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Estrogen plays an important role in osteoporosis prevention. We herein report the possible novel signaling pathway of 17β-estradiol (E2) in the matrix mineralization of MC3T3-E1, an osteoblast-like cell line. In the culture media-containing stripped serum, in which small lipophilic molecules such as steroid hormones including E2 were depleted, matrix mineralization was significantly reduced. However, the E2 treatment induced this. The E2 effects were suppressed by ICI182,780, the estrogen receptor (ER)α, and the ERβ antagonist, as well as their mRNA knockdown, whereas Raloxifene, an inhibitor of estrogen-induced transcription, and G15, a G-protein-coupled estrogen receptor (GPER) 1 inhibitor, had little or no effect. Furthermore, the E2-activated matrix mineralization was disrupted by PMA, a PKC activator, and SB202190, a p38 MAPK inhibitor, but not by wortmannin, a PI3K inhibitor. Matrix mineralization was also induced by the culture media from the E2-stimulated cell culture. This effect was hindered by PMA or heat treatment, but not by SB202190. These results indicate that E2 activates the p38 MAPK pathway via ERs independently from actions in the nucleus. Such activation may cause the secretion of certain signaling molecule(s), which inhibit the PKC pathway. Our study provides a novel pathway of E2 action that could be a therapeutic target to activate matrix mineralization under various diseases, including osteoporosis. [ABSTRACT FROM AUTHOR]

The Japanese Network of Cardiovascular Departments for Adult Congenital Heart Disease (JNCVD-ACHD) was founded in 2011 for the lifelong care of adult patients with congenital heart disease (ACHD patients). This network maintains the first Japanese ACHD registry. From 2011 to 2019, the JNCVD-ACHD registered 54 institutions providing specialized care for ACHD patients in 32 of the 47 prefectures in Japan. The registry collected data on the disease profile for 24,048 patients from 50 institutions and the patient characteristics for 9743 patients from 24 institutions. The most common ACHDs were atrial septal defect (20.5 %), ventricular septal defect (20.5 %), tetralogy of Fallot (12.9 %), and univentricular heart (UVH)/single ventricle (SV; 6.6 %). ACHD patients without biventricular repair accounted for 37.0 % of the population. Also examined were the serious anatomical and/or pathophysiological disorders such as pulmonary arterial hypertension (3.0 %) including Eisenmenger syndrome (1.2 %), systemic right ventricle under biventricular circulation (sRV-2VC; 2.8 %), and Fontan physiology (6.0 %). The sRV-2VC cases comprised congenitally corrected transposition of the great arteries without anatomical repair (61.9 %) and transposition of the great arteries with atrial switching surgery (38.1 %). The primary etiology (86.4 %) for Fontan physiology was UVH/SV. In addition, developmental/chromosomal/genetic disorders were heterotaxy syndromes (asplenia, 0.9 %; polysplenia, 0.7 %), trisomy 21 (4.0 %), 22q11.2 deletion (0.9 %), Turner syndrome (0.2 %), and Marfan syndrome (1.1 %). Although the specific management of ACHD has systematically progressed in Japan, this approach is still evolving. For ideal ACHD care, the prospective goals for the JNCVD-ACHD are to create local networks and provide a resource for multicenter clinical trials to support evidence-based practice. [Display omitted] • JNCVD-ACHD registers 54 centers for adult congenital heart disease (CHD). • JNCVD-ACHD establishes lifelong care for adults with CHD. • The JNCVD-ACHD patient registry shows characteristics and challenges of adult CHD. • JNCVD-ACHD is a resource for multi-center clinical trials for adult CHD care. [ABSTRACT FROM AUTHOR]

A retrospective chart survey of the clinical features of indolent adult T-cell leukemia/lymphoma (ATL) was conducted in the Miyazaki Prefecture, Japan. This study enrolled 24 smoldering-type ATLs, 10 favorable chronic-type ATLs, and 20 unfavorable chronic-type ATLs diagnosed between 2010 and 2018. Among them, 4, 3, and 10 progressed to acute-type ATLs during their clinical course. The median survival time (MST) in smoldering-type ATL and favorable chronic-type ATL was not reached, and their 4-year overall survival (OS) was 73% and 79%, respectively. Compared with this, the prognosis of unfavorable chronic-type ATL was poor. Its MST was 3.32 years, and the 4-year OS was 46% (p = 0.0095). In addition to the three features that determine the unfavorable characteristics of chronic-type ATL, namely, increased lactate dehydrogenase, increased blood urea nitrogen, and decreased albumin, the high-risk category by the indolent ATL-Prognostic Index, which was defined by an increment of soluble interleukin-2 receptor (sIL2-R) of >6000 U/mL, could explain the poor prognosis in indolent ATL patients. The level of sIL-2R might be an indicator of the initiation of therapy for indolent ATL. [ABSTRACT FROM AUTHOR]

