Development of Magnetic Resonance-Compatible Head Immobilization Device and Initial Experience of Magnetic Resonance-Guided Radiation Therapy for Central Nervous System Tumors.

PURPOSE: We aimed to develop and investigate positional reproducibility using a fixation device (Unity Brain tumor Immobilization Device [UBID]) in patients with brain tumor undergoing magnetic resonance (MR)-guided radiation therapy (RT) with a 1.5 Tesla (T) MR-linear accelerator (MR-LINAC) to evaluate its feasibility in clinical practice and report representative cases of patients with central nervous system (CNS) tumor. MATERIALS AND METHODS: Quantitative analysis was performed by comparing images obtained by placing only the MR phantom on the couch with those obtained by placing UBID next to the MR phantom. Twenty patients who underwent RT for CNS tumors using 1.5T MR-LINAC between June and October 2022 were retrospectively analyzed. Among them, 5 did not use UBID, whereas 15 used UBID. The positional reproducibility of UBID was evaluated using the median interfractional and intrafractional errors in the first 10 fractions. RESULTS: Each MR quality factor of the MR phantom with UBID satisfied the criteria presented by Elekta. Median values of median shifts in the mediolateral, anteroposterior, and craniocaudal axes for interfractional errors were 2.98, 2.35, and 1.40 mm, respectively. For intrafractional errors, the median values were 0.05, 0.03, and 0.06 mm, respectively. The median values of the median rotations in pitch, roll, and yaw for both interfractional and intrafractional rotations were 0.00°. One patient diagnosed with an optic nerve sheath meningioma received RT with motion monitoring during irradiation. In 2 patients, changes in the tumor cavity and residual lesions were observed in the MRI obtained using 1.5T MR-LINAC on the day of the first treatment and immediately before the 21st fraction, respectively; therefore, offline/online adaptation was performed. CONCLUSIONS: The reproducible and immobile UBID is clinically feasible in patients with CNS tumors receiving RT with 1.5T MR-LINAC. Based on our initial experience, we developed a workflow for 1.5T MR-LINAC treatment of CNS tumors.

Proteomic analysis reveals activation of platelet- and fibrosis-related pathways in hearts of ApoE-/- mice exposed to diesel exhaust particles.

Air pollution is an environmental risk factor linked to multiple human diseases including cardiovascular diseases (CVDs). While particulate matter (PM) emitted by diesel exhaust damages multiple organ systems, heart disease is one of the most severe pathologies affected by PM. However, the in vivo effects of diesel exhaust particles (DEP) on the heart and the molecular mechanisms of DEP-induced heart dysfunction have not been investigated. In the current study, we attempted to identify the proteomic signatures of heart fibrosis caused by diesel exhaust particles (DEP) in CVDs-prone apolipoprotein E knockout (ApoE-/-) mice model using tandem mass tag (TMT)-based quantitative proteomic analysis. DEP exposure induced mild heart fibrosis in ApoE-/- mice compared with severe heart fibrosis in ApoE-/- mice that were treated with CVDs-inducing peptide, angiotensin II. TMT-based quantitative proteomic analysis of heart tissues between PBS- and DEP-treated ApoE-/- mice revealed significant upregulation of proteins associated with platelet activation and TGFß-dependent pathways. Our data suggest that DEP exposure could induce heart fibrosis, potentially via platelet-related pathways and TGFß induction, causing cardiac fibrosis and dysfunction.

Insight into the Role of Entropy in Promoting Electrochemical CO2 Reduction by Imidazolium Cations.

The electroreduction of CO2 plays an important role in achieving a net-zero carbon economy. Imidazolium cations can be used to enhance the rate of CO2 reduction reactions, but the origin of this promotion remains poorly understood. In this work, we show that in the presence of 1-ethyl-3-methylimidazolium (EMIM+), CO2 reduction on Ag electrodes occurs with an apparent activation energy near zero, while the applied potential influences the rate through the pre-exponential factor. Our findings suggest that the CO2 reduction rate is controlled by the initial state entropy, which depends on the applied potential through the organization of cations at the electrochemical interface. Further characterization shows that the C2-proton of EMIM+ is consumed during the reaction, leading to the collapse of the cation organization and a decrease in the catalytic performance. Our results have important implications for understanding the effect of potential on reaction rates, as they indicate that the common picture based on vibrational activation of electron transfer reactions is insufficient for describing the impact of potential in complex systems, such as CO2 reduction in the presence of imidazolium cations.

