Comparison of hemostatic ability between spray coagulation and forced coagulation modes in endoscopic submucosal dissection in patients with early gastric neoplasms: a study protocol for multicenter randomized controlled trial (Spray-G trial).

BACKGROUND: Endoscopic submucosal dissection (ESD) is the standard treatment for early gastric neoplasms (EGN). Controlling intraoperative bleeding is crucial for ensuring safe and reliable procedures. ESD using the spray coagulation mode (SCM-ESD) has been developed to control bleeding more effectively than ESD using the conventional forced coagulation mode (FCM-ESD). This study aims to compare the hemostatic efficacies of SCM-ESD and FCM-ESD. METHODS: This multicenter, prospective, parallel, randomized, open-label superiority trial will be conducted in five Japanese institutions. Patients with a preoperative diagnosis of intramucosal EGC will be randomized to undergo either SCM-ESD or FCM-ESD. The primary outcome measure is the completion of ESD with an electrosurgical knife alone, without the use of hemostatic forceps. Secondary outcomes include the number and duration of hemostasis using hemostatic forceps, procedure time, curability, and safety. A total of 130 patients will be enrolled in this study. DISCUSSION: This trial will provide evidence on the hemostatic efficacy of SCM-ESD compared with FCM-ESD in patients with intramucosal EGN, potentially improving the safety and reliability of ESD procedures. TRIAL REGISTRATION: The trial has been registered at the University Hospital Medical Information Network Clinical Trials Registration (UMIN-CTR) as UMIN000040518. The reception number is R000054009.

Kinetic properties of 137Cs uptake by the cesium-accumulating eustigmatophycean microalga.

Cesium-137 (137Cs) is one of the radioactive substances that was released into the environment as a result of the Fukushima nuclear disaster. Radiocesium exposure is of great concern due to its potential environmental implications. However, research on 137Cs removal using algae is still limited. This is the first report to describe the kinetic properties of 137Cs uptake by Vacuoliviride crystalliferum in the presence and absence of potassium. In this work, we studied the kinetic properties of 137Cs uptake using a freshwater microalga, V. crystalliferum (NIES 2860). We also analyzed the effects of temperature, light, and potassium (K) on the 137Cs uptake. Results showed that V. crystalliferum can remove up to 90% of 157 nM 137Cs within an hour. At 20 °C, the removal increased by up to 96%, compared to less than 10% at 5 °C. However, the removal was inhibited by nearly 90% in the dark compared to the removal in the light, implying that V. crystalliferum cells require energy to accumulate 137Cs. In the inhibition assay, K concentrations ranged from 0 to 500 µM and the inhibitory constant (Ki) for K was determined to be 16.7 µM. While in the uptake assay without potassium (- K), the Michaelis constant (Km) for Cs was 45 nM and increased to 283 nM by the addition of 20 µM potassium (+ K), indicating that V. crystalliferum had a high affinity for 137Cs. In addition, the maximum uptake velocity (Vmax) also increased from 6.75 to 21.10 nmol (mg Chl h)-1, implying the existence of Cs active transport system. In conclusion, V. crystalliferum is capable of removing radioactive 137Cs from the environment and the removal was favorable at both normal temperature and in the light.

An adult case of congenital duodenal diaphragm that was successfully treated by endoscopic resection using a grasping-type scissor forceps.

Congenital duodenal diaphragm (CDD) is a rare disease that is usually diagnosed in the neonatal period; however, it is sometimes diagnosed later in the adult period. A 39-year-old woman was referred to our hospital due to tarry stool and anemia. Emergent esophagogastroduodenoscopy (EGD) revealed an obstructing membranous structure with a small orifice in the second portion of the duodenum, together with dilatation of the bulbar part. The membranous structure was accompanied by a Dieulafoy-like vessel on the backside, which was considered to have caused tarry stool and anemia. The Dieulafoy-like vessel was successfully treated by endoscopic hemostasis. Based on the computed tomographic gastrography and barium duodenography findings, it was diagnosed as CDD. Later, endoscopic resection of the diaphragm was conducted by an endoscopic submucosal dissection (ESD)-based procedure, with the use of an electrosurgical grasping-type scissor forceps (ClutchCutter [CC]). There were no procedure-related complications. The definite diagnosis of CDD was made based on the observation of typical structures in a pathological examination. This is the first case report of adult CDD that was successfully treated by endoscopic resection using ESD-based techniques with a CC.

