Percutaneous shunt vessel embolisation with Amplatzer vascular plugs II and IV in the treatment of dogs with splenophrenic shunts: four cases (2019-2022).

OBJECTIVES: To describe the treatment of four dogs with splenophrenic shunts using percutaneous shunting vessel embolisation with Amplatzer vascular plugs II and IV and provide information on their clinical outcomes. MATERIALS AND METHODS: Dogs with splenophrenic shunts treated at a veterinary hospital from January 2019 to December 2022 were identified through a medical record search. RESULTS: Six dogs with splenophrenic shunts were identified. Two dogs were excluded because they were treated with laparoscopic surgery. Four underwent percutaneous shunting vessel embolization with Amplatzer vascular plugs and were included in the case series. A sheath was placed in the left external jugular vein and a balloon catheter was advanced to the shunting vessel under fluoroscopy. Portal vein pressure was confirmed to be within an acceptable range during temporary balloon occlusion. Based on preoperative CT angiography and intraoperative contrast examination, Amplatzer vascular plugs II were selected for two dogs and IV were selected for two dogs. Under fluoroscopy, the plug was deployed into the shunting vessel, and angiography confirmed occlusion. In all cases, the increase in portal pressure after temporary occlusion was within the acceptable range, and complete occlusion of blood flow was possible with a single plug. There were no major procedure-related complications. No dogs developed post-ligation seizures or signs of portal hypertension. In addition, improvements in ammonia values were observed in all cases. CLINICAL SIGNIFICANCE: Percutaneous splenophrenic shunt embolisation using Amplatzer vascular plugs II and IV is technically feasible in dogs, and assessed by intra-procedure angiography, a single plug completely obstructed blood flow in all dogs. Based on the literature search, this is the first report describing Amplatzer vascular plugs for the treatment of splenophrenic shunts.

High-power laser experiment forming a supercritical collisionless shock in a magnetized uniform plasma at rest.

We present an experimental method to generate quasiperpendicular supercritical magnetized collisionless shocks. In our experiment, ambient nitrogen (N) plasma is at rest and well magnetized, and it has uniform mass density. The plasma is pushed by laser-driven ablation aluminum (Al) plasma. Streaked optical pyrometry and spatially resolved laser collective Thomson scattering clarify structures of plasma density and temperatures, which are compared with one-dimensional particle-in-cell simulations. It is indicated that just after the laser irradiation, the Al plasma is magnetized by a self-generated Biermann battery field, and the plasma slaps the incident N plasma. The compressed external field in the N plasma reflects N ions, leading to counterstreaming magnetized N flows. Namely, we identify the edge of the reflected N ions. Such interacting plasmas form a magnetized collisionless shock.

Nosocomial infection with rotavirus vaccine strain in paediatric patients with immunodeficiency.

In infants with immunodeficiency, rotavirus (RV) vaccines can be continuously excreted in stool. We analysed nosocomial infection with RV vaccine strain in immunodeficient paediatric patients. RV1 RNAs were detected in stool and serum samples from case A, who was vaccinated with RV1, and case B, who was not. PAGE analysis of serial stool samples of case A revealed several rearrangements of the RV genome. In case B, the only band pattern detected was the same as a rearrangement detected in case A at the same time. In summary, RV vaccination of infants with immunodeficiency poses a risk of nosocomial infections.

Differential biomechanical responses of elastic and muscular arteries to angiotensin II-induced hypertension.

Elastic and muscular arteries are distinguished by their distinct microstructures, biomechanical properties, and smooth muscle cell contractile functions. They also exhibit differential remodeling in aging and hypertension. Although regional differences in biomechanical properties have been compared, few studies have quantified biaxial differences in response to hypertension. Here, we contrast passive and active changes in large elastic and medium- and small-sized muscular arteries in adult mice in response to chronic infusion of angiotensin over 14 days. We found a significant increase in wall thickness, both medial and adventitial, in the descending thoracic aorta that associated with trends of an increased collagen:elastin ratio. There was adventitial thickening in the small-sized mesenteric artery, but also significant changes in elastic lamellar structure and contractility. An increased contractile response to phenylephrine coupled with a reduced vasodilatory response to acetylcholine in the mesenteric artery suggested an increased contractile state in response to hypertension. Overall reductions in the calculated gradients in pulse wave velocity and elastin energy storage capability from elastic-to-muscular arteries suggested a possible transfer of excessive pulsatile energy into the small-sized muscular arteries resulting in significant functional consequences in response to hypertension.

