Bipolar electrochemical sensor with perylene diimide-based cathodic luminophore for dopamine detection and imaging.

Bipolar electrochemical microscopy (BEM), which visualizes the concentration distribution of molecular species in biological systems by electrochemiluminescence (ECL), is expected to be applied to the high-spatiotemporal-resolution imaging of biomolecules, enabling the analysis of cellular functions. In the past, the molecular species that could be imaged by BEM were generally restricted to oxidized molecules due to the limitation derived from the ECL mechanism of the luminophore. Recently, the imaging of dopamine (DA), a reduced molecule, was achieved using Ru (bpy)32+/glutathione disulfide (GSSG) as a cathodic luminophore. However, a large driving voltage was required for ECL generation, resulting in a low S/N ratio. In this study, we employed N,N'-dimethyl-3,4,9,10-perylenetetracarboxylic diimide (PDI-CH3)/potassium peroxodisulfate (K2S2O8), which is a cathodic luminophore that can be reduced at a nobler potential to produce ECL than [Ru(bpy)3]2+/GSSG. First, the ECL mechanism of PDI-CH3/K2S2O8 was elucidated by using a PDI-CH3 drop-cast glassy carbon electrode (GCE) immersed in K2S2O8 solution as the working electrode in a 3-electrode system. The PDI-CH3 drop-casted GCE, a single closed bipolar electrode (c-BPE), was used as the cathode in the successful quantification of 50-500 µmol L-1 DA in a sample chamber in which a c-BPE anode was immersed, resulting in a high S/N. The selective detection of DA in the presence of ascorbic acid was achieved by modifying the anode with Nafion. Finally, DA imaging was demonstrated using a commercially available anisotropic conducting film with PDI-CH3 coating on the cathode surface as a c-BPE array. The change in the concentration distribution in the inflow of DA was successfully imaged based on the change in the ECL intensity at the c-BPE cathode. This BEM system is expected to be useful for DA imaging of the brain.

Male mice are susceptible to brain dysfunction induced by early-life acephate exposure.

Background: Acephate is a widely used organophosphate insecticide. Exposure to endocrine-disrupting chemicals, such as acephate, can interfere with neurodevelopment in childhood, increasing the risk of higher brain dysfunction later in life. Furthermore, brain dysfunction may be related to chemical exposure-related disturbances in the gut microbiota. However, the effects of early acephate exposure on the brains of adult males and females as well as on the adult gut environment remain poorly understood. Methods: This study investigated the effects of perinatal acephate exposure on the central nervous system and gut microbiota of mice, including sex differences and environmentally relevant concentrations. C57BL/6 N pups were exposed to acephate (0, 0.3, 10, and 300 ppm) via the dam in their drinking water from embryonic day (E) 11.5 to postnatal day 14. We examined its effects on the central nervous system of adult males and females. Results: In the male treatment group, impairments in learning and memory were detected. Immunohistochemical analysis revealed a decrease in SOX2-, NeuN-, DCX-, and GFAP-positive cells in the hippocampal dentate gyrus in males compared to the control group, whereas GFAP-positive cells were fewer in females. In addition, gut microbiota diversity was reduced in both sexes in the experimental group. Conclusion: Our study demonstrates that the effects of early-life exposure to acephate are more pronounced in males than in females and can lead to a lasting impact on adult behavior, even at low doses, and that the gut microbiota may reflect the brain environment.

The white ring sign is useful for differentiating between fundic gland polyps and gastric adenocarcinoma of the fundic gland type.

Background and study aims Gastric adenocarcinoma of the fundic gland type (GA-FG) is characterized by an elevated lesion with vessel dilation exhibiting branching architecture (DVBA). However, this feature is also found in fundic gland polyps (FGPs), posing a challenge in their differentiation. In this study, we aimed to investigate the clinicopathological features of gastric elevated lesions with DVBA and assess the efficacy of the white ring sign (WRS) as a novel marker for distinguishing between FGPs and GA-FGs. Methods We analyzed 159 gastric elevated lesions without DVBA and 51 gastric elevated lesions with DVBA, further dividing the latter into 39 in the WRS-positive group and 12 in the WRS-negative group. The clinicopathological features, diagnostic accuracy, and inter-rater reliability were analyzed. Results Univariate and multivariate analyses for gastric elevated lesions with DVBA identified the histological type consistent with FGPs and GA-FGs, along with the presence of round pits in the background gastric mucosa, as independent predictors. FGPs were present in 92.3% (36/39) of the WRS-positive group and GA-FGs were observed in 50.0% (6/12) of the WRS-negative group. WRS positivity and negativity exhibited high diagnostic accuracy, with 100% sensitivity, 80.0% specificity, and 94.1% accuracy for FGPs, and 100% sensitivity, 86.7% specificity, and 88.2% accuracy for GA-FGs. Kappa values for WRS between experts and nonexperts were 0.891 and 0.841, respectively, indicating excellent agreement. Conclusions WRS positivity and negativity demonstrate high diagnostic accuracy and inter-rater reliability for FGPs and GA-FGs, respectively, suggesting that WRS is a useful novel marker for distinguishing between FGPs and GA-FGs.