Anticoagulation Protocol for Secondary Prevention of Acute Ischemic Stroke Associated with Nonvalvular Atrial Fibrillation.

OBJECTIVES: There is no clear evidence regarding when to initiate oral anticoagulants (OACs) for secondary prevention of recurrent stroke in patients with atrial fibrillation (AF). Therefore, this study aimed to evaluate the safety and efficacy of a novel OAC initiation protocol for secondary prevention of acute ischemic stroke associated with AF. MATERIALS AND METHODS: In this multicenter prospective study 597 consecutive Japanese patients with acute ischemic stroke associated with nonvalvular AF received post-stroke OACs according to a protocol based on severity (clinical (NIHSS) and radiological (ASPECTS + W)), rt-PA use, reperfusion, and hemorrhagic transformation (HT). Primary outcomes of safety and efficacy, including symptomatic hemorrhage, cerebral stroke, and disability were evaluated at 14 and 90 days. RESULTS: Mean OAC initiation time was 2.60±2.14 days from onset. The shortest and longest mean initiation times were 0.47±0.50 and 6.16±0.72 days, respectively. Following OAC administration, no ICH was observed within 90 days. A significantly higher incidence of acute recurrent ischemic events occurred 14 days prior to OAC (4.7%) compared with chronic recurrence within 90 days (0.8%) (P = 0.00013, McNemar's test) . Recurrence prior to OAC use was significantly correlated with days to treatment (P = 0.00224), severity (NIHSS, ASPECTS+W: P = 0.0223, P = 0.0393, respectively), and HAS-BLED (P = 0.0395) and there were no correlations with CHADS2 (P = 0.277) or CHA2DS2-VASc (P = 0.246) (Wilcoxon rank sum-test). CONCLUSIONS: This comprehensive OAC initiation protocol was relatively safe and effective for secondary prevention of stroke in patients with AF. Risk of acute recurrence was high, indicating that OACs should be started as early as possible. (clinical trial registration number: 15B 128).

Preoperative Predictive Factors of Short-Term Outcome in Idiopathic Normal Pressure Hydrocephalus.

BACKGROUND: Surgical treatment of idiopathic normal pressure hydrocephalus (iNPH) by ventriculoperitoneal (VP) or lumboperitoneal (LP) shunting can achieve long-term recovery of activities of daily living; however, in a subset of patients, maintenance of independence lasted for <6 months. This study examined positive preoperative predictive factors of short-term outcome for shunted iNPH patients. METHODS: Over a 9-year period, consecutive patients from multiple centers diagnosed with probable iNPH underwent either VP or LP shunt surgery. Preoperative variables of age, symptom duration, iNPH severity, tap test response, and magnetic resonance imaging findings of disproportionately enlarged subarachnoid space hydrocephalus (DESH) or incomplete DESH were retrospectively evaluated in relation to 1-year postoperative outcome. RESULTS: Outcome for 154 shunt patients (12 VP, 142 LP) as measured by postoperative disability modified Rankin Scale (mRS) and iNPH-gait disturbance (GD) was the same regardless of age. Symptom duration was inversely correlated with both iNPH severity (P < 0.0001) and postoperative improvement at 1 year (P = 0.0015). Severity also correlated inversely with postoperative improvement at 1 year (P < 0.0001). Age was not significantly correlated with the degree of postoperative improvement (mRS: P = 0.487; iNPH grading scale [GD]: P = 0.725). Outcome at 1 year (mRS, gait domain, and activities of daily living significantly improved in patients with a good response to the tap test (P < 0.0001) Preoperative DESH correlated with improvement in mRS and GD (P < 0.0001). CONCLUSIONS: Mild preoperative iNPH severity, shorter preoperative symptom duration, good tap test response, and complete DESH were associated with good short-term postoperative outcome at 1 year. These positive factors may be useful for prediction of short-term surgical outcome in iNPH patients.

Detailed standardized protocol to prevent cerebrospinal fluid shunt infection.

