Cryo-EM structure and biochemical analyses of the nucleosome containing the cancer-associated histone H3 mutation E97K.

The Lys mutation of the canonical histone H3.1 Glu97 residue (H3E97K) is found in cancer cells. Previous biochemical analyses revealed that the nucleosome containing the H3E97K mutation is extremely unstable as compared to the wild-type nucleosome. However, the mechanism by which the H3E97K mutation causes nucleosome instability has not been clarified yet. In the present study, the cryo-electron microscopy structure of the nucleosome containing the H3E97K mutation revealed that the entry/exit DNA regions of the H3E97K nucleosome are disordered, probably by detachment of the nucleosomal DNA from the H3 N-terminal regions. This may change the intra-molecular amino acid interactions with the replaced H3 Lys97 residue, inducing structural distortion around the mutated position in the nucleosome. Consistent with the nucleosomal DNA end flexibility and the nucleosome instability, the H3E97K mutation exhibited reduced binding of linker histone H1 to the nucleosome, defective activation of PRC2 (the essential methyltransferase for facultative heterochromatin formation) with a poly-nucleosome, and enhanced nucleosome transcription by RNA polymerase II.

Revisiting the melting curve of H2O by Brillouin spectroscopy to 54 GPa.

The melting curve of H2O was investigated up to 54 GPa and ∼2000 K by Brillouin scattering spectroscopy in a diamond anvil cell. A CO2 laser was used for heating the H2O sample directly in order to reduce the risk of chemical reactions. The melting was identified based on the appearance of the Brillouin peaks derived from the liquid phase. The longitudinal wave velocity (Vp) of the liquid phase along the melting curve exhibits a smooth increase with pressure. The melting temperature of H2O shows no kink previously reported but a monotonic increase between 26 and 54 GPa. Present melting data suggest that the melting occurs from body-centered-cubic superionic phase in the pressure-temperature range investigated.

Fluid-like elastic response of superionic NH3 in Uranus and Neptune.

Nondipolar magnetic fields exhibited at Uranus and Neptune may be derived from a unique geometry of their icy mantle with a thin convective layer on top of a stratified nonconvective layer. The presence of superionic H2O and NH3 has been thought as an explanation to stabilize such nonconvective regions. However, a lack of experimental data on the physical properties of those superionic phases has prevented the clarification of this matter. Here, our Brillouin measurements for NH3 show a two-stage reduction in longitudinal wave velocity (V p) by ∼9% and ∼20% relative to the molecular solid in the temperature range of 1,500 K and 2,000 K above 47 GPa. While the first V p reduction observed at the boundary to the superionic α phase was most likely due to the onset of the hydrogen diffusion, the further one was likely attributed to the transition to another superionic phase, denoted γ phase, exhibiting the higher diffusivity. The reduction rate of V p in the superionic γ phase, comparable to that of the liquid, implies that this phase elastically behaves almost like a liquid. Our measurements show that superionic NH3 becomes convective and cannot contribute to the internal stratification.

International Cross-Sectional Study on the Effectiveness of Okada Purifying Therapy, a Biofield Therapy, for the Relief of Various Symptoms.

Objective: To investigate whether differences exist in the effectiveness/safety of a single session of Okada Purifying Therapy (OPT), a type of biofield therapy, among those from different ethnicity/cultures, and to analyze factors associated with the outcomes in a real-world setting. Design: Pre-post test design using convenience sampling methods. Setting: Home setting. Subjects: A total of 11,303 individuals aged 16 years or older from 14 different countries (>1000 individuals each from Japan, the United States, Thailand, Chile/Peru, and <200 individuals each from Portugal, Spain, Argentina, Mexico, Brazil, South Korea, Taiwan, Belgium, and France). More than 50% of the subjects were themselves OPT practitioners, and more than 50% of the treatments were administered in an environment where the practice of OPT was promoted. Intervention: Participants received a single session of OPT lasting 30 min or longer from the volunteer practitioners. They self-reported the changes in overall symptoms, physical pain, anxiety/depression, and dizziness/palpitation. Outcome measures: Improvement/exacerbation rates of each symptom and factors associated with symptom improvement were analyzed. Results: Of the participants, 77.5%, 75.6%, 78.4%, and 73.8% reported an improvement of overall symptoms, physical pain, anxiety/depression, and dizziness/palpitation, respectively. The improvement rates were consistently higher among participants from Chile/Peru than those from Japan, the United States, and Thailand (p < 0.001), and among those who had received a longer therapy (p < 0.001). Spanish/Portuguese speaking countries almost always showed high improvement rates; conversely, Japan showed a lower rate in each symptom. Participants' gender, reasons for participation, previous experience, and location of the session were also associated with the improvement of different symptoms. These findings occurred regardless of the participants' age or presence/absence of illness. In terms of safety, the exacerbation rates of symptoms were 2.8%, 2.5%, 0.8%, and 1.7%, respectively. Of those who expressed symptoms exacerbation, 71.6% recovered in a few hours. None of them needed emergency medical treatment. Conclusions: In those who were often sympathetic to OPT and/or in an authorized location, OPT was effective and safe across countries with ethnic/cultural differences; however, participants' country of residence and duration of the session were independently associated with the changes in various symptoms. (ClinicalTrials.gov NCT03994809).

