (hazard ratio: 4.55, 95% confidence interval: 1.51-13.71, P < 0.01; hazard ratio: 4.57, 95% confidence interval: 1.52-13.79, P < 0.01, respectively)., Conclusions: RAGLS is associated with all-cause mortality and hospitalization due to heart failure in patients with significant TR. Our results suggest that RA function is a sensitive marker for identifying the risk stratification of significant TR., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Purpose: Under-sampled scans with iterative reconstruction and high-frequency preserving transform (Us-IRHF) can increase the acquisition speed without degrading the image quality by recovering image information from under-sampled data. We investigate the clinical applicability of high spatial resolution magnetic resonance cholangiopancreatography (MRCP) images without extending the scanning time using Us-IRHF., Methods: A slit phantom was scanned with conventional- (without Us-IRHF), Us-IR- (without HF), and Us-IRHF scanning. The matrix size was 320 × 320 for Us-IR- and Us-IRHF- and 288 × 208 for conventional scanning. Modulation transfer function (MTF) focused on the 1.0 lp/cm gauge for each scanning was calculated. For clinical study we acquired respiratory-triggered 3D MRCP scans with and without Us-IRHF (U + -, U - MRCP) in 41 patients. The matrix size was 320 × 320 for U + - and 288 × 208 for U - MRCP. The acquisition time and the relative duct-to-periductal contrast ratios (RCs) for the right- and left intrahepatic bile-, the common bile-, and the main pancreatic duct were recorded. Visualization of each duct and overall image quality was scored on 5-point confidence scales. For visualization of each duct the score ranged from 1 (not visible) to 5 (visible with excellent details), for the image quality, it ranged from 1 (undiagnostic) to 5 (excellent). Superiority for the qualitative visualization score and non-inferiority for the RC values with prespecified margins were assessed., Results: Phantom study showed that compared to the conventional- and Us-IR (without HF) images, the MTF for the Us-IRHF image revealed the highest response. For clinical study, the mean acquisition time was 161 s for U + - and 165 s for U - MRCP. For all ducts, the RC value of U + MRCP was non-inferior to U - MRCP and the qualitative visualization score assigned to U + MRCP was superior to U - MRCP., Conclusion: Us-IRHF improved the image quality of high spatial resolution MRCP without extending the scanning time., (© 2024. The Author(s).)

The Nouabalé-Ndoki National Park (NNNP) in Republic of Congo has become a beacon for conservation in Central Africa. This manuscript documents the arrival of primatologists, the establishment of field stations and major discoveries in primate behavior and ecology. Field stations were strategically established to study primate behavior in a variety of different contexts from stationary platforms to forest follows of habituated groups. The implementation of new technologies and analyses have also been a hallmark of research at Ndoki. Scientists are shaping a new era in primatology at NNNP by building on past successes and promoting the next generation of Congolese conservationists to address environmental challenges. Results have proven crucial in discussions with government and industry and led to conservation gains such as the inclusion of the intact forests of the Goualougo and Djéké Triangles into the NNNP. The research stations have also become essential for developing a long-term certified sustainable international gorilla tourism program. Despite the many advancements for conservation such as increased protection of forests, development of internationally recognized protocols and large-scale capacity building initiatives, there are reasons for considerable concern in the near- and long-term for primates and their forest habitats in the Ndoki landscape. To address these concerns, we emphasize the long history of forming partnerships with local communities. We also discuss shared overlap featuring multicultural and environmental use of forest resources that is likely to be crucial in championing the conservation of the Ndoki forests for the next 25 years and beyond., (© 2024. The Author(s), under exclusive licence to Japan Monkey Centre.)

The delivery of functional molecules to the cell nucleus enables the visualization of nuclear function and the development of effective medical treatments. In this study, we successfully modified the Hoechst molecule, which is a well-documented nuclear-staining agent, using the strain-promoted azide-alkyne cycloaddition (SPAAC) reaction. We prepared Hoechst derivatives bearing an azide group (Hoe-N3) and characterized their SPAAC reactions in the presence of corresponding molecules with a dibenzylcyclooctyne unit (DBCO). The SPAAC reaction of Hoe-N3 with alkylamine bearing DBCO, fluorescent TAMRA, or Cy5 molecules bearing DBCO led to the formation of the coupling products Hoe-Amine, Hoe-TAMRA, and Hoe-Cy5, respectively. These Hoechst derivatives retained their DNA-binding properties. In addition, Hoe-TAMRA and Hoe-Cy5 exhibited properties of dual accumulation in the cell nucleus and mitochondria. Initial incubation of these molecules in living cells resulted in its accumulation in mitochondria, while after mitochondrial depolarization, it was smoothly released from mitochondria and translocated into the cell nucleus. Thus, mitochondrial depolarization could be monitored by measuring the emission of Hoe-TAMRA and Hoe-Cy5 at the cell nucleus., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Robotic surgery without contact-force feedback could be less safe, as forces exerted by the robot system may exceed tissue tolerance. This study aimed to evaluate the benefit of contact-force feedback., Methods: Nine junior and 11 senior surgeons performed two tasks using Saroa, a robotic surgical system with a force feedback function. In Task A, the participants estimated the order of stiffness of substances when feedback was on and off. In Task B, the effect of feedback on compression with a designated force (3 N) was assessed., Results: In Task A, the proportion of participants who correctly estimated the order of stiffness of the substances was similar when feedback was on and off. However, the median maximum force applied to the substances was significantly smaller when feedback was on than when it was off (5.0 vs. 6.9 N, p = .011), which was more obvious among the junior surgeons (5.0 vs. 7.7 N, p = .015) than among the senior surgeons (4.7 vs. 5.9 N, p = .288). In Task B, deviations from the designated force (3 N) for three substances were smaller when feedback was on (0, -0.1, and 0.7, respectively) than when it was off (-0.3, -0.5, and 1.3, respectively). Regarding the dispersion of the force to the substances, the interquartile range tended to be smaller with feedback; this trend was more obvious in the junior surgeons., Conclusion: With contact-force feedback, tissue stiffness could be estimated with a small force, particularly by the junior surgeons; specified force could be accurately applied to the tissue., (© 2024 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Third-party punishment (TPP) is an altruistic behavior or sense willing to punish transgressors as a third party not directly involved in the transgression. TPP is observed worldwide, regardless of tradition and culture, and is essential for morality in human society. Moreover, even preverbal infants display TPP-like judgement, suggesting that TPP is evolutionarily conserved and innate. Thus, it is possible that non-human animals display TPP-like behavior, although TPP has been said to be human-specific. We investigated whether or not male mature Wistar rats displayed TPP-like behaviors when they witnessed deadly aggression by an unknown aggressive mouse toward another unknown victim mouse. Normally reared rats did not display TPP-like behaviors, but rats reared with extensive affectionate handling by human caretakers as beloved pets contacted the unknown aggressive mice in a gentle manner leading to reduced aggression toward the unknown victim mice, even when the aggressive mice fought back. Furthermore, the handled rats touched unknown rat pups that were drowning in water and anesthesia-induced comatose rats more frequently than control rats. These findings suggest a possibility that TPP is not in fact human-specific and innate but rather an acquired behavior that flourishes in affectionate circumstances., (© 2024. The Author(s).)

