Second international guidelines for the diagnosis and management of hereditary hemorrhagic telangiectasia

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease with an estimated prevalence of 1 in 5000 that is characterized by the presence of vascular malformations (VMs). These result in chronic bleeding, acute hemorrhage, and complications from shunting through VMs. The goal of the Second International HHT Guidelines process was to develop evidence-based consensus guidelines for the management and prevention of HHT-related symptoms and complications. The guidelines were developed using the AGREE II (Appraisal of Guidelines for Research and Evaluation II) framework and GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. The guidelines expert panel included expert physicians (clinical and genetic) in HHT from 15 countries, guidelines methodologists, health care workers, health care administrators, patient advocacy representatives, and persons with HHT. During the preconference process, the expert panel generated clinically relevant questions in 6 priority topic areas. A systematic literature search was done in June 2019, and articles meeting a priori criteria were included to generate evidence tables, which were used as the basis for recommendation development. The expert panel subsequently convened during a guidelines conference to conduct a structured consensus process, during which recommendations reaching at least 80% consensus were discussed and approved. The expert panel generated and approved 6 new recommendations for each of the following 6 priority topic areas: epistaxis, gastrointestinal bleeding, anemia and iron deficiency, liver VMs, pediatric care, and pregnancy and delivery (36 total). The recommendations highlight new evidence in existing topics from the first International HHT Guidelines and provide guidance in 3 new areas: anemia, pediatrics, and pregnancy and delivery. These recommendations should facilitate implementation of key components of HHT care into clinical practice.

Cauda Equina and Filum Terminale Arteriovenous Fistulas: Anatomic and Radiographic Features.

Intradural AVF below the conus medullaris may develop either on the filum terminale or the cauda equina (lumbosacral and coccygeal radicular nerves). Although not a few filum terminale AVFs are found in the literature, only 3 detailed cauda equina AVFs have been reported. Here, we analyze the angiographic and MR imaging findings of our cauda equina and filum terminale AVF cases, supplemented with literature research to characterize the radiologic features of the 2 entities. On angiography, filum terminale AVFs were invariably supplied by the extension of the anterior spinal artery accompanied by a closely paralleling filum terminale vein. Cauda equina AVFs were fed by either a radicular or a spinal artery or both arteries, often with a characteristic wavy radicular-perimedullary draining vein. On thin-section axial MR imaging, the filum terminale AVF draining vein joined the spinal cord at the conus medullaris apex, but that of the cauda equina AVF joined above the conus medullaris apex.

Control system for the new RIKEN 28-GHz superconducting electron cyclotron resonance ion source for SRILAC.

A new RIKEN 28-GHz superconducting electron cyclotron resonance ion source (SC-ECRIS) has been installed for the superconducting RIKEN linear accelerator (SRILAC). The new SC-ECRIS control system mainly consists of programmable logic controllers (PLCs) embedded with the Experimental Physics and Industrial Control System. To improve the reliability as compared with previous control systems, two types of PLC central processing units, sequential and Linux, have been installed in the same unit. Past experience has shown that new types of designs that can rapidly respond to system scalability are key. By connecting PLC stations using star-topology field buses, their rapid and cost-effective response to system changes is realized for the new devices. Furthermore, a unique data acquisition system employing a 920-MHz-band radio was developed to measure analog data such as the temperature at the high-voltage stage.

Safer Vitrification of Mouse and Human Embryos Using the Novel Cryoroom Vitrification System for Assisted Reproductive Technology.

BACKGROUND: Vitrification is widely used for assisted reproductive technology (ART). Most vitrification devices require the skillful placement of embryos into the carrier and aspiration of excessive vitrification solution. OBJECTIVE: To evaluate the efficacy and safety of the Cryoroom as a vitrification device. MATERIALS AND METHODS: Mouse and human embryos were vitrified with Cryoroom or Cryotop, and the developmental potency was assessed in vitro. Mouse monozygotic twin blastocysts were vitrified with Cryoroom or Cryotop for microarray analysis. RESULTS AND DISCUSSION: In mouse and human embryos, there were no differences between the survival and developmental progress in each device. In silico, the Cryoroom device showed no changes, particularly in DNA methylation after vitrification compared with the Cryotop. These results showed that the form and function of the device may affect the gene expression levels in vitrified embryos. CONCLUSION: The Cryoroom represents a safe and potentially revolutionary vitrification device for ART.

Cardio-cephalic neural crest syndrome: A novel hypothesis of vascular neurocristopathy.

A novel hypothesis proposes that "cardio-cephalic neural crest (NC) syndrome," i.e. cephalic NC including cardiac NC, contributes to the concurrent occurrence of vascular diseases in the cardio- and cerebrovascular regions. NC is a transient structure present in early embryogenesis. Cephalic NC provides mesenchymal cells to the vascular media in these regions. Concurrent cardio- and cerebrovascular lesions have been reported in PHACE syndrome, ACTA2 mutation syndrome, and less frequently in the spontaneous occlusion of the circle of Willis (so-called moyamoya disease). Cardiovascular lesions in these syndromes include coarctation of the aorta, persistent truncus arteriosus, patent ductus arteriosus, and coronary artery disease, and cerebrovascular lesions include agenesis and stenosis/occlusion of the internal carotid arteries, and moyamoya phenomenon. These concurrent vascular lesions both in the cardio- and cerebrovascular regions might be related to cephalic NC. This hypothesis, although not proven, may facilitate a better understanding of the above-mentioned NC-related vascular pathologies and lead to appropriate diagnostic and therapeutic approaches for clinicians and chart future direction for researchers.

