Length of the Mitral Isthmus But Not Anatomical Location of Ablation Line Predicts Bidirectional Mitral Isthmus Block in Patients Undergoing Catheter Ablation of Persistent Atrial Fibrillation: A Randomized Controlled Trial

INTRODUCTION Mitral isthmus (MI) ablation is an effective option in patients undergoing ablation for persistent atrial fibrillation (AF). Achieving bidirectional conduction block across the MI is challenging, and predictors of MI ablation success remain incompletely understood. We sought to determine the impact of anatomical location of the ablation line on the efficacy of MI ablation. METHODS AND RESULTS A total of 40 consecutive patients (87% male; 54 ± 10 years) undergoing stepwise AF ablation were included. MI ablation was performed in sinus rhythm. MI ablation was performed from the left inferior PV to either the posterior (group 1) or the anterolateral (group 2) mitral annulus depending on randomization. The length of the MI line (measured with the 3D mapping system) and the amplitude of the EGMs at 3 positions on the MI were measured in each patient. MI block was achieved in 14/19 (74%) patients in group 1 and 15/21 (71%) patients in group 2 (P = NS). Total MI radiofrequency time (18 ± 7 min vs. 17 ± 8 min; P = NS) was similar between groups. Patients with incomplete MI block had a longer MI length (34 ± 6 mm vs. 24 ± 5 mm; P < 0.001), a higher bipolar voltage along the MI (1.75 ± 0.74 mV vs. 1.05 ± 0.69 mV; P < 0.01), and a longer history of continuous AF (19 ± 17 months vs. 10 ± 10 months; P < 0.05). In multivariate analysis, decreased length of the MI was an independent predictor of successful MI block (OR 1.5; 95% CI 1.1-2.1; P < 0.05). CONCLUSIONS Increased length but not anatomical location of the MI predicts failure to achieve bidirectional MI block during ablation of persistent AF.

Development of an Interleukin-1β Vaccine in Patients with Type 2 Diabetes

Interleukin-1β (IL-1β) is a key cytokine involved in inflammatory illnesses including rare hereditary diseases and common chronic inflammatory conditions as gout, rheumatoid arthritis, and type 2 diabetes mellitus, suggesting reduction of IL-1β activity as new treatment strategy. The objective of our study was to assess safety, antibody response, and preliminary efficacy of a novel vaccine against IL-1β. The vaccine hIL1bQb consisting of full-length, recombinant IL-1β coupled to virus-like particles was tested in a preclinical and clinical, randomized, placebo-controlled, double-blind study in patients with type 2 diabetes. The preclinical simian study showed prompt induction of IL-1β-specific antibodies upon vaccination, while neutralizing antibodies appeared with delay. In the clinical study with 48 type 2 diabetic patients, neutralizing IL-1β-specific antibody responses were detectable after six injections with doses of 900 µg. The development of neutralizing antibodies was associated with higher number of study drug injections, lower baseline body mass index, improvement of glycemia, and C-reactive protein (CRP). The vaccine hIL1bQb was safe and well-tolerated with no differences regarding adverse events between patients receiving hIL1bQb compared to placebo. This is the first description of a vaccine against IL-1β and represents a new treatment option for IL-1β-dependent diseases such as type 2 diabetes mellitus (ClinicalTrials.gov NCT00924105).Molecular Therapy (2016); doi:10.1038/mt.2015.227.

Comparison of telomere length in black and white teachers from South Africa: the sympathetic activity and ambulatory blood pressure in Africans study

