A comparison of the usefulness of nuclear beta‐catenin in the diagnosis of desmoid‐type fibromatosis among commonly used anti‐beta‐catenin antibodies

Desmoid-type fibromatosis (DF) is a locally aggressive but non-metastatic (myo)fibroblastic neoplasm. A hallmark of the tumor is nuclear positivity for beta-catenin in immunohistochemistry due mostly to CTNNB1 mutations. However, a recent study has reported that even beta-catenin ‘nuclear-negative’ DFs can harbor CTNNB1 mutations and that the positive ratio of nuclear beta-catenin in DF is different among antibodies. Here, we reviewed soft tissue lesions for which the possibility of DF was considered and compared the sensitivity and specificity of nuclear beta-catenin for the diagnosis of DF among commonly used anti-beta-catenin antibodies, i.e., clone beta-catenin 1, 17C2 and 14. We analyzed 26 cases of DF, 28 cases of benign fibroblastic lesions, and 27 cases of other soft tissue tumors. The sensitivity and specificity of nuclear beta-catenin for the diagnosis of DF were different among antibodies; 54% and 98% in clone beta-catenin 1, 85% and 84% in 17C2, and 96% and 62% in 14. IHC of LEF1 showed comparable results with IHC of beta-catenin, with a sensitivity of 88% and specificity of 76%. Additionally, when beta-catenin 1 was used, DFs showed characteristic dotted cytoplasmic staining, often appearing as rings. Our results might be helpful for making a correct diagnosis of DF

Ozone and Daily Mortality in Shanghai, China

BACKGROUND: Controversy remains regarding the relationship between ambient ozone and mortality worldwide. In mainland China, the largest developing country, there has been no prior study investigating the acute effect of O(3) on death risk. Given the changes in types of air pollution from conventional coal combustion to the mixed coal combustion/motor vehicle emissions in China’s large cities, it is worthwhile to investigate the acute effect of O(3) on mortality outcomes in the country. OBJECTIVES: We conducted a time-series study to investigate the relation between O(3) and daily mortality in Shanghai using 4 years of daily data (2001–2004). METHODS: We used the generalized additive model with penalized splines to analyze mortality, O(3) pollution, and covariate data in warm and cold seasons. We considered daily counts of all-cause mortality and several cause-specific subcategories (respiratory and cardiovascular). We also examined these associations among several subpopulations based on age and sex. RESULTS: O(3) was significantly associated with total and cardiovascular mortality in the cold season but not in the warm season. In the whole-year analysis, an increase of 10 μg/m(3) of 2-day average (lag01) O(3) corresponds to 0.45% [95% confidence interval (CI), 0.16–0.73%], 0.53% (95% CI, 0.10–0.96%), and 0.35% (95% CI, −0.40 to 1.09%) increase of total nonaccidental, cardiovascular, and respiratory mortality, respectively. In the cold season, the estimates increased to 1.38% (95% CI, 0.68–2.07%), 1.53% (95% CI, 0.54–2.52%), and 0.95% (95% CI, −0.71 to 2.60%), respectively. In the warm season, we did not observe significant associations for both total and cause-specific mortality. The results were generally insensitive to model specifications such as lag structure of O(3) concentrations and degree of freedom for time trend. Multipollutant models indicate that the effect of O(3) was not confounded by particulate matter ≤ 10 μm in diameter (PM(10)) or by sulfur dioxide; however, after adding nitrogen dioxide into the model, the association of O(3) with total and cardiovascular mortality became statistically insignificant. CONCLUSIONS: O(3) pollution has stronger health effects in the cold than in the warm season in Shanghai. Our analyses also strengthen the rationale for further limiting levels of O(3) pollution in outdoor air in the city

Structural basis for translation termination by archaeal RF1 and GTP-bound EF1 complex

ABSTRACT When a stop codon appears at the ribosomal A site, the class I and II release factors (RFs) terminate translation. In eukaryotes and archaea, the class I and II RFs form a heterodimeric complex, and complete the overall translation termination process in a GTP-dependent manner. However, the structural mechanism of the translation termination by the class I and II RF complex remains unresolved. In archaea, archaeal elongation factor 1 alpha (aEF1a), a carrier GTPase for tRNA, acts as a class II RF by forming a heterodimeric complex with archaeal RF1 (aRF1). We report the crystal structure of the aRF1 · aEF1a complex, the first active class I and II RF complex. This structure remarkably resembles the tRNA · EF-Tu complex, suggesting that aRF1 is efficiently delivered to the ribosomal A site, by mimicking tRNA. It provides insights into the mechanism that couples GTP hydrolysis by the class II RF to stop codon recognition and peptidyltRNA hydrolysis by the class I RF. We discuss the different mechanisms by which aEF1a recognizes aRF1 and aPelota, another aRF1-related protein and molecular evolution of the three functions of aEF1a

Association between suicide-related ideations and affective temperaments in the Japanese general adult population