Control system renewal for efficient operation in RIKEN 18 GHz electron cyclotron resonance ion source.

A RIKEN 18 GHz electron cyclotron resonance ion source (18 GHz ECRIS) is used as an external ion source at the Radioactive Ion Beam Factory (RIBF) accelerator complex to produce an intense beam of medium-mass heavy ions (e.g., Ca and Ar). In most components that comprise the RIBF, the control systems (CSs) are integrated by the Experimental Physics and Industrial Control System (EPICS). On the other hand, a non-EPICS-based system has hardwired controllers, and it is used in the 18 GHz ECRIS CS as an independent system. In terms of efficient and effective operation, the 18 GHz ECRIS CS as well as the RIBF CS should be renewed using EPICS. Therefore, we constructed an 18 GHz ECRIS CS by using programmable logic controllers with embedded EPICS technology. In the renewed system, an operational log system was developed as a new feature, for supporting of the 18 GHz ECRIS operation.

Structures and immunolocalization of Na+, K+ -ATPase, Na+ /H+ exchanger 3 and vacuolar-type H+ -ATPase in the gills of blennies (Teleostei: Blenniidae) inhabiting rocky intertidal areas.

The structure and immunolocalization of the ion transporters Na(+) ,K(+) -ATPase (NKA), Na(+) /H(+) exchanger (NHE3) and vacuolar-type H(+) -ATPase (VHA) were examined in the gills of teleosts of the family Blenniidae, which inhabit rocky shores with vertical zonation in subtropical seas. These features were compared among the following species with different ecologies: the amphibious rockskipper blenny Andamia tetradactylus, the intertidal white-finned blenny Praealticus tanegasimae and the purely marine yaeyama blenny Ecsenius yaeyamaensis. Light and electron microscopic observations indicated that thick gill filaments were arranged close to each other and alternately on two hemibranches of a gill arch in the opercular space of A. tetradactylus. Many mucous cells (MC) and mitochondrion-rich cells (MRC) were present in the interlamellar regions of the gill filament. An immunohistochemical study demonstrated that numerous NKA, NHE3 and some VHA were located predominantly on presumed MRCs of gill filaments and at the base of the lamellae. Analyses using serial (mirror image) sections of the gills indicated that only a few NKA immunoreactive cells (IRC) were colocalized with VHA on some MRCs in the filaments. In the gills of P. tanegasimae, NKA- and NHE3-IRCs were observed in the interlamellar region of the filaments and at the base of the lamellae. VHA-IRCs were located sparsely on the lamellae and filaments. In the gills of E. yaeyamaensis, the lamellae and filaments were thin and straight, respectively. MCs were located at the tip as well as found scattered in the interlamellar region of gill filaments. NKA-, NHE3- and VHA-IRCs were moderately frequently observed in the filaments and rarely on the lamellae. This study shows that the structure and distribution of ion transporters in the gills differ among the three blennid species, presumably reflecting their different ecologies.

Results of RIKEN superconducting electron cyclotron resonance ion source with 28 GHz.

We measured the beam intensity of highly charged heavy ions and x-ray heat load for RIKEN superconducting electron cyclotron resonance ion source with 28 GHz microwaves under the various conditions. The beam intensity of Xe(20+) became maximum at B(min) ∼ 0.65 T, which was ∼65% of the magnetic field strength of electron cyclotron resonance (B(ECR)) for 28 GHz microwaves. We observed that the heat load of x-ray increased with decreasing gas pressure and field gradient at resonance zone. It seems that the beam intensity of highly charged heavy ions with 28 GHz is higher than that with 18 GHz at same RF power.

Production of a highly charged uranium ion beam with RIKEN superconducting electron cyclotron resonance ion source.

A highly charged uranium (U) ion beam is produced from the RIKEN superconducting electron cyclotron resonance ion source using 18 and 28 GHz microwaves. The sputtering method is used to produce this U ion beam. The beam intensity is strongly dependent on the rod position and sputtering voltage. We observe that the emittance of U(35+) for 28 GHz microwaves is almost the same as that for 18 GHz microwaves. It seems that the beam intensity of U ions produced using 28 GHz microwaves is higher than that produced using 18 GHz microwaves at the same Radio Frequency (RF) power.

Binding analysis of peptides that recognize preferentially cis-azobenzene groups of synthetic polymers.