Porphyromonas gingivalis is the most pathogenic periodontal bacterium in the world. Recently, P. gingivalis has been considered responsible for dysbiosis during the development of periodontitis. This study aimed to evaluate a novel immunochromatographic device using monoclonal antibodies against P. gingivalis in subgingival plaques. A total of 72 patients with chronic periodontitis and 53 periodontally healthy volunteers underwent clinical and microbiological examinations. Subgingival plaque samples were analyzed for the presence of P. gingivalis and compared using real-time polymerase chain reaction (PCR). In the periodontitis group, a significant positive correlation was observed between the test device scores and the real-time PCR results. The specificity, positive predictive value, negative predictive value, and accuracy of the test device for P. gingivalis , as determined by real-time PCR, were 98%, 94%, 89%, and 90%, respectively. There were significant differences in bacterial counts by real-time PCR among the groups with different ranges of device scores. Additionally, there was a significant positive correlation between the device scores for P. gingivalis and periodontal parameters. These results suggest that this novel immunochromatographic device can be effectively used for rapid detection and semi-quantification of P. gingivalis in subgingival plaques.

Perilipins are evolutionarily conserved from insects to mammals. Drosophila lipid storage droplet-1 (LSD-1) is a lipid storage droplet membrane surface-binding protein family member and a counterpart to mammalian perilipin 1 and is known to play a role in lipolysis. However, the function of LSD-1 during specific tissue development remains under investigation. This study demonstrated the role of LSD-1 in salivary gland development. Knockdown of Lsd-1 in the salivary gland was established using the GAL4/UAS system. The third-instar larvae of knockdown flies had small salivary glands containing cells with smaller nuclei. The null mutant Drosophila also showed the same phenotype. The depletion of LSD-1 expression induced a delay of endoreplication due to decreasing CycE expression and increasing DNA damage. Lsd-1 genetically interacted with Myc in the third-instar larvae. These results demonstrate that LSD-1 is involved in cell cycle and cell death programs in the salivary gland, providing novel insight into the effects of LSD-1 in regulating salivary gland development and the interaction between LSD-1 and Myc., (© 2024 The Author(s). Archives of Insect Biochemistry and Physiology published by Wiley Periodicals LLC.)

Tracking hypoxic environments and changes in oxygen levels contribute to the elucidation of pathological mechanisms. In this study, we attempted to design molecular probes that can be activated to show fluorescence under hypoxic conditions and that can move to specific cell organelles. Considering that azide groups were selectively reduced to primary amines by reductases under hypoxic conditions, we prepared Hoechst and fluorophore Cy-5 derivatives with azide groups (Hoechst-N 3 and Cy-N 3 ) as hypoxia probes. Hoechst-N 3 and Cy-N 3 showed weak fluorescence, but once activated in the cytosol of hypoxic cells, they exhibited robust fluorescence and then moved to their target organelles, the cell nucleus and mitochondria. In addition, when these probes were administered to the cells in the proper sequence, each probe was activated in response to the intracellular oxygen concentration at that point and exhibited oxygen concentration-dependent fluorescence at the target organelle. By measuring the fluorescence intensity of the cell nucleus and mitochondria, we successfully traced the history of changes in intracellular oxygen levels. Thus, we achieved tracking and recording of oxygen status in the cells., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

We developed a system to detect multiple target biomolecules through sensing motif-tethered oligodeoxynucleotides. DNA-based molecular probes gave the primary amine motif upon reaction with the target biomolecules, glutathione (GSH) and H 2 O 2 . After labelling with biotin, the product DNAs were selectively collected to be quantified by qPCR.

Purpose: The aim of this study was to evaluate the treatment outcomes of neuroendoscopic cyst partial resection (ECPR) combined with stereotactic radiotherapy (SRT) for cystic craniopharyngiomas., Methods: In this retrospective study, 22 craniopharyngioma patients undergoing ECPR combined with SRT were included. This combination therapy was indicated for suprasellar cystic craniopharyngiomas in patients whose pituitary function was preserved but would be difficult to preserve in direct surgery. The outcomes of combination therapy, including tumor control and postoperative visual and pituitary functions, were investigated., Results: ECPR was safely performed, and cyst shrinkage was accomplished in all cases. After ECPR, visual function improved in 12 of 13 patients (92%) with visual field disturbance and did not deteriorate in any patients. Pituitary function was preserved in 14 patients (64%) and deteriorated in eight patients (36%) after ECPR. As a complication of ECPR, meningitis occurred because of a wound infection in one patient. In 18 of 22 patients (82%), the tumor was controlled without further treatment 19 - 87 months (median, 33 months) after SRT. Hypopituitarism was an adverse event after SRT in two of the 18 patients who achieved tumor control. Four patients (18%) had enlarged cysts after SRT. Postoperative pituitary function was significantly more likely to deteriorate in cases of extensive detachment from the ventricular wall, and retreatment was significantly more common in cases with hypothalamic extension., Conclusion: Although limited to some cases, ECPR combined with SRT is a less invasive and useful therapeutic option for suprasellar cystic craniopharyngiomas. However, its long-term prognosis requires further evaluation., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the proposed name change for non-alcoholic fatty liver disease (NAFLD). This study aimed to investigate the association of cardiovascular disease risk with MASLD and NAFLD in patients who underwent clinically indicated coronary computed tomography angiography (CCTA)., Methods: This retrospective study included 2289 patients (60% men; mean age: 68 years) with no history of coronary artery disease who underwent CCTA. The steatotic liver was defined as a hepatic-to-spleen attenuation ratio of < 1.0 on CT just before CCTA. MASLD is defined as the presence of hepatic steatosis along with at least one of the five cardiometabolic risk factors. Adverse CCTA findings were defined as obstructive and/or high-risk plaques. Major adverse cardiac events (MACE) encompassed composite coronary events, including cardiovascular death, acute coronary syndrome, and late coronary revascularization., Results: MASLD and NAFLD were identified in 415 (18%) and 368 (16%) patients, respectively. Adverse CCTA findings were observed in 40% and 38% of the patients with MASLD and with NAFLD, respectively. Adverse CCTA findings were significantly associated with MASLD (p = 0.007) but not NAFLD (p = 0.253). During a median follow-up of 4.4 years, 102 (4.4%) MACE were observed. MASLD was significantly associated with MACE (hazard ratio 1.82, 95% CI 1.18-2.83, p = 0.007), while its association with NAFLD was not significant (p = 0.070). By incorporating MASLD into a prediction model of MACE, including the risk score and adverse CCTA findings, global chi-squared values significantly increased from 87.0 to 94.1 (p = 0.008)., Conclusions: Patients with MASLD are likely to have a higher risk of cardiovascular disease than those with NAFLD. Concurrent assessment of MASLD during CCTA improves the identification of patients at a higher risk of cardiovascular disease among those with clinically indicated CCTA., (© 2024. The Author(s).)

