Objective. The aim of this study was to estimate rates and type of definitive surgical interventions for nephrolithiasis in Swedish patients with ankylosing spondylitis (AS) compared to the general ...population. Materials and methods. This national prospective cohort study linked data from Swedish population and healthcare registries. Incidence rates and interventions for nephrolithiasis during follow-up in patients with AS were compared to general population comparator (GPC) subjects. Results. In total, 8572 AS patients were followed for 49,959 person-years and 39,639 matched GPCs were followed for 225,221 person-years. Mean age at study entry was 46 years interquartile range (IQR) 36-56 years and 65% were male. In AS patients with a diagnosis of nephrolithiasis during the study period, 29% (72/250) underwent similar intervention for nephrolithiasis compared to 24% (114/466) GPCs (p = 0.21). The incidence rate ratio (RR) in overall AS patients was 2.9 95% confidence interval (CI) 2.1-3.8 during a median follow-up of 6.2 years (IQR 3.2-8.6 years). With prior diagnosis of nephrolithiasis, the RR for AS patients compared to GPCs was 3.7 (95% CI 1.8-7.7); without prior nephrolithiasis the RR was 2.1 (95% CI 1.5-3.0). Increasing age odds ratio (OR) 1.02, 95% CI 1.01-1.03, prior nephrolithiasis diagnosis (OR 3.3, 95% CI 1.97-5.62) and atherosclerotic cardiac disease (OR 2.0, 95% CI 1.03-3.91) were identified as predictors of intervention for nephrolithiasis. Conclusions. Patients with AS have an almost three-fold increased risk of surgical intervention for kidney stones, with similar management, compared to the general population.
Morphemes, the smallest meaning-bearing units of language, recur in many words. Therefore, morphological knowledge can facilitate the comprehension of novel words. This study tested the effectiveness ...of a morphological training program on children's learning and retention of exposed words and morphologically related unexposed words compared with an active control condition. Norwegian second graders (N = 717) unselected for ability were individually randomized to either a morphological (n = 366) or a mathematical training program (n = 351). Both programs lasted for 8 weeks and were delivered as self-contained apps in a classroom setting. The morphological training built on the principle that frequency of target elements together with variation of nontarget elements can support implicit learning. Treatment-blind examiners assessed participants' meaning-based knowledge (word comprehension and definitions) and code-based knowledge (word reading fluency and spelling) at pretraining, immediately post training, and at follow-up 6 months later. An intention-to-treat analysis showed lasting effects of the morphological training on meaning-based knowledge of exposed words (posttest: d = .37; follow-up: d = .31) and unexposed words containing trained morphemes (posttest: d = .27; follow-up: d = .27) and code-based knowledge of exposed words (posttest: d = .22; follow-up: d = .13). For code-based knowledge of unexposed words, there were significant training effects at the posttest (d = .12) but not follow-up (d = .05). There were no significant effects on a far-transfer measure of general vocabulary. These results demonstrate that a brief morphological training program can produce lasting and educationally meaningful gains in students' word knowledge.
Educational Impact and Implications StatementWords can consist of several meaningful parts, or morphemes, such as -ist in guitarist and re- in reuse. Understanding common morphemes helps children infer the meanings of new words. In this study, we tested the effects of working with an educational application (app) focusing on morphemes. Children completed app exercises such as sorting words or pictures according to their meaning, combining morphemes to build words, or identifying the correct word or morpheme to fit a sentence or picture context. We found that the app was effective in improving Norwegian second graders' ability to explain, understand, read, and spell words, including words which were not shown in the app, but which contained trained morphemes. The brief low-cost training produced long-term effects with a minimal burden on teachers.