Adventitial remodeling protects against aortic rupture following late smooth muscle-specific disruption of TGFß signaling.

Altered signaling through transforming growth factor-beta (TGFß) increases the risk of aortic dissection in patients, which has been confirmed in mouse models. It is well known that altered TGFß signaling affects matrix turnover, but there has not been a careful examination of associated changes in structure-function relations. In this paper, we present new findings on the rupture potential of the aortic wall following late postnatal smooth muscle cell (SMC)-specific disruption of type I and II TGFß receptors in a mouse model with demonstrated dissection susceptibility. Using a combination of custom computer-controlled biaxial tests and quantitative histology and immunohistochemistry, we found that loss of TGFß signaling in SMCs compromises medial properties but induces compensatory changes in the adventitia that preserve wall strength above that which is needed to resist in vivo values of wall stress. These findings emphasize the different structural defects that lead to aortic dissection and rupture - compromised medial integrity and insufficient adventitial strength, respectively. Relative differences in these two defects, in an individual subject at a particular time, likely reflects the considerable phenotypic diversity that is common in clinical presentations of thoracic aortic dissection and rupture. There is, therefore, a need to move beyond examinations of bulk biological assays and wall properties to cell- and layer-specific studies that delineate pathologic and compensatory changes in wall biology and composition, and thus the structural integrity of the aortic wall that can dictate differences between life and death.

Paradoxical aortic stiffening and subsequent cardiac dysfunction in Hutchinson-Gilford progeria syndrome.

Hutchinson-Gilford progeria syndrome (HGPS) is an ultra-rare disorder with devastating sequelae resulting in early death, presently thought to stem primarily from cardiovascular events. We analyse novel longitudinal cardiovascular data from a mouse model of HGPS (LmnaG609G/G609G) using allometric scaling, biomechanical phenotyping, and advanced computational modelling and show that late-stage diastolic dysfunction, with preserved systolic function, emerges with an increase in the pulse wave velocity and an associated loss of aortic function, independent of sex. Specifically, there is a dramatic late-stage loss of smooth muscle function and cells and an excessive accumulation of proteoglycans along the aorta, which result in a loss of biomechanical function (contractility and elastic energy storage) and a marked structural stiffening despite a distinctly low intrinsic material stiffness that is consistent with the lack of functional lamin A. Importantly, the vascular function appears to arise normally from the low-stress environment of development, only to succumb progressively to pressure-related effects of the lamin A mutation and become extreme in the peri-morbid period. Because the dramatic life-threatening aortic phenotype manifests during the last third of life there may be a therapeutic window in maturity that could alleviate concerns with therapies administered during early periods of arterial development.

Mechanical feedback cooling assisted by optical cavity cooling of the thermal vibration of a microcantilever.

This study describes a new two-step process to cool the thermal vibration of microcantilevers. The process combines active mechanical feedback cooling and optical cavity cooling. A micro-Fabry-Perot interferometer, built in-house, is set atop a microcantilever to measure the vibration amplitude, the high optical power density of which induces cavity cooling in the optical cavity. Using a two-step cooling procedure, the equivalent temperature of the thermal vibration of a microcantilever is lowered from room temperature to the theoretical cooling limit of 0.063 K, a much lower temperature than that achieved via simple cavity cooling (18 K), and then by mechanical feedback cooling (0.135 K) obtained for the same type of microcantilevers in previous studies. This experimental demonstration showcases a new type of cooling process of the amplitude of thermal vibration for micro-mechanical resonators to a lower temperature and does not need additional cooling using a conventional cryogenic refrigerator.

Topological transitions among skyrmion- and hedgehog-lattice states in cubic chiral magnets.