BACKGROUND Neurogenic pulmonary edema (NPE) is a rare complication of neurological insults, such as traumatic brain injury and intracranial hemorrhage, in children. NPE frequently accompanies left ventricular (LV) dysfunction mediated via central catecholamine surge and inflammation. A high serum natriuretic (BNP) level was prolonged even after the LV contraction was improved in this case with severe myocardial injury. The overloading stress to the LV wall can last several days over the acute phase of NPE. CASE REPORT A 6-year-old boy developed NPE after the removal of a brain tumor in the cerebellar vermis, which was complicated by hydrocephalus. Simultaneously, he experienced LV dysfunction involving reduced global contraction with severe myocardial injury diagnosed by abnormally elevated cardiac troponin I level (1611.6 pg/ml) combined with a high serum BNP level (2106 pg/ml). He received mechanical ventilation for 4 days until the improvement of his pulmonary edema in the Intensive Care Unit (ICU). On the next day, after the withdrawal of mechanical ventilation, he was discharged from the ICU to the pediatric unit. Although the LV contraction was restored to an almost normal range in the early period, it took a total of 16 days for the serum BNP level to reach an approximate standard range (36.9 pg/ml). CONCLUSIONS Even in a pediatric patient with NPE, we recommend careful monitoring of the variation of cardiac biomarkers such as BNP until confirmation of return to an approximate normal value because of the possible sustained overloading stress to the LV wall.

Background: Periodontitis is the most common oral disease in dogs, and its progression and severity are influenced by risk factors, such as age and body size. Recent studies have assessed the canine oral microbiota in relation to different stages of periodontitis and niches within the oral cavity. However, knowledge of the bacterial composition at different ages and body sizes, especially in puppies, is limited. This study aimed to characterize the oral microbiota in the healthy gingiva of small breed puppies using next-generation sequencing. Additionally, we assessed the impact of dental care practices and the presence of retained deciduous teeth on the oral microbiota., Results: In this study, plaque samples were collected from the gingival margin of 20 small breed puppies (age, 6.9 ± 0.6 months). The plaque samples were subjected to next-generation sequencing targeting the V3-V4 region of the 16 S rRNA. The microbiota of the plaque samples was composed mostly of gram-negative bacteria, primarily Proteobacteria (54.12%), Bacteroidetes (28.79%), and Fusobacteria (5.11%). Moraxella sp. COT-017, Capnocytophaga cynodegmi COT-254, and Bergeyella zoohelcum COT-186 were abundant in the oral cavity of the puppies. In contrast, Neisseria animaloris were not detected. The high abundance of Pasteurellaceae suggests that this genus is characteristic of the oral microbiota in puppies. Dental care practices and the presence of retained deciduous teeth showed no effects on the oral microbiota., Conclusions: In this study, many bacterial species previously reported to be detected in the normal oral cavity of adult dogs were also detected in 6-8-month-old small breed dogs. On the other hand, some bacterial species were not detected at all, while others were detected in high abundance. These data indicate that the oral microbiota of 6-8-month-old small breed dogs is in the process of maturating in to the adult microbiota and may also have characteristics of the small dog oral microbiota., (© 2024. The Author(s).)

Although the use of immune checkpoint inhibitors (ICIs)-targeted agents for unresectable hepatocellular carcinoma (HCC) is promising, individual response variability exists. Therefore, we developed an artificial intelligence (AI)-based model to predict treatment efficacy using pre-ICIs contrast-enhanced computed tomography (CT) imaging characteristics. We evaluated the efficacy of atezolizumab and bevacizumab in 43 patients at the Nagasaki University Hospital from 2020 to 2022 using the modified Response Evaluation Criteria in Solid Tumors. A total of 197 Progressive Disease (PD), 271 Partial Response (PR), and 342 Stable Disease (SD) contrast CT images of HCC were used for training. We used ResNet-18 as the Convolutional Neural Network (CNN) model and YOLOv5, YOLOv7, YOLOv8 as the You Only Look Once (YOLO) model with precision-recall curves and class activation maps (CAMs) for diagnostic performance evaluation and model interpretation, respectively. The 3D t-distributed Stochastic Neighbor Embedding was used for image feature analysis. The YOLOv7 model demonstrated Precision 53.7%, Recall 100%, F1 score 69.8%, mAP@0.5 99.5% for PD, providing accurate and clinically versatile predictions by identifying decisive points. The ResNet-18 model had Precision 100% and Recall 100% for PD. However, the CAMs sites did not align with the tumors, suggesting the CNN model is not predicting that a given CT slice is PD, PR, or SD, but that it accurately predicts Individual Patient's CT slices. Preparing substantial training data for tumor drug effect prediction models is challenging compared to general tumor diagnosis models; hence, large-scale validation using an efficient YOLO model is warranted., (© 2024. The Author(s).)

The excited state properties of thionated 5-fluorouridine (2',3',5'-tri-O-acetyl-5-fluoro-4-thiouridine; ta5F4TUrd), synthesized with Lawesson's reagent, have been intensively investigated with nanosecond transient absorption spectroscopy, time-resolved thermal lensing, near-infrared emission, and quantum chemical calculation. The intrinsic triplet lifetime of ta5F4TUrd was determined to be 4.2 ± 0.7 μs in acetonitrile, and the formation quantum yield of the excited triplet state was as large as 0.79 ± 0.01 . The quenching rate constants of the triplet ta5F4TUrd by the dissolved oxygen molecule and by the self-quenching process were found to be nearly equal to the diffusion-controlled rate of acetonitrile. The quantum yield of the singlet molecular oxygen produced through energy transfer between the triplet ta5F4TUrd and the dissolved oxygen, Φ Δ , was successfully determined to be 0.61 ± 0.02 under the oxygen-saturated condition. From the oxygen concentration dependence of the Φ Δ value, the fraction of triplet ta5F4TUrd quenched by dissolved oxygen which gives rise to the 1 O 2 * formation, S Δ , was successfully obtained to be 0.78 ± 0.01 , which was the largest among the thionucleobases and the thionucleosides reported so far. This could be due to the lower energy and/or the ππ* character of the triplet state., (© 2024 American Society for Photobiology.)