OBJECTIVE: While cerebrospinal fluid (CSF) shunt surgery plays an essential role in the treatment of hydrocephalus, postoperative infection due to the implantation of foreign materials is still one of the most common and potentially serious complications of this procedure. Because no previously reported protocol has been proven to prevent postoperative infection after CSF shunt surgeries in adults, the authors investigated the effectiveness of a protocol introduced in their institution. METHODS: A detailed standardized surgical protocol to prevent infection in patients undergoing CSF shunt surgeries was introduced in the authors' institution in December 2011. The protocol included a series of detailed rules regarding the surgical procedure, the surgical environment to minimize contamination from air, double gloving, local injection of antibiotics, and postoperative management. The rate of CSF shunt infection during the 3 years after surgery before and after implementation of the protocol was compared in patients undergoing their first CSF shunt surgeries. The inclusion periods were from January 2006 to November 2011 for the preprotocol group and from December 2011 to December 2014 for the postprotocol group. RESULTS: The study included 124 preprotocol patients and 52 postprotocol patients. The mean patient age was 59 years in both groups, ranging from 40 days to 88 years. Comparison of patient background factors, including known risk factors for surgical site infections, showed no significant difference between the patient groups before and after implementation of the protocol. While 9 patients (7.3%) developed shunt infections before protocol implementation, no shunt infections (0%) were observed in patients who underwent surgery after protocol implementation. The difference was statistically significant (p = 0.047). CONCLUSIONS: The authors' detailed protocol for CSF shunt surgeries was effective in preventing postoperative infection regardless of patient age.

Luteinizing Hormone Facilitates Antral Follicular Maturation and Survival via Thecal Paracrine Signaling in Cattle.

LH supplementation in assisted reproductive technology cycles improves the ongoing pregnancy rate in women with poor ovarian response (POR). However, our knowledge of the precise role of LH during the follicular phase of the menstrual cycle is incomplete. To explore the role of LH in the maturation of small antral follicles, we used an in vitro two-cell system that involved coculturing bovine granulosa cells (GCs) and theca cells (TCs) on a collagen membrane. Treatment of TCs with LH stimulated androgen production in TCs by inducing the expression of androgenic factors, subsequently increasing estrogen biosynthesis in GCs by providing androgen substrates, and inducing aromatase expression. LH stimulation of TCs induced functional LH receptor expression in GCs, a response modulated by the synthesis and action of estrogen. In the presence of TCs, LH stimulation of TCs and FSH stimulation of GCs increased the expression of IGF-1, IGF-2, and IGF-1 receptor in GCs. LH-induced expression of thecal IGF-1 protected GCs from apoptosis and promoted GC survival. Furthermore, LH stimulation of TCs increased FSH sensitivity in GCs. Thus, the LH-TC axis may be involved in the acquisition of LH dependence and the survival of small antral follicles by upregulating androgen/estrogen biosynthesis and activating the IGF system. The use of LH supplementation in ovarian stimulation may increase gonadotropin sensitivity in small antral follicles and promote follicular growth and survival by suppressing GC apoptosis and follicular atresia, resulting in multiple follicular development, even in patients with POR.

Clinical significance of atypical squamous cells of undetermined significance after treatment for cervical intraepithelial grade 3 neoplasia: A retrospective single-center cohort study.

The aim of the present study was to evaluate the clinical significance of atypical squamous cells of undetermined significance (ASC-US) following cervical conization for cervical intraepithelial neoplasia (CIN) grade 3. This study was a retrospective cohort analysis. The medical records of women treated with conization for CIN 2-3 were reviewed and 142 patients with CIN 3 who had been diagnosed using the conization specimens were selected. The mean follow-up period after conization was 41.8 months. Cytological abnormalities after conization were observed in 19.0% of the patients and consisted of ASC-US (13.4%) and worse than low-grade squamous intraepithelial lesion (LSIL; 5.6%). Recurrence was defined as a diagnosis worse than CIN 2, and the recurrence rate was 29.6% among patients with abnormal cytology. The recurrence rate was 15.7% in the ASC-US group and 71.4% in the worse than LSIL group. There was no significant difference in the time of initial identification of abnormal cytology after treatment between the worse than LSIL and the ASC-US groups (P=0.054). However, the ASC-US group had a significantly better cumulative recurrence-free rate compared with the worse than LSIL group (P<0.05). Women with ASC-US following treatment for CIN appear to be at a relatively high risk. Regarding the risk stratification of women following treatment for CIN, if surveillance cytology shows ASC-US, immediate colposcopy is recommended, along with long-term follow-up.