Manipulating topological spin textures is a key for exploring unprecedented emergent electromagnetic phenomena. Whereas switching control of magnetic skyrmions, e.g., the transitions between a skyrmion-lattice phase and conventional magnetic orders, is intensively studied towards development of future memory device concepts, transitions among spin textures with different topological orders remain largely unexplored. Here we develop a series of chiral magnets MnSi1-xGex, serving as a platform for transitions among skyrmion- and hedgehog-lattice states. By neutron scattering, Lorentz transmission electron microscopy and high-field transport measurements, we observe three different topological spin textures with variation of the lattice constant controlled by Si/Ge substitution: two-dimensional skyrmion lattice in x = 0-0.25 and two distinct three-dimensional hedgehog lattices in x = 0.3-0.6 and x = 0.7-1. The emergence of various topological spin states in the chemical-pressure-controlled materials suggests a new route for direct manipulation of the spin-texture topology by facile mechanical methods.

Sarcopenia, the depletion of muscle mass, an independent predictor of respiratory complications after oncological esophagectomy.

Surgery for esophageal carcinoma is known to be associated with high morbidity. Recent studies have reported a correlation of nutritional and inflammatory parameters with postoperative course. This study aims to clarify the risk factors for operative morbidity after resection of esophageal carcinoma. Consecutive patients who underwent esophagectomy for esophageal squamous cell carcinoma at our institute were included (n = 102; 89 males and 13 females; mean age: 67.3 years). Clinicopathological characteristics, presence or absence of sarcopenia, and modified Glasgow prognostic score were assessed, and their correlation with postoperative complications was investigated using univariate and multivariate analyses. Sarcopenia was defined using a combination of muscle mass area and body mass index. Of the included 102 patients, 45 (44.1%) exhibited sarcopenia (sarcopenia group), while 57 (55.9%) did not (non-sarcopenia group). No significant difference was observed between the groups regarding surgical procedures and tumor stage; furthermore, there was no mortality. Twenty-six patients developed respiratory complications (including 20 cases of pneumonia). On univariate analysis, sarcopenia, modified Glasgow prognostic score, and American Society of Anesthesiologists physical status were found to be significantly associated with the development of postoperative respiratory complications. On multivariate analysis, sarcopenia was found to be an independent risk factor for postoperative respiratory complications after esophagectomy. We believe that identifying patients at risk and providing preoperative nutritional support as well as physical therapy aimed at strengthening of body muscles may help reduce the incidence of postoperative respiratory complications in such patients.

Laparoendoscopic Single-site Plus 1-port Donor Nephrectomy: Division of Roles to Shorten Warm Ischemic Time.

BACKGROUND: In this study we present our new surgical procedure, laparoendoscopic single-site surgery plus 1 for donor nephrectomy (LESS+1-DN), which shortens warm ischemic time (WIT) and improves surgical outcomes. METHODS: From January 2013 to February 2017, 15 patients who underwent LESS-DN and 41 patients who underwent LESS+1-DN at our institution were evaluated retrospectively. Patients were divided into 3 groups: group A, 15 cases of LESS-DN; group B, the first 15 patients who underwent LESS+1-DN; and group C, 26 patients who underwent subsequent LESS+1-DN. To reduce WIT, we clearly defined the roles of the surgeon and first assistant in the 26 subsequent LESS+1-DN cases. The surgeon dissected the renal pedicle and harvested the kidney graft using a recovery bag and the first assistant held the recovery bag. RESULTS: The mean operative time in group C (213.7 minutes) was significantly shorter than that in groups A (253.3 minutes) and B (253.8 minutes). The WIT in group C (195.2 seconds) was significantly shorter than that in groups A (389.8 seconds) and B (313.2 seconds). Open conversion was required in 1 case in group A. None of the donors required conversion to open surgery and no perioperative complications occurred in groups B and C. Linear regression analysis of the LESS+1-DN operative times and consecutive case numbers demonstrated a shallow learning curve (R2 = 0.392, P < .05). CONCLUSION: Our new procedure that divides the roles of the operator and the first assistant contributed significantly to a shortening of WIT. Dividing roles can facilitate a safer laparoscopic donor nephrectomy.