In the late phase after Fontan surgery, organ dysfunction due to high central venous pressure (CVP) is a major clinical problem. We have described the cases of two patients with portosystemic shunts who exhibited hyperammonemia and high cardiac output associated with peripheral vasodilatation after Fontan surgery. A high CVP in these patients may have resulted in the formation of a portosystemic shunt. We performed coil embolization and balloon-occluded retrograde transvenous obliteration for each case. The possibility of a portosystemic shunt as a postoperative complication of Fontan surgery should always be considered. Early detection and therapeutic intervention seem necessary from the viewpoint of stabilizing the Fontan circulation and delaying the progression of liver disorder. < Learning objectives: A portosystemic shunt may develop due to the high central venous pressure after Fontan surgery independent of hepatic disorder and should be considered as a potential cause of unexplained hyperammonemia and high cardiac output status. Transcatheter closure of the portosystemic shunt may improve the clinical status.> [ABSTRACT FROM AUTHOR]

Objective and Method: Adult T‐cell leukemia/lymphoma (ATL) is an aggressive peripheral T‐cell lymphoma with poor prognosis. We retrospectively reviewed the medical records of 312 patients with aggressive ATL and analyzed the effect of chemotherapy dose intensity on prognosis in clinical practice. Result: As first‐line therapy, 62 patients underwent best supportive care (BSC) or single‐agent chemotherapy, and 235 underwent intensive chemotherapy. The median survival time (MST) was 0.58 years in the 312 total patients, and 0.13 years and 0.75 years in the BSC/single‐agent chemotherapy group and intensive chemotherapy group, respectively. The median average relative dose intensity (ARDI) of patients who received intensive chemotherapy was 60%. We divided patients into 3 groups according to ARDI. Those in the top tertile of ARDI (ARDI ≥ 75%, n = 82) had better overall survival compared with those in the intermediate tertile (45% ≤ ARDI < 75%, n = 79) (P <.0001), with MSTs of 4.69 and 0.75 years, respectively. The occurrence of organ dysfunction and infectious complications was comparable between the two ARDI groups. Conclusion: Higher ARDI improves prognosis in patients with aggressive ATL in clinical practice. [ABSTRACT FROM AUTHOR]

Left ventricular noncompaction (LVNC) is a hereditary cardiomyopathy and is associated with high morbidity and mortality. However, the role and significance of school screening for LVNC have not been fully elucidated. In this multicenter, retrospective cohort study, a total of 105 children with LVNC were included from 2000 to 2017. At the initial presentation, 44 patients (41.9%) were diagnosed by school screening. One (1.0%) patient underwent heart transplantation and four (3.8%) patients died during the study. Electrocardiogram data showed a high prevalence of fragmented QRS (33.4%) and J wave (15.7%). Treatments were needed in eight (18.2%) patients who were detected by school screening. The multivariable proportional hazards model showed T-wave abnormality on electrocardiogram in first graders was independent risk factors for major adverse cardiac events (odds ratio 4.94, p value = 0.0007). Moreover, dilation of the left atrium on chest X-ray and low ejection fraction on echocardiogram at the initial treatment were independent risk factors for treatment (odds ratio 1.7 × 107 and 22.3, p = 0.0362 and 0.0028, respectively). This study is the first report focusing on school screening in a large pediatric cohort with LVNC. With the use of abnormalities in electrocardiogram, school screening may be a good detector of and predictor for LVNC. [ABSTRACT FROM AUTHOR]

Crystalline SiO2 clusters of nearly square shape were fabricated from amorphous silicon deposited on a clean Si(001) surface, where the deposited silicon was oxidized in the presence of atomic hydrogen and annealed in an O2 atmosphere. The side of these clusters was aligned along the [110] and [110] azimuths of the Si(001) substrate. The crystallinity of the clusters was verified by grazing incidence x-ray diffraction and low-energy electron diffraction. The crystal structure of SiO2 clusters was estimated to be β-tridymite, whose [1010] and [0001] axes were parallel to the <110> axes of the substrate Si(001). When the Si(001) surface without deposited amorphous silicon was oxidized by the method described above, single-crystal SiO2 clusters were also prepared. However, the shape, the size, and the number density of the clusters were different from those of the clusters made from the amorphous silicon. [ABSTRACT FROM AUTHOR]

We synthesized micrometer-sized three-dimensional superlattices consisting of gold (Au) nanocrystals modified with three types of water-soluble thiolates in different dimensions: mercaptosuccinic acid (MSA), N-(2-mercaptopropionyl)-glysine (MPG), and glutathione in its reduced form (GTR). The nanoparticles were assembled at an air/water interface by decreasing the repulsive interactions between the surface modifiers. This was accomplished by adjusting acid concentration. Using x ray and transmission electron diffractometry, MSA- and MPG-modified Au nanoparticle superlattices were identified as hcp single-crystal structures, while the GTR-modified nanoparticle superlattices were determined to be a fcc single-crystal structure. Optical absorption studies show that the surface plasmon peaks redshifted as the nanoparticle density of the assemblages increased and the peak widths decreased when the nanoparticles formed lattice arrangements. In contrast, optical absorption studies of randomly assembled nanoparticles demonstrated increased peak widths as nanoparticle density increased. To explain these observed characteristic features in the surface plasmons, we introduced a qualitative model for the electronic polarizability of these superlattices. [ABSTRACT FROM AUTHOR]

