The role of arterial stiffness in the onset of Takotsubo cardiomyopathy observed with noradrenaline administration and intracranial blood injection in rabbits.

Takotsubo cardiomyopathy (TCM) has been reported to occur after subarachnoid hemorrhage, and the involvement of a critical activity of catecholamines has been mentioned, but the details of its onset have not been fully clarified. Recently, proper arterial stiffness could be measured with cardio-ankle vascular index. Therefore, we aimed to clarify the role of arterial stiffness in onset of TCM using rabbits under infusion of noradrenaline and injection of blood into brain ventricle. Rabbits were divided into three groups: infusion of noradrenaline (group A), infusion of noradrenaline + injection of saline into the brain ventricle (group B), infusion of noradrenaline + injection of blood in the brain ventricle (group C). Aortic arterial stiffness beta (Aß) and femoral arterial stiffness beta (Fß) were defined according to definition of the cardio-ankle vascular index. Blood pressure (BP), Aß, Fß, and femoral vessel resistance (FVR) were measured. Left ventricular movement were monitored with echocardiography. BP increased uniformly in all three groups. Fß in the group A, B and C increased from 3.6 ± 3.2, 3.6 ± 3.6 and 3.9_ ± 4.2 to 15 ± 2, 17.9 ± 2.4, 34.8 ± 9.1 due to the ICP enhancements in addition to noradrenaline administration, respectively. Fß in groups B and C was significantly larger than that in group A. On echocardiography, a much higher akinesic area of the apex was observed in group C compared with group A and B. Cardiac movements similar to TCM were observed slightly in group B and definitely in group C. Noradrenaline administration infusion and blood injection into the brain ventricle induced TCM accompanying with enhanced femoral arterial stiffness. These results suggested that elevated arterial stiffness might be involved in the formation of TCM in addition to a critical activity of catecholamines and an increase in intracranial pressure with blood injection.

Comparison of 1.5 T and 3 T non-contrast-enhanced MR angiography for visualization of uterine and ovarian arteries before uterine artery embolization.

OBJECTIVES: This study aimed to compare the performance of non-contrast-enhanced magnetic resonance angiography (NCE-MRA) at 1.5 T and 3 T for the visualization of uterine and ovarian arteries (OAs) before uterine artery embolization (UAE). METHODS: Preprocedural pelvic NCE-MRA images of 85 symptomatic patients undergoing UAE for the treatment of uterine leiomyomas were reviewed by two specialists in pelvic MRI. Left and right uterine arteries (UAs) were judged separately and scored on a 5-point scale. Score 5 was the highest, in which the UA could be visualized inside the musculature, forming a peritumoral plexus. Score 1 was the lowest, where visualization was limited to the descending segment. The detection of enlarged OAs was also compared. The Mann-Whitney U and Fisher exact tests were used for statistical analysis. p < 0.05 was considered to be statistically significant. RESULTS: Of the 170 UAs, 110 were classified at 1.5 T and 60 were classified at 3 T. Median (interquartile range [IQR]) score was 3 (IQR: 2-4) for visualization at 1.5 T vs 5 (IQR: 4-5) for 3 T. The scores for UA visualization were significantly higher at 3 T (p < 0.05). For enlarged OAs, NCE-MRA at 1.5 T and 3 T visualized 7 and 5 enlarged OAs, respectively; there was no significant difference between the two field strengths (p = 0.36). CONCLUSIONS: NCE-MRA performed at 3 T can visualize UAs over a greater range than at 1.5 T. No difference was found regarding the detection of enlarged OAs. KEY POINTS: • Preprocedural MRA can provide interventional radiologists with valuable information, including the origin and course of the uterine arteries and the existence of collateral feeders to the tumor. • This study demonstrates the superiority of non-contrast-enhanced MRA performed at 3 T over that performed at 1.5 T in the visualization of the uterine arteries in patients undergoing uterine artery embolization for the treatment of uterine leiomyomas. • Non-contrast-enhanced MRA is a useful imaging modality for patients with symptomatic leiomyoma undergoing uterine artery embolization in whom contrast administration is unfeasible. If available, it is preferable to perform the examination with a 3 T MR unit rather than a 1.5 T MR unit.