Feedback damping of a microcantilever at room temperature to the minimum vibration amplitude limited by the noise level.

Cooling the vibration amplitude of a microcantilever as low as possible is important to improve the sensitivity and resolutions of various types of scanning type microscopes and sensors making use of it. When the vibration amplitude is controlled to be smaller using a feed back control system, it is known that the obtainable minimum amplitude of the vibration is limited by the floor noise level of the detection system. In this study, we demonstrated that the amplitude of the thermal vibration of a microcantilever was suppressed to be about 0.15 pmHz(-1/2), which is the same value with the floor noise level, without the assistance of external cryogenic cooling. We think that one of the reason why we could reach the smaller amplitude at room temperature is due to stiffer spring constant of the lever, which leads to higher natural frequency and consequently lower floor noise level. The other reason is considered to be due to the increase in the laser power for the diagnostics, which lead to the decrease in the signal to noise ratio determined by the optical shot noise.

Candidate genes in panic disorder: meta-analyses of 23 common variants in major anxiogenic pathways.

The utilization of molecular genetics approaches in examination of panic disorder (PD) has implicated several variants as potential susceptibility factors for panicogenesis. However, the identification of robust PD susceptibility genes has been complicated by phenotypic diversity, underpowered association studies and ancestry-specific effects. In the present study, we performed a succinct review of case-control association studies published prior to April 2015. Meta-analyses were performed for candidate gene variants examined in at least three studies using the Cochrane Mantel-Haenszel fixed-effect model. Secondary analyses were also performed to assess the influences of sex, agoraphobia co-morbidity and ancestry-specific effects on panicogenesis. Meta-analyses were performed on 23 variants in 20 PD candidate genes. Significant associations after correction for multiple testing were observed for three variants, TMEM132D rs7370927 (T allele: odds ratio (OR)=1.27, 95% confidence interval (CI): 1.15-1.40, P=2.49 × 10(-6)), rs11060369 (CC genotype: OR=0.65, 95% CI: 0.53-0.79, P=1.81 × 10(-5)) and COMT rs4680 (Val (G) allele: OR=1.27, 95% CI: 1.14-1.42, P=2.49 × 10(-5)) in studies with samples of European ancestry. Nominal associations that did not survive correction for multiple testing were observed for NPSR1 rs324891 (T allele: OR=1.22, 95% CI: 1.07-1.38, P=0.002), TPH1 rs1800532 (AA genotype: OR=1.46, 95% CI: 1.14-1.89, P=0.003) and HTR2A rs6313 (T allele: OR=1.19, 95% CI: 1.07-1.33, P=0.002) in studies with samples of European ancestry and for MAOA-uVNTR in female PD (low-active alleles: OR=1.21, 95% CI: 1.07-1.38, P=0.004). No significant associations were observed in the secondary analyses considering sex, agoraphobia co-morbidity and studies with samples of Asian ancestry. Although these findings highlight a few associations, PD likely involves genetic variation in a multitude of biological pathways that is diverse among populations. Future studies must incorporate larger sample sizes and genome-wide approaches to further quantify the observed genetic variation among populations and subphenotypes of PD.

Immunohistochemical expression of p63, Ki67 and ß-catenin in canine transitional cell carcinoma and polypoid cystitis of the urinary bladder.

Transitional cell carcinoma (TCC) is a urinary bladder tumour associated with high mortality in dogs. In this study, we investigated the feasibility of using p63, Ki67 or ß-catenin as a clinical marker for predicting biological behaviour and prognosis in canine TCC. Expression levels of these proteins in TCC (n = 25), polypoid cystitis (n = 5) and normal urinary bladder (n = 5) were scored after immunohistochemical staining. The staining scores for p63 (P < 0.01) and ß-catenin (P < 0.05) in TCC were significantly lower than those in normal urinary bladder and polypoid cystitis. In contrast, Ki67 (P < 0.01) staining scores in TCC were significantly higher than those in normal urinary bladder and polypoid cystitis. In TCC, low p63 expression was significantly related to the presence of vessel invasion (P < 0.05) and metastasis (P < 0.01) as well as short survival time (P < 0.05). These findings show that p63 could be a reliable marker for predicting prognosis in canine TCC.

