A Case of Disseminated and Fulminant Plasmacytomas That Developed during Bortezomib Treatment

Multiple myeloma is an incurable and slow growing plasma cell neoplasm. The introduction of new drugs has increased the number of treatment options. Bortezomib, the first-in-class proteasome inhibitor, has been shown to have a significant antitumor activity in the treatment of relapse/refractory patients with multiple myeloma. Additionally, plasmacytomas have shown significant response to bortezomib. In this case report, we describe a patient who developed disseminated and fulminant extramedullary plasmacytomas during combination chemotherapy treatment with bortezomib within a short period, after having shown clinical improvement

Visualizing Orbital Content of Electronic Bands in Anisotropic 2D Semiconducting ReSe2

Many properties of layered materials change as they are thinned from their bulk forms down to single layers, with examples including indirect-to-direct band gap transition in 2H semiconducting transition metal dichalcogenides as well as thickness-dependent changes in the valence band structure in post-transition metal monochalcogenides and black phosphorus. Here, we use angle-resolved photoemission spectroscopy to study the electronic band structure of monolayer ReSe$_{2}$, a semiconductor with a distorted 1T structure and in-plane anisotropy. By changing the polarization of incoming photons, we demonstrate that for ReSe$_{2}$, in contrast to the 2H materials, the out-of-plane transition metal $d_{z^{2}}$ and chalcogen $p_{z}$ orbitals do not contribute significantly to the top of the valence band which explains the reported weak changes in the electronic structure of this compound as a function of layer number. We estimate a band gap of 1.7 eV in pristine ReSe$_{2}$ using scanning tunneling spectroscopy and explore the implications on the gap following surface-doping with potassium. A lower bound of 1.4 eV is estimated for the gap in the fully doped case, suggesting that doping-dependent many-body effects significantly affect the electronic properties of ReSe$_{2}$. Our results, supported by density functional theory calculations, provide insight into the mechanisms behind polarization-dependent optical properties of rhenium dichalcogenides and highlight their place amongst two-dimensional crystals.Comment: 37 pages (including Supporting Information), 7 figures in the main tex

Characteristics and outcomes of endoscopically resected colorectal cancers that arose from sessile serrated adenomas and traditional serrated adenomas

Background/AimsThe efficacy and safety of endoscopic resection of colorectal cancer derived from sessile serrated adenomas or traditional serrated adenomas are still unknown. The aims of this study were to verify the characteristics and outcomes of endoscopically resected early colorectal cancers developed from serrated polyps.MethodsAmong patients who received endoscopic resection of early colorectal cancers from 2008 to 2011, cancers with documented pre-existing lesions were included. They were classified as adenoma, sessile serrated adenoma, or traditional serrated adenoma according to the baseline lesions. Clinical characteristics, pathologic diagnosis, and outcomes were reviewed.ResultsOverall, 208 colorectal cancers detected from 198 patients were included: 198 with adenoma, five with sessile serrated adenoma, and five with traditional serrated adenoma. The sessile serrated adenoma group had a higher prevalence of high-grade dysplasia (40.0% vs. 25.8%, P<0.001) than the adenoma group. During follow-up, local recurrence did not occur after endoscopic resection of early colorectal cancers developed from serrated polyps. In contrast, two cases of metachronous recurrence were detected within a short follow-up period.ConclusionsCautious observation and early endoscopic resection are recommended when colorectal cancer from serrated polyp is suspected. Colorectal cancers from serrated polyp can be treated successfully with endoscopy

Effects of Gyejibongnyeong-hwan on dysmenorrhea caused by blood stagnation: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Gyejibongnyeong-hwan (GJBNH) is one of the most popular Korean medicine formulas for menstrual pain of dysmenorrhea. The concept of blood stagnation in Korean medicine is considered the main factor of causing abdominal pain, or cramps, during menstrual periods. To treat the symptoms, GJBNH is used to fluidify the stagnated blood and induce the blood flow to be smooth, reducing pain as the result. The purpose of this trial is to identify the efficacy of GJBNH in dysmenorrhea caused by blood stagnation.</p> <p>Methods</p> <p>This study is a multi-centre, randomised, double-blind, controlled trial with two parallel arms: the group taking GJBNH and the group taking placebo. 100 patients (women from age 18 to 35) will be enrolled to the trial. Through randomization 50 patients will be in experiment arm, and the other 50 patients will be in control arm. At the second visit (baseline), all participants who were already screened that they fulfil both the inclusion and the exclusion criteria will be randomised into two groups. Each group will take the intervention three times per day during two menstrual cycles. After the treatment for two cycles, each patient will be followed up during their 3^rd, 4^thand 5^thmenstrual cycles. From the screening (Visit 1) through the second follow-up (Visit 6) the entire process will take 25 weeks.</p> <p>Discussion</p> <p>This trial will provide evidence for the effectiveness of GJBNH in treating periodical pain due to dysmenorrhea that is caused by blood stagnation. The primary outcome between the two groups will be measured by changes in the Visual Analogue Score (VAS) of pain. The secondary outcome will be measured by the Blood Stagnation Scale, the Short-form McGill questionnaire and the COX menstrual symptom scale. Analysis of covariance (ANCOVA) and repeated measured ANOVA will be used to analyze the data analysis.</p> <p>Trial registration</p> <p>Current Controlled Trials: <a href="http://www.controlled-trials.com/ISRCTN30426947">ISRCTN30426947</a></p

Characteristics of stable chronic obstructive pulmonary disease patients in the pulmonology clinics of seven Asian cities

