Infantile outcome at 3 years of age among monochorionic twins with Type-II or -III selective fetal growth restriction with isolated oligohydramnios who underwent fetoscopic laser photocoagulation.

OBJECTIVE: This study aimed to examine infantile outcomes at 3 years of age with selective fetal growth restriction (sFGR) Types II and III with isolated oligohydramnios who underwent fetoscopic laser photocoagulation (FLP). METHODS: This multicenter prospective cohort study included monochorionic diamniotic twins who underwent FLP for sFGR between 16 and 25 weeks of gestation. The indication for performing FLP was in cases of sFGR Type II or III with oligohydramnios, where the maximal vertical pocket was ≤2 cm among twins with FGR. This was done in the absence of a typical twin-twin transfusion syndrome diagnosis. The primary outcome was the intact survival (IS) rate of infants at the corrected age of 40 weeks and 3 years. IS at the corrected age of 40 weeks was defined as survival without grade III or IV intraventricular hemorrhage or cystic periventricular leukomalacia, and IS at 3 years of age was defined as survival without neurodevelopmental morbidity, including cerebral palsy, neurodevelopmental impairment with a total developmental quotient of ≤70, bilateral deafness, or bilateral blindness. RESULTS: Among 45 patients with sFGR, 30 (66.7%) were classified as having Type II and 15 (33.3%) as Type III sFGR. The prevalence of IS at the corrected age of 40 weeks was 51.1% (n=23) in FGR twins and 95.5% (n=42) in larger twins. The prevalence of IS at 3 years of age was 46.7% (n=21) in FGR twins and 86.4% (n=38) in larger twins. Among the 24 FGR twins who were not diagnosed with IS at 3 years of age, 91.7% (22 of 24 cases) suffered fetal or infantile demise other than miscarriage and neurodevelopmental impairment. All larger twins who were not diagnosed with IS at 3 years of age (n=6, 13.6%) had neurological morbidity, in addition to one case of miscarriage. CONCLUSIONS: FGR twins and larger twins, when subjected to FLP due to sFGR coupled with umbilical artery Doppler abnormalities and isolated oligohydramnios, exhibit low rates of neurological morbidity and low mortality, respectively. Therefore, FLP for Type II or III sFGR with oligohydramnios may be a feasible and preferable management option. This article is protected by copyright. All rights reserved.

Spontaneous intranasal tumours in degus (Octodon degus): 20 cases (2007-2020).

OBJECTIVE: The objective of this retrospective study was to describe the clinical and histopathological findings associated with intranasal tumours in degus. MATERIALS AND METHODS: Medical records of degus diagnosed with intranasal neoplasms on histopathological examination between the years 2007 and 2020 at one hospital were included in the study. RESULTS MEDICAL RECORDS OF DEGUS: Twenty degus (10 males and 10 females) were eligible for inclusion. Initial clinical signs included sneezing, abnormal nasal sounds, and nasal discharge, followed by anorexia and frequent nose rubbing. On radiography, 15 out of 20 animals showed space-occupying lesions in the nasal cavity. CT was performed in 16 animals and revealed various degrees of changes, including abnormal radiopacity within the nasal cavity and damaged nasal septum. Rhinostomy and excisional biopsy was performed in all 20 animals. Six out of 20 patients died during the perioperative period. Six and seven degus survived for 3 months and 1 year, respectively. One animal was lost to follow-up. In 16 cases the histological diagnosis was consistent with fibromas, while in 4 cases with osteomas. CLINICAL SIGNIFICANCE: Intranasal neoplasms in degus are mostly benign mesenchymal tumours with various degrees of bone formation, which is unique to this animal species. This occurrence should be considered as an important differential diagnosis for upper respiratory tract disease in degus.

Optimisation of Radiation Therapy in Bladder Preservation Therapy for Patients With Clinical Stage T2N0M0 Bladder Cancer.