Virological analysis of inherited chromosomally integrated human herpesvirus-6 in three hematopoietic stem cell transplant patients.

We analyzed 3 hematopoietic stem cell transplant (HSCT) recipients with inherited chromosomally integrated human herpesvirus-6 (inherited CIHHV-6). Cases 1 (inherited CIHHV-6A) and 2 (inherited CIHHV-6B) were inherited CIHHV-6 recipients. Case 3 received bone marrow from a donor with inherited CIHHV-6B. Following HSCT, HHV-6B was isolated from Case 1. HHV-6A and -6B messenger RNAs were detected in Cases 1 and 3.

Long-term entecavir therapy results in falls in serum hepatitis B surface antigen levels and seroclearance in nucleos(t)ide-naïve chronic hepatitis B patients.

Entecavir (ETV) is reported to result in suppression of hepatitis B virus DNA (HBV DNA) replication with minimal drug resistance. However, information on the long-term effect of such therapy on serum hepatitis B surface antigen (HBsAg) level and elimination of HBsAg is not available. ETV therapy was started in 553 nucleos(t)ide-naïve patients with chronic hepatitis B infection (HBeAg positive: 45%) in our hospital. Serum HBsAg levels were measured serially by the Architect assay. The median baseline HBsAg was 2180 IU/mL (0.12-243 000 IU/mL), and median follow-up period was 3.0 years, with 529, 475, 355, 247 and 163 patients followed-up for 1, 2, 3, 4 and 5 years, respectively. At year 5, the mean log HBsAg decline from baseline was -0.48 log IU/mL, and the cumulative HBsAg clearance rate was 3.5%. Multivariate analysis identified HBV DNA level at baseline (<3.0 log copies IU/mL, odd ratio = 10.2; 95% confidence interval = 1.87-55.5, P = 0.007) and HBsAg level (<500 IU/mL, odd ratio = 29.4; 95% confidence interval = 2.80-333, P = 0.005) as independent predictors of HBsAg seroclearance. These results indicate that although serum HBsAg level declines gradually during ETV therapy, HBsAg seroclearance remains a rare event.

Therapeutic adenoviral gene transfer of a glycosyltransferase for prevention of peritoneal dissemination and metastasis of gastric cancer.

Increased expression of sialyl Lewis(x/a) carbohydrates, ligands for E-selectin, correlates with clinically advanced stages and metastasis of gastric and colon cancers. In contrast, Sd(a) carbohydrate is abundantly detected in the normal gastrointestinal mucosa but dramatically reduced or lost in cancer tissues. A glycosyltransferase, ß1,4N-acetylgalactosaminyltransferase 2 (B4GALNT2) that catalyzes Sd(a) carbohydrate synthesis, is silenced in cancer. In the present study, we aimed at reducing the expression of sialyl Lewis(x/a) of cancer cells in vivo by forced expression of B4GALNT2 and Sd(a), thereby preventing dissemination/metastasis, especially metastasis triggered by surgical maneuvers. We used a fiber-modified adenovirus (Ad) vector that contained a chimeric construct with a serotype 5 shaft and a serotype 3 knob. Using this Ad5/3 vector, we successfully introduced the B4GALNT2 gene into a human gastric cancer cell line KATO III in vitro and confirmed replacement of sialyl Lewis(x) to Sd(a) with a decrease in E-selectin-dependent adhesion. Administration of Ad5/3-B4GALNT2 vectors into the peritoneal cavity of mice after inoculation of KATO III cells with laparotomy significantly reduced the incidence of metastasis. Our results indicate that the transfer of a single gene encoding B4GALNT2 modified carbohydrate chains of cancer cells in vivo and decreased tumor dissemination and metastasis.

Analysis of rapid increase in the plasma density during the ramp-up phase in a radio frequency negative ion source by large-scale particle simulation.