Background: Suicide rates are vastly higher in Japan than in many other countries, although the associations between affective temperaments and suicide-related ideations in the general adult population remain unclear. Therefore, we aimed to elucidate these associations in the present study. Methods: We analyzed data from 638 Japanese volunteers who completed both the Patient Health Questionnaire (PHQ-9) and the Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego Auto-questionnaire (TEMPS-A). Participants were then divided into three groups based on PHQ-9 summary scores and responses to the suicide-related ideation item: non-depressive control group (NC; N = 469), depressive symptoms without suicide-related ideations group (non-SI; N = 135), and depressive symptoms with suicide-related ideations group (SI; N = 34). The depressive symptoms were defined for PHQ-9 summary scores ≥5, and the suicide-related ideations were defined for PHQ-9 #9 score ≥1. We then compared TEMPS-A scores among the groups using Kruskal-Wallis tests. Then the 95% confidence intervals of differences in TEMPS-A subscale scores between the NC and non-SI groups, or between NC and SI groups, were calculated. Results: Participants of the SI group exhibited significantly higher scores on the depressive, irritable, and anxious temperament subscales than those of the non-SI group. Similarly, women of the SI group exhibited significantly higher scores of the depressive and irritable temperament subscales than women of the non-SI group, while men of the SI group exhibited significantly higher depressive temperament scores than those of the non-SI group. Among all participants and only men, cyclothymic subscale scores were higher in those of the SI group than the non-SI group (not significant), although the 95% confidence intervals did not overlap. Limitations: The cross-sectional study design was the main limitation. Conclusions: Depressive, irritable, and anxious temperaments are significant risk factors for suicide-related ideations in the Japanese general adult population. Furthermore, irritable temperament in women and depressive temperament in men are associated with suicide-related ideations

Immunologic Monitoring of Cellular Responses by Dendritic/Tumor Cell Fusion Vaccines

Although dendritic cell (DC)- based cancer vaccines induce effective antitumor activities in murine models, only limited therapeutic results have been obtained in clinical trials. As cancer vaccines induce antitumor activities by eliciting or modifying immune responses in patients with cancer, the Response Evaluation Criteria in Solid Tumors (RECIST) and WHO criteria, designed to detect early effects of cytotoxic chemotherapy in solid tumors, may not provide a complete assessment of cancer vaccines. The problem may, in part, be resolved by carrying out immunologic cellular monitoring, which is one prerequisite for rational development of cancer vaccines. In this review, we will discuss immunologic monitoring of cellular responses for the evaluation of cancer vaccines including fusions of DC and whole tumor cell

Effects of continuous supplementation of Acanthopanax senticosus Harms on the cardiac autonomic function of community-dwelling elderly individuals during resting and standing tests: a randomized controlled trial

BackgroundCardiac autonomic function (CAF) decreases with aging, and Acanthopanax senticosus Harms (ASH) consumption reportedly induces anti-stress effects. This study aimed to assess the effect of continuous supplementation of ASH on CAF during resting and standing tests in the elderly population.MethodsThis double-blind, randomized controlled trial was conducted in the morning in a laboratory setting and was carried out between June 2017 and July 2017 at Kambaikan, Doshisha University (Karasuma-higashi-iru, Imadegawa-dori, Kamigyo-ku, Kyoto 602-8580, Japan). In total, 28 community-dwelling elderly individuals (mean ± standard deviation = 72.5 ± 4.5 years) were included. Each subject was instructed to consume ASH or placebo supplements twice daily for 4 weeks. An autonomic reflex orthostatic tolerance recorder was used to measure CAF in pre- and post-intervention phases. Parameters were measured in a seated position and included coefficient of variation of R-R intervals (CVRR), low frequency (LF), high frequency (HF), LF/HF ratio, blood pressure, and heart rate (HR). Changes in each parameter were evaluated before and after standing. All parameters were defined as the difference between the mean value obtained in a standing position for 2 min and that obtained in a 2-min seated position.ResultsA two-way analysis of variance revealed a significant group-time interaction effect on CVRR, HF, and ΔLF/HF ratio. Following the intervention, CVRR, HF, LF/HF ratio, systolic blood pressure (SBP), HR, ΔLF/HF ratio, ΔSBP, and ΔHR improved significantly in the ASH group only.ConclusionsFour-week supplementation of ASH improved CAF in community-dwelling elderly individuals during resting and standing tests.Clinical Trial Registrationhttps://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000031218, UMIN Clinical Trials Registry (UMIN000027251)

Generation of Small 32P-Labeled Peptides as a Potential Approach to Colorectal Cancer Therapy

Cancers have been revealed to be extremely heterogenous in terms of the frequency and types of mutations present in cells from different malignant tumors. Thus, it is likely that uniform clinical treatment is not optimal for all patients, and that the development of individualized therapeutic regimens may be beneficial. We describe the generation of multiple, unique small peptides nine to thirty-four amino acids in length which, when labeled with the radioisotope 32P, bind with vastly differing efficiencies to cell lines derived from different colon adenocarcinomas. In addition, the most effective of these peptides permanently transfers the 32P radioisotope to colorectal cancer cellular proteins within two hours at a rate that is more than 150 times higher than in cell lines derived from other cancers or from the normal tissues tested. Currently, the only two FDA-approved radioimmunotherapeutic agents in use both employ antibodies directed against the B cell marker CD20 for the treatment of non-Hodgkin's lymphoma. By using the method described herein, large numbers of different 32P-labeled peptides can be readily produced and assayed against a broad spectrum of cancer types. This report proposes the development and use of 32P-labeled peptides as potential individualized peptide-binding therapies for the treatment of colon adenocarcinoma patients

On the irrationality measure function in average

We study asymptotics for the intergal of irrationality measure functions.Comment: Summary in English, fulltext in Russia

Current Immunotherapeutic Approaches in Pancreatic Cancer

Pancreatic cancer is a highly aggressive and notoriously difficult to treat. As the vast majority of patients are diagnosed at advanced stage of the disease, only a small population is curative by surgical resection. Although gemcitabine-based chemotherapy is typically offered as standard of care, most patients do not survive longer than 6 months. Thus, new therapeutic approaches are needed. Pancreatic cancer cells that develop gemcitabine resistance would still be suitable targets for immunotherapy. Therefore, one promising treatment approach may be immunotherapy that is designed to target pancreatic-cancer-associated antigens. In this paper, we detail recent work in immunotherapy and the advances in concept of combination therapy of immunotherapy and chemotherapy. We offer our perspective on how to increase the clinical efficacy of immunotherapies for pancreatic cancer