OBJECTIVE Telomere length is a marker of biological aging that has been linked to cardiovascular disease risk. The black South African population is witnessing a tremendous increase in the prevalence of cardiovascular disease, part of which might be explained through urbanization. We compared telomere length between black South Africans and white South Africans and examined which biological and psychosocial variables played a role in ethnic difference in telomere length. METHODS We measured leukocyte telomere length in 161 black South African teachers and 180 white South African teachers aged 23 to 66 years without a history of atherothrombotic vascular disease. Age, sex, years having lived in the area, human immunodeficiency virus (HIV) infection, hypertension, body mass index, dyslipidemia, hemoglobin A1c, C-reactive protein, smoking, physical activity, alcohol abuse, depressive symptoms, psychological distress, and work stress were considered as covariates. RESULTS Black participants had shorter (median, interquartile range) relative telomere length (0.79, 0.70-0.95) than did white participants (1.06, 0.87-1.21; p < .001), and this difference changed very little after adjusting for covariates. In fully adjusted models, age (p < .001), male sex (p = .011), and HIV positive status (p = .023) were associated with shorter telomere length. Ethnicity did not significantly interact with any covariates in determining telomere length, including psychosocial characteristics. CONCLUSIONS Black South Africans showed markedly shorter telomeres than did white South African counterparts. Age, male sex, and HIV status were associated with shorter telomere length. No interactions between ethnicity and biomedical or psychosocial factors were found. Ethnic difference in telomere length might primarily be explained by genetic factors.

Changes of Root Length and Root-to-Crown Ratio after Apical Surgery: An Analysis by Using Cone-beam Computed Tomography

INTRODUCTION Apical surgery is an important treatment option for teeth with post-treatment periodontitis. Although apical surgery involves root-end resection, no morphometric data are yet available about root-end resection and its impact on the root-to-crown ratio (RCR). The present study assessed the length of apicectomy and calculated the loss of root length and changes of RCR after apical surgery. METHODS In a prospective clinical study, cone-beam computed tomography scans were taken preoperatively and postoperatively. From these images, the crown and root lengths of 61 roots (54 teeth in 47 patients) were measured before and after apical surgery. Data were collected relative to the cementoenamel junction (CEJ) as well as to the crestal bone level (CBL). One observer took all measurements twice (to calculate the intraobserver variability), and the means were used for further analysis. The following parameters were assessed for all treated teeth as well as for specific tooth groups: length of root-end resection and percentage change of root length, preoperative and postoperative RCRs, and percentage change of RCR after apical surgery. RESULTS The mean length of root-end resection was 3.58 ± 1.43 mm (relative to the CBL). This amounted to a loss of 33.2% of clinical and 26% of anatomic root length. There was an overall significant difference between the tooth groups (P < .05). There was also a statistically significant difference comparing mandibular and maxillary teeth (P < .05), but not for incisors/canines versus premolars/molars (P = .125). The mean preoperative and postoperative RCRs (relative to CEJ) were 1.83 and 1.35, respectively (P < .001). With regard to the CBL reference, the mean preoperative and postoperative RCRs were 1.08 and 0.71 (CBL), respectively (P < .001). The calculated changes of RCR after apical surgery were 24.8% relative to CEJ and 33.3% relative to CBL (P < .001). Across the different tooth groups, the mean RCR was not significantly different (P = .244 for CEJ and 0.114 for CBL). CONCLUSIONS This CBCT-based study demonstrated that the RCR is significantly changed after root-end resection in apical surgery irrespective of the clinical (CBL) or anatomic (CEJ) reference levels. The lowest, and thus clinically most critical, postoperative RCR was observed in maxillary incisors. Future clinical studies need to show the impact of resection length and RCR changes on the outcome of apical surgery.

Statistical testing against baseline was common in dental research

OBJECTIVES To assess the presence of within-group comparisons with baseline in a subset of leading dental journals and to explore possible associations with a range of study characteristics including journal and study design. STUDY DESIGN AND SETTING Thirty consecutive issues of five leading dental journals were electronically searched. The conduct and reporting of statistical analysis in respect of comparisons against baseline or otherwise along with the manner of interpretation of the results were assessed. Descriptive statistics were obtained, and chi-square test and Fisher's exact were undertaken to test the association between trial characteristics and overall study interpretation. RESULTS A total of 184 studies were included with the highest proportion published in Journal of Endodontics (n = 84, 46%) and most involving a single center (n = 157, 85%). Overall, 43 studies (23%) presented interpretation of their outcomes based solely on comparisons against baseline. Inappropriate use of baseline testing was found to be less likely in interventional studies (P < 0.001). CONCLUSION Use of comparisons with baseline appears to be common among both observational and interventional research studies in dentistry. Enhanced conduct and reporting of statistical tests are required to ensure that inferences from research studies are appropriate and informative.