Analysis of effects of acute hypovolemia on arterial stiffness in rabbits monitored with cardio-ankle vascular index.

Although elasticity of the conduit arteries is known to be contribute effective peripheral circulation via Windkessel effects, the relationship between changes in intra-aortic blood volume and conduit artery elasticity remains unknown. Here we assessed the effects of change in intra-aortic blood volume induced by blood removal and subsequent blood transfusion on arterial stiffness and the involvement of autonomic nervous activity using our established rabbit model in the presence or absence of the ganglion blocker hexamethonium (100 mg/kg). Blood removal at a rate of 1 mL/min gradually decreased the blood pressure and blood flow of the common carotid artery but increased a stiffness indicator the cardio-ankle vascular index, which was equally observed in the presence of hexamethonium. These results suggest that arterial stiffness acutely responds to changes in intra-aortic blood volume independent of autonomic nervous system modification.

TNFR2 pathways are fully active in cancer regulatory T cells.

Tumor necrosis factor receptor 2 (TNFR2), a membrane-bound tumor necrosis factor receptor expressed by regulatory T cells (Tregs), participates in Treg proliferation. Although a specific TNFR2 pathway has been reported, the signaling mechanism has not been completely elucidated. This study sought to clarify TNFR2 signaling in human Tregs using amplicon sequencing and single-cell RNA sequencing to assess Tregs treated with a TNFR2 agonist antibody. Pathway enrichment analysis based on differentially expressed genes highlighted tumor necrosis factor α signaling via nuclear factor kappa B, interleukin-2 signal transducer and activator of transcription 5 signaling, interferon-γ response, and cell proliferation-related pathways in Tregs after TNFR2 activation. TNFR2-high Treg-focused analysis found that these pathways were fully activated in cancer Tregs, showing high TNFR2 expression. Collectively, these findings suggest that TNFR2 orchestrates multiple pathways in cancer Tregs, which could help cancer cells escape immune surveillance, making TNFR2 signaling a potential anticancer therapy target.

Cardio-Vascular Interaction Evaluated by Speckle-Tracking Echocardiography and Cardio-Ankle Vascular Index in Hypertensive Patients.

Hypertension increases arterial stiffness, leading to dysfunction and structural changes in the left atrium (LA) and left ventricle (LV). However, the effects of hypertension on the right atrium (RA) and the right ventricle are still not fully understood. The purpose of this study was to clarify whether there is an interaction not only in the left ventricular system but also in the right ventricular system in hypertensive patients with preserved LV ejection fraction. The current retrospective observational study included patients (n = 858) with some risk of metabolic abnormalities (hypertension, diabetes, and dyslipidemia) who had visited our hospital and undergone echocardiography between 2015 and 2018. Among them, we retrospectively studied 165 consecutive hypertensive patients with preserved LV ejection fraction who had echocardiography performed on the same day as a cardio-ankle vascular index (CAVI) in our hospital. The phasic function of both atria was evaluated by two-dimensional speckle-tracking echocardiography. CAVI was measured using Vasela 1500 (Fukuda Denshi®). In the univariate analysis, CAVI was significantly correlated with LA and RA conduit function (LA conduit function, r = -0.448, p = 0.0001; RA conduit function, r = -0.231, p = 0.003). A multivariate regression analysis revealed that LA and RA conduit function was independently associated with CAVI (LA, t = -5.418, p = 0.0001; RA, t = -2.113, p = 0.036). CAVI showed a possibility that the association between heart and vessels are contained from not only LA phasic function but also RA phasic function in hypertensive patients.