Two-color pump-probe interferometry of ultra-fast light-matter interaction.

Two-color side-view probing of light-matter interaction from minute focal volume of a tightly focused fs-laser pump pulse reveals charge dynamics with high 0.9 µm optical resolution and approximately ~45fs temporal resolution defined by pulse duration. Use of two colors is advantageous for probing optically excited plasma regions with different density. Holographical digital focusing and spatial filtering were implemented to obtain the same resolution images for subsequent Fourier analysis. Fast plasma density decay with time constant ~150 fs was resolved and is consistent with self-trapping. Potential applications of an optical control over light-induced defects with deep-sub-wavelength resolution is discussed.

Ultra-Early Combination Antiplatelet Therapy with Cilostazol for the Prevention of Branch Atheromatous Disease: A Multicenter Prospective Study.

BACKGROUND AND PURPOSE: The optimal use of antiplatelet therapy for intracranial branch atheromatous disease (BAD) is not known. METHODS: We conducted a prospective multicenter, single-group trial of 144 consecutive patients diagnosed with probable BAD. All patients were treated within 12 h of symptom onset to prevent clinical progression using dual antiplatelet therapy with cilostazol plus one oral antiplatelet drug (aspirin or clopidogrel). Endpoints of progressive BAD in the dual therapy group at 2 weeks were compared with a matched historical control group of 142 patients treated with single oral antiplatelet therapy using either cilostazol, aspirin, or clopidogrel. RESULTS: Progressive motor paresis occurred in 14 patients (9.7%) in the aggressive antiplatelet group, compared with 48 (33.8%) in the matched single antiplatelet group. Multivariate logistic regression analysis revealed the following variables to be associated with a better prognosis for BAD: baseline modified Rankin Scale score, dual oral antiplatelet therapy with cilostazol, and dyslipidemia (odds ratios of 0.616, 0.445, and 0.297, respectively). Hypertension was associated with a worse prognosis for BAD (odds ratio of 1.955). CONCLUSIONS: Our trial showed that clinical progression of BAD was significantly reduced with the administration of ultra-early aggressive combination therapy using cilostazol compared to treatment with antiplatelet monotherapy.

Gastric Hyperplastic Polyp with Xanthoma Observed by Magnification Narrow-Band Imaging Endoscopy and Endoscopic Ultrasonography : Report of a Case.

We experienced an extremely rare case of gastric hyperplastic polyp with xanthoma. A 73-year-old Japanese man was transferred to our hospital from a referral hospital for further evaluation of a pedunculated gastric polyp and early gastric cancer. Esophagogastroduodenoscopy (EGD) revealed a yellow-whitish pedunculated polyp arising from the anterior wall of the fornix. Magnification narrow-band imaging (NBI) endoscopy revealed extended and tortuous microcapillaries and a swollen interfoveolar pattern on the polyp's surface, but there was no sign of malignancy. Endoscopic ultrasonography (EUS) revealed an irregularity of the first layer and a thickened second layer. The third layer was intact. A hyperechoic area was seen in the thickened second layer. Endoscopic submucosal dissection (ESD) for early carcinoma of the antrum and endoscopic mucosal resection (EMR) for a polyp in the fornix were performed in one session. Histological examination of the specimen of the fornix polyp revealed lengthened, branched and dilatated gastric foveolae and a tight sheet of foamy histiocytes in the stroma. The background mucosa of the polyp was atrophic. The pathologic evidence was gastric hyperplastic polyp with proliferation of xanthoma. The early cancer of the antrum was intramucosal tubular adenocarcinoma and was resected curatively.

Protective effect of dienogest on chemotherapy-induced reduced fertility in female rats.