The Anti-Endometriotic Effect of Cyperi Rhizoma Extract, Inhibiting Cell Adhesion and the Expression of Pain-Related Factors through Akt and NF-kB Pathways.

Rhizomes of Cyperus rotundus have been widely used as a traditional medicine in Asia for the treatment of gynecological diseases. However, there is no scientific evidence demonstrating the effect of C. rotundus rhizomes on endometriosis, which is characterized by the adhesion of endometrial tissues outside the uterus, resulting in chronic and severe pelvic pain. The aim of this study was to investigate the effects of Cyperi rhizoma extract (CRE) on cell adhesion and the expression of pain-related factors (neurotrophins) in endometriotic cells, and to elucidate the underlying molecular mechanisms. CRE inhibited the adhesion of human endometriotic 12Z cells to peritoneal mesothelial Met5A cells using by adhesion assays. The mRNA expression of adhesion molecules [P-cadherin and matrix metalloproteinase (MMP)-2] was downregulated by CRE treatment. In addition, CRE significantly inhibited the mRNA expression of neurotrophins (BDNF, NGF, NT-3 and NT-4/5) in 12Z cells. Moreover, Akt overexpression markedly neutralized the inhibition of cell adhesion by CRE and expression of neurotrophins in 12Z cells. Furthermore, it was found that CRE suppressed NF-kB activation through the Akt pathway. These data suggest that CRE exerts anti-endometriotic activities by the inhibition of cell adhesion and neurotrophin expression, through the negative regulation of the Akt and NF-kB pathways in endometriotic cells.

Real-world evidence on the strategy of olmesartan-based triple single-pill combination in Korean hypertensive patients: a prospective, multicenter, observational study (RESOLVE-PRO).

BACKGROUND: In this prospective, multicenter, non-comparative observational study, the effectiveness and safety of the triple single-pill combination (SPC) of olmesartan/amlodipine/hydrochlorothiazide (OM/AML/HCTZ) were evaluated in a real clinical practice setting in Korean patients with essential hypertension. METHODS: A total of 3752 patients were enrolled and followed for 12 months after administration of OM/AML/HCTZ. Primary endpoint was change from baseline to month 6 in the mean systolic blood pressure (SBP). Secondary endpoints included changes from baseline in the mean SBP at month 3, 9, 12 and the mean diastolic blood pressure (DBP) at month 3, 6, 9, 12; changes in the mean SBP/DBP according to age and underlying risk factors; and blood pressure control rate (%) at different time points. Adherence to and satisfaction with OM/AML/HCTZ treatment among patients and physicians were assessed by medication possession ratio (MPR) and numeric rating scale, respectively, as exploratory endpoints. Safety was evaluated by the incidence and severity of adverse events (AEs) as well as the discontinuation rate due to AEs. RESULTS: OM/AML/HCTZ administration led to significant reductions in the mean SBP/DBP by 11.5/6.6, 12.3/7.0, 12.3/7.2, and 12.8/7.4 mmHg from baseline to month 3, 6, 9 and 12, respectively (P < 0.0001). The BP reductions were maintained throughout the 1-year observation period in all patients with different age groups and risk factors (diabetes mellitus, cardiovascular disease, and renal disease). The BP control rate (%) of < 140/90 mmHg was 65.9, 67.9, 68.9, and 70.6% at month 3, 6, 9, and 12, respectively. The mean MPR during the observation period was 0.96. The safety results were consistent with the previously reported safety profile of OM/AML/HCTZ. CONCLUSIONS: Treatment with the triple SPC of OM/AML/HCTZ demonstrated significant effectiveness in reducing SBP/DBP and achieving target BP control with high adherence over the 1-year observation period in Korean hypertensive patients and was well-tolerated. TRIAL REGISTRATION: CRIS, KCT0002196 , Registered 3 May 2016.

Evaluation of optimal treatment planning for radiotherapy of synchronous bilateral breast cancer including regional lymph node irradiation.