Evolution of patients with chronic thromboembolic pulmonary hypertension treated by balloon pulmonary angioplasty, according to their anticoagulant regimens.

Patients with chronic thromboembolic pulmonary hypertension (CTEPH) need anticoagulant therapy for life. Conventionally, vitamin K antagonists (VKAs) have been used and data about direct oral anticoagulants (DOACs) in CTEPH patients are lacking. Recently, balloon pulmonary angioplasty (BPA) has emerged as a treatment option for CTEPH. However, there are no reports examining the effects of DOACs and VKAs on the hemodynamics of patients after BPA. The aim of this study was to compare DOACs and VKAs regarding the hemodynamic changes in patients with CTEPH treated by BPA. Patients who were treated by BPA and underwent follow-up right heart catheterization 6 ± 1 months after the final BPA procedure were included in this study. The subjects were divided into two groups based on the anticoagulant administered, and hemodynamic changes (mean pulmonary artery pressure, mPAP; pulmonary vascular resistance, PVR; cardiac index, CI) were assessed. Of the 65 consecutive patients, 29 met the inclusion criteria (DOAC-group n = 14, VKA-group n = 15). Compared to pre-BPA, post-BPA hemodynamic parameters were improved in both groups. There was no significant difference between the two groups regarding pre-BPA, post-BPA, 6Mo-f/u and Δhemodynamic parameters (difference between 6Mo-f/u and post-BPA, ΔmPAP, - 0.7 ± 3.3 vs. - 2.7 ± 5.4 mmHg, p = 0.24; ΔPVR, - 41.9 ± 80.9 vs. - 16.4 ± 74.1 dyne s/cm5, p = 0.38; ΔCI, - 0.06 ± 0.35 vs. - 0.10 ± 0.35 L/min/m2, p = 0.80; DOAC-group vs. VKA-group, respectively). Hemodynamic improvement by BPA was maintained over 6 months of follow-up irrespective of the type of anticoagulant administered in CTEPH patients.

The evaluation of lymph node cell proliferation response by liposomes loaded with major histocompatibility complex class II binding aquaporin 4 antigen peptide.

Autoimmune responses to aquaporin 4 (AQP4) cause neuromyelitis optica (NMO); thus, specific immunotolerance to this self-antigen could represent a new NMO treatment. We generated the liposome-encapsulated AQP4 peptide 201-220 (p201-220) to induce immunotolerance. Liposomes were generated using phosphatidylserine and the polyglycidol species PG8MG. The in vivo tissue distribution of the liposomes was tested using an ex vivo imaging system. To confirm the antigen presentation capacity of PG8MG liposomes, dendritic cells were treated with PG8MG liposome-encapsulated AQP4 p201-220 (AQP4-PG8MG liposomes). Immunotolerance induction by AQP4-PG8MG liposomes was evaluated using the ex vivo cell proliferation of lymph node cells isolated from AQP4 p201-220-immunized AQP4-deficient mice. Fluorescent dye-labeled PG8MG liposomes were distributed to the lymph nodes. AQP4 p201-220 was presented on dendritic cells. AQP4-PG8MG liposomes were tended to suppress immune responses to AQP4 p201-220. Thus, the encapsulation of AQP4 peptides in PG8MG liposomes represents a new strategy for suppressing autoimmune responses to AQP4.

Bilateral Pallidal Stimulation with Directional Leads for Primary Focal Lingual Dystonia.