Crystalline Si[O.sub.2] clusters of square shape are prepared from amorphous silicon deposited on a clean Si(001) surface, where the deposited silicon is oxidized in the presence of atomic hydrogen and annealed in an [O.sub.2] atmosphere. The studies have shown that the shape, the size, and the number density of the clusters are different from those of the clusters made from the amorphous silicon.

Small gold clusters (< 1 nm), protected by monolayers of glutathione, N-(2-mercaptopropionyl)glycine, or mercaptosuccinic acid, are prepared by reducing the corresponding Au(I)-thiolate polymers and are fractioned by size using polyacrylamide gel electrophoresis (PAGE). The observation implies that deformation of the underlying gold cores is induced by interligand interactions.

Summary: Background: Conventional treatments of chronic hepatitis B virus (HBV) infection rarely achieve a decline of serum hepatitis B surface antigen (HBsAg) levels and eradication of the virus. Aim: To elucidate the antiviral mechanisms of a human microRNA, miR‐302c‐3p, against HBV replication. Methods: The antiviral effect of miR‐302c‐3p was evaluated in vitro and in vivo by transfecting the miR‐302c‐3p mimic into HBV‐infected HepG2‐hNTCP‐C4 cells and HBV transgenic mice respectively. Results: miR‐302c‐3p decreased not only HBV replication but also production of HBsAg. Pregenomic RNA and HBsAg mRNA concentrations decreased in the cells treated with miR‐302c‐3p. Interestingly, the amount of cccDNA was significantly reduced in the miR‐302c‐3p‐treated cells, in association with disappearance of the HBV core protein. An RNA immunoprecipitation assay showed that miR‐302c‐3p decreased the binding of the HBV polymerase to the pregenomic RNA by hybridising with the ε‐loop region. A number of host genes were downregulated in miR‐302c‐3p‐treated cells, including BMPR2 and HNF4A. Knockdown of these two genes by corresponding siRNAs also suppressed HBV replication and HBsAg secretion. The antiviral effect of miR‐302c‐3p was also observed in HBV transgenic mice. Conclusion: miR‐302c‐3p had anti‐HBV activity, in vitro and in vivo, via several mechanisms. [ABSTRACT FROM AUTHOR]

The self-correcting processes and inclusions of water molecules in the crystal during the equilibrium growth are discovered. The results have shown that water clusters are trapped in the interstice of superlattices and connect the building gold nanoparticles through hydrogen bonding.

Whetten and co-workers fractionated gold clusters protected by monolayers of glutathione (GSH=gamma-Glu-Cys-Gly) by using polyacrylamide gel electrophoresis (PAGE) and identified the most abundant species as Au28(SG)16 by mass spectrometric characterization of electrophoratically fractioned Au:SG clusters. Results provide basic guidelines for studies on structures, stabilities and optical properties of small gold MPC's as well as for development of new cluster based materials.

Objective The efficacy of mogamulizumab in adult T-cell leukemia/lymphoma ( ATLL) was reported in a previous phase 2 study. Compared with patients in clinical trials, however, most patients in real-life settings have demonstrated worse outcomes. Method We retrospectively analyzed 96 patients with relapsed/refractory ATLL who received mogamulizumab treatment. Results Relapsed/refractory ATLL patients with a median age of 70 years received a median of five courses of mogamulizumab. Hematologic toxicity and skin rash were the most common adverse events, and both were manageable. Of 96 patients, 87 were evaluable for efficacy. The overall response rate was 36%, and the median progression-free survival ( PFS) and overall survival ( OS) from the start of mogamulizumab therapy were 1.8 and 4.0 months, respectively. Of the original 96 patients, only 25 fulfilled the inclusion criteria of the phase 2 study. Those who met the criteria demonstrated longer median PFS and OS durations of 2.7 and 8.5 months, respectively. The median OS from diagnosis in relapsed/refractory ATLL patients receiving mogamulizumab was 12 months, longer than the 5.8 months in a historical cohort without mogamulizumab. Conclusion In clinical practice, mogamulizumab exhibited antitumor activity in patients with relapsed/refractory ATLL, with an acceptable toxicity profile. Mogamulizumab therapy improved the OS of ATLL patients. [ABSTRACT FROM AUTHOR]

We herein report a severe case of pyoderma gangrenosum occurring in a burn patient and discuss the possibility of occult complications of this pathological state in daily treatment. [ABSTRACT FROM PUBLISHER]