Aim: To evaluate the association between trypsin-like protease (TLP) activity in the oral cavity as an indicator of periodontal health status and kidney function in Japanese workers., Materials and Methods: This cross-sectional study included 1117 Japanese workers (mean age = 43.8 years). Tongue-swab TLP activity was quantified as a* value (the redness intensity of the matrix disc of the TLP activity assessment kit; a larger value indicates more intense enzymatic activity in the samples and poorer periodontal health status). Kidney function was assessed using the estimated glomerular filtration rate (eGFR; a lower value indicates poorer kidney function). We performed ordinal logistic regression analyses to assess the association of the a* value with three eGFR categories: ≥90, 60-89 and <60 mL/min/1.73 m 2 ., Results: The prevalence for each eGFR category was as follows: ≥90 (31.6%), 60-89 (63.8%) and <60 mL/min/1.73 m 2 (4.6%). After adjusting for potential confounders, the a* value was found to be significantly associated with reduced kidney function. The multivariable-adjusted odds ratio (95% confidence interval) for reduced kidney function was 1.12 (1.02-1.22) per unit increase in the a* value., Conclusions: Higher TLP activity was associated with reduced kidney function in Japanese workers., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To investigate the diagnostic performance of a calcium-removal image reconstruction algorithm with photon-counting detector-computed tomography (PCD-CT), a technology that hides only the calcified plaque from the spectral data in coronary calcified lesions., Methods: This retrospective study included 17 patients who underwent PCD-coronary CT angiography (CCTA) with at least one significant coronary stenosis (≥50 %) with calcified plaque by CCTA and invasive coronary angiography (ICA) performed within 60 days of CCTA. A total of 162 segments with calcified plaque were evaluated for subjective image quality using a 4-point scale. Their calcium-removal images were reconstructed from conventional images, and both images were compared with ICA images as the reference standard. The contrast-to noise ratios for both images were calculated., Results: Conventional and calcium-removal images had a subjective image quality of 2.7 ± 0.5 and 3.2 ± 0.9, respectively (p < 0.001). The percentage of segments with a non-diagnostic image quality was 32.7 % for conventional images and 28.3 % for calcium-removal images (p < 0.001). The segment-based diagnostic accuracy revealed an area under the receiver operating characteristic curve of 0.87 for calcium-removal images and 0.79 for conventional images (p = 0.006). Regarding accuracy, the specificity and positive predictive value of calcium-removal images were significantly improved compared with those of conventional images (80.5 % vs. 69.5 %, p = 0.002 and 64.1 % vs. 52.0 %, p < 0.001, respectively). The objective image quality of the mean contrast-to-noise ratio did not differ between the images (13.9 ± 3.6 vs 13.3 ± 3.4, p = 0.356) CONCLUSIONS: Calcium-removal images with PCD-CT can potentially be used to evaluate diagnostic performance for calcified coronary artery lesions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Currently, widely used robotic surgical systems do not provide force feedback. This study aimed to evaluate the impact and benefits of a force feedback function on the suturing procedure., Methods: Twenty surgeons were recruited and divided into young (Y-group, n = 11) and senior (S-group, n = 9) groups, based on their years of surgical experience. The effect of the force feedback function on suturing quality was evaluated using an objective assessment system (A-LAP mini, Kyoto Kagaku Co., Ltd., Kyoto, Japan). Each participant completed the suturing task on intestinal model sheets with the robotic contact force feedback on and off. The task accomplishment time (s), maximal force (Newton, N) applied to the robotic forceps, and quality of suturing (assessed by A-LAP mini) were recorded as performance parameters., Results: In total, the maximal force applied to the robotic forceps was significantly decreased with the robotic force feedback switched on (median [interquartile range]: 2.8 N (2.3-3.2)) as compared with when the feedback was switched off (3.4 N (2.7-4.0), P < 0.001). The contact force feedback function did not affect the objectively assessed suturing score (18 points (17.7-19.0) versus 18 points (17.0-19.0), P = 0.421). The contact force feedback function slightly shortened the task accomplishment time in the Y-group (552.5 s (466.5-832) versus 605.5 s (476.2-689.7), P = 0.851) but not in the S-group (566 s (440.2-703.5) versus 470.5 s (419.7-560.2), P = 0.164)., Conclusions: With the contact force feedback function, the suturing task was completed with a smaller maximal force, while maintaining the quality of suturing. Because the benefits are more apparent in young surgeons, robots with the contact force feedback function will facilitate the educational process in novice surgeons., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Gadoxetic acid is both an extracellular- and hepatocyte-specific contrast agent. Signals from the extracellular space may lower the contrast between lesions and the surrounding hepatic parenchyma. To improve hepatocyte-specific enhancement, we developed an intracellular contrast-enhancing fat-saturated T1-weighted gradient-echo nature of the sequence (ICE-TIGRE). It incorporates the motion-sensitized driven-equilibrium (MSDE) pulse to suppress signals from the blood flow. We investigated the optimal ICE-TIGRE scanning parameters, i.e., the order of the MSDE and the fat saturation pulses, the duration time, and the b value of the MSDE pulse, using a phantom and three volunteers without applying gadoxetic acid. ICE-TIGRE successfully increased the contrast between the liver parenchyma and the portal vein. To maintain fat saturation, the preparation pulse order should be MSDE-fat saturation. A duration time of 21 ms should be applied to minimize the effect of the T2 factor on the T1 contrast, and a b value of 60 s/mm 2 should be applied to maximize the diffusion contrast for ICE-TIGRE with the imaging system used in this study.

Various artificial oligodeoxynucleotides (ODNs) that contribute to gene regulation have been developed and their diversity and multifunctionality have been demonstrated. However, few artificial ODNs are actively transported to the cell nucleus, despite the fact that gene regulation also takes place in both the cell nucleus and the cytoplasm. In this study, to prepare ODNs with the ability to accumulate in the cell nucleus, we introduced Hoechst molecules into ODNs that act as carriers of functional molecules to the cell nucleus (Hoe-ODNs). We synthesized Hoe-ODNs and confirmed that they bound strongly to DNA duplexes. When single-stranded Hoe-ODNs or double-stranded ODNs consisting of Hoe-ODNs and its complementary strand were administered into living cells, both ODNs were efficiently accumulated in the cell nucleus. In addition, antisense ODNs, which were tethered with Hoechst unit, were delivered into the cell nucleus and efficiently suppressed the expression of their target RNA. Thus, we constructed a delivery system that enables the transport of ODNs into cell nucleus., (© 2023 Wiley-VCH GmbH.)