There have been limited studies regarding stereotactic and functional neurosurgery for lingual dystonia. Here, we report a patient with primary lingual dystonia who showed significant improvement after bilateral deep brain stimulation (DBS). A 42-year-old woman presented with a 5- to 6-year history of tongue protrusion; however, she lacked a significant medical or medication history before onset. She presented with gradually worsening symptoms and was diagnosed with idiopathic lingual dystonia. Her tongue was injected with botulinum toxin on 6 occasions; however, it had a limited effect. Oral medications were ineffective. She underwent DBS since her involuntary tongue movements were causing nocturnal breathing problems. Directional leads were bilaterally inserted into the internal segment of the globus pallidus (GPi). The directional part of each lead was inserted at the GPi bottom on both sides. The posteromedial contacts were used to deliver stimulation. After 1.5 years, the patient's Burke-Fahn-Marsden dystonia rating scale score improved from 9 to 1.5 and 2 to 1 for movement and disability, respectively. This case demonstrated the effectiveness of bilateral GPi-DBS. Placing the directional part of the lead in the GPi bottom could improve the stimulation effects.

[Case Report of Four Patients Received Ramucirumab Monotherapy as Second-Line Chemotherapy for Advanced Gastric Cancer].

Ramucirumab monotherapy is one of the conditionally recommended regimens in second-line chemotherapy for advanced gastric cancer. However, there are few clinical data on ramucirumab monotherapy in Japanese patients. Herein, we present 4 case reports of advanced gastric cancer patients who received ramucirumab monotherapy. The 4 patients' age ranged from 65-81 years old(median: 70 years old), with a 3:1 male to female ratio. Since all cases were in poor performance status, administration of cell-killing anticancer drugs such as paclitaxel was contraindicated, and ramucirumab monotherapy was selected as an alternative. Ramucirumab was administrated 2-8 times(median: 3 times), resulting to a stable disease in 1 patient, and progression-free survival was noted to be 3-16 weeks(median: 5 weeks). Regarding complications, Grade 2 hypertension occurred in 1 patient, and no serious adverse events were observed. Ramucirumab monotherapy is a well-tolerated second-line chemotherapy for patients with advanced gastric cancer in poor performance status, and it is expected to have some disease control effect.

Effect of nicorandil administration on cardiac burden and cardio-ankle vascular index after coronary intervention.

Myocardial injury is a problem associated with percutaneous coronary intervention (PCI). This study aimed to clarify the role of nicorandil administration in preventing myocardial injury. This study included patients with stable angina who underwent PCI from November 2013 to June 2016. Of 58 consecutive patients, the first 20 patients received only saline infusion after PCI (control group); the other 38 patients received a continuous intravenous infusion of nicorandil and saline after PCI (nicorandil group). Troponin I and brain natriuretic peptide (BNP) levels were measured. Vascular parameters, such as blood pressure (BP), cardiac output, cardio-ankle vascular index (CAVI), and estimated systemic vascular resistance (eSVR), were measured. Troponin I of both groups increased 12 h after PCI. Changes in BNP levels between immediately after PCI and 12 h after PCI were significantly higher in the control than in the nicorandil group (10.8 ± 44.2 vs. - 2.6 ± 14.6 pg/ml, p = 0.04). In the nicorandil group, BP, eSVR, and CAVI decreased significantly at 12 h after PCI compared with those immediately after PCI (p < 0.0001), whereas no change was observed in the control group. In a single linear analysis, the change in BP (r = 0.36, p < 0.01) and nicorandil administration (r = - 0.47, p < 0.001) was significantly correlated with the change in CAVI, multiple regression analysis revealed that the changes in CO and eSVR were significant contributing factors for the changes in CAVI. PCI could result in myocardial injury and/or cardiac burden in patients with stable angina. Nicorandil administration after PCI may be effective in relieving the burden by decreasing arterial stiffness (CAVI).

Full recovery from drummer's dystonia with foot and arm symptoms after stereotactic ventro-oral thalamotomy: a case report.

Ventro-oral (Vo) thalamotomy is effective in patients with focal task-specific dystonias (FTSDs), but only in those with upper-limb symptoms. We describe a patient with drummer's dystonia who completely recovered after Vo thalamotomy. A 37-year-old man who started playing drums at 14 began having difficulty performing fine movements with his right foot when drumming at 22. He experienced right hand cramps while drumming 3 months before visiting our hospital. He was diagnosed with FTSD. Left Vo thalamotomy was performed, which led to complete improvement of symptoms. Vo thalamotomy may be effective for FTSD patients with upper- and lower-extremity symptoms.