BACKGROUND: We evaluated the optimal radiotherapy (RT) plan for synchronous bilateral breast cancer (SBBC), especially treatment plans including the regional lymph node (LN) area. METHODS: This study was conducted using 15 patients with SBBC (5 with small breasts, 5 with large breasts, and 5 who underwent a left total mastectomy). The clinical target volume (CTV) was defined as the volume enveloping the bilateral whole breasts/chest wall and left regional LN area. We established the following plans: 1) volumetric-modulated arc therapy (VMAT)-the only plan using two pairs of partial arcs for the whole target volume, 2) VMAT using one partial arc for the left CTV followed by a 3D tangential technique for the right breast (primary hybrid plan), and 3) VMAT for the left CTV followed by a tangential technique using an automatically calculated prescription dose for the right breast, considering the background dose from the left breast VMAT plan (modified hybrid plan). The Tukey test and one-way analysis of variance were used to compare the target coverage and doses to organs at risk (OARs) of the three techniques. RESULTS: For target coverage, the VMAT-only and modified hybrid plans showed comparable target coverage in terms of Dmean (50.33 Gy vs. 50.53 Gy, p = 0.106). The primary hybrid plan showed the largest distribution of the high-dose volume, with V105% of 25.69% and V110% of 6.37% for the planning target volume (PTV) (p < 0.001). For OARs including the lungs, heart, and left anterior descending artery, the percentages of volume at various doses (V5Gy, V10Gy, V20Gy, V30Gy) and Dmean were significantly lower in both the primary and modified hybrid plans compared to those of the VMAT-only plan. These results were consistent in subgroup analyses of breast size and morphological variation. CONCLUSIONS: The modified hybrid plan, using an automatically calculated prescription dose for the right breast and taking into consideration the background dose from the left breast VMAT plan, showed comparable target coverage to that of the VMAT-only plan, and was superior for saving OARs. However, considering that VMAT can be adjusted according to the physician's intention, further evaluation is needed for developing a better plan.

Effect of tibolone on the survival of early stage cervical adenocarcinoma patients.

OBJECTIVE: Gynecologic oncologists are uncertain about the safety of tibolone application in cervical adenocarcinoma (AC) patients. This study examined the possible adverse effects of tibolone on the survival of cervical AC patients. METHODS: Medical records of 70 cervical AC patients with International Federation of Gynecology and Obstetrics stages IA to IB were reviewed. A bilateral salpingo-oophorectomy was performed in all patients, and survival outcomes between tibolone users (n=38) and non-users (n=32) were compared. RESULTS: A comparison of the tibolone users with non-users revealed similar clinicopathological variables. Progression-free survival (P=0.34) and overall survival (P=0.22) were similar in the users and non-users. The risks of progression (hazard ratio [HR], 1.71; 95% confidence interval [CI], 0.46-6.37; P=0.43) and death (HR, 1.59; 95% CI, 0.06-45.66; P=0.79) were also similar in both groups. CONCLUSION: Tibolone has no adverse effect on the survival of cervical AC patients and can be administered safely to this population. These findings may be helpful in improving the quality of life of cervical AC patients.

Perirenal capsule and scrotal involvement in immunoglobulin G4-related kidney disease: case-based review.

Immunoglobulin G4-related disease (IgG4-RD) is a chronic, immune-mediated-, systemic disease that is characterized by IgG4 plasma cell infiltration with fibrotic changes in various organs. The most affected organs are pancreas and salivary glands. Kidney can be rarely involved, and is usually represented as a renal mass and organomegaly. Usually, elevated levels of serum IgG4 more than 135 mg/dl with organ-specific features and biopsy results showing enriched infiltration of IgG4-positive plasma cells are needed to diagnose the disease. However, we experienced two unusual cases of IgG4-RD involving kidney. IgG4-related kidney disease (IgG4-RKD) was first reported as an extra pancreatic feature of autoimmune pancreatitis(AIP) in 2004. Herein, we describe two cases of such unique presentation of IgG4RKD and a literature review focusing on clinicopathologic features of IgG4RKD. Our cases are distinct in the fact that IgG4RD invades unusual organs such as perinephric capsule or scrotum. We reported the patient who showed extinct perirenal capsule invasion with multi-organ involvement including exocrine glands in comparison to previous IgG4RKD that often involved in renal parenchyma and renal pelvis lesions. And the other patient had scrotal invasion with multifocal renal parenchymes. Referring to the features observed in these two cases, we could propose that as every organ can be related to IgG4RD, we propose clinicians to confirm the disease using imaging, serologic, and pathologic studies. We also reviewed previous reports of IgG4-RKD and summarized diverse imaging findings and pathologic features.

Influence of previous abdominal surgery on clinical outcomes of patients undergoing total laparoscopic hysterectomy.

