Progression of late postoperative atrial fibrillation in patients with tetralogy of Fallot

1 Introduction

ToF patients are at risk for ventricular deterioration at a relatively young age, which can be aggravated by AF development. Therefore, knowledge on AF development and its timespan of progression is essential to guide treatment strategies for AF.

2 Objective

We examined late postoperative AF onset and progression in ToF patients during long‐term follow‐up after ToF correction. In addition, coexistence of AF with regular supraventricular tachyarrhythmias (SVT) and ventricular tachyarrhythmias (VTA) was analyzed.

3 Methods and results

ToF patients (N  =  29) with AF after ToF correction referred to the electrophysiology department between 2000 and 2015 were included. All available rhythm registrations were reviewed for AF, regular SVT, and VTA. AF progression was defined as transition from paroxysmal AF to (longstanding) persistent/permanent AF or from (longstanding) persistent AF to permanent AF. At the age of 44 ± 12 years, ToF patients presented with paroxysmal (N  =  14, 48%), persistent (N  =  13, 45%) or permanent AF (N  =  2, 7%). Age of AF development was similar among patients who either underwent initial shunt creation (N  =  15, 45 ± 11 [25–57] years) or primary total ToF correction (N  =  14, 43 ± 13 [26–66] years) (P  =  0.785). AF coexisted with regular SVT (N  =  18, 62%) and VTA (N  =  13, 45%). Progression of AF occurred in 11 patients (38%) within 5 ± 5 years after AF onset despite antiarrhythmic drug class II (AAD, P  =  0.052) or III (P  =  0.587) usage.

4 Conclusions

AF in our ToF population developed at a young age and showed rapid progression. Rhythm control by pharmacological therapy was ineffective in preventing AF progression.     

Worldwide vitamin D status

The aim of the present study is to summarize existing literature on vitamin D levels in adults in different continents and different countries worldwide. The best determinant of vitamin D status is the serum concentration of 25-hydroxyvitamin D (25(OH)D). Most investigators agree that serum 25(OH)D should be higher than 50 nmol/l, but some recommend higher serum levels. Traditional risk groups for vitamin D deficiency include pregnant women, children, older persons, the institutionalized, and non-western immigrants. This chapter shows that serum 25(OH)D levels are not only suboptimal in specific risk groups, but also in adults in many countries. Especially, in the Middle-East and Asia, vitamin D deficiency in adults is highly prevalent.     

Standardized ADOS Scores: Measuring Severity of Autism Spectrum Disorders in a Dutch Sample

The validity of the calibrated severity scores on the ADOS as reported by Gotham et al. (J Autism Dev Disord 39: 693–705, 2009), was investigated in an independent sample of 1248 Dutch children with 1455 ADOS administrations (modules 1, 2 and 3). The greater comparability between ADOS administrations at different times, ages and in different modules, as reached by Gotham et al. with the calibrated severity measures, seems to be corroborated by the current study for module 1 and to a lesser extent for module 3. For module 2, the calibrated severity scores need to be further investigated within a sample that resembles Gotham’s sample in age and level of verbal functioning.     

Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria

Macrophages mediate crucial innate immune responses via caspase-1-dependent processing and secretion of interleukin 1β (IL-1β) and IL-18. Although infection with wild-type Salmonella typhimurium is lethal to mice, we show here that a strain that persistently expresses flagellin was cleared by the cytosolic flagellin-detection pathway through the activation of caspase-1 by the NLRC4 inflammasome; however, this clearance was independent of IL-1β and IL-18. Instead, caspase-1-induced pyroptotic cell death released bacteria from macrophages and exposed the bacteria to uptake and killing by reactive oxygen species in neutrophils. Similarly, activation of caspase-1 cleared unmanipulated Legionella pneumophila and Burkholderia thailandensis by cytokine-independent mechanisms. This demonstrates that activation of caspase-1 clears intracellular bacteria in vivo independently of IL-1β and IL-18 and establishes pyroptosis as an efficient mechanism of bacterial clearance by the innate immune system.     