Objective: Safety data regarding the usage of etoricoxib and other nonsteroidal anti-inflammatory drugs (NSAIDs) in ankylosing spondylitis (AS) and other spondyloarthritis (SpA) patients are rather ...limited. To estimate and compare rates of gastrointestinal, renovascular, and cardiovascular adverse events in patients exposed to etoricoxib, celecoxib, non-selective NSAIDs (nsNSAIDs) or totally unexposed to NSAIDs. Methods: This is a national register-based cohort study on patients with AS or SpA (N=21,872) identified in the Swedish national patient register (NPR) 1987 - 2009. Treatment exposure was assessed time-dependently based on the prescription drugs register from 2006 - 2009 adjusting for socio-demography, and comorbidities derived from national population-based registers. Results: Exposure to etoricoxib, celecoxib and nsNSAID were 7.6%, 3.9% and 71.2%, respectively. No major risk differences for serious cardiovascular, gastrointestinal or renal adverse events were seen among the three exposure groups. Patients unexposed to NSAIDs had more baseline co-morbidities and an increased relative risk for congestive heart failure events during the study period 2.0 (95% 1.3 to 3.2). The relative risk for atherosclerotic events was non-significant when compared to the nsNSAID group 1.0 (95% CI: 0.7 to 1.5), while the risk for gastrointestinal events was lower for unexposed patients 0.5 (0.4 to 0.7). Conclusion: Overall, serious adverse events related to nsNSAID, etoricoxib and celecoxib were similar and in the range of what would be expected in a group of SpA patients. Patients unexposed to NSAIDs had considerable more baseline co-morbidities and increased risk for congestive heart failure, reflecting a selection of patients being prescribed NSAID in clinical practice. This article is protected by copyright. All rights reserved.
Objective.The aims of this study were to study aberrant expression and coexpression of the cell cycle associated proteins TP53, p21, p27, cyclin D1, cdk4, RB, EGFR, and MDM2 in cervical carcinomas, ...to correlate protein alterations with histopathological and clinical parameters, and to evaluate whether these alterations provide prognostic information.
Methods.Seventy-four cervical carcinomas and 10 cases of normal cervical epithelium from patients with benign uterine leiomyomas were investigated immunohistochemically for aberrant expression of the cell cycle associated proteins using the biotin–streptavidin–peroxidase method and the OptiMax Plus automated cell staining system.
Results.In normal cervical epithelium p27 immunostaining was identified in more than 50% of the cells, cdk4 in 5–50% of the cells, and EGFR in less than 5% of the cells, whereas no immunostaining for TP53, p21, MDM2, or cyclin D1 was detected. Positive RB protein staining was identified in all cases of normal cervical epithelium. RB protein staining was also identified in all carcinomas of the cervix uteri. Overexpression of p21 was found in 96% of the tumors, MDM2 in 35%, cdk4 in 69%, cyclin D1 in 3%, and EGFR in 20% of the tumors. A low level of p27 was observed in 65% of the cases. In a previous study, the TP53 protein level has been found to be elevated in 41 of the 74 (55%) cases included in this work. Significant coexpression was seen for TP53 and MDM2 (P= 0.001); concording results were observed in 67% of the cases. There was no difference in aberrant expression or coexpression of any of the cell cycle regulatory proteins related to histological type, grade of differentiation, FIGO stage, or relapse-free survival.
Conclusion.The high number of cases showing increased levels of p21 and cdk4 and decreased levels of p27 suggests that these proteins may be important in the pathogenesis of cervical carcinoma. Furthermore aberrant expression of MDM2 in a smaller but significant fraction of cases indicates that these proteins could also be involved in the development of these cancers. Finally our results indicate that MDM2 may protect against HPV-induced TP53 protein degradation.
Objective: To analyse the occurrence of atrial fibrillation (AF) and thromboembolism in a randomised comparison of rate adaptive single chamber atrial pacing (AAIR) and dual chamber pacing (DDDR) in ...patients with sick sinus syndrome and normal atrioventricular (AV) conduction, in which left atrial dilatation and decreased left ventricular fractional shortening had been observed in the DDDR group. Methods: 177 consecutive patients with sick sinus syndrome (mean (SD) age 74 (9) years, 104 women) were randomly assigned to treatment with one of three pacemakers: AAIR (n = 54), DDDR with a short rate adaptive AV delay (n = 60) (DDDR-s); or DDDR with a fixed long AV delay (n = 63) (DDDR-l). Analysis was intention to treat. Results: Mean follow up was 2.9 (1.1) years. AF at one or more ambulatory visits was significantly less common in the AAIR group (4 (7.4%) v 14 (23.3%) in the DDDR-s group v 11 (17.5%) in the DDDR-l group; p = 0.03, log rank test). The risk of developing AF in the AAIR group compared with the DDDR-s group was significantly decreased after adjustment for brady-tachy syndrome in a Cox regression analysis (relative risk 0.27, 95% confidence interval (CI) 0.09 to 0.83, p = 0.02). The benefit of AAIR was highest among patients with brady-tachy syndrome. Brady-tachy syndrome and a thromboembolic event before pacemaker implantation were independent predictors of thromboembolism during follow up (relative risk 7.5, 95% CI 1.6 to 36.2, p = 0.01, and relative risk 4.7, 95% CI 1.2 to 17.9, p = 0.02, respectively). Conclusions: During a mean follow up of 2.9 years AAIR was associated with significantly less AF. The beneficial effect of AAIR was still significant after adjustment for brady-tachy syndrome. Brady-tachy syndrome was associated with an increased risk of thromboembolism.
