Impact of mirabegron extended-release on the treatment of overactive bladder with urge urinary incontinence, urgency, and frequency

Overactive bladder is a highly prevalent disorder with a significant impact on quality of life. Antimuscarinic agents are commonly used, but persistence is limited due to unsatisfactory efficacy and/or tolerability. Mirabegron is the first beta-3 adrenoceptor agonist approved for the treatment of overactive bladder syndrome. This paper reviews the pharmacology, mechanism of action, efficacy, and safety of mirabegron. A PubMed search of all English articles pertaining to mirabegron was performed. An alternative to antimuscarinics, mirabegron has a unique mechanism, improves overactive bladder symptoms and quality of life, and has limited adverse effects and few contraindications

Measuring and improving health care quality: nursing\u27s contribution to the state of science

Concern over the quality of health care is a recurring topic in the United States. A “state of the science” invitational conference on quality health care, titled “Measuring and Improving Health Care Quality, Towards Meaningful Solutions To Pressing Problems, Nursing’s Contribution to the State of the Science” was held April 18–20, 2002 in Philadelphia at the Annenberg Center for Public Policy, University of Pennsylvania. This conference stemmed from the work of the American Academy of Nursing (AAN) Expert Panel on Quality Health Care and had its genesis in June 1996 during the AAN Expert Panel on Quality’s Conference titled, “Outcome Measures and Care Delivery Systems.” This conference was also responsive to recent reports published by the Institute of Medicine (IOM) and others, which have concluded that quality problems can lead to poorer health and that widespread quality problems exist throughout American medicine

Minimum entropy decomposition : unsupervised oligotyping for sensitive partitioning of high-throughput marker gene sequences

© The Author(s), 2014. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in ISME Journal 9 (2015): 968–979, doi:10.1038/ismej.2014.195.Molecular microbial ecology investigations often employ large marker gene datasets, for example, ribosomal RNAs, to represent the occurrence of single-cell genomes in microbial communities. Massively parallel DNA sequencing technologies enable extensive surveys of marker gene libraries that sometimes include nearly identical sequences. Computational approaches that rely on pairwise sequence alignments for similarity assessment and de novo clustering with de facto similarity thresholds to partition high-throughput sequencing datasets constrain fine-scale resolution descriptions of microbial communities. Minimum Entropy Decomposition (MED) provides a computationally efficient means to partition marker gene datasets into ‘MED nodes’, which represent homogeneous operational taxonomic units. By employing Shannon entropy, MED uses only the information-rich nucleotide positions across reads and iteratively partitions large datasets while omitting stochastic variation. When applied to analyses of microbiomes from two deep-sea cryptic sponges Hexadella dedritifera and Hexadella cf. dedritifera, MED resolved a key Gammaproteobacteria cluster into multiple MED nodes that are specific to different sponges, and revealed that these closely related sympatric sponge species maintain distinct microbial communities. MED analysis of a previously published human oral microbiome dataset also revealed that taxa separated by less than 1% sequence variation distributed to distinct niches in the oral cavity. The information theory-guided decomposition process behind the MED algorithm enables sensitive discrimination of closely related organisms in marker gene amplicon datasets without relying on extensive computational heuristics and user supervision.AME was supported by a G. Unger Vetlesen Foundation grant to the Marine Biological Laboratory and the Alfred P Sloan Foundation

The 'Melanoma-enriched' microRNA miR-4731-5p acts as a tumour suppressor

We previously identified miR-4731-5p (miR-4731) as a melanoma-enriched microRNA following comparison of melanoma with other cell lines from solid malignancies. Additionally, miR-4731 has been found in serum from melanoma patients and expressed less abundantly in metastatic melanoma tissues from stage IV patients relative to stage III patients. As miR-4731 has no known function, we used biotin-labelled miRNA duplex pull-down to identify binding targets of miR-4731 in three melanoma cell lines (HT144, MM96L and MM253). Using the miRanda miRNA binding algorithm, all pulled-down transcripts common to the three cell lines (n=1092) had potential to be targets of miR-4731 and gene-set enrichment analysis of these (via STRING v9.1) highlighted significantly associated genes related to the ‘cell cycle’ pathway and the ‘melanosome’. Following miR-4731 overexpression, a selection (n=81) of pull-down transcripts underwent validation using a custom qRT-PCR array. These data revealed that miR-4731 regulates multiple genes associated with the cell cycle (e.g. CCNA2, ORC5L, and PCNA) and the melanosome (e.g. RAB7A, CTSD, and GNA13). Furthermore, members of the synovial sarcoma X breakpoint family (SSX) (melanoma growth promoters) were also down-regulated (e.g. SSX2, SSX4, and SSX4B) as a result of miR-4731 overexpression. Moreover, this down-regulation of mRNA expression resulted in ablation or reduction of SSX4 protein, which, in keeping with previous studies, resulted in loss of 2D colony formation. We therefore speculate that loss of miR-4731 expression in stage IV patient tumours supports melanoma growth by, in part; reducing its regulatory control of SSX expression levels

Is season of birth related to disordered eating and personality in women with eating disorders?