[Pulmonary Cryptcoccosis Mimicking Malignant Tumor;Report of a Case].

Pulmonary cryptococcosis is difficult to distinguish from lung cancer clinically, and is often diagnosed by surgery. A 72-year-old woman, who underwent distal pancreatectomy and splenectomy for pancreatic carcinoma. Four months after surgery, a tumor shadow was detected in the left lung as a groundglass nodule (GGN)of 12 mm in diameter, which was found to change to 15 mm with increased density by the computed tomography(CT)scan after 2 months. The nodule showed positive accumulation of fluorodeoxyglucose(FDG)by positron emission tomography(PET), and was suspected of malignant tumor. She underwent a partial resection of the left lung under thoracoscopy.

[Elastofibroma Dorci;Report of a Case].

Elastofibroma is a relatively rare tumor that occurs commonly at the apex of scapula in elderly people. We report a case of elastofibroma of a female in her seventies. She visited our hospital with complaints of painful mass in her back, which was increasing in size. On the magnetic resonance imaging (MRI),the T1 and the T2-weighted images showed the same signal intensity as the muscle between the right scapula and the intercostal muscles. The internal fat component was cord-like, with high signal intensity. Based on the site of the tumor and characteristic findings on imaging, it was diagnosed as elastofibroma and resection was performed. Pathological findings revealed bundle-like proliferation of fibrous and spherical hyaline substances, together with collagen fibers. The hyaline substance stained in black on Elastica van Gieson staining and was confirmed to be elastic fiber. Thus, it was diagnosed as elastofibroma. The patient is on regular follow-up, with no recurrence after surgery.

[Rapidly Developing Pulmonary Cyst Complicated by Pneumothorax Occurred in the Early Post-operative Period after Lung Segmentectomy].

The patient was a 74-year-old man who had undergone surgery for rectal cancer 9 years before and had developed left lung metastasis(S3)3 years and 4 months prior to admission. He had received video assisted left lung wedge resection. He presented with a growing nodular lesion close to the remaining left lung margin and elevated serum carcinoembryonic antigen(CEA)levels, and underwent open extended segmentectomy. The chest drain tube was removed on 3rd post-operative day, but he developed left pneumothorax on 4th post-operative day and a computed tomography(CT)scan revealed a cystic lesion 5.0 cm in size at the base of his left lung. Revision surgery was performed on 8th post-operative day. A pulmonary cyst on the diaphragmatic surface of the lung(S10)was found and location of the air leak was confirmed in the same area. Following wedge resection of the cyst-containing region, the leak ceased completely. Rapid manifestation of a newly formed pulmonary cyst during the acute post-operative period is rare.

Myocardial triglyceride content in patients with left ventricular hypertrophy: comparison between hypertensive heart disease and hypertrophic cardiomyopathy.

Proton magnetic resonance spectroscopy (1H-MRS) enables the assessment of myocardial triglyceride (TG) content, which is reported to be associated with cardiac dysfunction and morphology accompanied by metabolic disorder and cardiac hemodynamic status. The clinical usefulness of myocardial TG content measurements in patients with left ventricular hypertrophy (LVH) has not been fully investigated. We examined whether myocardial TG content assessed by 1H-MRS was useful for diagnosis in patients with LVH. To quantify myocardial TG content, we conducted 1H-MRS in 35 subjects with LVH. Left ventricular function was measured by cardiac magnetic resonance imaging. Patients were assigned to a hypertensive heart disease (HHD, n = 10) or hypertrophic cardiomyopathy (HCM, n = 25) group based on the histology and/or late gadolinium enhancement pattern. The myocardial TG content was significantly higher in the HHD group than in the HCM group (2.14 ± 1.29 vs. 1.09 ± 0.72 %, P < 0.001). Myocardial TG content were significantly and negatively correlated with LV mass (r = -0.41, P < 0.04) and stroke volume (r = -0.64, P < 0.05) in the HCM group and HHD group, respectively. In a multivariate analysis, LV mass volume and diagnosis of HCM or HHD were independent factors of the myocardial TG content. The results suggest that myocardial metabolism may differ between HCM and HHD patients and that measurement of myocardial TG content by 1H-MRS may be useful for evaluating the myocardial metabolic features of LVH.