Background: Diabetic retinopathy (DR) is a sight-threatening condition that causes progressive retina damage. Student-run free clinics represent a valuable opportunity to provide DR screenings to high-risk populations. We characterized the patient population, evaluated the performance, and conducted a needs assessment of DR screenings at the University of California, San Diego Student-Run Ophthalmology Free Clinic, which provides care to predominantly uninsured, Latino patients., Methods: Retrospective chart review was conducted of all patients seen at the free clinic since 2019 with a diagnosis of type II diabetes. Date and outcome of all DR-related screenings or visits from 2015 onward, demographics information, and DR risk factors such as A1c and insulin dependence were recorded. Predictors of diabetic retinopathy and frequency of DR screenings for each patient were analyzed using multiple logistic regression, t-test for equality of means, and Pearson's correlation., Results: Of 179 uninsured diabetic patients receiving care at the free clinic, 71% were female and average age was 59. 83% had hypertension, 93% had hyperlipidemia, and 79% had metabolic syndrome. Prevalence of non-proliferative DR was 34% and that of proliferative DR was 15% in diabetic patients. The free clinic capacity in recent years plateaued at just under 50% of patients seen for DR screening or visit per year, though average wait time was over 2 years between visits. Patients with higher no-show rates had less frequent DR screenings. Chronic kidney disease and poor glycemic control were the strongest predictors of DR., Conclusion: The student-run free ophthalmology clinic has been effective in providing screening and follow-up care for DR patients. Creation of a protocol to identify which patients are at highest risk of DR and should be seen more urgently, addressing no-shows, and implementation of a tele-retina program are potential avenues for improving clinic efficiency in a resource-limited setting for vulnerable populations., Competing Interests: Disclosures The authors have no conflicts of interest to disclose.

Background: Previous studies have shown that patients with Coronavirus Disease 2019 (COVID-19) are likely to be affected by delirium and other psychiatric complications. We aimed to evaluate the relation between COVID-19 vaccination status and referral of patients hospitalized with COVID-19 for consultation-liaison psychiatry services., Method: From the medical records used for this retrospective, single hospital-based study, 576 patients were identified who were over 18 years-of-age and hospitalized with a diagnosis of COVID-19 between March 2020 and March 2022. The data of 531 for whom the vaccine history was obtained from the medical records were available for analysis: 455 without and 76 with referral to consultation-liaison psychiatry. A history of COVID-19 vaccination at least two times was used in the analysis of the odds for referral to liaison psychiatric consultation: 95% confidence interval (CI) in multivariable logistic regression. The adjustment factors included sex, age, body mass index (BMI), severity of COVID-19, C-reactive protein level, medical history, and therapeutic factors such as the use of remdesivir, steroids, or mechanical ventilation., Results: The prevalence of psychiatric consultation was 14.3%. Patients without vaccination had a 7-times greater OR (95%CI:2.08-23.58) than vaccinated patients for a referral for consultation-liaison psychiatry services after adjusting for confounding factors., Conclusion: Non-vaccination was associated with a greater likelihood of referral for consultation-liaison psychiatry service among these hospitalized Japanese patients with COVID-19, even after adjusting for clinical and therapeutic factors. It is possible that vaccination greatly lessens the need for the referral of COVID-19 patients for consultation-liaison psychiatry services., (© 2023. The Author(s).)

Hard X-ray photoelectron spectroscopy (HAXPES) is a powerful tool for investigating the chemical and electronic states of bulk and buried interfaces non-destructively due to its large probing depth. To obtain a much larger probing depth and measure deeper regions than conventional HAXPES, we have developed a high-energy HAXPES (HE-HAXPES) system excited by photon energies up to 30 keV. This system is achieved by combining an applied bias voltage on the sample with a conventional hemispherical electron energy analyzer. By utilizing this system, we successfully observed a Si 1s peak from the bulk-Si substrate underneath the 110-nm-thick SiO2 film at a photon energy of 30 keV. Moreover, the system found that the asymmetrical spectral shape of the Si substrate signal originated from the electronic state, which is upward band bending formed at the interface between the SiO2 film and Si substrate. The HE-HAXPES system, excited by photon energy up to 30 keV, could be a very useful tool to yield genuine insights into the chemical and electronic states in deeply buried regions., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

Background: Reports on the effectiveness of spinal cord stimulation (SCS) for the alleviation of fibromyalgia syndrome (FMS) pain are scarce. We report two cases of effective high-frequency SCS at 1000 Hz against upper- and lower-limb pain in patients with FMS., Case Presentation: Two women with widespread pain were diagnosed with FMS and the pain gradually worsened. A 1-week SCS trial was conducted in each patient. In both cases, the patients complained of unpleasant sensations during 10-Hz SCS. However, the pain was alleviated after 1000-Hz stimulation without irritation. Therefore, leads and a generator were implanted, after which they felt almost no pain. Moreover, the dose of the oral medication could be reduced and the patients returned to their daily lives., Conclusion: SCS at 1000 Hz may effectively treat pain associated with FMS. Therefore, performing an SCS trial for patients with FMS with intractable pain might be worthwhile., (© 2023. The Japanese Society of Anesthesiologists.)