The Influence of a Multimodal Health Program with Diet, Art, and Biofield Therapy on the Quality of Life of People in Japan.

OBJECTIVE: To investigate whether the frequency of the practice of each of diet, art, and biofield therapy influences improvement in quality of life (QOL), and to examine whether the simultaneous practice of all three components increasingly improves QOL in a real-world setting. DESIGN: Pre-post-test design using convenience sampling methods. SETTING: Home setting. SUBJECTS: A total of 4681 individuals aged 16 years or older who answered the questionnaire appropriately. INTERVENTION: Participants agreed to practice the three components daily and self-evaluated the frequency of their weekly practice for three consecutive months. At the beginning and end of the study, they completed the MOA quality-of-life questionnaire (10-item MOA quality-of-life questionnaire [MQL-10]). OUTCOME MEASURES: Factors associated with the increase in MQL-10 scores for each component, and the relationship between the simultaneous practice of multiple components and the changes in MQL-10 scores were analyzed. RESULTS: Frequent practice of the diet and/or art components was associated with an increase in the term-end MQL-10 score (p < 0.001); however, receiving biofield therapy frequently was not. Participants' age, gender, and qualification as a practitioner of biofield therapy had no relationship with changes in scores, but the reasons for participation had a significant influence on changes in scores (p < 0.001). Participants who initially did not practice any components frequently but who subsequently increased the number of components and frequency of each practice had a higher likelihood of exhibiting an increase in the term-end score (p < 0.01). Participants who initially practiced all three components frequently but later decreased the number of components practiced frequently had a lower chance of increase and a higher risk of decrease in scores (p < 0.01). CONCLUSIONS: The data suggest that the frequent practice of the diet and art components is associated with improvement in QOL. Simultaneous practice of diet, art, and biofield therapy is more likely to improve QOL. ( ClinicalTrials.gov NCT01927250).

[A Case of Long-Term Clinical Complete Response after Chemotherapy for Locally Advanced Rectal Cancer].

With the advancement ofchemotherapy against colorectal cancer, clinical complete responses(cCR)are more frequently observed. We report a case oflocally advanced rectal cancer with maintained long-term cCR after chemotherapy alone. Detailed examinations ofa man in his 60s revealed that he had poorly controlled diabetes mellitus, with elevated serum CEA and CA19-9 levels. Colonoscopy revealed rectal cancer(Rba). Besides the prostate invasion observed in the CT scan, intestinal obstruction was caused by a tumor that required surgical removal. However, the tumor was unresectable due to prostate and pelvic wall metastases; therefore, only sigmoid colostomy was performed. After 6 courses of mFOLFOX6, the tumor shrunk, and prostate invasion reduced as confirmed by the CT scan. Chemotherapy was switched to sLV/5FU2 due to the occurrence of peripheral neuropathy. No tumor was found after 20 courses of treatment, and cCR was achieved after 58 courses ofcontinuous and consecutive treatment. Throughout the treatment, radical resection was proposed to the patient; however, the surgery was not performed because of his lifestyle, ie, heavy smoking, which resulted in poor blood sugar control. The patient appears to be tumor free for 7 years after the initiation of chemotherapy.

Subtypes of the Type II Pit Pattern Reflect Distinct Molecular Subclasses in the Serrated Neoplastic Pathway.

