Case Report: Identification of a CARD8 variant in all three patients with PFAPA syndrome complicated with Kawasaki disease.

Background: Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA syndrome), and Kawasaki disease (KD) are both considered to be disorders of the innate immune system, and the potential role of inflammasome activation in the immunopathogenesis of both diseases has been previously described. Case presentation: Herein, we report the clinical courses of three patients who presented a rare combination of PFAPA syndrome and KD. Two patients who presented KD later developed the PFAPA syndrome, of whom one developed recurrent KD 2 years after the initial diagnosis. The third patient developed KD one year after the onset of PFAPA syndrome. The presence of both of these conditions within individual patients, combined with the knowledge that inflammasome activation is involved in both PFAPA syndrome and KD, suggests a shared background of inflammatory dysregulation. To elucidate the mechanism underlying shared inflammatory dysregulation, we investigated the roles of Nod-like receptors (NLRs) and their downstream inflammasome-related genes. All the patients had a frameshift variant in CARD8 (CARD8-FS). A previous study demonstrated a higher frequency of CARD8-FS, whose product loses CARD8 activity and activates the NLRP3 inflammasome, in patients with the PFAPA syndrome. Additionally, the NLRP3 inflammasome is known to be activated in patients with KD. Together, these results suggest that the CARD8-FS variant may also be essential in KD pathogenesis. As such, we analyzed the CARD8 variants among patients with KD. However, we found no difference in the variant frequency between patients with KD and the general Japanese population. Conclusions: We report the clinical courses of three patients with a rare combination of PFAPA syndrome and KD. All the patients had the CARD8-FS variant. However, we could not find a difference in the variant frequency between patients with KD and the general Japanese population. As the frequency of KD is much higher than that of PFAPA among Japanese patients, and the cause of KD is multifactorial, it is possible that only a small portion of patients with KD harbor CARD8-FS as a causative gene.

Hoarseness as the first symptom in a patient with acute suppurative thyroiditis secondary to a pyriform sinus fistula: a case report.

BACKGROUND: Pyriform sinus fistulas (PSFs) are rare congenital anomalies of the third or fourth brachial pouch. Dyspnea is reportedly secondary to compression by a neck mass. However, hoarseness, as the first symptom of PSF, has not yet been reported. CASE PRESENTATION: This report describes an 11-year-old girl presenting with hoarseness as the first symptom of PSF. Hoarseness occurred 2 days prior to admission. On admission, she had fever, hoarseness, and an elastic soft mass on her left anterior neck. Contrast-enhanced computed tomography of the cervical region demonstrated an abscess partially infiltrating the thyroid gland and an air pocket near the pyriform sinus. Pharyngoscopy revealed swelling of the left arytenoid region, with purulent retention. The left vocal cord was swollen but not paralyzed. Additionally, the laboratory data indicated thyrotoxicosis. Suspecting a PSF infection, parenteral treatment with cefotaxime and dexamethasone was initiated. On the following day, the hoarseness disappeared, and the fever resolved. Four weeks after onset, the thyroid hormone levels returned to the normal range, and a barium esophagogram revealed residual contrast in the left pyriform sinus, leading to a diagnosis of PSF. CONCLUSION: PSF presenting with hoarseness as the first symptom in patients should be considered.

Facility upgrade for superheavy-element research at RIKEN.

The RIKEN Nishina Center (RNC) executed an accelerator upgrade project for the heavy-ion linac (called RILAC). A superconducting RIKEN linear accelerator (SRILAC) and a new superconducting electron-cyclotron-resonance ion source (SC-ECRIS) to boost the final energy and intensity were constructed, aimed at synthesizing a new superheavy element, 119, through a hot fusion reaction. The project included the construction of a gas-filled recoil ion separator (GARIS-III) suitable for detecting the residues of the hot-fusion reaction. To avoid research interruption during the SRILAC construction period (2017-2019) and gain experience in hot-fusion reaction processes, GARIS-II located in the GARIS experimental hall in LINAC building was moved to the E6 experimental hall in Nishina building. Certain exploratory measurements were performed employing the beams accelerated by RILAC2 and the RIKEN ring cyclotron (RRC), which is a part of the existing accelerator complex of the radioactive isotope beam factory (RIBF). Further, commissioning experiments with the upgraded facility (SRILAC and GARIS-III) were performed. The upgrade project and its commissioning results are chronologically described in this article.

Commercial Pressure Retarded Osmosis Systems for Seawater Desalination Plants.