A single dose of clothianidin exposure induces varying sex-specific behavioral changes in adulthood depending on the developmental stage of its administration.

Clothianidin (CLO), a neonicotinoid that is widely used in forests and agricultural areas, was recently reported to cause toxicity in mammals. Although sensitivity to chemicals varies between sexes and developmental stages, studies that comprehensively evaluate both males and females are limited. Therefore, in this study we utilized murine models to compare the sex-specific differences in behavioral effects following CLO exposure at different developmental stages. We orally administered CLO to male and female mice as a single high-dose solution (80 mg/kg) during the postnatal period (2-week-old), adolescence (6-week-old), or maturity (10-week-old), and subsequently evaluated higher brain function. The behavioral battery test consisted of open field, light/dark transition, and contextual/cued fear conditioning tests conducted at three and seven months of age. After the behavioral test, the brains were dissected and prepared for immunohistochemical staining. We observed behavioral abnormalities in anxiety, spatial memory, and cued memory only in female mice. Moreover, the immunohistochemical analysis showed a reduction in astrocytes within the hippocampus of female mice with behavioral abnormalities. The behavioral abnormalities observed in female CLO-treated mice were consistent with the typical behavioral abnormalities associated with hippocampal astrocyte dysfunction. It is therefore possible that the CLO-induced behavioral abnormalities are at least in part related to a reduction in astrocyte numbers. The results of this study highlight the differences in behavioral effects following CLO exposure between sexes and developmental stages.

Perioperative strategies and management of giant anterior mediastinal tumors: a narrative review.

Background and Objective: Giant anterior mediastinal tumors sometimes may cause circulatory collapse and respiratory failure, known as mediastinal mass syndrome (MMS). The prediction and prevention of MMS is challenging. The aim of this study is to summarize the evaluation methods for MMS and formulate treatment strategies for giant anterior mediastinal tumors. Methods: We performed a thorough analysis of recent international literature on giant anterior mediastinal tumors (>10 cm in diameter) and MMS published in the PubMed database. The search spanned the duration of the preceding 10 years from August 19, 2023, and only studies published in English were included. Key Content and Findings: Mature teratomas and liposarcomas are the most common giant anterior mediastinal tumors and MMS develops most frequently in case of malignant lymphomas. Here, we propose a new treatment strategy for giant anterior mediastinal tumors. Based on imaging findings, giant anterior mediastinal tumors can be classified as cystic or solid and further blood investigation data are useful for a definitive diagnosis. When malignant lymphoma or malignant germ cell tumor is highly suspected, the first choice of treatment is not surgery but chemotherapy and radiotherapy. Moreover, image-guided drainage may be effective if giant cystic anterior tumors develop into MMS. The risk classification of MMS is important for treating giant anterior mediastinal tumors. If the MMS risk classification is 'unsafe' or 'uncertain', the intraoperative management deserves special attention. The surgical approach should however be based on tumor localization and invasion of surrounding tissues. Multidisciplinary team coordination is indispensable in the treatment of giant anterior mediastinal tumors. Conclusions: When giant anterior mediastinal tumors are encountered, it is important to follow the appropriate treatment strategy, focusing on the development of MMS based on imaging findings and symptoms.

BET bromodomain inhibition potentiates radiosensitivity in models of H3K27-altered diffuse midline glioma.

Diffuse midline glioma (DMG) H3K27-altered is one of the most malignant childhood cancers. Radiation therapy remains the only effective treatment yet provides a 5-year survival rate of only 1%. Several clinical trials have attempted to enhance radiation antitumor activity using radiosensitizing agents, although none have been successful. Given this, there is a critical need for identifying effective therapeutics to enhance radiation sensitivity for the treatment of DMG. Using high-throughput radiosensitivity screening, we identified bromo- and extraterminal domain (BET) protein inhibitors as potent radiosensitizers in DMG cells. Genetic and pharmacologic inhibition of BET bromodomain activity reduced DMG cell proliferation and enhanced radiation-induced DNA damage by inhibiting DNA repair pathways. RNA-Seq and the CUT&RUN (cleavage under targets and release using nuclease) analysis showed that BET bromodomain inhibitors regulated the expression of DNA repair genes mediated by H3K27 acetylation at enhancers. BET bromodomain inhibitors enhanced DMG radiation response in patient-derived xenografts as well as genetically engineered mouse models. Together, our results highlight BET bromodomain inhibitors as potential radiosensitizer and provide a rationale for developing combination therapy with radiation for the treatment of DMG.