Impact of the arc length on GNSS analysis results

Homogeneously reprocessed combined GPS/GLONASS 1- and 3-day solutions from 1994 to 2013, generated by the Center for Orbit Determination in Europe (CODE) in the frame of the second reprocessing campaign REPRO-2 of the International GNSS Service, as well as GPS- and GLONASS-only 1- and 3-day solutions for the years 2009 to 2011 are analyzed to assess the impact of the arc length on the estimated Earth Orientation Parameters (EOP, namely polar motion and length of day), on the geocenter, and on the orbits. The conventional CODE 3-day solutions assume continuity of orbits, polar motion components, and of other parameters at the day boundaries. An experimental 3-day solution, which assumes continuity of the orbits, but independence from day to day for all other parameters, as well as a non-overlapping 3-day solution, is included into our analysis. The time series of EOPs, geocenter coordinates, and orbit misclosures, are analyzed. The long-arc solutions were found to be superior to the 1-day solutions: the RMS values of EOP and geocenter series are typically reduced between 10 and 40 %, except for the polar motion rates, where RMS reductions by factors of 2–3 with respect to the 1-day solutions are achieved for the overlapping and the non-overlapping 3-day solutions. In the low-frequency part of the spectrum, the reduction is even more important. The better performance of the orbits of 3-day solutions with respect to 1-day solutions is also confirmed by the validation with satellite laser ranging.

Implicit probabilistic sequence learning: Correlated streams and sequence length matter

We investigated whether a pure perceptual stream is sufficient for probabilistic sequence learning to occur within a single session or whether correlated streams are necessary, whether learning is affected by the transition probability between sequence elements, and how the sequence length influences learning. In each of three experiments, we used six horizontally arranged stimulus displays which consisted of randomly ordered bigrams xo and ox. The probability of the next possible target location out of two was either .50/.50 or .75/.25 and was marked by an underline. In Experiment 1, a left vs. right key response was required for the x of a marked bigram in the pure perceptual learning condition and a response key press corresponding to the marked bigram location (out of 6) was required in the correlated streams condition (i.e., the ring, middle, or index finger of the left and right hand, respectively). The same probabilistic 3-element sequence was used in both conditions. Learning occurred only in the correlated streams condition. In Experiment 2, we investigated whether sequence length affected learning correlated sequences by contrasting the 3-elements sequence with a 6-elements sequence. Significant sequence learning occurred in all conditions. In Experiment 3, we removed a potential confound, that is, the sequence of hand changes. Under these conditions, learning occurred for the 3-element sequence only and transition probability did not affect the amount of learning. Together, these results indicate that correlated streams are necessary for probabilistic sequence learning within a single session and that sequence length can reduce the chances for learning to occur.

Cloning of a full-length cDNA encoding bovine interleukin 4 by the polymerase chain reaction

A human interleukin 4 (hIL-4)-encoding cDNA (hIL4) probe was used to screen a bovine genomic library, and three clones containing sequences with homology to the human and mouse IL4 cDNAs were isolated. Sequence information obtained from one of these genomic clones was used to design an oligodeoxyribonucleotide primer corresponding to the transcription start point region for use in the polymerase chain reaction (PCR). The PCR-RACE protocol, designed for the rapid amplification of cDNA ends, was successfully used to generate a full-length bovine IL4 (bIL4) cDNA clone from polyadenylated RNA isolated from concanavalin A-stimulated bovine lymph node cells. The bIL4 cDNA is 570 bp in length and contains an open reading frame of 405 nucleotides (nt), coding for a 15.1-kDa precursor of 135 amino acids (aa), which should be reduced to 12.6 kDa for unglycosylated bIL4 after cleavage of a putative hydrophobic leader sequence of 24 aa. The aa sequence contains one possible Asn-linked glycosylation site. Bovine IL4 is shorter than mouse (mIL4) and hIL4, because of a 51-nt deletion in the coding region. Comparison of the overall nt and deduced aa sequences shows a greater homology of bIL4 with hIL4 than with mIL4. This homology is not evenly distributed, however, with the nt sequences 5' and 3' of the coding region showing a much greater homology between all three species than the coding sequence.