Reduced fertility is one of the main long-term consequences of chemotherapy given for lymphoma, leukemia, and other malignancies in young women. We examined with a female rat model whether and how dienogest, a fourth-generation progestin, modulates reduced fertility following exposure to gonadotoxic chemotherapy. Female rats were administered cyclophosphamide with or without GnRH agonist and different concentrations of dienogest for 20 days. Animals were sacrificed on Day 29, and the numbers of follicle at primordial, preantral and antral stage in the ovaries were counted histologically. Rats treated with sterile saline solution (as control), cyclophosphamide, cyclophosphamide plus GnRH agonist, and cyclophosphamide plus dienogest were also mated with male rats to evaluate their fertility and pregnancy outcomes. Cyclophosphamide significantly reduced the number of primordial follicles, whereas dienogest suppressed depletion of primordial follicle pool induced by chemotherapy. Although the rats exposed to cyclophosphamide alone failed to deliver live births, co-treatment with dienogest improved the pregnancy outcomes of treated rats. The protective effect of dienogest on chemotherapy-induced ovarian damage and reduced fertility was comparable to that of GnRH agonist. The present results suggest that the co-administration of dienogest and chemotherapy may be a useful strategy in preserving ovarian function and fertility in premenopausal women facing gonadotoxic chemotherapy.

Abrogation of CC chemokine receptor 9 ameliorates collagen-induced arthritis of mice.

INTRODUCTION: Biological drugs are effective in patients with rheumatoid arthritis (RA), but increase severe infections. The CC chemokine receptor (CCR) 9 antagonist was effective for Crohn's disease without critical adverse effects including infections in clinical trials. The present study was carried out to explore the pathogenic roles of chemokine (C-C motif) ligand (CCL) 25 and its receptor, CCR9, in autoimmune arthritis and to study if the CCR9 antagonist could be a new treatment for RA. METHODS: CCL25 and CCR9 expression was examined with immunohistochemistry and Western blotting. Concentration of interleukin (IL)-6, matrix metalloproteinase (MMP)-3 and tumor necrosis factor (TNF)-α was measured with enzyme-linked immunosorbent assays. Effects of abrogating CCR9 on collagen-induced arthritis (CIA) was evaluated using CCR9-deficient mice or the CCR9 antagonist, CCX8037. Fluorescence labeled-CD11b+ splenocytes from CIA mice were transferred to recipient CIA mice and those infiltrating into the synovial tissues of the recipient mice were counted. RESULTS: CCL25 and CCR9 proteins were found in the RA synovial tissues. CCR9 was expressed on macrophages, fibroblast-like synoviocytes (FLS) and dendritic cells in the synovial tissues. Stimulation with CCL25 increased IL-6 and MMP-3 production from RA FLS, and IL-6 and TNF-α production from peripheral blood monocytes. CIA was suppressed in CCR9-deficient mice. CCX8037 also inhibited CIA and the migration of transferred CD11b+ splenocytes into the synovial tissues. CONCLUSIONS: The interaction between CCL25 and CCR9 may play important roles in cell infiltration into the RA synovial tissues and inflammatory mediator production. Blocking CCL25 or CCR9 may represent a novel safe therapy for RA.

Cannabinoid receptor 2 as a potential therapeutic target in rheumatoid arthritis.

BACKGROUND: Some of cannabinoids, which are chemical compounds contained in marijuana, are immunosuppressive. One of the receptors, CB receptor 1 (CB1), is expressed predominantly by the cells in the central nervous system, whereas CB receptor 2 (CB(2)) is expressed primarily by immune cells. Theoretically, selective CB(2) agonists should be devoid of psychoactive effects. In this study, we investigated therapeutic effects of a selective CB(2) agonist on arthritis. METHODS: The expression of CB(2) was analyzed with immunohistochemistry and Western blotting. Interleukin (IL)-6, matrix metalloproteinase-3 (MMP-3), and chemokine (C-C motif) ligand 2 (CCL2) were quantified with enzyme-linked immunosorbent assays (ELISA). Osteoclastogenesis was assessed with tartrate-resistant acid phosphatase staining and the resorption of coated-calcium phosphate. Effect of JWH133, a selective CB(2) agonist, on murine collagen type II (CII)-induced arthritis (CIA) was evaluated with arthritis score, and histological and radiographic changes. IFN-γ and IL-17 production by CII-stimulated splenocytes and serum anti-CII Ab were analyzed by ELISA. RESULTS: Immunohistochemistry showed that CB(2) was expressed more in the synovial tissues from the rheumatoid joints than in those from the osteoarthritis joints. CB(2) expression on RA FLS was confirmed with Western blot analysis. JWH133 inhibited IL-6, MMP-3, and CCL2 production from tumor necrosis factor-α-stimulated fibroblast-like synoviocytes (FLS) derived from the rheumatoid joints, and osteoclastogenesis of peripheral blood monocytes. Administration of JWH133 to CIA mice reduced the arthritis score, inflammatory cell infiltration, bone destruction, and anti-CII IgG1 production. CONCLUSION: The present study suggests that a selective CB(2) agonist could be a new therapy for RA that inhibits production of inflammatory mediators from FLS, and osteoclastogenesis.