OBJECTIVE: To evaluate the potential effects of previous abdominal surgery on post-operative outcome and incidence of complications after total laparoscopic hysterectomy (TLH). METHODS: Between June 2008 and December 2016, 331 patients who underwent TLH were retrospectively reviewed. Participating patients were divided into 2 groups according to previous abdominal surgery. We compared the 2 groups based on estimated blood loss, operation time, hospital stay, surgery-related complications, and conversion to laparotomy rates. RESULTS: Group 1 included patients without a history of abdominal surgery (n=186), group 2 included patients with a history of abdominal surgery (n=145). The complication rate was 3.2% in group 1 and 2.8% in group 2. Other post-operative outcome and complications such as estimated blood loss, hospital stay and conversion to laparotomy rates did not differ significantly between groups. Adhesiolysis was significantly more common in group 2 (P<0.001) and operation time was significantly longer in the group 2 (P=0.004). The rate of conversion to laparotomy was higher in group 2, but this difference was not significant (P=0.115). Group 2 patients were divided into subgroups according to the number of surgery. In subgroups analysis of group 2, there were 70 patients who had one previous abdominal surgery and 75 patients who had 2 or more previous surgeries. Moreover, there were significant differences in adhesiolysis (P=0.004) and conversion to laparotomy (P=0.034). There were no significant differences in other complications observed upon subgroup analysis. CONCLUSION: TLH can be conducted successfully regardless of previous abdominal surgery. Patients with previous abdominal surgery are suitable and feasible candidates for TLH.

The efficacy of pre-delivery prophylactic trans-catheter arterial balloon occlusion of bilateral internal iliac artery in patients with suspected placental adhesion.

OBJECTIVE: Prophylactic trans-catheter arterial balloon occlusion (PTABO) before cesarean section of placenta previa totalis has been introduced to prevent massive hemorrhage. The purpose of this study is to evaluate the clinical usefulness of PTABO in cases of suspected placental adhesion and to examine antepartal risk factors and perinatal outcomes in women with placental adhesion. METHODS: Between January 2012 and December 2015, 77 patients who had undergone ultrasonography for evaluation of placenta previa were enrolled in this study. Seventeen of these patients with suspected placental adhesion by ultrasonography and Pelvic MRI underwent PTABO before cesarean section and another 59 patients underwent cesarean section without PTABO. Antepartal risk factors and peripartum maternal and neonatal outcomes were compared between patients with PTABO and those without PTABO. RESULTS: More advanced maternal age, longer in gestational weeks at delivery, and more common previous cesarean section history were observed in the PTABO group. Placenta adhesion, abnormal Doppler findings, and frequency of transfusion were more common in the PTABO group. However there was no significant difference in estimated blood loss, hospital days, and neonatal outcome. It had occurred 3 cases of hysterectomy and 1 case of uterine artery embolization after cesarean section in the PTABO group. CONCLUSION: Close surveillance of antepartum risk factors for placental adhesion using ultrasonography and pelvic magnetic resonance imaging is important to prevention of massive hemorrhage during cesarean section. PTABO before cesarean section might result in reduced blood loss and requirement for transfusion during the operation.

Clinical application of 3D-printed-step-bolus in post-total-mastectomy electron conformal therapy.

The 3D-printed boluses were used during the radiation therapy of the chest wall in six patients with breast cancer after modified radical mastectomy (MRM). We measured the in-vivo skin doses while both conventional and 3D-printed boluses were placed on the chest wall and compared the mean doses delivered to the ipsilateral lung and the heart. The homogeneity and conformity of the dose distribution in the chest wall for both types of boluses were also evaluated. The uniformity index on the chest skin was improved when the 3D-printed boluses were used, with the overall average skin dose being closer to the prescribed one in the former case (-0.47% versus -4.43%). On comparing the dose-volume histogram (DVH), it was found that the 3D-printed boluses resulted in a reduction in the mean dose to the ipsilateral lung by up to 20%. The precision of dose delivery was improved by 3% with the 3D-printed boluses; in contrast, the conventional step bolus resulted in a precision level of 5%. In conclusion, the use of the 3D-printed boluses resulted in better dose homogeneity and conformity to the chest wall as well as the sparing of the normal organs, especially the lung. This suggested that their routine use on the chest wall as a therapeutic approach during post-mastectomy radiation therapy offers numerous advantages over conventional step boluses.

Eclalbasaponin II induces autophagic and apoptotic cell death in human ovarian cancer cells.