Background and objectives Chronic obstructive pulmonary disease (COPD) is responsible for significant morbidity and mortality worldwide. We evaluated the characteristics of stable COPD patients in the pulmonology clinics of seven Asian cities and also evaluated whether the exposure to biomass fuels and dusty jobs were related to respiratory symptoms, airflow limitation, and quality of life in the COPD patients. Methods: This cross-sectional observational study recruited 922 COPD patients from seven cities of Asia. The patients underwent spirometry and were administered questionnaires about their exposure to cigarette smoking, biomass fuels, and dusty jobs in addition to respiratory symptoms and health related quality of life. Results: Of the patients, there appeared to be variations from city to city in the history of exposure to biomass fuels and dusty jobs and also in respiratory symptoms of cough, phlegm, wheeze, and dyspnea. These symptoms were more frequent in those COPD patients with a history of exposure to biomass fuels than without and those with a history of exposure to dusty jobs than without (P < 0.01 for all comparisons). Airflow limitation was more severe in those COPD patients with a history of exposure to biomass fuels than without (52.2% predicted versus 55.9% of post-bronchodilator forced expiratory volume in 1 second [FEV1], P = 0.009); quality of life was poorer in those with exposure to biomass fuels than without (40.4 versus 36.2 of the St George’s Respiratory Questionnaire [SGRQ] total score, P = 0.001). Airflow limitation was more severe in those COPD patients with a history of exposure to dusty jobs than without (51.2% predicted versus 57.3% of post-bronchodilator FEV1, P < 0.001); quality of life was poorer in those with dusty jobs than without (41.0 versus 34.6 of SGRQ score, P = 0.006). Conclusion: In Asian cities, the characteristics of COPD patients vary and the history of exposure to biomass fuels or dusty jobs was related to frequency of symptoms, severe airflow limitation, and poor quality of life

O-GlcNAc modification of leucyl-tRNA synthetase 1 integrates leucine and glucose availability to regulate mTORC1 and the metabolic fate of leucine

All living organisms have the ability to sense nutrient levels to coordinate cellular metabolism. Despite the importance of nutrient-sensing pathways that detect the levels of amino acids and glucose, how the availability of these two types of nutrients is integrated is unclear. Here, we show that glucose availability regulates the central nutrient effector mTORC1 through intracellular leucine sensor leucyl-tRNA synthetase 1 (LARS1). Glucose starvation results in O-GlcNAcylation of LARS1 on residue S1042. This modification inhibits the interaction of LARS1 with RagD GTPase and reduces the affinity of LARS1 for leucine by promoting phosphorylation of its leucine-binding site by the autophagy-activating kinase ULK1, decreasing mTORC1 activity. The lack of LARS1 O-GlcNAcylation constitutively activates mTORC1, supporting its ability to sense leucine, and deregulates protein synthesis and leucine catabolism under glucose starvation. This work demonstrates that LARS1 integrates leucine and glucose availability to regulate mTORC1 and the metabolic fate of leucine. Leucyl-tRNA synthetase 1 (LARS1) is a leucine sensor for mTORC1 signaling and regulates leucine utilization depending on glucose availability. Here, the author show that O-GlcNAcylation of LARS1 is crucial for its ability to regulate mTORC1 activity and leucine metabolism upon glucose starvation

Pre-Operative Prediction of Advanced Prostatic Cancer Using Clinical Decision Support Systems: Accuracy Comparison between Support Vector Machine and Artificial Neural Network

OBJECTIVE: The purpose of the current study was to develop support vector machine (SVM) and artificial neural network (ANN) models for the pre-operative prediction of advanced prostate cancer by using the parameters acquired from transrectal ultrasound (TRUS)-guided prostate biopsies, and to compare the accuracies between the two models. MATERIALS AND METHODS: Five hundred thirty-two consecutive patients who underwent prostate biopsies and prostatectomies for prostate cancer were divided into the training and test groups (n = 300 versus n = 232). From the data in the training group, two clinical decision support systems (CDSSs-[SVM and ANN]) were constructed with input (age, prostate specific antigen level, digital rectal examination, and five biopsy parameters) and output data (the probability for advanced prostate cancer [> pT3a]). From the data of the test group, the accuracy of output data was evaluated. The areas under the receiver operating characteristic (ROC) curve (AUC) were calculated to summarize the overall performances, and a comparison of the ROC curves was performed (p < 0.05). RESULTS: The AUC of SVM and ANN is 0.805 and 0.719, respectively (p = 0.020), in the pre-operative prediction of advanced prostate cancer. CONCLUSION: The performance of SVM is superior to ANN in the pre-operative prediction of advanced prostate cancer.ope

Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis

New therapeutic strategies are needed to combat the tuberculosis pandemic and the spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) forms of the disease, which remain a serious public health challenge worldwide1, 2. The most urgent clinical need is to discover potent agents capable of reducing the duration of MDR and XDR tuberculosis therapy with a success rate comparable to that of current therapies for drug-susceptible tuberculosis. The last decade has seen the discovery of new agent classes for the management of tuberculosis3, 4, 5, several of which are currently in clinical trials6, 7, 8. However, given the high attrition rate of drug candidates during clinical development and the emergence of drug resistance, the discovery of additional clinical candidates is clearly needed. Here, we report on a promising class of imidazopyridine amide (IPA) compounds that block Mycobacterium tuberculosis growth by targeting the respiratory cytochrome bc1 complex. The optimized IPA compound Q203 inhibited the growth of MDR and XDR M. tuberculosis clinical isolates in culture broth medium in the low nanomolar range and was efficacious in a mouse model of tuberculosis at a dose less than 1 mg per kg body weight, which highlights the potency of this compound. In addition, Q203 displays pharmacokinetic and safety profiles compatible with once-daily dosing. Together, our data indicate that Q203 is a promising new clinical candidate for the treatment of tuberculosis