Numerical simulations become useful for the developing RF-ICP (Radio Frequency Inductively Coupled Plasma) negative ion sources. We are developing and parallelizing a two-dimensional three velocity electromagnetic Particle-In-Cell code. The result shows rapid increase in the electron density during the density ramp-up phase. A radial electric field due to the space charge is produced with increase in the electron density and the electron transport in the radial direction is suppressed. As a result, electrons stay for a long period in the region where the inductive electric field is strong, and this leads efficient electron acceleration and a rapid increasing of the electron density.

Enhancement of leptin receptor signaling by SOCS3 deficiency induces development of gastric tumors in mice.

Leptin acts on its receptor (ObR) in the hypothalamus to inhibit food intake and energy expenditure. Leptin and ObR are also expressed in the gastrointestinal tract; however, the physiological significance of leptin signaling in the gut remains uncertain. Suppressor of cytokine signaling 3 (SOCS3) is a key negative feedback regulator of ObR-mediated signaling in the hypothalamus. We now show that gastrointestinal epithelial cell-specific SOCS3 conditional knockout (T3b-SOCS3 cKO) mice developed gastric tumors by enhancing leptin production and the ObRb/signal transducer and activator of transcription 3 (STAT3) signaling pathway. All T3b-SOCS3 cKO mice developed tumors in the stomach but not in the bowels by 2 months of age, even though the SOCS3 deletion occurred in both the epithelium of stomach and bowels. The tumors developed in the absence of the inflammatory response and all cKO mice died within 6 months. These tumors displayed pathology and molecular alterations, such as an increase in MUC2 (Mucin 2, oligomeric mucus/gel-forming) and TFF3 (trefoil factor 3), resembling human intestinal-type gastric tumors. Administration of antileptin antibody to T3b-SOCS3 cKO mice reduced hyperplasia of gastric mucosa, which is the step of the initiation of gastric tumor. These data suggest that SOCS3 is an antigastric tumor gene that suppresses leptin overexpression and ObRb/STAT3 hyperactivation, supporting the hypothesis that the leptin/ObRb/STAT3 axis accelerates tumorigenesis and that it may represent a new therapeutic target for the treatment of gastric cancer.

Swine hybrid aneurysm model for endovascular surgery training.

The aim of this study was to develop a technically simple swine aneurysm-training model by inserting a silicone aneurysm circuit in the cervical vessels. A silicone aneurysm circuit was created by designing multiple aneurysms in size and configuration on a silicone vessel. Five swine underwent surgical implantation of this circuit in the cervical vessels: one end in the common carotid artery and the other in the external jugular vein. Using this model, an aneurysm coiling procedure was simulated under fluoroscopic guidance, roadmapping and digital subtraction angiography. Creating an aneurysm model for training purposes by this method was technically simple and enabled the formation of a wide variety of aneurysms in a single procedure. The quality of the model was uniform and the model was reproducible. Coiling training using this model resembled a realistic clinical situation. The swine hybrid aneurysm-training model was advantageous from the standpoint of technical simplicity in the creation and variety of aneurysms it provided. The swine hybrid aneurysm model may be an additional option for aneurysm coiling training.

TWEAK/Fn14 pathway promotes a T helper 2-type chronic colitis with fibrosis in mice.

Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK), a TNF superfamily member, induces damage of the epithelial cells (ECs) and production of inflammatory mediaters through its receptor Fn14 in a model of acute colitis. In our current study of chronic colitis induced by repeated rectal injection of a hapten, we found that inflammation, fibrosis, and T helper 2 (Th2)-type immunity were significantly reduced in Fn14 gene knockout (KO) mice when compared with wild-type (WT) control mice. Expression of thymic stromal lymphopoietin (TSLP) was lower in Fn14 KO colon ECs than in WT ECs. TWEAK potentiates the induction of TSLP by interleukin-13 (IL-13) in colon explants from WT but not in Fn14 KO tissue. TSLP receptor KO mice exhibit milder chronic colitis, similar to that in Fn14 KO mice. TWEAK and IL-13 synergistically promote fibroblast proliferation. Thus we propose an IL-13-TWEAK/Fn14-TSLP axis as a key mechanism underlying chronic colitis with fibrosis.