Comparison of diagnostic accuracy between linked color imaging and autofluorescence imaging in patients with ulcerative colitis: A prospective observational study.

BACKGROUND AND AIM: Image enhancement endoscopy techniques, such as linked color imaging (LCI) and autofluorescence imaging (AFI), have shown promise in diagnosing mucosal inflammation in ulcerative colitis (UC). However, no studies have directly compared the diagnostic efficacy of LCI and AFI. This prospective observational study aimed to compare their diagnostic accuracy for histological healing in UC. METHODS: This study included 81 UC patients, resulting in a total of 204 endoscopic images captured using LCI and AFI, respectively. Spearman's rank correlation coefficients assessed the correlation between LCI and AFI coloration and Geboes histopathology score (GHS). Six endoscopists, who were blinded to clinicopathological features, evaluated these images, and subsequently, the diagnostic accuracy was evaluated. RESULTS: Spearman's rank correlation coefficients between LCI index, AFI index (reverse gamma value), and GHS were 0.324 and -0.428, respectively (P < 0.001), indicating a significant correlation between LCI and AFI coloration and histological healing. In LCI and AFI classifications, mean values for diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 76.3 ± 2.2 versus 77.8 ± 2.7, 91.8 ± 4.0 versus 83.2 ± 7.6, 53.4 ± 10.0 versus 70.0 ± 5.3, 74.0 ± 3.5 versus 80.0 ± 1.6, and 82.9 ± 5.2 versus 75.5 ± 7.5, respectively. No significant difference in diagnostic accuracy existed between LCI and AFI classifications. However, LCI displayed higher sensitivity than AFI while AFI showed higher specificity compared with LCI (P < 0.05). CONCLUSIONS: LCI and AFI offer comparable diagnostic accuracy for histological healing. Clinically, it is necessary to recognize diagnostic features characterized by higher sensitivity in LCI and greater specificity in AFI.

Extremely slow-growing cerebellar ganglioglioma in an elderly patient.

Background: Gangliogliomas account for 0.4% of primary brain tumors. They mainly occur in the supratentorial compartment and typically affect only children and young adults. We present an especially rare case of cerebellar ganglioglioma in an elderly patient. Case Description: A 76-year-old Japanese woman presented with headache and nausea from 1 month previously. She had been diagnosed with a cerebellar tumor in her childhood, but the lesion was asymptomatic at that time, and there was no evidence of an increase in size, so it had been monitored without surgery. At the time of presentation, she had not been examined for approximately ten years. On admission, magnetic resonance imaging indicated a T2 hypertense cyst in the cerebellar vermis. Post-contrast T1 imaging showed an enhanced mural nodule in the cyst. Cerebral angiography showed that none of the vertebral arteries were significant feeders. The tumor was removed through posterior fossa craniotomy. The histopathological diagnosis was ganglioglioma. The patient's headache and nausea improved after surgery. Conclusion: Our patient presented a very rare case of extremely slow-growing elderly ganglioglioma in the cerebellum. In patients with gangliogliomas, long-term follow-up is important because the disease may become symptomatic at an older age.

Treatment for complete extensor tendon rupture: A case report on extensor pollicis longus tendon transfer and tenodesis procedure to radius for a patient with rheumatoid arthritis.

The complete loss of finger extension leads to significant inconvenience in daily life and often requires surgical treatment. Despite some disadvantages, the Boyes method, which uses the flexor digitorum superficialis tendon, is commonly performed for complete extensor rupture. We report the case of a 73-year-old woman living alone diagnosed with a subcutaneous rupture of all extensor tendons from the index to the little finger. The favourable range of motion of her wrist allowed us to perform extensor tenodesis. Additionally, the patient had a dislocated thumb interphalangeal (IP) joint, enabling us to use the extensor pollicis longus tendon for tendon transfer in combination with thumb IP joint fusion. The patient demonstrated favourable finger range-of-motion outcomes at the 6-month postoperative assessment. The case shows that extensor pollicis longus tendon transfer and tenodesis may be a viable treatment option for patients with complete extensor rupture accompanied by thumb IP joint deformity and normal wrist range of motion.

Ansa Cervicalis External Branch Anastomosis to Restore High Tone Voice in Thyroid Surgery.