A randomized trial was done to compare single-chamber atrial (AAI) and dual-chamber (DDD) pacing in patients with sick sinus syndrome (SSS). Primary end points were changes in left atrial (LA) size ...and left ventricular (LV) size and function as measured by M-mode echocardiography.
In patients with SSS and normal atrioventricular conduction, it is still not clear whether the optimal pacing mode is AAI or DDD pacing.
A total of 177 consecutive patients (mean age 74 +/- 9 years, 73 men) were randomized to treatment with one of three rate-adaptive (R) pacemakers: AAIR (n = 54), DDDR with a short atrioventricular delay (n = 60) (DDDR-s), or DDDR with a fixed long atrioventricular delay (n = 63) (DDDR-l). Before pacemaker implantation and at each follow-up, M-mode echocardiography was done to measure LA and LV diameters. Left ventricular fractional shortening (LVFS) was calculated. Analysis was on an intention-to-treat basis.
Mean follow-up was 2.9 +/- 1.1 years. In the AAIR group, no significant changes were observed in LA or LV diameters or LVFS from baseline to last follow-up. In both DDDR groups, LA diameter increased significantly (p < 0.05), and in the DDDR-s group, LVFS decreased significantly (p < 0.01). Atrial fibrillation was significantly less common in the AAIR group, 7.4% versus 23.3% in the DDDR-s group versus 17.5% in the DDDR-l group (p = 0.03, log-rank test). Mortality, thromboembolism, and congestive heart failure did not differ between groups.
During a mean follow-up of 2.9 +/- 1.1 years, DDDR pacing causes increased LA diameter, and DDDR pacing with a short atrioventricular delay also causes decreased LVFS. No changes occur in LA or LV diameters or LVFS during AAIR pacing. Atrial fibrillation is significantly less common during AAIR pacing.
Clinical depression is accompanied by changes in sleep patterning, which is controlled in a circadian fashion. It is thus desirable that animal models of depression mirror such diurnally-specific ...state alterations, along with other behavioral and physiological changes. We previously found several changes in behavior indicative of a depression-like phenotype in offspring of rats subjected to repeated, variable prenatal stress (PNS), including increased locomotor activity during specific periods of the circadian cycle. We, therefore, investigated whether PNS rats also exhibit alterations in sleep/wakefulness behavior around the change from light-to-dark phase. Control and PNS Sprague-Dawley rats were implanted with electrodes for continuous monitoring of electroencephalic activity used to determine behavioral state. The distribution of slow-wave sleep (SWS), rapid eye movement sleep (REMS) and wakefulness was compared for periods before and after lights were turned off, between baseline conditions and after exposure to an acute stressor. Both REMS and SWS amounts were increased in PNS rats relative to control animals in the beginning of the dark phase. REMS changes were due to an increase in REMS bout number, rather than in bout duration. During this circadian time period, we did not find any sex differences in the state changes. These results indicate that PNS affects baseline sleep patterning in both male and female rats around active-phase onset.
Mucin-type O-glycosylation is initiated by UDP-N-acetylgalactosamine:polypeptideN-acetylgalactosaminyltransferases (GalNAc-transferases). The role each GalNAc-transferase plays in O-glycosylation is ...unclear. In this report we characterized the specificity and kinetic properties of three purified recombinant GalNAc-transferases. GalNAc-T1, -T2, and -T3 were expressed as soluble proteins in insect cells and purified to near homogeneity. The enzymes have distinct but partly overlapping specificities with short peptide acceptor substrates. Peptides specifically utilized by GalNAc-T2 or -T3, or preferentially by GalNAc-T1 were identified. GalNAc-T1 and -T3 showed strict donor substrate specificities for UDP-GalNAc, whereas GalNAc-T2 also utilized UDP-Gal with one peptide acceptor substrate. Glycosylation of peptides based on MUC1 tandem repeat showed that three of five potential sites in the tandem repeat were glycosylated by all three enzymes when one or five repeat peptides were analyzed. However, analysis of enzyme kinetics by capillary electrophoresis and mass spectrometry demonstrated that the three enzymes react at different rates with individual sites in the MUC1 repeat. The results demonstrate that individual GalNAc-transferases have distinct activities and the initiation of O-glycosylation in a cell is regulated by a repertoire of GalNAc-transferases.
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