SNP- and haplotype-based genome-wide association studies for growth, carcass, and meat quality traits in a Duroc multigenerational population.

BACKGROUND: The aim of the present study was to compare the power of single nucleotide polymorphism (SNP)-based genome-wide association study (GWAS) and haplotype-based GWAS for quantitative trait loci (QTL) detection, and to detect novel candidate genes affecting economically important traits in a purebred Duroc population comprising seven-generation pedigree. First, we performed a simulation analysis using real genotype data of this population to compare the power (based on the null hypothesis) of the two methods. We then performed GWAS using both methods and real phenotype data comprising 52 traits, which included growth, carcass, and meat quality traits. RESULTS: In total, 836 animals were genotyped using the Illumina PorcineSNP60 BeadChip and 14 customized SNPs from regions of known candidate genes related to the traits of interest. The power of SNP-based GWAS was greater than that of haplotype-based GWAS in a simulation analysis. In real data analysis, a larger number of significant regions was obtained by SNP-based GWAS than by haplotype-based GWAS. For SNP-based GWAS, 23 genome-wide significant SNP regions were detected for 17 traits, and 120 genome-wide suggestive SNP regions were detected for 27 traits. For haplotype-based GWAS, 6 genome-wide significant SNP regions were detected for four traits, and 11 genome-wide suggestive SNP regions were detected for eight traits. All genome-wide significant SNP regions detected by haplotype-based GWAS were located in regions also detected by SNP-based GWAS. Four regions detected by SNP-based GWAS were significantly associated with multiple traits: on Sus scrofa chromosome (SSC) 1 at 304 Mb; and on SSC7 at 35-39 Mb, 41-42 Mb, and 103 Mb. The vertnin gene (VRTN) in particular, was located on SSC7 at 103 Mb and was significantly associated with vertebrae number and carcass lengths. Mapped QTL regions contain some candidate genes involved in skeletal formation (FUBP3; far upstream element binding protein 3) and fat deposition (METTL3; methyltransferase like 3). CONCLUSION: Our results show that a multigenerational pig population is useful for detecting QTL, which are typically segregated in a purebred population. In addition, a novel significant region could be detected by SNP-based GWAS as opposed to haplotype-based GWAS.

Fluorophore-Conjugated Holliday Junctions for Generating Super-Bright Antibodies and Antibody Fragments.

The site-specific modification of proteins with fluorophores can render a protein fluorescent without compromising its function. To avoid self-quenching from multiple fluorophores installed in close proximity, we used Holliday junctions to label proteins site-specifically. Holliday junctions enable modification with multiple fluorophores at reasonably precise spacing. We designed a Holliday junction with three of its four arms modified with a fluorophore of choice and the remaining arm equipped with a dibenzocyclooctyne substituent to render it reactive with an azide-modified fluorescent single-domain antibody fragment or an intact immunoglobulin produced in a sortase-catalyzed reaction. These fluorescent Holliday junctions improve fluorescence yields for both single-domain and full-sized antibodies without deleterious effects on antigen binding.

Corrigendum: Effect of balloon pulmonary angioplasty on cardio-ankle vascular index and biventricular remodeling in patients with chronic thromboembolic pulmonary hypertension.

[This corrects the article DOI: 10.3389/fcvm.2023.1325846.].