AIMS: A novel bladder preservation therapy, the OMC (Osaka Medical College) regimen, which combines radiation therapy with balloon-occluded arterial infusion of anticancer agents, is a treatment option for patients with muscle-invasive bladder cancer (MIBC). We retrospectively analysed the effects of changes in radiation dose and irradiation field on treatment efficacy and adverse events.The purpose of this study is to use the results of this study to help determine a course of radiation therapy for bladder preservation therapy of cT2N0M0 MIBC. MATERIALS AND METHODS: We examined 352 patients with clinical stage T2N0M0 (cT2N0M0) MIBC classified into the following groups based on the irradiation method: group A, the whole pelvis (50 Gy/25 fractions) + local bladder (10 Gy/5 fractions); group B, the small pelvis (50 Gy/25 fractions) + local bladder (10 Gy/5 fractions); group C, the whole pelvis (40 Gy/20 fractions) + local bladder (10 Gy/5 fractions). RESULTS: The complete response rate, 3-year overall survival and progression-free survival rates in group A were 92.9%, 94.9% and 82.1%, respectively; in group B were 87.2%, 86.7% and 76.7%, respectively; and in group C were 95.2%, 92.6% and 71.1%, respectively. No significant differences between the groups were noted. The incidence of ≥grade 3 urinary tract and gastrointestinal toxicities were not significantly different among the groups (group A: 7.8%, 1.7%; B, 11.1%, 0%; C, 7.1%, 1.8%, respectively). The 3-year progression-free rates of the common iliac lymph node (CILN) region in patients who received whole-pelvis and small-pelvis irradiation were 99.0 and 89.0% (P < 0.01), respectively, with the latter group having significantly high lymph node recurrence in the CILN region. CONCLUSIONS: Our findings showed that the optimal radiation therapy for patients with cT2N0M0 MIBC undergoing the OMC regimen is whole-pelvis irradiation including the CILN region, with a total dose of 50 Gy/25 fractions.

Impact of Magnetic Field Configuration on Heat Transport in Stellarators and Heliotrons.

We assess the magnetic field configuration in modern fusion devices by comparing experiments with the same heating power, between a stellarator and a heliotron. The key role of turbulence is evident in the optimized stellarator, while neoclassical processes largely determine the transport in the heliotron device. Gyrokinetic simulations elucidate the underlying mechanisms promoting stronger ion scale turbulence in the stellarator. Similar plasma performances in these experiments suggests that neoclassical and turbulent transport should both be optimized in next step reactor designs.

Spontaneous oral tumours in 18 rabbits (2005-2015).

This retrospective study of a series of 18 cases aimed to describe the clinical and pathological findings of oral tumours in rabbits, as there have been few reports detailing spontaneous oral tumours in this species. A total of 13 different tumour types were diagnosed: squamous cell carcinoma (three), ameloblastoma (two), fibrosarcoma (two), osteosarcoma (two), cementoma (one), complex odontoma (one), giant cell epulis (one), sarcoma (one), chondrosarcoma (one), trichoepithelioma (one), papilloma (one), malignant melanoma (one) and basal cell carcinoma (one). Odontogenic tumours were relatively common in this study as compared to the oral tumours typically identified in dogs and cats. The most common clinical sign in this study was feeding abnormalities. Surgical excision and radiation therapy were found to be effective in rabbits.

Spontaneous intranasal tumours in rabbits: 7 cases (2007-2019).

OBJECTIVES: Neoplasms that arise in the nasal cavity are reported infrequently in rabbits. This case series aims to review and determine the clinical behaviour of neoplasms in the nasal cavity in rabbits. MATERIALS AND METHODS: A retrospective study was conducted on seven pet rabbits diagnosed with intranasal tumours to describe the clinical and histopathological findings and prognoses after surgery and/or radiotherapy. RESULTS: The most common clinical signs were nasal snoring when breathing, nasal discharge, and subsequent dyspnoea and anorexia. Six different histopathological types of tumours were diagnosed: intranasal adenocarcinoma, squamous cell carcinoma, osteosarcoma, carcinoid tumour, osteoma, and lymphoma. Skull radiography only revealed the abnormalities in three of seven cases but on CT, the intranasal masses were more clearly identified in all cases. All cases received tumour resection through rhinostomy and four cases received radiotherapy after surgery. In the six cases with a known outcome, the survival time after surgery was more than 13 months. CLINICAL SIGNIFICANCE: This case series provides an insight of the behavior of intranasal neoplasms in rabbits. Surgical treatment and radiotherapy could improve their clinical sings.

Transition between Isotope-Mixing and Nonmixing States in Hydrogen-Deuterium Mixture Plasmas.