Peptides identified by the PD method against a film surface composed of azobenzene-containing synthetic polymers were characterized by QCM measurements. Among the four peptides analyzed, the c16 peptide with the sequence Trp-His-Thr-Leu-Pro-Asn-Ala showed the highest binding affinity to the films rich in cis-azobenzene groups. SPR served to determine the association/dissociation constants of the c16 peptide against the trans- and cis-azobenzene groups. The binding constants were estimated to be 1.3 × 10(5) and 1.4 × 10(6) /M, respectively, indicating a high specificity of the c16 peptide for cis-azobenzene conformer. Then mutants of the c16 peptide were synthesized and characterized to gain information on the structural requirements for the cis-form specificity. An Ala-scan clearly revealed that all the amino acid residues of the c16 peptide were essential for the specificity. More importantly, the results with peptides of inverted sequence and containing Gly insertions confirmed that the specificity is strictly derived from the primary sequence of the c16 peptide.

Biological significance of plasminogen activator inhibitor-1 expression in ovarian clear cell adenocarcinoma.

PURPOSE: Ovarian clear cell adenocarcinoma (OCCA) has been reported to display different characteristics from other histological types of epithelial ovarian cancer, and especially differs from serous adenocarcinoma. We investigated plasminogen activator inhibitor-1 (PAI-1) expression in patients with OCCA and attempted to assess its biological significance. METHODS: Fifty-seven patients with OCCA were enrolled. We used formalin-fixed, paraffin-embedded sections of the primary tumor obtained at the first operation to investigate the immunohistochemical expression of PAI-1 and the association of PAI-1 expression with various clinicopathologic factors. RESULTS: The 57 patients were classified into a high PAI-1 expression group and a low expression group. Comparison between the two groups revealed that the percentage of patients with concomitant endometriosis was significantly larger in the high expression group, while the percentage of Stage I patients with positive peritoneal cytology was significantly larger in the low expression group. Comparison of cumulative 5-year survival rates showed that the high expression group had a better prognosis than the low expression group. CONCLUSION: These data suggest an association between concomitant endometriosis and increased expression of PAI-1 in OCCA. The data also suggest that PAI-1 expression influences both peritoneal dissemination of early OCCA and the prognosis.

First results from the new RIKEN superconducting electron cyclotron resonance ion source (invited).

The next generation heavy ion accelerator facility, such as the RIKEN radio isotope (RI) beam factory, requires an intense beam of high charged heavy ions. In the past decade, performance of the electron cyclotron resonance (ECR) ion sources has been dramatically improved with increasing the magnetic field and rf frequency to enhance the density and confinement time of plasma. Furthermore, the effects of the key parameters (magnetic field configuration, gas pressure, etc.) on the ECR plasma have been revealed. Such basic studies give us how to optimize the ion source structure. Based on these studies and modern superconducting (SC) technology, we successfully constructed the new 28 GHz SC-ECRIS, which has a flexible magnetic field configuration to enlarge the ECR zone and to optimize the field gradient at ECR point. Using it, we investigated the effect of ECR zone size, magnetic field configuration, and biased disk on the beam intensity of the highly charged heavy ions with 18 GHz microwaves. In this article, we present the structure of the ion source and first experimental results with 18 GHz microwave in detail.

Development of "extended radical retropubic prostatectomy": a surgical technique for improving margin positive rates in prostate cancer.

AIMS: The objective of this study was to introduce a surgical approach called "extended radical retropubic prostatectomy (ERRP)" developed to reduce positive surgical margin rates in prostate cancer. METHODS: Modified surgical procedures in ERRP included apical dissection (division of the dorsal venous complex far distal to the prostatic urethral junction), excision of the bilateral neurovascular bundles (wide resection of structure between the exterior of the urethra and the rectal surface, which contains the neurovascular bundle), perirectal dissection (complete resection of perirectal tissue by dissecting the anterior rectal surface until the muscle layer of the rectum was encountered) and seminal vesicle excision (dissection that leaves seminal vesicles protected by Denonvilliers' fascia with the surrounding fatty and fascial coverings without pulling seminal vesicles from the prostate). This study included 127 consecutive patients who did not request the preservation of potency and underwent ERRP without any neoadjuvant therapies. RESULTS: Median value of preoperative serum prostate specific antigen in 127 patients was 18.1 ng/ml. Median operative time and estimated blood loss in these patients were 209 min and 744 ml, respectively. The pathological stage was diagnosed as pT2, pT3a, pT3b and pT4 in 51, 52, 20 and 4, respectively, while positive surgical margin was detected in 14 of the 127 patients. Furthermore, during the observation period of this study (median, 46 months), biochemical recurrence was detected in 11 of the 127 patients. CONCLUSIONS: The ERRP technique could successfully decrease the positive surgical margin rate even in patients with comparatively adverse disease characteristics.

Cerebral diagnostic and therapeutic angiography for neonatal arteriovenous fistulas.

SUMMARY: Cerebral diagnostic and therapeutic angiography for neonatal arteriovenous fistulas is reported. Three neonatal boys with vein of Galen aneurysmal malformation (1 patient) and dural arteriovenous fistulas (2 patients) presented severe congestive heart failure soon after birth, and were treated by transarterial and/or transvenous embolization using various access routes. In the neonatal period, umbilical approach and direct cervical approach provide unique access routes in addition to the usual transfemoral route. Characteristics of neonatal angiography are discussed.