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BACKGROUND Urgency is a complaint of sudden, compelling desire to pass urine, which is difficult to defer, caused by involuntary contraction of the detrusor muscle during the bladder-filling stage. To enable detrusor inhibition, electrotherapy resources such as transcutaneous tibial nerve stimulation (TTNS) and parasacral transcutaneous electrical stimulation (PTES) have been used. The objective this study is to publish the study protocol that aims to investigate whether urgency decreases after treatment with both of the techniques. METHODS This randomized controlled clinical trial will include 99 women, aged more than 18 years old, with urgency (score ≥ 8 in the Overactive Bladder-Validated 8-Question Awareness Tool [OAB-V8]). Women will be randomly allocated into three groups TTNS, PTES, and placebo. The following questionnaires will be applied the Anamnesis Record, the Incontinence Questionnaire Overactive Bladder, the King's Health Questionnaire, the 24-Hour Voiding Diary, and the OAB-V8, at four differenion in special populations, such as amputees or people with severe lower limb sensory impairment. TRIAL REGISTRATION Brazilian Registry of Clinical Trials (ReBEC) ID RBR-9rf33n, date of registration 17 May 2018.BACKGROUND Primary dysmenorrhoea (PDM) is defined as a series of pain-dominated symptoms during and after menstruation without organic lesions. Nonsteroidal anti-inflammatory drugs and oral contraceptives are usually recommended as first-line therapy for the clinical treatment of PDM, but their widespread long-term application is controversial. Radial extracorporeal shock wave therapy (rESWT) has been widely applied in musculoskeletal rehabilitation because of its secure and noninvasive characteristics and its confirmed effect in improving pain symptoms. This research seeks to explore the efficacy of rESWT for PDM and the changes in brain function of patients with PDM. METHODS This clinical research will be a randomised, blind, sham-controlled trial. Thirty-six patients with PDM will be randomly divided into the rESWT group (n = 18) and the sham rESWT group (n = 18). In the rESWT group, treatment will be applied once within 48 h of menstruation at six abdominal myofascial trigger points. The sham rESWT group ondary results will focus on improving the neurobiological understanding of disease treatment. TRIAL REGISTRATION China Clinical Trial Register, ChiCTR1900020678. Registered on 13 January 2019.BACKGROUND Polycystic ovary syndrome (PCOS) is a complex endocrine syndrome with poorly understood mechanisms. To provide patients with PCOS with individualized therapy, it is critical to precisely diagnose the phenotypes of the disease. However, the criteria for diagnosing the different phenotypes are mostly based on symptoms, physical examination and laboratory results. This study aims to compare the accuracy and efficacy of diagnosing PCOS by integrating metabolomic markers with common clinical characteristics. METHODS This is a prospective, multicenter, analyst-blinded, randomized controlled trial. Participants will be grouped into (1) people without PCOS (healthy control group), (2) patients diagnosed with PCOS based on clinical indices (experimental group 1), and (3) patients diagnosed with PCOS based on metabolomic indices (experimental group 2). A total of 276 participants, including 60 healthy people and 216 patients with PCOS, will be recruited. The 216 patients with PCOS will be randomly assigned to the two experimental groups in a 11 ratio, and each group will receive a different 6-month treatment. The primary outcome for the experimental groups will be the effect of PCOS treatment. DISCUSSION The results of this trial should help to determine whether using metabolomic indices is more accurate and effective than using clinical characteristics in diagnosing the phenotypes of PCOS. The results could provide a solid foundation for the accurate diagnosis of different PCOS subgroups and for future research on individualized PCOS therapy. TRIAL REGISTRATION Chinese Clinical Trial Registry, ID ChiCTR-INR-1800016346. Registered 26 May 2018.BACKGROUND Cancer stem cells (CSCs) can self-renew, proliferate into differentiated cells, or enter a quiescent state and are regarded to cause chemoresistance and recurrence. An integrative analysis of transcription factors (TF) and miRNAs was performed in ovarian CSC-enriched spheroid-forming cells (SFCs) to identify factors relevant to ovarian CSCs. METHODS Fresh tumor cells from three ovarian cancer patients were cultured in standard and in selective medium. The mRNAs and miRNAs that exhibited significant differential expression between SFCs and adherent cells were identified using mRNA and miRNAs microarrays. Target genes of miRNAs were further selected if predicted with TargetScan by half of the miRNAs or more. Gene enrichment analysis was performed on over- or under-expressed mRNAs and target genes of miRNAs using DAVID tools. Complex regulatory networks were combined from TF-genes and miRNA-genes interactions using the MAGIA webtool. RESULTS A total of 1245 mRNA and 55 miRNAs were differentially expressed (p-value less then  0.05, paired t-test). Elevation of transcription-related processes and suppression of focal adhesion pathway were noted in SFCs, according to the enrichment analyses. Transcriptional hyperactivity is a known characteristic of the stem cell transcriptome. The integrative network suggested that cell cycle was arrested in SFCs where over-expressed EGR1 and under-expressed MYC and miR-130a-3p had multiple connections with target genes. CONCLUSIONS MYC, EGR1, and miR-130a-3p were hubs in our integrative analysis of ovarian CSC-enriched SFCs, suggesting that ovarian cancer SFCs display a stem cell identity with the quiescent phenotype where adhesion- and cell cycle-related genes were suppressed.BACKGROUND Impulsivity and compulsivity are related to emotional and social maladjustment and