Aims: Heart failure with a preserved ejection fraction (HFpEF) is associated with chronic inflammation. We aimed to investigate the association between pericoronary adipose tissue attenuation (PCATA) on coronary computed tomography angiography as a novel noninvasive marker of pericoronary inflammation and the presence of HFpEF., Methods and Results: This retrospective study included 607 outpatients (median age, 65 years; 50% male) who underwent both echocardiography and coronary computed tomography angiography. Patients with obstructive coronary artery disease were excluded from this study. PCATA was compared between patients with and without HFpEF, which was diagnosed according to the Heart Failure Association (HFA)-PEFF score. PCATA was assessed at the proximal 40-mm segments of all three major coronary arteries on coronary computed tomography angiography. Patients with HFpEF had higher PCATA in all coronary arteries compared to the control participants: left anterior descending artery (LAD), -65.2 ± 6.9 Hounsfield units (HU) vs. -68.1 ± 6.7 HU; left circumflex artery (LCX), -62.7 ± 6.8 HU vs. -65.4 ± 6.6 HU; and right coronary artery (RCA), -63.6 ± 8.5 HU vs. -65.5 ± 7.7 HU (P < 0.01). Multivariate logistic regression analysis, including conventional risk factors, revealed that PCATA per standard deviation in the LAD (odds ratio [OR], 1.449; 95% confidence interval [CI], 1.152-1.823), LCX (OR, 1.634; 95% CI, 1.283-2.081), and RCA (OR, 1.388; 95% CI, 1.107-1.740) were independently associated with HFpEF. The association between PCATA and HFpEF was mostly consistent across various patient clinical characteristics. The left ventricular mass and left atrial volume index showed a mild correlation with LAD-PCATA (ρ = 0.13 [P < 0.01] and ρ = 0.24 [P < 0.01]) and LCX-PCATA (ρ = 0.16 [P < 0.01] and ρ = 0.23 [P < 0.01])., Conclusions: High PCATA score was significantly associated with the presence of HFpEF. Our results suggest that inflammation in the pericoronary artery adipose tissue is one of the underlying mechanisms of HFpEF., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Detection of multiple DNA/RNA targets is essential for understanding cellular function. Herein, we propose a general method for the simultaneous detection of plural nucleic acids based on surface-enhanced Raman scattering (SERS) using gold nanoparticles bearing functional oligodeoxynucleotides (ODNs) on their surface. Modified ODNs bearing an acetylene tag hybridized with their complementary ODNs on the surface of the gold nanoparticles, inducing a strong SERS signal of the acetylene tag. The addition of the target nucleic acid to the system resulted in a spontaneous displacement of the strand on the particle and dissociation of the alkyne-tagged ODN from the particle, resulting in a dramatic decrease in signal intensity. By using an alkyne tag for each of the multiple target nucleic acids, each target could be detected simultaneously. In addition, we successfully detected cellular microRNA. Different targets showed changes with different wavenumbers in the Raman spectra, allowing for the detection of multiple nucleic acids., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Coronary artery ectasia (CAE) is a cause of juvenile myocardial infarction. The causes of CAE include arteriosclerosis, vasculitis such as Kawasaki disease, and genetic contribution. There are few reports about familial aggregation of CAE-related juvenile myocardial infarction. We report an unusual case of father-son juvenile myocardial infarction owing to CAE. ( Level of Difficulty: Beginner. )., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Objectives: To identify the prevalence of non-bronchial systemic culprit arteries and their relationship to bleeding lobes in patients with hemoptysis with bronchiectasis and chronic pulmonary infection who underwent de novo bronchial artery embolization (BAE)., Methods: Data of 83 consecutive patients with bronchiectasis and chronic pulmonary infection (non-tuberculous mycobacteriosis, aspergillosis, and tuberculosis) who underwent de novo BAE between January 2019 and December 2020 were retrospectively reviewed. The prevalence of culprit arteries was investigated., Results: Fifty-five patients (66%) had 172 non-bronchial systemic culprit arteries. The bleeding lobes were the right upper, right middle, right lower, left upper, and left lower lobes in 14 (17%), 20 (24%), 7 (8%), 31 (37%), and 11 (13%) patients, respectively. The internal thoracic (49%; n = 41), intercostal (28%; n = 23), and inferior phrenic (28%; n = 23) arteries were the top three non-bronchial systemic culprit arteries, which were involved in all five types of bleeding lobes. The costocervical trunk and thoracoacromial and lateral thoracic arteries were predominant in patients with upper lobe bleeding. Ligament arteries were predominant in patients with left lower lobe bleeding., Conclusions: These findings will better ensure the identification of non-bronchial systemic culprit arteries in patients with hemoptysis with bronchiectasis and chronic pulmonary infection. All systemic arteries, especially those which are adjacent to the lung lesions, should be evaluated carefully using MDCT; the internal thoracic, intercostal, and inferior phrenic arteries should be proactively assessed using angiography., Key Points: • Non-bronchial systemic culprit arteries were identified in 66% of patients with hemoptysis with bronchiectasis and chronic pulmonary infection who underwent de novo bronchial artery embolization. • The internal thoracic (49%), intercostal (28%), and inferior phrenic (28%) arteries were the top three arteries, which were involved in all five types of bleeding lobes. • The costocervical trunk and thoracoacromial and lateral thoracic arteries were prominent in patients with upper lobe bleeding, and the ligament artery was prominent in patients with left lower lobe bleeding., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

Background: Although pulmonary endarterectomy is the treatment of choice for chronic thromboembolic pulmonary hypertension, not all patients are eligible. While balloon pulmonary angioplasty is an alternative for such patients, its efficacy and safety may differ between patients with and without surgically accessible lesions., Methods: This study involved 344 patients treated with balloon pulmonary angioplasty who were ineligible for pulmonary endarterectomy. Based on the angiographical lesion location, patients were divided into the surgically accessible (Group 1) and inaccessible (Group 2) groups, and percent changes in hemodynamics and clinical parameters before and after balloon pulmonary angioplasty were investigated. We also conducted survival analyses using Kaplan-Meier analysis., Results: While no differences in baseline characteristics were identified between the groups, balloon pulmonary angioplasty significantly improved hemodynamics in both groups, without any difference regarding the incidence of complications. Meanwhile, the percent changes in the mean pulmonary arterial pressure, pulmonary vascular resistance, 6-min walk distance, right ventricular area index on echocardiography, and the achievement rate of World Health Organization functional class I after balloon pulmonary angioplasty were significantly lower in Group 1 than in Group 2. The cumulative survival rates at 1, 5, and 10 years after balloon pulmonary angioplasty were not significantly different between the two groups (Group 1: 92.5%, 86.1%, 84.3%; and Group 2: 96.5%, 92.9%, 90.1%, respectively)., Conclusions: The outcome of balloon pulmonary angioplasty in inoperable patients with surgically accessible proximal lesions was acceptable; however, further investigations are necessary to clarify the optimal treatment for such patients., (Copyright © 2023 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Competing Interests: K.N., H.I. are members of Circulation Reports’ Editorial Team.

Physical symptoms such as fatigue and muscle weakness, and psychiatric symptoms like depression and anxiety are considered as complications and sequelae of COVID-19. This epidemiological study investigated the actual status of psychiatric symptoms and disorders caused by COVID-19, from four major university hospitals and five general hospitals in Fukuoka Prefecture, Japan, having a population of 5 million. We conducted a survey of psychiatric disorders associated with COVID-19 using Diagnosis Procedure Combination (DPC) data and the psychiatric records of the hospitals. In the study period from January 2019 to September 2021, 2743 COVID-19 admissions were determined from DPC data across the nine sites. These subjects had significantly more anxiety, depression, and insomnia, and were receiving higher rates of various psychotropic medications than controls influenza and respiratory infections. A review of psychiatric records revealed that the frequency of organic mental illness with insomnia and confusion was proportional to the severity of COVID-19 infection and that anxiety symptoms appeared independent of infection severity. These results indicate that COVID-19 is more likely to produce psychiatric symptoms such as anxiety and insomnia than conventional infections., Competing Interests: None., (© 2023 The Authors.)

Background: Psychological distress has been frequently observed in frontline healthcare workers under stress during the coronavirus disease 2019 (COVID-19) epidemic; however, it is unclear if there are differences in the stress and symptoms experienced by staff members who work exclusively in a COVID-19 ward and support staff temporarily deployed to a COVID-19 ward. The present study investigated psychosocial stress specific to the care for patients with COVID-19 and psychological distress among ward staff working exclusively with COVID-19 and temporary support staff., Methods: The participants were full-time nurses and doctors working in COVID-19 wards or the ICU who provided face-to-face care to patients with COVID-19 during the COVID-19 outbreak in February of 2021. The data of 67 staff members (21 exclusively working with Covid-19 patients (group A) and 46 in the temporary support group (group B)) was available for study. Psychosocial stress specific to healthcare professionals during this COVID-19 outbreak (Tokyo Metropolitan Distress Scale for Pandemic [TMDP]) and general psychological distress (K6) were assessed., Results: The K6 score was significantly lower in group B than in group A (p = .006), but no significant difference was found in the total score of TMDP or its subscales. Positive correlations were found between TMDP and K6 for group B (p = .011), as was the number of days of care on TMDP-social (rs = .456, p = .001)., Conclusion: Even though support staff members experienced lower psychological distress than staff working exclusively with COVID-19, COVID-19-related psychosocial stress specific to HCWs was comparable. The support staff also presented psychological distress associated with psychosocial stress specific to healthcare professionals during this COVID-19 outbreak, and the COVID-19-related social stress was enhanced as the number of working days increased. Our results show that all staff, not only those working exclusively with COVID-19 patients but also other support staff should be provided with care focusing on COVID-19-related psychosocial occupational stress., (© 2023. The Author(s).)