Recurrent mitral valve regurgitation with neutrophil infiltration in a patient with multiple aseptic abscesses.

Aseptic abscess (AA) is characterized by accumulation of neutrophils without evidence of infection, no response to antibiotics, and rapid response to corticosteroids. We report a case of multiple abscesses in the subcutaneous tissues and joints, and severe mitral valve regurgitation. Although AA did not respond to antibiotic therapy, it improved dramatically with corticosteroid treatment. However, repeated valvuloplasty was required for the mitral valve regurgitation. The mitral valve tissue showed neutrophil infiltration without any bacterial invasion. This is the first case of AA to show involvement of cardiac valves, indicating the importance of systematic examination for patients with AA and cardiac valve involvement.

Difference in physiological responses of growth, photosynthesis and calcification of the coccolithophore Emiliania huxleyi to acidification by acid and CO2 enrichment.

Ocean acidification, one of the great global environmental issues at present, is expected to result in serious damage on marine calcareous organisms such as corals and calcifying algae, which potentially release huge amounts of CO2 from the ocean to the atmosphere. The coccolithophore, Emiliania huxleyi (Haptophyceae), which frequently produces blooms, has greatly contributed to the biological CO2 pump. This study was aimed at analyzing effects of how E. huxleyi responds to acidification. Acidification was performed by two methods, namely by just adding HCl under bubbling ordinary air at 8.2-8.4, 7.6-7.8 and 7.1-7.3 (acidification by HCl) and by bubbling with ordinary air or with increased CO2 concentration such as 406, 816 and 1,192 ppm that maintained pH of the medium at 8.0-8.3, 7.6-7.9 and 7.5-7.7 (acidification by CO2 enrichment). As a result, cell growth and cellular calcification of E. huxleyi were strongly damaged by acidification by HCl, but not by acidification by CO2 enrichment. The activities of photosystems such as F v/F m and ϕPSII were not affected by any acidification conditions while photosynthetic O2 evolution was slightly stimulated. A (45)Ca-radiotracer experiment revealed that Ca(2+)-uptake was strongly suppressed by acidification with HCl. This suppression recovered after increasing the dissolved inorganic carbon (DIC) concentration and further stimulated by an additional increase in DIC concentration. The production of storage and coccolith polysaccharides was increased by acidification by HCl and also highly stimulated by acidification with CO2 enrichment. The present study clearly showed that the coccolithophore, E. huxleyi, has an ability to respond positively to acidification with CO2 enrichment, but not just acidification.

Global searches for microalgae and aquatic plants that can eliminate radioactive cesium, iodine and strontium from the radio-polluted aquatic environment: a bioremediation strategy.

The Fukushima 1 Nuclear Power Plant accident in March 2011 released an enormously high level of radionuclides into the environment, a total estimation of 6.3 × 10¹7 Bq represented by mainly radioactive Cs, Sr, and I. Because these radionuclides are biophilic, an urgent risk has arisen due to biological intake and subsequent food web contamination in the ecosystem. Thus, urgent elimination of radionuclides from the environment is necessary to prevent substantial radiopollution of organisms. In this study, we selected microalgae and aquatic plants that can efficiently eliminate these radionuclides from the environment. The ability of aquatic plants and algae was assessed by determining the elimination rate of radioactive Cs, Sr and I from culture medium and the accumulation capacity of radionuclides into single cells or whole bodies. Among 188 strains examined from microalgae, aquatic plants and unidentified algal species, we identified six, three and eight strains that can accumulate high levels of radioactive Cs, Sr and I from the medium, respectively. Notably, a novel eustigmatophycean unicellular algal strain, nak 9, showed the highest ability to eliminate radioactive Cs from the medium by cellular accumulation. Our results provide an important strategy for decreasing radiopollution in Fukushima area.