BACKGROUND: Colorectal serrated lesions (SLs) are important premalignant lesions whose clinical and biological features are not fully understood. AIMS: We aimed to establish accurate colonoscopic diagnosis and treatment of SLs through evaluation of associations among the morphological, pathological, and molecular characteristics of SLs. METHODS: A total of 388 premalignant and 18 malignant colorectal lesions were studied. Using magnifying colonoscopy, microsurface structures were assessed based on Kudo's pit pattern classification system, and the Type II pit pattern was subcategorized into classical Type II, Type II-Open (Type II-O) and Type II-Long (Type II-L). BRAF/KRAS mutations and DNA methylation of CpG island methylator phenotype (CIMP) markers (MINT1, - 2, - 12, - 31, p16, and MLH1) were analyzed through pyrosequencing. RESULTS: Type II-O was tightly associated with sessile serrated adenoma/polyps (SSA/Ps) with BRAF mutation and CIMP-high. Most lesions with simple Type II or Type II-L were hyperplastic polyps, while mixtures of Type II or Type II-L plus more advanced pit patterns (III/IV) were characteristic of traditional serrated adenomas (TSAs). Type II-positive TSAs frequently exhibited BRAF mutation and CIMP-low, while Type II-L-positive TSAs were tightly associated with KRAS mutation and CIMP-low. Analysis of lesions containing both premalignant and cancerous components suggested Type II-L-positive TSAs may develop into KRAS-mutated/CIMP-low/microsatellite stable cancers, while Type II-O-positive SSA/Ps develop into BRAF-mutated/CIMP-high/microsatellite unstable cancers. CONCLUSIONS: These results suggest that Type II subtypes reflect distinct molecular subclasses in the serrated neoplasia pathway and that they could be useful hallmarks for identifying SLs at high risk of developing into CRC.

Involvement of 11-ketotestosterone in hooknose formation in male pink salmon (Oncorhynchus gorbuscha) jaws.

Mature male Pacific salmon (Oncorhynchus spp.) develop a hooknose, as a secondary male sexual characteristic, during the spawning period. It is likely that androgens regulate hooknose formation. However, endocrinological and histochemical details about the relationship between androgens and hooknose formation are poorly understood. In this study, we performed assays of serum androgens, detection of androgen receptor (AR) in hooknose tissues, external morphological measurement of hooknose-related lengths, and microscopic observation of hooknose tissues of pink salmon (O. gorbuscha) at different stages of sexual maturation. Expression of the arß gene was detected in hooknose tissues of males but not females. The elongation of these tissues was mediated directly via androgens. Serum 11-ketotestosterone (11-KT) concentrations indicated a significant positive correlation with both jaw lengths during sexual maturation of males. In the upper jaw, cartilage tissue developed during hooknose formation, and AR-immunoreactive chondrocytes were located in the rostal-vetral regions of hooknose cartilage in maturing male. The chondrocytes in maturing males before entering into rivers exhibited rich-cytoplasm with high cell activity than at other sexual development stages. On the other hand, in the lower jaw, the development of the spongiosa-like bone meshworks. AR-immunoreactivity was detected in a proportion of the osteocytes and osteoblast-like cells in the spongiosa-like bone meshworks. These results indicate that hooknose formation in pink salmon, which is associated with the buildup of a structure with sufficient strength that it can be used to attack other males on the spawning ground, is regulated by 11-KT.

[A Case of Transverse Colon Cancer Metastasized to the Spermatic Cord after Resection of Peritoneal Dissemination].

We report a rare case of spermatic cord metastasis from colon cancer. A man in his 50s underwent extended right hemicolectomy for transverse colon cancer followed by resection of a peritoneal recurrence. After receiving adjuvant chemotherapy for 6 months, he became aware of a right inguinal mass. A spermatic cord tumor was noted on computed tomography(CT) and FDG/PET-CT. He underwent radical orchiectomy. The resected tumor was histologically compatible with the colon cancer. Although he received additional chemotherapy, right inguinal recurrence was resected 6 months after orchiectomy. Colon cancer is the second most common origin, after gastric cancer, of metastatic spermatic tumor. As several metastatic routes have been reported, peritoneal seeding is mostly suspected in this case.

Shock compression response of forsterite above 250 GPa.