We assessed the relation between season of birth and eating disorder symptoms and personality characteristics in a sample of 880 women with eating disorders and 580 controls from two Price Foundation Studies. Eating disorder symptoms were assessed using the Structured Interview of Anorexic and Bulimic Disorders and the Structured Clinical Interview for DSM-IV. Personality traits were assessed using the Temperament and Character Inventory and the Frost Multidimensional Perfectionism Scale. Date of birth was obtained from a sociodemographic questionnaire. No significant differences were observed 1) in season of birth across eating disorder subtypes and controls; nor 2) for any clinical or personality variables and season of birth. We found no evidence of season of birth variation in eating disorders symptoms or personality traits. Contributing to previous conflicting findings, the present results do not support a season of birth hypothesis for eating disorders

Associations between Mycobacterium avium subsp. paratuberculosis antibodies in bulk tank milk, season of sampling and protocols for managing infected cows

BACKGROUND: The objective of this study was to identify associations between the concentration of Mycobacterium avium subsp. paratuberculosis (MAP) antibodies in bulk milk and potential risk factors in herd management and herd characteristics, explaining high MAP antibody titers in milk. An extensive questionnaire was administered to 292 organic and conventional dairy farms from New York, Wisconsin and Oregon. Bulk milk samples were taken from each farm for MAP enzyme-linked immunosorbent assay (ELISA). A general linear model was constructed with MAP ELISA value as the outcome variable and the management factors and herd characteristics as independent variables, while at the same time controlling for the study design variables of state, herd size, and production system (organic or conventional). High bulk tank MAP ELISA value may be due to either a high prevalence of MAP in a herd with many cows contributing to the antibody titer or due to a few infected cows that produce large quantities of antibodies. RESULTS: Results of the regression models indicated that bulk milk ELISA value was associated with season of sampling and the presence or absence of protocols for managing MAP-positive cows. The concentration of MAP antibodies in bulk milk varied seasonally with a peak in the summer and low concentrations in the winter months. When compared to farms that had never observed clinical Johne’s disease, keeping MAP-positive cows or only culling them after a period of delay was associated with an increase in optical density. CONCLUSIONS: The seasonal variation in MAP antibody titers, with a peak in the summer, may be due to a seasonal increase in MAP-bacterial load. Additionally, seasonal calving practices may contribute to seasonal fluctuations in MAP antibody titers in bulk tank milk. Keeping MAP-positive cows increases the antibody titer in bulk milk, likely due to direct antibody production in the infected cow and indirect triggering of antibody production in herdmates.Keywords: Antibodies, ELISA, Cattle, Mycobacteirum avium subsp. paratuberculosis, Bulk-tank milkKeywords: Antibodies, ELISA, Cattle, Mycobacteirum avium subsp. paratuberculosis, Bulk-tank mil

The Prognostic and Predictive Value of Melanoma-related MicroRNAs Using Tissue and Serum: A MicroRNA Expression Analysis

The overall 5-year survival for melanoma is 91%. However, if distant metastasis occurs (stage IV), cure rates are = 82%) when = 4 miRNAs were expressed. Moreover, the 'MELmiR-7' panel characterised overall survival of melanoma patients better than both serum LDH and S100B (delta log likelihood=11, p < 0.001). This panel was found to be superior to currently used serological markers for melanoma progression, recurrence, and survival; and would be ideally suited to monitor tumour progression in patients diagnosed with early metastatic disease (stages IIIa-c/IV M1a-b) to detect relapse following surgical or adjuvant treatment. (C) 2015 The Authors. Published by Elsevier B. V

Preliminary Competencies for Comparative Effectiveness Research

The Clinical and Translational Science Award (CTSA) Workgroup for Comparative Effectiveness Research (CER) Education, Training, and Workforce Development identified a need to delineate the competencies that practitioners and users of CER for patient centered outcomes research, should acquire. With input from CTSA representatives and collaborators, we began by describing the workforce. We recognize the workforce that conduct CER and the end users who use CER to improve the health of individuals and communities. We generated a preliminary set of competencies and solicited feedback from the CER representatives at each member site of the CTSA consortium. We distinguished applied competencies (i.e., skills needed by individuals who conduct CER) from foundational competencies that are needed by the entire CER workforce, including end users of CER. Key competency categories of relevance to both practitioners and users of CER were: 1) Asking relevant research questions; 2) Recognizing or designing ideal CER studies; 3) Executing or using CER studies; 4) Using appropriate statistical analyses for CER; and 5) Communicating and disseminating CER study results to improve health. While CER is particularly broad concept, we anticipate that these preliminary, relatively generic competencies will be used in tailoring curricula to individual learners from a variety of programmatic perspectives

Exercise caution: Over-exercise is associated with suicidality among individuals with disordered eating

We conducted four studies to examine the relationship between over-exercise and suicidality. Study 1 investigated whether over-exercise predicted suicidal behavior after controlling for other eating disorder behaviors in a patient sample of 204 women (144 with Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) Bulimia Nervosa [BN]). Study 2 tested the prospective association between over-exercise and acquired capability for suicide (ACS) in a sample of 171 college students followed for 3–4 weeks. Study 3 investigated whether pain insensitivity accounted for the relationship between over-exercise and ACS in a new sample of 467 college students. Study 4 tested whether ACS accounted for the relationship between over-exercise and suicidal behavior in a sample of 512 college students. In Study 1, after controlling for key covariates, over-exercise was the only disordered eating variable that maintained a significant relationship with suicidal behavior. In Study 2, Time 1 over-exercise was the only disordered eating behavior that was associated with Time 2 ACS. In Study 3, pain insensitivity accounted for the relationship between over-exercise and ACS. In Study 4, ACS accounted for the relationship between over-exercise and suicidal behavior. Over-exercise appears to be associated with suicidal behavior, an association accounted for by pain insensitivity and the acquired capability for suicide; notably, this association was found across a series of four studies with different populations