The transition between isotope-mixing and nonmixing states in hydrogen-deuterium mixture plasmas is observed in the isotope (hydrogen and deuterium) mixture plasma in the Large Helical Device. In the nonmixing state, the isotope density ratio profile is nonuniform when the beam fueling isotope species differs from the recycling isotope species and the profile varies significantly depending on the ratio of the recycling isotope species, although the electron density profile shape is unchanged. The fast transition from nonmixing state to isotope-mixing state (nearly uniform profile of isotope ion density ratio) is observed associated with the change of electron density profile from peaked to hollow profile by the pellet injection near the plasma periphery. The transition from nonmixing to isotope-mixing state strongly correlates with the increase of turbulence measurements and the transition of turbulence state from TEM to ion temperature gradient is predicted by gyrokinetic simulation.

Isotope effects in self-organization of internal transport barrier and concomitant edge confinement degradation in steady-state LHD plasmas.

The isotope effect, which has been a long-standing mystery in the turbulent magnetically confined plasmas, is the phenomena that the plasma generated with heavier hydrogen isotope show a mitigated transport. This is on the contrary to what is predicted with the simple scaling theory, in which the heavier ions easily diffuse because of its larger gyro-radius. Thanks to the newly developed analysis method and a comprehensive parameter scan experiment in the steady-state plasmas in the Large Helical Device (LHD), the isotope effect was clearly observed in the self-organized internal transport barrier (ITB) structure for the first time. Comparing the ITB intensity in deuterium (D) and hydrogen (H) plasmas, two distinct hydrogen isotope effects are found: stronger ITB is formed in D plasmas and a significant edge confinement degradation accompanied by the ITB formation emerges in H plasmas. This observation sheds light on a new aspect of the turbulent plasmas regarding how the basic properties of the fluid material affect the turbulent structure formation in the open-system.

Weaning stage hyperglycemia induces glucose-insensitivity in arcuate POMC neurons and hyperphagia in type 2 diabetic GK rats.

Hyperphagia triggers and accelerates diabetes, and prevents proper dietary control of glycemia. Inversely, the impact of hyperglycemia on hyperphagia and possible mechanistic cause common for these two metabolic disorders in type 2 diabetes are less defined. The present study examined the precise developmental process of hyperglycemia and hyperphagia and explored the alterations in the hypothalamic arcuate nucleus (ARC), the primary feeding and metabolic center, in Goto-Kakizaki (GK) rats with type 2 diabetes and nearly normal body weight. At mid 3 to 4 weeks of age, GK rats first exhibited hyperglycemia, and then hyperphagia and reduced mRNA expressions for anorexigenic pro-opiomelanocortin (POMC) and glucokinase in ARC. Furthermore, [Ca2+]i responses to high glucose in ARC POMC neurons were impaired in GK rats at 4 weeks. Treating GK rats from early 3 to mid 6 weeks of age with an anti-diabetic medicine miglitol not only suppressed hyperglycemia but ameliorated hyperphagia and restored POMC mRNA expression in ARC. These results suggest that the early hyperglycemia occurring in weaning period may lead to impaired glucose sensing and neuronal activity of POMC neurons, and thereby induce hyperphagia in GK rats. Correction of hyperglycemia in the early period may prevent and/or ameliorate the progression of hyperphagia in type 2 diabetes.

Assessment of diastolic function of normal fetal heart using dual-gate Doppler.

OBJECTIVES: The ratio of mitral peak early diastolic filling to early diastolic mitral annular velocity (E/e') reflects diastolic cardiac function in adults. Dual-gate Doppler (DD) enables measurements of E/e' in the same heart beat. This study was designed to assess the utility of the DD method for measurement of fetal E/e' and determine reference ranges for normal fetuses. METHODS: This prospective study comprised normal singleton pregnancies undergoing fetal echocardiography between 16 and 36 weeks of gestation. According to the DD method, E-wave velocity on pulsed-wave Doppler and e'-wave on tissue Doppler imaging were measured simultaneously on an apical or basal four-chamber view, and fetal E/e' was calculated. Spearman's correlation coefficient was used to assess the relationship between gestational age (GA) and E-wave and e'-wave velocities and E/e'. RESULTS: A total of 133 pregnancies were included in this study and all E/e' measurements were successful. Significant correlation was observed between GA and both left ventricular (LV) E/e' (r s  = -0.666, P < 0.001) and right ventricular (RV) E/e' (r s  = -0.607, P < 0.001). The regression equations for bilateral E/e' were: LV-E/e' = 17.341 - 0.631GA + 0.008 × GA2 (mean ± SD, R 2  = 0.440 ± 1.333); and RV-E/e' = 19.156 - 0.794GA + 0.012GA2 (R 2  = 0.419 ± 1.329). CONCLUSIONS: Bilateral E/e' of normal fetuses, measured using the DD method, decreased with GA, which is considered to be related to myocardial maturity. DD is a useful and convenient method for evaluating fetal E/e' in order to assess diastolic function in the prenatal period. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Lachrymal Gland Basal Cell Adenocarcinoma in a Ferret (Mustela putorius furo).