Forsterite (Mg2SiO4) is one of the major planetary materials, and its behavior under extreme conditions is important to understand the interior structure of large planets, such as super-Earths, and large-scale planetary impact events. Previous shock compression measurements of forsterite indicate that it may melt below 200 GPa, but these measurements did not go beyond 200 GPa. We report the shock response of forsterite above ~250 GPa, obtained using the laser shock wave technique. We simultaneously measured the Hugoniot and temperature of shocked forsterite and interpreted the results to suggest the following: (i) incongruent crystallization of MgO at 271 to 285 GPa, (ii) phase transition of MgO at 285 to 344 GPa, and (iii) remelting above ~470 to 500 GPa. These exothermic and endothermic reactions are seen to occur under extreme conditions of pressure and temperature. They indicate complex structural and chemical changes in the system MgO-SiO2 at extreme pressures and temperatures and will affect the way we understand the interior processes of large rocky planets as well as material transformation by impacts in the formation of planetary systems.

Epigenetic silencing of NTSR1 is associated with lateral and noninvasive growth of colorectal tumors.

Our aim was to identify DNA methylation changes associated with the growth pattern and invasiveness of colorectal cancers (CRCs). Comparison of the methylation statuses of large (≥ 20 mm in diameter along the colonic surface) noninvasive tumors (NTs) and small (<20 mm in diameter along the colonic surface) invasive tumors (ITs) using CpG island microarray analysis showed neurotensin receptor 1 (NTSR1) to be hypermethylated in large NTs. Quantitative bisulfite pyrosequencing revealed that NTSR1 is frequently methylated in colorectal tumors, with large NTs exhibiting the highest methylation levels. The higher NTSR1 methylation levels were associated with better prognoses. By contrast, NTSR1 copy number gains were most frequent among small ITs. Methylation of NTSR1 was associated with the gene's silencing in CRC cell lines, whereas ectopic expression of NTSR1 promoted proliferation and invasion by CRC cells. Analysis of primary tumors composed of adenomatous and malignant portions revealed that NTSR1 is frequently methylated in the adenomatous portion, while methylation levels are generally lower in the cancerous portions. These results suggest that NTSR1 methylation is associated with lateral and noninvasive growth of colorectal tumors, while low levels of methylation may contribute to the malignant potential through activation of NTSR1. Our data also indicate that NTSR1 methylation may be a prognostic biomarker in CRC.

Analysis of DNA methylation in bowel lavage fluid for detection of colorectal cancer.

Aberrant DNA methylation could potentially serve as a biomarker for colorectal neoplasms. In this study, we assessed the feasibility of using DNA methylation detected in bowel lavage fluid (BLF) for colorectal cancer screening. A total of 508 BLF specimens were collected from patients with colorectal cancer (n = 56), advanced adenoma (n = 53), minor polyp (n = 209), and healthy individuals (n = 190) undergoing colonoscopy. Methylation of 15 genes (miR-1-1, miR-9-1, miR-9-3, miR-34b/c, miR-124-1, miR-124-2, miR-124-3, miR-137, SFRP1, SFRP2, APC, DKK2, WIF1, LOC386758, and ZNF582) was then analyzed in MethyLight assays, after which receiver operating characteristic (ROC) curves were analyzed to assess the diagnostic performance of BLF methylation. Through analyzing BLF specimens in a training set (n = 345), we selected the three genes showing the greatest sensitivity for colorectal cancer detection (miR-124-3, 71.8%; LOC386758, 79.5%; and SFRP1, 74.4%). A scoring system based on the methylation of those three genes (M-score) achieved 82% sensitivity and 79% specificity, and the area under the ROC curve (AUC) was 0.834. The strong performance of this system was then validated in an independent test set (n = 153; AUC = 0.808). No significant correlation was found between M-score and the clinicopathologic features of the colorectal cancers. Our results demonstrate that DNA methylation in BLF specimens may be a useful biomarker for the detection of colorectal cancer.

Aberrant methylation of microRNA-34b/c is a predictive marker of metachronous gastric cancer risk.