Aims: Pericoronary adipose tissue (PCAT) attenuation on coronary computed tomography angiography (CTA) is a noninvasive biomarker for pericoronary inflammation and is associated with cardiac mortality. We aimed to investigate the association between PCAT attenuation and endothelial dysfunction assessed using flow-mediated dilation (FMD)., Methods: A total of 119 outpatients who underwent both coronary CTA and FMD measurements were examined. PCAT attenuation values were assessed at the proximal 40-mm segments of all three major coronary arteries on coronary CTA. Endothelial function was assessed using FMD. Patients were then classified into two groups: those with endothelial dysfunction (FMD ＜4%, n=44) and those without endothelial dysfunction (FMD ≥ 4%, n=75)., Results: In all three coronary arteries, PCAT attenuation was significantly higher in patients with endothelial dysfunction than in those without endothelial dysfunction. Multivariate logistic regression analysis revealed that PCAT attenuation in the right coronary artery (odds ratio [OR]=1.543; 95% confidence interval [CI]=1.004-2.369, p=0.048) and left anterior descending artery (OR=1.525, 95% CI=1.004-2.369, p=0.049) was an independent predictor of endothelial dysfunction. Subgroup analysis of patients with adverse CTA findings (significant stenosis and/or high-risk plaque) and those with coronary artery calcium score ＞100 showed that high PCAT attenuation in all three coronary arteries was a significant predictor of endothelial dysfunction., Conclusion: High PCAT attenuation was significantly associated with FMD-assessed endothelial dysfunction in patients with suspected coronary artery disease. Our results suggest that endothelial dysfunction is one of the pathophysiological mechanisms linking pericoronary inflammation to cardiac mortality.

Purpose: The wavelet denoising with geometry factor weighting (g-denoising) method can reduce the image noise by adapting to spatially varying noise levels induced by parallel imaging. The aim of this study was to investigate the clinical applicability of g-denoising on hepatobiliary-phase (HBP) images with gadoxetic acid., Methods: We subjected 53 patients suspected of harboring hepatic neoplastic lesions to gadoxetic acid-enhanced HBP imaging with and without g-denoising (g + HBP and g - HBP). The matrix size was reduced for g + HBP images to avoid prolonging the scanning time. Two radiologists calculated the SNR, the portal vein-, and paraspinal muscle contrast-to-noise ratio (CNR) relative to the hepatic parenchyma (liver-to-portal vein- and liver-to-muscle CNR). Two other radiologists independently graded the sharpness of the liver edge, the visibility of intrahepatic vessels, the image noise, the homogeneity of liver parenchyma, and the overall image quality using a 5-point scale. Differences between g - HBP and g + HBP images were determined with the two-sided Wilcoxon signed-rank test., Results: The liver-to-portal- and liver-to-muscle CNR and the SNR were significantly higher on g + HBP- than g - HBP images (P < 0.01), as was the qualitative score for the image noise, homogeneity of liver parenchyma, and overall image quality (P < 0.01). Although there were no significant differences in the scores for the sharpness of the liver edge or the score assigned for the visibility of intrahepatic vessels (P = 0.05, 0.43), with g + HBP the score was lower in three patients for the sharpness of the liver edge and in six patients for the visibility of intrahepatic vessels., Conclusion: At gadoxetic acid-enhanced HBP imaging, g-denoising yielded a better image quality than conventional HBP imaging although the anatomic details may be degraded.

The early elevation of cardiac troponins within 24 hours after noncardiac surgery is reportedly associated with increased postoperative morbidities. Several predisposing factors, including the frequent occurrence of hypoxia and increased pulmonary arterial pressure, may likely contribute to this elevation, especially after intrathoracic surgery. Therefore, this retrospective study aimed to elucidate the incidence and characteristics of the early elevation of cardiac troponin I after intrathoracic surgery. This study included 320 patients who underwent intrathoracic surgery between January 1, 2018, and June 30, 2021. Specific perioperative variables were retrospectively collected from their electrical clinical records. The serum concentration of high-sensitivity cardiac troponin I (hs cTnI) was measured twice immediately after the intensive care unit arrival and on the following day. We grouped these patients into two: the early elevation of hs cTnI (EECT) group (hs cTnI value > 26.2 ng/L by at least 1 measurement) and the non-early elevation (non-EECT) group. Patient characteristics were then compared between these groups. The hs cTnI level elevated within 24 hours postoperatively in 103 patients (32.2%). In univariate analysis, intraoperative variables, including the duration of unilateral ventilation (199.2 minutes, P = .0025) and surgery (210.6 minutes, P = .0012), estimated blood loss volume (406.7 mL, P = .0022), percentage of stored red blood cell (RBC) transfusion (10.7%, P = .0059), and percentage of lobectomy or combination of other lung resection types (88.3%, P = .00188), were significantly higher in the EECT group than in the non-EECT group. In the log-rank test, prolonged hospitalization was more prevalent in the EECT group (P = .0485). Furthermore, multivariate analysis revealed 3 independent risk factors for the early elevation of hs cTnI: coexisting chronic renal failure (odds ratio [OR], 3.25), lobectomy or combined resections (OR, 2.65), and stored RBC transfusion (OR, 3.41). The early elevation of hs cTnI commonly occurs after intrathoracic surgery, with an incidence of 32.2%. Its 3 independent risk factors are coexisting chronic renal failure, lung resection type, and stored RBC transfusion., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Radiation therapy for head and neck cancers is frequently associated with adverse effects on the surrounding normal tissue. Irreversible damage to radiation-sensitive acinar cells in the salivary gland (SG) causes severe radiation-induced xerostomia (RIX). Currently, there are no effective drugs for treating RIX. We investigated the efficacy of treatment with conditioned medium derived from stem cells from human exfoliated deciduous teeth (SHED-CM) in a mouse RIX model. Intravenous administration of SHED-CM, but not fibroblast-CM (Fibro-CM), prevented radiation-induced cutaneous ulcer formation (p < 0.0001) and maintained SG function (p < 0.0001). SHED-CM treatment enhanced the expression of multiple antioxidant genes in mouse RIX and human acinar cells and strongly suppressed radiation-induced oxidative stress. The therapeutic effects of SHED-CM were abolished by the superoxide dismutase inhibitor diethyldithiocarbamate (p < 0.0001). Notably, quantitative liquid chromatography-tandem mass spectrometry shotgun proteomics of SHED-CM and Fibro-CM identified eight proteins activating the endogenous antioxidant system, which were more abundant in SHED-CM than in Fibro-CM (p < 0.0001). Neutralizing antibodies against those activators reduced antioxidant activity of SHED-CM (anti-PDGF-D; p = 0.0001, anti-HGF; p = 0.003). Our results suggest that SHED-CM may provide substantial therapeutic benefits for RIX primarily through the activation of multiple antioxidant enzyme genes in the target tissue., (© 2023. The Author(s).)