A 1 cm diameter mass was detected in the caudal superotemporal area of the left eye of a 6-year-old neutered male ferret (Mustela putorius furo). The mass and the left eye were removed surgically. Microscopical examination revealed a tumour of the adnexal gland of the eye that had invaded the surrounding ocular muscle. The tumour was composed of basal-type epithelial cells arranged in a solid, or occasionally tubular, pattern. Immunohistochemically, the tumour cells expressed cytokeratin and p63, but not smooth muscle actin. Based on these findings, the tumour was diagnosed as a basal cell adenocarcinoma of the lachrymal gland. In addition to the tumour, the retina of the left eye was detached and folded at the centre of the globe. This is the first report of a non-human case of basal cell adenocarcinoma of the lachrymal gland.

IL-10 gene transfer upregulates arcuate POMC and ameliorates hyperphagia, obesity and diabetes by substituting for leptin.

BACKGROUND: Obesity and metabolic syndrome are the major risk factors for cardiovascular disease. Obesity is caused by increased food intake and/or decreased energy expenditure. Leptin potently inhibits food intake and promotes energy expenditure. These effects of leptin involve the activation of proopiomelanocortin (POMC) neurons in the hypothalamus arcuate nucleus (ARC). Disruption of leptin signaling in POMC neuron is considered one of the major causes for obesity. AIMS: The present study aimed to examine whether overexpression of interleukin-10 (IL-10) could substitute for the leptin action and ameliorate obesity in leptin-deficient Lep(ob/ob) mice. DESIGN: Adeno-associated virus (AAV) expressing murine IL-10 (AAV-mIL-10) was injected into the skeletal muscle to overexpress IL-10 in mice. These mice were subsequently subjected to analysis of body weight, food intake, glucose metabolism and underlying mechanisms. RESULTS: In Lep(ob/ob) mice, AAV-IL-10 ameliorated hyperphagia, obesity, glucose intolerance and insulin resistance, as well as attenuated tumor necrosis factor-α expression. The IL-10 treatment also improved glucose-induced insulin release. Furthermore, IL-10 treatment increased POMC mRNA expression in ARC and phosphorylation of signal transducer and activator of transcription-3 (STAT3) in ARC and white adipose tissue (WAT). In neuron-specific STAT3-null mice that exhibited obesity and hyperphagia, AAV-mIL-10 administration failed to affect food intake, body weight and phosphorylation of STAT3 in WAT. CONCLUSIONS: These results demonstrate that peripheral overexpression of IL-10 induces STAT3 phosphorylation in ARC POMC neurons, and thereby ameliorates hyperphagia and obesity caused by leptin deficiency. IL-10 gene transfer may provide an effective approach for preventing progression of metabolic syndrome due to leptin resistance.

Cross-Scale Interactions between Electron and Ion Scale Turbulence in a Tokamak Plasma.

Multiscale gyrokinetic turbulence simulations with the real ion-to-electron mass ratio and ß value are realized for the first time, where the ß value is given by the ratio of plasma pressure to magnetic pressure and characterizes electromagnetic effects on microinstabilities. Numerical analysis at both the electron scale and the ion scale is used to reveal the mechanism of their cross-scale interactions. Even with the real-mass scale separation, ion-scale turbulence eliminates electron-scale streamers and dominates heat transport, not only of ions but also of electrons. Suppression of electron-scale turbulence by ion-scale eddies, rather than by long-wavelength zonal flows, is also demonstrated by means of direct measurement of nonlinear mode-to-mode coupling. When the ion-scale modes are stabilized by finite-ß effects, the contribution of the electron-scale dynamics to the turbulent transport becomes non-negligible and turns out to enhance ion-scale turbulent transport. Damping of the ion-scale zonal flows by electron-scale turbulence is responsible for the enhancement of ion-scale transport.