Triterpenoids echinocystic acid and its glycosides, isolated from several Eclipta prostrata, have been reported to possess various biological activities such as anti-inflammatory, anti-bacterial, and anti-diabetic activity. However, the cytotoxicity of the triterpenoids in human cancer cells and their molecular mechanism of action are poorly understood. In the present study, we found that eclalbasaponin II with one glucose moiety has potent cytotoxicity in three ovarian cancer cells and two endometrial cancer cells compared to an aglycone echinocystic acid and eclalbasaponin I with two glucose moiety. Eclalbasaponin II treatment dose-dependently increased sub G1 population. Annexin V staining revealed that eclalbasaponin II induced apoptosis in SKOV3 and A2780 ovarian cancer cells. In addition, eclalbasaponin II-induced cell death was associated with characteristics of autophagy; an increase in acidic vesicular organelle content and elevation of the levels of LC3-II. Interestingly, autophagy inhibitor BaF1 suppressed the eclalbasaponin II-induced apoptosis. Moreover, eclalbasaponin II activated JNK and p38 signaling and inhibited the mTOR signaling. We further demonstrated that pre-treatment with a JNK and p38 inhibitor and mTOR activator attenuated the eclalbasaponin II-induced autophagy. This suggests that eclalbasaponin II induces apoptotic and autophagic cell death through the regulation of JNK, p38, and mTOR signaling in human ovarian cancer cells.

Hypertriglyceridemia-induced acute pancreatitis in pregnancy causing maternal death.

Acute pancreatitis in pregnancy is rare and occurs in approximately 3 in 10,000 pregnancies. It rarely complicates pregnancy, and can occur during any trimester, however over half (52%) of cases occur during the third trimester and during the post-partum period. Gallstones are the most common cause of acute pancreatitis. On the other hand, acute pancreatitis caused by hypertriglyceridemia due to increase of estrogen during the gestational period is very unusual, but complication carries a higher risk of morbidity and mortality for both the mother and the fetus. We experienced a case of pregnant woman who died of acute exacerbation of hypertriglyceridemia-induced acute pancreatitis at 23 weeks of gestation. We report on progress and management of this case along with literature reviews.

α-Terthienylmethanol, isolated from Eclipta prostrata, induces apoptosis by generating reactive oxygen species via NADPH oxidase in human endometrial cancer cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Eclipta prostrate L. (syn. E. alba Hassk), commonly known as False Daisy, has been used in traditional medicine in Asia to treat a variety of diseases, including cancer. Although an anti-tumor effect has been suggested for E. prostrata, the exact anti-tumor effects and underlying molecular mechanisms of its bioactive compounds are poorly understood. The aim of this study was to identify compounds with anti-cancer activity from E. prostrata and to investigate their mechanism of action. MATERIALS AND METHODS: To assess cell viability, cell cycle progression, and apoptosis, we performed MTT assays and FACS analysis using Annexin and PI staining. We also investigated reactive oxygen species (ROS) production and caspase activation using flow cytometry and Western blot analysis, respectively. Cytosolic translocation of cytochrome c was measured using an ELISA kit. Antioxidants, MAPK signaling inhibitors, NADPH oxidase inhibitors, and siRNA were used to elucidate the molecular mechanism of action of the compound. RESULTS: We isolated five terthiophenes from the n-hexane fraction of E. prostrata; of these, α-terthienylmethanol possessed potent cytotoxic activity against human endometrial cancer cells (Hec1A and Ishikawa) (IC50<1µM). The growth inhibitory effect of α-terthienylmethanol was mediated by the induction of apoptosis, as shown by the accumulation of sub-G1 and apoptotic cells. In addition, α-terthienylmethanol triggered caspase activation and cytochrome c release into the cytosol in a time-dependent manner. Moreover, α-terthienylmethanol increased the intracellular level of ROS and decreased that of GSH, and the antioxidants N-acetyl-l-cysteine and catalase significantly attenuated α-terthienylmethanol-induced apoptosis. We further demonstrated that inhibition of the NADPH oxidase attenuated α-terthienylmethanol-induced cell death and ROS accumulation in endometrial cancer cells. CONCLUSION: Overall, these results suggest that α-terthienylmethanol, a naturally occurring terthiophene isolated from E. prostrata, induces apoptosis in human endometrial cancer cells by ROS production, partially via NADPH oxidase.

High performance polyimide with high internal free volume elements.

This paper reports a new polyimide design with high internal free volume elements for fast mass transport simultaneously with high selectivity. Here, we show that the polymer design using a three-dimensional rigid molecular structure having internal void space can lead to the formation of high fractional free volume with proper cavity size to separate small gas molecules with high selectivities as high permeabilities. These findings could strongly impact emerging gas separation applications using polymeric membranes such as natural gas purification and biogas purification to get clean energy resources.