often underlie psychiatric disorders. Recently, alterations in microbiota composition have been shown to have implications for brain development and social behavior via the microbiota-gut-brain axis. However, the exact mechanisms are not fully identified. Recent evidence suggests the modulatory effect of synbiotics on gut microbiota and the contribution of these agents in ameliorating symptoms of many psychiatric diseases. To date, no randomized controlled trial has been performed to establish the feasibility and efficacy of this intervention targeting the reduction of impulsivity and compulsivity. We hypothesize that supplementation with synbiotics may be an effective treatment in adults with high levels of impulsivity and/or compulsivity. METHODS/DESIGN This is a prospective, multicenter, double-blind, randomized controlled trial with two arms treatment with a synbiotic formula versus placebo treatment. The primaryw-up. DISCUSSION This is the first randomized controlled trial to determine the effects of supplementation with synbiotics on reducing impulsive and compulsive behavior. This clinical trial can contribute to explaining the mechanisms involved in the crosstalk between the intestinal microbiome and the brain. NVP-BEZ235 in vitro If effects can be established by reducing impulsive and compulsive behavior, new cost-effective treatments might become available to these patients. link2 TRIAL REGISTRATION ClinicalTrials.gov, NCT03495375. Registered on 26 February 2018.Following publication of the original article [1], we have been notified that the author Joan Calzada should not have been included to the team of authors. The authors' team, thus, should be as follows.BACKGROUND During severe immunosuppression or treatment with specific biological drugs, human polyomavirus JC (JCPyV) may establish a lytic infection in oligodendrocytes, leading to progressive multifocal leukoencephalopathy (PML). Beyond AIDS, which represents the most common predisposing condition, several biological drugs have been associated to the development of PML, such as natalizumab, fingolimod and dimethyl fumarate, which have been showed to increase the risk of PML in the multiple sclerosis (MS) population. JCPyV non-coding control region (NCCR) can be found in two different forms a virulent neurotropic pathogenic form and a latent non-pathogenic form. The neurotropic forms contain a rearranged NCCR and are typically found in the cerebrospinal fluid, brain or blood of PML patients. CASE PRESENTATION We sequenced and critically examined JCPyV NCCR from isolates detected in the cerebrospinal fluid of four newly diagnosed progressive multifocal leukoencephalopathy patients two HIV-positive and two HIV-negative multiple sclerosis patients. More complex NCCR rearrangements were observed in the two HIV-positive patients compared to the HIV-negative multiple sclerosis patients with PML. CONCLUSIONS The comparison of HIV-positive and HIV-negative MS patients with PML, allowed us to evidence the presence of a common pattern of JCPyV NCCR rearrangement, characterized by the deletion of the D-block, which could be one of the initial rearrangements of JCPyV NCCR needed for the development of PML.BACKGROUND Traumatic brain injury (TBI) is one of the major health and socioeconomic problems in the world. Immune-enhancing enteral formula has been proven to significantly reduce infection rate in TBI patients. One of the ingredients that can be used in immunonutrition formulas to reduce inflammation and oxidative stress is pycnogenol. OBJECTIVE The objective of this work is to survey the effect of pycnogenol on the clinical, nutritional, and inflammatory status of TBI patients. METHODS This is a double-blind, randomized controlled trial. Block randomization will be used. link3 An intervention group will receive pycnogenol supplementation of 150 mg for 10 days and a control group will receive a placebo for the same duration. Inflammatory status (IL-6, IL- 1β, C-reactive protein) and oxidative stress status (malondialdehyde, total antioxidant capacity), at the baseline, at the 5th day, and at the end of the study (10th day) will be measured. Clinical and nutritional status will be assessed three times during the intervention. The Sequential Organ Failure Assessment (SOFA) questionnaire for assessment of organ failure will be filled out every other day. The mortality rate will be calculated within 28 days of the start of the intervention. Weight, body mass index, and body composition will be measured. All analyses will be conducted by an initially assigned study arm in an intention-to-treat analysis. DISCUSSION We expect that supplementation of 150 mg pycnogenol for 10 days will improve clinical and nutritional status and reduce the inflammation and oxidative stress of the TBI patients. TRIAL REGISTRATION This trial is registered at clinicaltrials.gov (ref NCT03777683) at 12/13/2018.BACKGROUND Current there are different screws fixation methods used for fixation of the talar neck fracture. However, the best method of screws internal fixation is still controversial. Few relevant studies have focused on this issue, especially by finite element analysis. The purpose of this study was to explore the mechanical stability of dual screws internal fixation methods with different approaches and the best biomechanical environment of the fracture section, so as to provide reliable mechanical evidence for the selection of clinical internal fixation. METHODS The computed tomography (CT) image of the healthy adult male ankle joint was used for three-dimensional reconstruction of the ankle model. Talus neck fracture and screws were constructed by computer-aided design (CAD). Then, 3D model of talar neck fracture which fixed with antero-posterior (AP) parallel dual screws, antero-posterior (AP) cross dual screws, postero-anterior (PA) parallel dual screws, and postero-anterior (PA) cross dual screws were simulated.

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