Ghrelin signalling in ß-cells regulates insulin secretion and blood glucose.

Insulin secretion from pancreatic islet ß-cells is stimulated by glucose. Glucose-induced insulin release is potentiated or suppressed by hormones and neural substances. Ghrelin, an acylated 28-amino acid peptide, was isolated from the stomach in 1999 as the endogenous ligand for the growth hormone (GH) secretagogue-receptor (GHS-R). Circulating ghrelin is produced predominantly in the stomach and to a lesser extent in the intestine, pancreas and brain. Ghrelin, initially identified as a potent stimulator of GH release and feeding, has been shown to suppress glucose-induced insulin release. This insulinostatic action is mediated by Gα(i2) subtype of GTP-binding proteins and delayed outward K⁺ (Kv) channels. Interestingly, ghrelin is produced in pancreatic islets. The ghrelin originating from islets restricts insulin release and thereby upwardly regulates the systemic glucose level. Furthermore, blockade or elimination of ghrelin enhances insulin release, which can ameliorate glucose intolerance in high-fat diet fed mice and ob/ob mice. This review focuses on the insulinostatic action of ghrelin, its signal transduction mechanisms in islet ß-cells, ghrelin's status as an islet hormone, physiological roles of ghrelin in regulating systemic insulin levels and glycaemia, and therapeutic potential of the ghrelin-GHS-R system as the target to treat type 2 diabetes.

Cardiac mesenchymal progenitors from postmortem cardiac tissues retained cellular characterization.

BACKGROUND AND OBJECTIVE: Currently, cells for transplantation in regenerative medicine are derived from either autologous or allogeneic tissue. The former has the drawbacks that the quality of donor cells may depend on the condition of the patient, while the quantity of the cells may also be limited. To solve these problems, we investigated the potential of allogeneic cardiac mesenchymal progenitors (CMPs) derived from postmortem hearts, which may be immunologically privileged similar to bone marrow-derived mesenchymal progenitors. MATERIALS AND METHODS: We examined whether viable CMPs could be isolated from C57/B6 murine cardiac tissues harvested at 24 hours postmortem. After 2- to 3-week propagation with a high dose of basic fibroblast growth factor, we performed cellular characteristics analyses, which included proliferation and differentiation property flow cytometry and microarray analyses. RESULTS: Postmortem CMPs had a longer lag phase after seeding than CMPs obtained from living tissues, but otherwise had similar characteristics in all the analyses. In addition, global gene expression analysis by microarray showed that cells derived from postmortem and living tissues had similar characteristics. CONCLUSION: These results indicate that allogeneic postmortem CMPs have potential for cell transplantation because they circumvent the issue of both the quality and quantity of donor cells.

Direct human mitochondrial transfer: a novel concept based on the endosymbiotic theory.

Mitochondria play an essential role in eukaryotes, and mitochondrial dysfunction is implicated in several diseases. Therefore, intercellular mitochondrial transfer has been proposed as a mechanism for cell-based therapy. In addition, internalization of isolated mitochondria cells by simple coincubation was reported to improve mitochondrial function in the recipient cells. However, substantial evidence for internalization of isolated mitochondria is still lacking, and its precise mechanism remains elusive. We tested whether enriched mitochondria can be internalized into cultured human cells by simple coincubation using fluorescence microscopy and flow cytometry. Mitochondria were isolated from endometrial gland-derived mesenchymal cells (EMCs) or EMCs stably expressing mitochondrial-targeted red fluorescent protein (EMCs-DsRed-mito), and enriched by anti-mitochondrial antibody-conjugated microbeads. They were coincubated with isogeneic EMCs stably expressing green fluorescent protein (GFP). Live fluorescence imaging clearly showed that DsRed-labeled mitochondria accumulated in the cytoplasm of EMCs stably expressing GFP around the nucleus. Flow cytometry confirmed the presence of a distinct population of GFP and DsRed double-positive cells within the recipient cells. In addition, transfer efficiency depended on mitochondrial concentration, indicating that human cells may possess the inherent ability to internalize mitochondria. Therefore, this study supports the application of direct transfer of isogeneic mitochondria as a novel approach for the treatment of diseases associated with mitochondrial dysfunction.