The effect of repeated exposure to fruit drinks on intake, pleasantness and boredom in young and elderly adults

The effect of a repeated monotonous exposure on ad libitum intake, pleasantness and boredom in elderly people in a real life situation is unclear. We therefore investigated the effects of repeated exposure to ad libitum intake of three orange-based drinks on boredom and acceptance in young and elderly people. Young (n=32) and elderly women (n=36) participated in a randomized within subjects cross over trial with three intervention periods of 12 days each followed by a 2-day wash out period. During each intervention period, the participants received 1 L of one type of drink per day. The three drinks varied in sweetness intensity. Intake was measured by weighing the returned packets and pleasantness, boredom and sweetness were rated on a 10-point scale. For the young women, mean consumption of the three drinks (p<0.01) and pleasantness decreased (p<0.01) and boredom increased (p<0.001). For the elderly women, consumption increased (p=0.03) whereas pleasantness (p=0.34) and boredom (p=0.40) were stable. In the young women, the orange peach drink which had the highest sugar content contributed the most to the effect of the repeated exposure. The consumption and pleasantness ratings for this drink decreased (r=-1.05, p=0.01 and r=-0.07, p=0.007, respectively) and boredom increased (r=0.12, p<0.001). In conclusion, elderly women experienced no increased boredom whereas young women did.     

Differential Fairness Decisions and Brain Responses After Expressed Emotions of Others in Boys with Autism Spectrum Disorders

Little is known about how emotions expressed by others influence social decisions and associated brain responses in autism spectrum disorders (ASD). We investigated the neural mechanisms underlying fairness decisions in response to explicitly expressed emotions of others in boys with ASD and typically developing (TD) boys. Participants with ASD adjusted their allocation behavior in response to the emotions but reacted less unfair than TD controls in response to happiness. We also found reduced brain responses in the precental gyrus in the ASD versus TD group when receiving happy versus angry reactions and autistic traits were positively associated with activity in the postcentral gyrus. These results provide indications for a role of precentral and postcentral gyrus in social-affective difficulties in ASD.     

Sensitivity to ionizing radiation and chemotherapeutic agents in gemcitabine-resistant human tumor cell lines

PURPOSE: To determine cross-resistance to anti-tumor treatments in 2',2'difluorodeoxycytidine (dFdC, gemcitabine)-resistant human tumor cells. METHODS AND MATERIALS: Human lung carcinoma cells SW-1573 (SWp) were made resistant to dFdC (SWg). Sensitivity to cisplatin (cDDP), paclitaxel, 5-fluorouracil (5-FU), methotrexate (MTX), cytarabine (ara-C), and dFdC was measured by a proliferation assay. Radiosensitivity and radioenhancement by dFdC of this cell panel and the human ovarian carcinoma cell line A2780 and its dFdC-resistant variant AG6000 were determined by clonogenic assay. Bivariate flowcytometry was performed to study cell cycle changes. RESULTS: In the SWg, a complete deoxycytidine kinase (dCK) deficiency was found on mRNA and protein level. This was accompanied by a 10-fold decrease in dCK activity which resulted in the >1000-fold resistance to dFdC. Sensitivity to other anti-tumor drugs was not altered, except for ara-C (>100-fold resistance). Radiosensitivity was not altered in the dFdC-resistant cell lines SWg and AG6000. High concentrations (50-100 microM dFdC) induced radioenhancement in the dFdC-resistant cell lines similar to the radioenhancement obtained at lower concentrations (10 nM dFdC) in the parental lines. An early S-phase arrest was found in all cell lines after dFdC treatment where radioenhancement was achieved. CONCLUSIONS: In the dFdC-resistant lung tumor cell line SWg, the deficiency in dCK is related to the resistance to dFdC and ara-C. No cross-resistance was observed to other anti-tumor drugs used for the treatment in lung cancer. Sensitivity to ionizing radiation was not altered in two different dFdC-resistant cell lines. Resistance to dFdC does not eliminate the ability of dFdC to sensitize cells to radiation.