OBJECTIVES: Injury to the external branch of the superior laryngeal nerve (EBSLN) causes low-pitch voice and voice fatigue, particularly in female subjects, and available treatments are limited. Here, we assess a novel surgical procedure to restore a high-tone voice: ansa cervicalis to EBSLN anastomosis (A-E anastomosis). METHODS: Between November 2012 and April 2022, 13 patients (12 female) underwent unilateral EBSLN resection and A-E anastomosis, while 20 (16 female) underwent EBSLN resection during thyroid surgery. Patients (4494 women and 1025 men) with normal laryngoscopy scheduled for thyroid surgery served as normal controls. Phonatory function was examined using a Phonation Analyzer PA-1000 preoperatively and intermittently postoperatively. RESULTS: In patients who underwent A-E anastomosis, high-tone voice pitch decreased significantly postoperatively (673.9-471.5 Hz, p = 0.047), with restoration achieved within 5 months. The mean voice pitch in female patients who underwent A-E anastomosis, EBSLN resection, and controls were 580.4, 522.8, and 682.0 Hz, respectively, indicating a significant decrease in EBSLN resection patients than controls (p = 0.002). The (mean - 1SD) of high-tone voice pitch in female controls was 497 Hz; exceeding this may indicate recovery to a high-tone voice. Overall, 73% (8/11) of A-E anastomosis patients exceeded this value, which was marginally larger than the 43% (6/14) who underwent EBSLN resection. Data on male subjects are limited. There were no cases of adverse functional or cosmetic events. CONCLUSIONS: A-E anastomosis, a novel simple procedure, restored high-tone voice to some extent without any adverse events and thus warrants further investigation. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3868-3873, 2024.

Prediction of MGMT promotor methylation status in glioblastoma by contrast-enhanced T1-weighted intensity image.

Background: The study aims to explore MRI phenotypes that predict glioblastoma's (GBM) methylation status of the promoter region of MGMT gene (pMGMT) by qualitatively assessing contrast-enhanced T1-weighted intensity images. Methods: A total of 193 histologically and molecularly confirmed GBMs at the Kansai Network for Molecular Diagnosis of Central Nervous Tumors (KANSAI) were used as an exploratory cohort. From the Cancer Imaging Archive/Cancer Genome Atlas (TCGA) 93 patients were used as validation cohorts. "Thickened structure" was defined as the solid tumor component presenting circumferential extension or occupying >50% of the tumor volume. "Methylated contrast phenotype" was defined as indistinct enhancing circumferential border, heterogenous enhancement, or nodular enhancement. Inter-rater agreement was assessed, followed by an investigation of the relationship between radiological findings and pMGMT methylation status. Results: Fleiss's Kappa coefficient for "Thickened structure" was 0.68 for the exploratory and 0.55 for the validation cohort, and for "Methylated contrast phenotype," 0.30 and 0.39, respectively. The imaging feature, the presence of "Thickened structure" and absence of "Methylated contrast phenotype," was significantly predictive of pMGMT unmethylation both for the exploratory (p = .015, odds ratio = 2.44) and for the validation cohort (p = .006, odds ratio = 7.83). The sensitivities and specificities of the imaging feature, the presence of "Thickened structure," and the absence of "Methylated contrast phenotype" for predicting pMGMT unmethylation were 0.29 and 0.86 for the exploratory and 0.25 and 0.96 for the validation cohort. Conclusions: The present study showed that qualitative assessment of contrast-enhanced T1-weighted intensity images helps predict GBM's pMGMT methylation status.

The clinical efficacy and safety of granulocyte and monocyte adsorptive apheresis in patients with Crohn's disease: A multicenter retrospective pilot study.

INTRODUCTION: A remission induction therapy of granulocyte and monocyte adsorptive apheresis (GMA) was given to patients with Crohn's disease (CD). However, establishing an appropriate treatment strategy for GMA in patients with CD remains unclear. METHODS: This study evaluated the clinical efficacy and subsequent clinical progression after GMA in patients with CD who underwent GMA in seven independent institutions in Japan from 2010 to 2023. RESULTS: Sixteen patients were enrolled. The overall remission and response rates were 25.0% and 68.8%, respectively. All patients responding to GMA received biologics that were continuously used and 36.4% of patients remained on the same biologics 52 weeks after GMA. Notably, all patients who continued the same biologics had previously experienced a loss of response to biologics. CONCLUSION: GMA may exhibit effectiveness even in cases with refractory CD. Moreover, it represents a potential novel therapeutic option for refractory CD with loss of response to biologics.

Cardiac sarcoidosis in a patient with ulcerative colitis: A case report and literature review.