The development of renewable energy technologies is of global importance. To realize a sustainable society, fossil-resource-independent technologies, such as solar- and wind-power generation, should be widely adopted. Pressure retarded osmosis (PRO) is one such potential renewable energy technology. PRO requires salt water and fresh water, both of which can be found at seawater desalination plants. The total power generation capacity of PRO, using concentrated seawater and fresh water, is 3 GW. A large amount of energy is required for seawater desalination; therefore, the introduction of renewable energy should be prioritized. Kyowakiden Industry Co., Ltd., has been working on introducing PRO to seawater desalination plants since 2001 and is attracting attention for its ongoing PRO pilot plant with a scale of 460 m3/d, using concentrated seawater and treated sewage water. In this study, we evaluated the feasibility of introducing PRO in existing desalination plants. The feasibility was examined based on technology, operation, and economy. Based on the number of seawater desalination plants in each country and the electricity charges, it was determined whether the introduction of PRO would be viable.

Sequential Washing with Electrolyzed Alkaline and Acidic Water Effectively Removes Pathogens from Metal Surfaces.

Removal of pathogenic organisms from reprocessed surgical instruments is essential to prevent iatrogenic infections. Some bacteria can make persistent biofilms on medical devices. Contamination of non-disposable equipment with prions also represents a serious risk to surgical patients. Efficient disinfection of prions from endoscopes and other instruments such as high-resolution cameras remains problematic because these instruments do not tolerate aggressive chemical or heat treatments. Herein, we develop a new washing system that uses both the alkaline and acidic water produced by electrolysis. Electrolyzed acidic water, containing HCl and HOCl as active substances, has been reported to be an effective disinfectant. A 0.15% NaCl solution was electrolyzed and used immediately to wash bio-contaminated stainless steel model systems with alkaline water (pH 11.9) with sonication, and then with acidic water (pH 2.7) without sonication. Two bacterial species (Staphylococcus aureus and Pseudomonas aeruginosa) and a fungus (Candida albicans) were effectively removed or inactivated by the washing process. In addition, this process effectively removed or inactivated prions from the stainless steel surfaces. This washing system will be potentially useful for the disinfection of clinical devices such as neuroendoscopes because electrolyzed water is gentle to both patients and equipment and is environmentally sound.

Subvalvular aortic stenosis diagnosed by 3D transesophageal echocardiography.

The patient was a 13-year-old male with chief complaints of exertional chest pain and dyspnea. Cardiac murmur was suspected in a medical checkup at 1 month old, at which time he was diagnosed with subvalvular aortic stenosis. He had subsequently been under follow-up observation at a nearby hospital for subvalvular aortic stenosis. He was admitted to our department for surgery due to aggravation of symptoms that had occurred over the previous year. Transthoracic echocardiography after admission showed an abnormal structure in the subvalvular aortic area, and the maximum pressure gradient between the left ventricle and aortic valve was 84 mmHg. The preoperative valve area was 0.71 cm(2), as measured by the Doppler method. Measurement of valve area by the trace method was difficult. Transesophageal echocardiography (TEE) showed a septum-like structure extending from the ventricular septum in the subvalvular area. On 3D TEE, the valve areas in the systolic and diastolic phases were 0.86 and 0.49 cm(2), respectively. Postoperative echocardiography showed resection of the structure in the subvalvular area, and the postoperative course was favorable.

Differential localization of sphingomyelin synthase isoforms in neurons regulates sphingomyelin cluster formation.

Sphingomyelin (SM) plays important roles in regulating structure and function of plasma membrane, but how intracellular localization of SM is regulated in neuronal cells is not understood. Here we show that two isoforms of SM synthase (SMS) are differentially expressed in neuronal subtypes and that only SMS2 proteins localize in neurites of hippocampal neurons. Moreover, SMS proteins induce Lysenin-binding SM clusters exclusively in their vicinity although neurons hardly contain such cluster under control condition. These findings indicate three important notions about SM metabolism in neurons. First, the activity of SMS is the rate-limiting step of SM cluster formation. Second, the SM content or clustering can be modulated by SMS activity. Third, SMS1 and SMS2 play distinct roles in regulating local SM clustering. Particularly, SMS2, rather than SMS1, is likely to be the major enzyme that is important for SM synthesis in the long neurites and its tip, the growth cone.

A slightly elevated level of N-terminal pro-brain natriuretic peptide can predict coronary artery disease in a population with normal left ventricular function.