BACKGROUND: Metachronous gastric cancer (GC) can develop after endoscopic resection of GC and cannot be predicted based on clinical signature. Aberrant DNA methylation in noncancerous gastric mucosa is strongly implicated in gastric carcinogenesis and could be a useful biomarker of GC risk. We evaluated the clinical utility of DNA methylation as a biomarker of metachronous GC risk. METHOD: We carried out scheduled follow-up endoscopy in 129 patients after curative endoscopic resection of GC. Biopsy specimens were collected from noncancerous mucosa in the gastric antrum and body, after which quantitative methylation analysis of miR-34b/c, SFRP1, SFRP2, SFRP5, DKK2 and DKK3 was carried out using bisulfite pyrosequencing. The utility of the methylation for predicting the risk of metachronous GC development was assessed using Kaplan-Meier and Cox proportional hazards model analyses. RESULTS: During the follow-up period, 17 patients (13%) developed metachronous GCs. The cumulative incidence of metachronous GC was significantly higher among patients with elevated miR-34b/c, SFRP2 and DKK2 methylation in their gastric body. MiR-34b/c showed the strongest association with the risk of metachronous GC, and the cumulative incidence of metachronous GC was much higher in the high-miR-34b/c-methylation group than the low-methylation group. Multivariate analysis adjusted for age, sex, H. pylori status and pathological findings showed miR-34b/c methylation in gastric body to be an independent predictor of metachronous GC risk. CONCLUSION: Our results suggest that methylation of miR-34b/c in the mucosa of the noncancerous gastric body may be a useful biomarker for predicting the risk of metachronous GC.

Aberrant methylation of RASGRF1 is associated with an epigenetic field defect and increased risk of gastric cancer.

Aberrant DNA methylation is implicated in the epigenetic field defect seen in gastric cancer. Our aim in this study was to identify predictive biomarkers by screening for DNA methylation in noncancerous background gastric mucosa from patients with gastric cancer. Using methylated-CpG island amplification coupled with CpG island microarray (MCAM) analysis, we identified 224 genes that were methylated in the noncancerous gastric mucosa of patients with gastric cancer. Among them, RASGRF1 methylation was significantly elevated in gastric mucosa from patients with either intestinal or diffuse type gastric cancer, as compared with mucosa from healthy individuals (8.3% vs. 22.4%, P < 0.001; 8.3% vs. 19.4%, P < 0.001). RASGRF1 methylation was independent of mucosal atrophy and could be used to distinguish both serum pepsinogen test-positive [sensitivity, 70.0%; specificity, 86.7%; area under the receiver operator characteristic (ROC) curve, AUC, 0.763] and -negative patients with gastric cancer (sensitivity, 72.2%; specificity, 87.0%; AUC, 0.844) from healthy individuals. Ectopic expression of RASGRF1 suppressed colony formation and Matrigel invasion by gastric cancer cells, suggesting it may be involved in gastric tumorigenesis. Collectively, our data suggest that RASGRF1 methylation is significantly involved in an epigenetic field defect in the stomach, and that it could be a useful biomarker to identify individuals at high risk for gastric cancer.

Molecular dissection of premalignant colorectal lesions reveals early onset of the CpG island methylator phenotype.

The concept of the CpG island methylator phenotype (CIMP) in colorectal cancer (CRC) is widely accepted, although the timing of its occurrence and its interaction with other genetic defects are not fully understood. Our aim in this study was to unravel the molecular development of CIMP cancers by dissecting their genetic and epigenetic signatures in precancerous and malignant colorectal lesions. We characterized the methylation profile and BRAF/KRAS mutation status in 368 colorectal tissue samples, including precancerous and malignant lesions. In addition, genome-wide copy number aberrations, methylation profiles, and mutations of BRAF, KRAS, TP53, and PIK3CA pathway genes were examined in 84 colorectal lesions. Genome-wide methylation analysis of CpG islands and selected marker genes revealed that CRC precursor lesions are in three methylation subgroups: CIMP-high, CIMP-low, and CIMP-negative. Interestingly, a subset of CIMP-positive malignant lesions exhibited frequent copy number gains on chromosomes 7 and 19 and genetic defects in the AKT/PIK3CA pathway genes. Analysis of mixed lesions containing both precancerous and malignant components revealed that most aberrant methylation is acquired at the precursor stage, whereas copy number aberrations are acquired during the progression from precursor to malignant lesion. Our integrative genomic and epigenetic analysis suggests early onset of CIMP during CRC development and indicates a previously unknown CRC development pathway in which epigenetic instability associates with genomic alterations.

Evaluation of magnifying colonoscopy in the diagnosis of serrated polyps.