RATIONALE: Both ulcerative colitis (UC) and sarcoidosis are chronic inflammatory diseases with unknown etiologies and are rare. However, the odds ratio in UC patients has been reported to range from 1.7 to 2.1, suggesting a potential etiology between sarcoidosis and UC. Furthermore, the underlying etiologies of UC and sarcoidosis remain unidentified. Sharing the experience of a UC patient with cardiac sarcoidosis could provide valuable insights to prevent sudden death in UC patients. PATIENT CONCERNS: A 71-year-old Japanese woman was diagnosed with UC at 58-year-old and maintained remission on mesalazine treatment. She complained of just palpitation; therefore, she consulted a cardiologist. DIAGNOSES: The patient received a diagnosis of cardiac sarcoidosis with complicating ulcerative colitis based on the results of N-terminal prohormone of the brain natriuretic peptide (NT-proBNP), imaging examinations, and histology. INTERVENTION: The patient was treated with prednisolone and methotrexate. The prednisolone was then tapered, and the methotrexate dose was adjusted based on her symptoms, imaging results, and laboratory findings. OUTCOME: She no longer had any symptoms, and the abnormal FDG uptake had disappeared after 2 years. LESSON: In UC patients, periodic or additional (in case of symptomatic) electrocardiography and NT-proBNP are recommended for the early detection of cardiac sarcoidosis, a life-threatening complication.

Tumor volume-doubling rate is negatively associated with patient age in papillary thyroid microcarcinomas under active surveillance.

BACKGROUND: Active surveillance of low-risk papillary thyroid microcarcinomas has gained popularity worldwide as a management strategy. We previously reported that young age was associated with tumor enlargement by ≥3 mm. Here, we used the tumor volume-doubling rate to study the age-related tumor volume dynamics of papillary thyroid microcarcinomas under active surveillance. METHODS: Between 2005 and 2019, 2,896 patients diagnosed with low-risk papillary thyroid microcarcinomas underwent active surveillance. We excluded patients who underwent ultrasound examination fewer than 4 times, had coexisting Graves' disease, or were treated with levothyroxine at the time of diagnosis, and we enrolled 2,129 patients for this study. We divided them into 3 subsets based on the age at diagnosis: young (<40 years), middle-aged (40-59 years), and elderly (≥60 years). The tumor volume-doubling rate was calculated based on ultrasound-derived tumor sizes and the respective examination date for each patient. RESULTS: Overall, 140 patients (6.6%) had moderate or rapid growth (tumor volume-doubling rate ≥0.3/year), and the incidence significantly decreased with advanced age (P < .01): 11.3%, 7.1%, and 5.0% in the young, middle-aged, and elderly groups, respectively. Tumor regression (tumor volume-doubling rate <0/year) was detected in 1,200 patients (56.4%), and the incidence significantly increased with age (P < .01): 44.6%, 55.3%, and 60.0% in the young, middle-aged, and elderly groups, respectively. On multivariate analysis, both the ≥60 years and 40 to 59 years age groups were independent negative predictors of papillary thyroid microcarcinoma enlargement and positive predictors of tumor regression. CONCLUSION: Tumor volume-doubling rate analysis demonstrated that the incidence of tumor enlargement decreased and that of tumor regression increased with advancing age in patients with papillary thyroid microcarcinomas.

[Validation of Method for Nitrite Determination in Foods].

In general, nitrite in food is extracted under slightly alkaline conditions, deproteinized, and analyzed by a colorimetric method using color development by diazotization. However, depending on the sample, the sample solution may become cloudy and difficult to filter by the deproteinization treatment of the analytical method. Recently, an improved analytical method that solves these problems has been reported. Therefore, a validation study was performed on the improved analytical method was performed. The concentrations of sodium nitrite added to cod roe, fish sausage, and ham, which were not labeled with sodium nitrite, were set at the upper limits of the standards for use. We set the target values of 70-120% for trueness, less than 15% for intralaboratory reproducibility, and less than intralaboratory reproducibility for repeatability. As a result, the target values were met for the three samples verified: 88-92% for trueness, 2.0-3.0% for repeatability, and 3.2-4.3% for intralaboratory reproducibility. In addition, an interlaboratory study was conducted by eight institutes on the improved analytical method for nitrite. At each institution, sodium nitrite was added to the same three samples as in the validation study, at concentrations equivalent to twice the lower limit of quantification and the upper limit of the standards for use and analyzed in triplicate. The estimated trueness from the obtained analyses ranged from 82 to 95%, the repeatability ranged from 2.3 to 5.8%, and the inter-room reproducibility ranged from 3.5 to 11%. Thus, the improved analytical method could be useful for determining nitrite in foods.