Cardiovascular diseases and liver diseases are closely related. Non-alcoholic fatty liver disease has the same risk factors as those for atherosclerotic cardiovascular disease and may also be a risk factor for atherosclerotic cardiovascular disease on its own. Heart failure causes liver fibrosis, and liver fibrosis results in worsened cardiac preload and congestion. Although some previous reports regard the association between cardiovascular diseases and liver disease, the management strategy for liver disease in patients with cardiovascular diseases is not still established. This review summarized the association between cardiovascular diseases and liver disease. In patients with non-alcoholic fatty liver disease, the degree of liver fibrosis progresses with worsening cardiovascular prognosis. In patients with heart failure, liver fibrosis could be a prognostic marker. Liver stiffness assessed with shear wave elastography, the fibrosis-4 index, and non-alcoholic fatty liver disease fibrosis score is associated with both liver fibrosis in patients with liver diseases and worse prognosis in patients with heart failure. With the current population ageing, the importance of management for cardiovascular diseases and liver disease has been increasing. However, whether management and interventions for liver disease improve the prognosis of cardiovascular diseases has not been fully understood. Future investigations are needed.

Microglia play a central role in neuroinflammatory processes by releasing proinflammatory mediators. This process is tightly regulated along with neuronal activities, and neurotransmitters may link neuronal activities to the microglia. In this study, we showed that primary cultured rat microglia express the dopamine (DA) D1 receptor (D1R) and D4R, but not D2R, D3R, or D5R. In response to a D1R-specific agonist SKF-81297 (SKF), the cultured microglia exhibited increased intracellular cAMP levels. DA and SKF suppressed lipopolysaccharide (LPS)-induced expression of interleukin-1β (IL-1β) and tumor necrosis α (TNFα) in cultured microglia. Microglia in the normal mature rat prefrontal cortex (PFC) were sorted and significant expression of D1R, D2R, and D4R was observed. A delirium model was established by administering LPS intraperitoneally to mature male Wistar rats. The model also displayed sleep-wake disturbances as revealed by electroencephalogram and electromyogram recordings as well as increased expression of IL-1β and TNFα in the PFC. DA levels were increased in the PFC 21 h after LPS administration. Increased cytokine expression was observed in sorted microglia from the PFC of the delirium model; however, TNFα, but not IL-1β expression, was abruptly decreased 21 h after LPS administration in the delirium model, whereas DA levels were increased. A D1R antagonist SCH23390 partially abolished the TNFα expression change. This suggests that endogenous DA may play a role in suppressing neuroinflammation. Administration of the DA precursor L-DOPA or SKF to the delirium model rats inhibited the expression of IL-1β and TNFα. The simultaneous administration of clozapine, a D4R antagonist, strengthened the suppressive effects of L-DOPA. These results suggest that D1R mediates the suppressive effects of LPS-induced neuroinflammation, in which microglia may play an important role. Agonists for D1R may be effective for treating delirium., Competing Interests: Declaration of competing interest The authors declare no competing interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

We report a method for the synthesis of azafluoranthenes under neutral reaction conditions in a highly atom-economical manner by the iridium-catalyzed [2 + 2 + 2] cycloaddition of 1,8-dialkynylnaphthalenes with nitriles. A variety of nitriles react with methyl- or phenyl-substituted 1,8-dialkynylnaphthalenes to give a wide range of azafluoranthenes. Azafluoranthenes bearing an amino group show intense fluorescence at around 500 nm. Comparison of the fluorescence properties of amine-substituted azafluoranthenes with related compounds revealed the importance of the amine moiety for obtaining a high fluorescence quantum yield. The choice of the solvent affected the emission maxima and the fluorescence quantum yield. Azafluoranthenes bearing pyrrolidine exhibited blue-shifted emission bands in a non-polar solvent and gave a fluorescence quantum yield of 0.76 in toluene. A Lippert-Mataga plot and computational studies provide insight into the origin of the fluorescence of azafluoranthenes. Furthermore, cellular experiments using human breast adenocarcinoma cells SK-BR-3 demonstrated the feasibility of using azafluoranthenes as fluorescent probes.

Six methyl pheophorbide-a derivatives were prepared by linking a tryptamine side chain at the C-13 1 , C-15 2 and C-17 3 positions of pheophorbide-a. Prepared conjugates were characterized and evaluated for their photocytotoxicity against A549 cells. The conjugate 6 a with strong absorption at 413 nm (Soret band), 663-671 nm (Q bands) and comparable fluorescence quantum yield (0.26) was found to exhibit significant cytotoxicity (659 nM). Molecular integration of pheophorbide-a and tryptamines showed synergistic effects as the most potent conjugate 6 a was identified with enhanced photocytotoxicity when compared to methyl pheophorbide-a. The conjugate 6 a was smoothly taken up by A549 cells and exhibited intracellular localization predominantly to lysosome in the cytoplasm. Upon photoirradiation 6 a generated singlet oxygen to show potent cytotoxicity toward A549 cells., (© 2022 Wiley-VCH GmbH.)

Raman probes have attracted widespread attention for the visualization and identification of biomolecules, because they can be applied to identify detailed chemical structures, detect multiple molecules simultaneously, and visualize cellular functional molecules. However, the biological application of Raman probes is still limited because of their weak signal intensity. Herein, we present a molecular system that shows an enhanced Raman signal using a nonfluorescent dye. We introduced a DABCYL molecule bearing an acetylene unit into thymidine at the 5-position. The resulting modified nucleobase, d DA U, showed a robust signal around 2200 cm -1 , which was attributed to the acetylene unit, due to resonance Raman induced by the DABCYL group. We further prepared a DNA aptamer modified with d DA U, and characterized the change of the Raman spectra. Combination with gold nanoparticles, which enhanced the Raman signal by surface-enhanced Raman scattering (SERS), allowed sensitive detection of cellular adenosine derivatives including ATP. Thus, the present system is a promising tool for the detection of biological materials by Raman spectroscopy.