AIM: To elucidate the colonoscopic features of serrated lesions of the colorectum using magnifying colonoscopy. METHODS: Broad division of serrated lesions of the colorectum into hyperplastic polyps (HPs), traditional serrated adenomas (TSAs), and sessile serrated adenomas/polyps (SSA/Ps) has been proposed on the basis of recent molecular biological studies. However, few reports have examined the colonoscopic features of these divisions, including magnified colonoscopic findings. This study examined 118 lesions excised in our hospital as suspected serrated lesions after magnified observation between January 2008 and September 2011. Patient characteristics (sex, age), conventional colonoscopic findings (location, size, morphology, color, mucin) and magnified colonoscopic findings (pit pattern diagnosis) were interpreted by five colonoscopists with experience in over 1000 colonoscopies, and were compared with histopathological diagnoses. The pit patterns were categorized according to Kudo's classification, but a more detailed investigation was also performed using the subclassification [type II-Open (type II-O), type II-Long (type II-L), or type IV-Serrated (type IV-S)] proposed by Kimura T and Yamano H. RESULTS: Lesions comprised 23 HPs (23/118: 19.5%), 39 TSAs (39/118: 33.1%: with cancer in one case), 50 SSA/Ps (50/118: 42.4%: complicated with cancer in three cases), and six others (6/118: 5.1%). We excluded six others, including three regular adenomas, one hamartoma, one inflammatory polyp, and one juvenile polyp for further analysis. Conventional colonoscopy showed that SSA/Ps were characterized as larger in diameter than TSAs and HPs (SSA/P vs HP, 13.62 ± 8.62 mm vs 7.74 ± 3.24 mm, P < 0.001; SSA/Ps vs TSA, 13.62 ± 8.62 mm vs 9.89 ± 5.73 mm, P < 0.01); common in the right side of the colon [HPs, 30.4% (7/23): TSAs, 20.5% (8/39): SSA/P, 84.0% (42/50), P < 0.001]; flat-elevated lesion [HPs, 30.4% (7/23): TSAs, 5.1% (2/39): SSA/Ps, 90.0% (45/50), P < 0.001]; normal-colored or pale imucosa [HPs, 34.8% (8/23): TSAs, 10.3% (4/39): SSA/Ps, 80% (40/50), P < 0.001]; and with large amounts of mucin [HPs, 21.7% (5/23): TSAs, 17.9% (7/39): SSA/Ps, 72.0% (36/50), P < 0.001]. In magnified colonoscopic findings, 17 lesions showed either type II pit pattern alone or partial type II pit pattern as the basic architecture, with 14 HPs (14/17, 70.0%) and 3 SSA/Ps. Magnified colonoscopy showed the type II-O pit pattern as characteristic of SSA/Ps [sensitivity 83.7% (41/49), specificity 85.7% (54/63)]. Cancer was also present in three lesions, in all of which a type VI pit pattern was also present within the same lesion. There were four HPs and four TSAs each. The type IV-S pit pattern was characteristic of TSAs [sensitivity 96.7% (30/31), specificity 89.9% (72/81)]. Cancer was present in one lesion, in which a type VI pit pattern was also present within the same lesion. In our study, serrated lesions of the colorectum also possessed the features described in previous reports of conventional colonoscopic findings. The pit pattern diagnosis using magnifying colonoscopy, particularly magnified colonoscopic findings using subclassifications of surface architecture, reflected the pathological characteristics of SSA/Ps and TSAs, and will be useful for colonoscopic diagnosis. CONCLUSION: We suggest that this system could be a good diagnostic tool for SSA/Ps using magnifying colonoscopy.

A large cross-sectional, descriptive study of self-reports after biofield therapy in Japan: demography, symptomology, and circumstances of treatment administration.

