Introduction: Appraising the quality of studies included in systematic reviews combining qualitative, quantitative and mixed methods studies is challenging. To address this challenge, a critical appraisal tool was developed: the Mixed Methods Appraisal Tool (MMAT). The aim of this paper is to present the MMAT. Development: The MMAT was developed in 2006 and was subject to pilot and interrater reliability testing. A revised new version of the MMAT was developed using the results from usefulness testing as well as a literature review on critical appraisal tools and a modified e-Delphi study with methodological experts to identify the core relevant criteria to include in the MMAT. Tool description: The MMAT includes quality criteria of five categories of study designs: (a) qualitative, (b) randomized controlled trial, (c) nonrandomized, (d) quantitative descriptive and (e) mixed methods studies. The MMAT focuses on core relevant methodological criteria and has five criteria per category of study design. Conclusion: The MMAT offers an alternative solution by proposing a unique tool that can appraise the quality of different study designs. Also, by limiting to core criteria, the MMAT can provide a more time efficient appraisal.

Objective: The mixed methods appraisal tool (MMAT) was developed for critically appraising different study designs. This study aimed to improve the content validity of three of the five categories of studies in the MMAT by identifying relevant methodological criteria for appraising the quality of qualitative, survey, and mixed methods studies.Study Design and Setting: First, we performed a literature review to identify critical appraisal tools and extract methodological criteria. Second, we conducted a two-round modified e-Delphi technique. We asked three method-specific panels of experts to rate the relevance of each criterion on a five-point Likert scale.Results: A total of 383 criteria were extracted from 18 critical appraisal tools and a literature review on the quality of mixed methods studies, and 60 were retained. In the first and second rounds of the e-Delphi, 73 and 56 experts participated, respectively. Consensus was reached for six qualitative criteria, eight survey criteria, and seven mixed methods criteria. These results led to modifications of eight of the 11 MMAT (version 2011) criteria. Specifically, we reformulated two criteria, replaced four, and removed two. Moreover, we added six new criteria.Conclusion: Results of this study led to improve the content validity of this tool, revise it, and propose a new version (MMAT version 2018). Ó

The review of clinical data related to the three drugs (including conventional treatment) compared with conventional treatment plus placebo indicates that in the short term (12-24 weeks), the three treatments are clinically effective in relation to assessment of ASAS, BASDAI and BASFI. Indirect comparisons of treatments were limited and did not show a significant difference in effectiveness between the three agents. The short-term economic assessment indicates that none of the three anti-TNF-alpha agents is likely to be considered cost-effective at current acceptability thresholds, with infliximab consistently the least favourable option. There is an absence of evidence concerning a number of limiting factors related to patients suffering from AS, the disease itself and its treatment. In order to obtain robust estimates of the longer term clinical effectiveness and cost-effectiveness of anti-TNF-alpha agents for AS, clinical trials that aim to address these limiting factors need to be conducted.

Although RNA-based biological processes and therapeutics have gained increasing interest, purification of in vitro transcribed RNA generally relies on gel-based methods that are time-consuming, tedious and denature the RNA. Here, we present a reliable procedure for affinity batch purification of RNA, which exploits the high-affinity interaction between the boxB RNA and the N-peptide from bacteriophage λ. The RNA of interest is synthesized with an ARiBo tag, which consists of an activatable ribozyme (the glmS ribozyme) and the λBoxB RNA. This ARiBo-fusion RNA is initially captured on Glutathione-Sepharose resin via a GST/λN-fusion protein, and the RNA of interest is subsequently eluted by ribozyme self-cleavage using glucosamine-6-phosphate. Several GST/λN-fusion proteins and ARiBo tags were tested to optimize RNA yield and purity. The optimized procedure enables one to quickly obtain (3 h) highly pure RNA (>99%) under native conditions and with yields comparable to standard denaturing gel-based protocols. It is widely applicable to a variety of RNAs, including riboswitches, ribozymes and microRNAs. In addition, it can be easily adapted to a wide range of applications that require RNA purification and/or immobilization, including isolation of RNA-associated complexes from living cells and high-throughput applications.

Although there are some differences, the SPIN Cohort is broadly comparable with other large prevalent SSc cohorts, increasing confidence that insights gained from the SPIN Cohort should be generalizable, although it should be noted that all three cohorts include primarily White participants.

The adenine and guanine riboswitches regulate gene expression in response to their purine ligand. X-ray structures of the aptamer moiety of these riboswitches are characterized by a compact fold in which the ligand forms a Watson–Crick base pair with residue 65. Phylogenetic analyses revealed a strict restriction at position 39 of the aptamer that prevents the G39–C65 and A39–U65 combinations, and mutational studies indicate that aptamers with these sequence combinations are impaired for ligand binding. In order to investigate the rationale for sequence conservation at residue 39, structural characterization of the U65C mutant from Bacillus subtilis pbuE adenine riboswitch aptamer was undertaken. NMR spectroscopy and X-ray crystallography studies demonstrate that the U65C mutant adopts a compact ligand-free structure, in which G39 occupies the ligand-binding site of purine riboswitch aptamers. These studies present a remarkable example of a mutant RNA aptamer that adopts a native-like fold by means of ligand mimicking and explain why this mutant is impaired for ligand binding. Furthermore, this work provides a specific insight into how the natural sequence has evolved through selection of nucleotide identities that contribute to formation of the ligand-bound state, but ensures that the ligand-free state remains in an active conformation.

Background: Osteoporosis (OP) is a skeletal disorder characterized by reduced bone strength and predisposition to increased risk of fracture, with consequent increased risk of morbidity and mortality. It is therefore an important public health problem. International and Canadian associations have issued clinical guidelines for the diagnosis and treatment of OP. In this study, we identified potential predictors of bone mineral density (BMD) testing and OP treatment, which include place of residence.

To document regional structural and cellular proliferation changes in the developing mouse colon, tissues from fetal, suckling, and weanling mice were analyzed by light microscopy (LM), transmission electron microscopy (TEM), scanning electron microscopy (SEM), [3H]-thymidine incorporation studies, and radioautography. The proximal and distal colon were studied independently at all ages. At 17-18 days of gestation, the mouse proximal colonic mucosa was projected into high and low longitudinal folds disposed in a V-shaped pattern. From birth up to 9 days, the mucosal folds observed by SEM can easily be misinterpreted as being a succession of high and low villus-like structures at LM level. TEM study confirmed the presence of highly specialized absorptive cells in the upper halves of the mucosal folds during this period. No recognizable crypts were noted at birth. Instead, LM and radioautography showed the presence of cell aggregates developing at the base of the epithelium at all levels of the mucosal folds. These cell aggregates evolved into rudimentary crypts giving fully differentiated crypts by day 16 with radiolabeled cells located in the midcrypt portion. As opposed to the proximal segment, a flat mucosa interspersed with well defined short crypts at birth was observed in the distal colon. During the following days, crypts further developed and by 16 days, the radiolabeled epithelial cells were still exclusively located at the base of the crypt. TEM observations illustrated that specialized cells as those found in the proximal segment did not differentiate in this segment.(ABSTRACT TRUNCATED AT 250 WORDS)