The prognostic and diagnostic values of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) in ischemic heart disease have already been investigated in many previous studies. Although NT-pro-BNP is affected by many factors, these previous studies did not strictly exclude them. This study included 110 patients who received coronary arteriography between November 2007 and September 2009. Excluded from the study were those patients who had clinical symptoms of heart failure, asynergy by echocardiography or left ventriculography (LVG), atrial fibrillation, prior myocardial infarction, valvular disease, lung disease, anemia or renal dysfunction. We compared the laboratory data, LVG and early transmitral-to-early diastolic annular velocity ratio (E/E (a)) in echocardiography between the group with coronary stenosis and the group without it. NT-pro-BNP and the low-density lipoprotein/high-density lipoprotein ratio (LDL/HDL) independently associated with the presence of coronary artery stenosis (odds ratio of NT-pro-BNP, each 50 pg/ml 2.367, 95% confidence interval 1.302-4.303, p = 0.005). The area under the curve of the receiver-operating characteristic (ROC) curve of NT-pro-BNP, used to predict coronary artery stenosis, was 0.801 (0.719-0.883, p < 0.001). According to the ROC curve, the optimal cut-off level for predicting coronary stenosis was 64.3 pg/ml (sensitivity 82.5%, false-positive 34%). NT-pro-BNP is an attractive supplemental marker to predict the presence of coronary artery stenosis in a population that strictly excluded any affecting factors. In the population without factors affecting NT-pro-BNP, a slight increase suggests the presence of ischemic heart disease. The normal criteria for NT-pro-BNP in the patients undergoing coronary angiography may be much lower than the one currently used.

Intervention for jailed diagonal branch is not necessary while stenting the left anterior descending artery.

OBJECTIVES: To evaluate whether or not to treat diagonal branches interventionally while implanting sirolimus-eluting stents (SES) in left anterior descending artery (LAD). BACKGROUND: Percutaneous coronary intervention (PCI) procedures are complicated, especially in the case of a bifurcation lesion. The complicated strategy of PCI may increase the quantity of contrast medium, fluoroscopy time, and the number of devices. METHODS: We retrospectively included 35 patients with stable angina who were treated with SES between July 2005 and December 2006. They had 40 LAD/diagonal branch bifurcation lesions. The diagonal branches had a diameter greater than 1.5 mm. We finished the procedure without inflating diagonal branches when their flow showed thrombolysis in myocardial infarction (TIMI) flow grade 3, even if the ostium of the branches had severe stenosis. Follow-up angiographies were performed 6 months later. The LAD and ostium of diagonal branches were evaluated according to the quantitative coronary angiography (QCA) measurements. RESULTS: The percent diameter stenosis (%DS) of the ostium of diagonal branches was worse post-PCI than at baseline (P = 0.0101). When comparing the follow-up values with the baseline values, there were no significant differences. Additionally, follow-up values were significantly better than the post-PCI values (P = 0.0016). There was no hospitalization for heart failure, angina, or cardiac death. There was only one restenosis in LAD at follow-up, and no diagonal branch became totally occluded or delayed. CONCLUSIONS: In the diagonal branches, the minimal lumen diameter decreased and diameter stenosis progressed temporarily; however, both parameters recovered at the time of follow-up.

A case of chronic dissecting aortic aneurysm complicated with rupture into the right atrium: Diagnosis by transesophageal echocardiography.

Although rupture of a dissecting aortic aneurysm into the pericardial sac, pleural cavities, or mediastinum is a frequently encountered complication of this entity, rupture into a right-sided cardiac chamber is extremely rare. An 80-year-old woman was admitted to this institution because of dyspnea and facial edema. One year before admission, a diagnosis of dissecting aortic aneurysm (Stanford A type) was made based on results of magnetic resonance imaging and transesophageal echocardiography (TEE); however, the patient and her family refused surgical therapy. On admission, blood pressure was 120/60 mmHg, and a Levine 3/6° continuous murmur was audible at the third and fourth intercostal spaces of the right sternal border. Chest x-ray film showed moderate cardiomegaly, congested lung fields, and bilateral pleural effusion. A two-dimensional echocardiogram revealed severe aortic root dilatation 80 mm in diameter with the intimal flap. Color flow Doppler imaging demonstrated abnormal flow toward the back space in dilated ascending aorta. Continuous wave Doppler imaging showed the peak velocity of this flow to be 4.8 m/s. This high-velocity flow strongly suggested that the dissecting aortic aneurysm had ruptured into the right-sided cardiac chamber, and shunt flow from the false lumen of the aortic aneurysm into the right atrium was directly visualized by TEE. Our diagnosis, based on these findings, was chronic dissecting aortic aneurysm with communication into the right atrium. In view of the patient's deteriorating clinical condition, cardiac catheterization was not performed before surgery. Surgery revealed an aneurysm of the ascending aorta measuring 90 mm in diameter and multiple fistulas approximately 2 to 3 mm in diameter arising from the false lumen of the aorta into the right atrium at the base of the atrial appendage. The patient underwent successful replacement of the ascending aorta and closure of the aorto-right atrial fistulas. She had an uneventful postoperative course and was discharged 7 weeks after surgery.