BACKGROUND: Practitioners apply biofield therapy in diverse situations; however, most previously published reports investigated its efficacy in a clinical setting with a few expert practitioners administering it. OBJECTIVE: The study intended to determine the factors associated with self-reported symptom change after a single session of Okada Purifying Therapy (OPT), a form of biofield therapy, in various settings and to analyze its optimal therapeutic environments. DESIGN: This cross-sectional study used simple questionnaires. The research team trained 100 instructors of OPT to act as investigators for the study. The team recorded the initial lecture to those instructors on video, and the instructors used it to train other certified OPT practitioners in 222 locations. All investigators were volunteers. SETTINGS: The OPT sessions took place in various environments, including at MOA International Corporation's affiliated institutes, with or without clinics; at investigators' homes; and at participants' homes. PARTICIPANTS: The study involved 44 587 participants in total; all were Japanese, aged 16 or older, and suffering from physical pain, palpitation/dizziness, or anxiety/depression. INTERVENTION: The intervention involved one session of OPT lasting 30 minutes or longer administered by the volunteer practitioners. OUTCOME MEASURES: The research team evaluated the severity of symptoms before and after the intervention. The team examined (1) the self-reported change in each category of symptoms as measured after a session and (2) the adjusted odds ratio of the variables related to the outcomes. RESULTS: Of the analyzed participants, 69.7%, 67.5%, and 71.2% reported an improvement in the severity of physical pain, palpitation/dizziness, and anxiety/depression, respectively. Those rates, however, varied based on the participant's gender, the duration or location of the intervention, and the reason for participation. The improvement rate was consistently highest among female participants whose reason for participation involved a hope that OPT would relieve their symptoms or promote their health and who had received the therapy for more than 30 minutes in settings other than their own homes. This finding occurred regardless of the recipient's knowledge of the therapy or past experience of the intervention. The participant's gender, the duration of the intervention, and its location were also significant factors for marked improvements (a decrease in symptoms of 2 or 3 levels) in self-reported symptoms. In evaluating safety, the research team found that the exacerbation rates of reported symptoms were 2.5%, 1.1%, and 0.7% for physical pain, palpitation/dizziness, and anxiety/depression, respectively. None of those who expressed exacerbation of symptoms needed emergency medical treatment. No factor was associated consistently with the exacerbation. CONCLUSION: After a single session of biofield therapy, the participants' responses varied according to their gender, the duration and location of the intervention, and the reasons for participation.

Publication criteria for evoked magnetic fields of the human brain: a proposal.

Magnetoencephalography (MEG) is a record of the magnetic fields produced by the electrical activities of the brain using MEG systems. There are three types of sensors for MEG systems: magnetometer and two types of gradiometer. Among them, two types of gradiometer, axial and planar, have been used worldwide. Unfortunately, the waveforms recorded by the two types of gradiometer are often different from each other. This poses a serious problem in comparing and evaluating the data from the two gradiometers. We consider that the MEG study should be published in a way that allows other workers using different types of gradiometer to evaluate and replicate the results of MEG studies. There have been, however, no publication criteria for reports of studies on stimulus-evoked or event-related magnetic fields in human subjects. In this article, we propose publication criteria for evoked or event-related magnetic fields of the human brain: original waveforms of selected channels covering a region of interest, a root mean-squared (RMS) waveform and a contour map at an appropriate time.

A novel pit pattern identifies the precursor of colorectal cancer derived from sessile serrated adenoma.

OBJECTIVES: Sessile serrated adenomas (SSAs) are known to be precursors of sporadic colorectal cancers (CRCs) with microsatellite instability (MSI), and to be tightly associated with BRAF mutation and the CpG island methylator phenotype (CIMP). Consequently, colonoscopic identification of SSAs has important implications for preventing CRCs, but accurate endoscopic diagnosis is often difficult. Our aim was to clarify which endoscopic findings are specific to SSAs. METHODS: The morphological, histological and molecular features of 261 specimens from 226 colorectal tumors were analyzed. Surface microstructures were analyzed using magnifying endoscopy. Mutation in BRAF and KRAS was examined by pyrosequencing. Methylation of p16, IGFBP7, MLH1 and MINT1, -2, -12 and -31 was analyzed using bisulfite pyrosequencing. RESULTS: Through retrospective analysis of a training set (n=145), we identified a novel surface microstructure, the Type II open-shape pit pattern (Type II-O), which was specific to SSAs with BRAF mutation and CIMP. Subsequent prospective analysis of an independent validation set (n=116) confirmed that the Type II-O pattern is highly predictive of SSAs (sensitivity, 65.5%; specificity, 97.3%). BRAF mutation and CIMP occurred with significant frequency in Type II-O-positive serrated lesions. Progression of SSAs to more advanced lesions was associated with further accumulation of aberrant DNA methylation and additional morphological changes, including the Type III, IV and V pit patterns. CONCLUSIONS: Our results suggest the Type II-O pit pattern is a useful hallmark of the premalignant stage of CRCs with MSI and CIMP, which could serve to improve the efficacy of colonoscopic surveillance.