A Pilot Study of the Tuning in to Kids Parenting Program in Iran for Reducing Preschool Children�s Anxiety

Objectives: Tuning in to Kids (TIK) is a group parenting program that targets parent emotion socialization (emotional awareness and regulation, meta-emotion and emotion coaching skills) to improve children�s functioning. The aim of this pilot study was to investigate the effectiveness of this program when used with parents of anxious preschool children. Methods: The study used a randomized controlled design. Fifty-six mothers of children who scored one standard deviation above the mean on the parent report of the Preschool Anxiety Scale (PAS) were selected from 358 families who expressed interest in participating in a parenting program. Selected participants were randomly assigned to intervention (n = 30) or control (n = 26) conditions. Participants in the intervention condition attended the 6 session TIK program followed by two booster sessions at monthly intervals thereafter. Post-intervention and 6- months later the PAS was re-administered to participants in both conditions. Results: Mixed Repeated Measure ANOVA analysis showed a significant difference between participants in the two conditions on parent-reported anxiety at post-test and 6-month follow-up. Clinical significance analyses showed 69 of the intervention group in comparison to 18 of the control group had parent-reported change into the normal range for anxiety scores. These changes remained stable at 6-month follow-up (60 compared to 23). Conclusion: The study suggests that the TIK program shows preliminary effectiveness when used in Iran with preschool children with anxiety. © 2019, The Author(s)

N 6 -Formyllysine as a Biomarker of Formaldehyde Exposure: Formation and Loss of N 6 -Formyllysine in Nasal Epithelium in Long-Term, Low-Dose Inhalation Studies in Rats

Exposure to both endogenous and exogenous formaldehyde has been established to be carcinogenic, likely by virtue of forming nucleic acid and proteins adducts such as N6-formyllysine. To better assess N6-formyllysine as a biomarker of formaldehyde exposure, we studied accumulation of N6-formyllysine adducts in tissues of rats exposed by inhalation to 2 ppm [13C2H2]-formaldehyde for 7, 14, 21, and 28 days (6 h/day) and investigated adduct loss over a 7-day postexposure period using liquid chromatography-coupled tandem mass spectrometry. Our results showed formation of exogenous adducts in nasal epithelium and to some extent in trachea but not in distant tissues of lung, bone marrow, or white blood cells, with a 2-fold increase over endogenous N6-formyllysine over a 3-week exposure period. Postexposure analyses indicated a biexponential decay of N6-formyllysine in proteins extracted from different cellular compartments, with half-lives of ∼25 and ∼182 h for the fast and slow phases, respectively, in cytoplasmic proteins. These results parallel the behavior of DNA adducts and DNA-protein cross-links, with protein adducts cleared faster than DNA-protein cross-links, and point to the potential utility of N6-formyllysine protein adducts as biomarkers of formaldehyde

Dosimetry of N 6 -Formyllysine Adducts Following [ 13 C 2 H 2 ]-Formaldehyde Exposures in Rats

With formaldehyde as the major source of endogenous N6-formyllysine protein adducts, we quantified endogenous and exogenous N6-formyllysine in the nasal epithelium of rats exposed by inhalation to 0.7, 2, 5.8, and 9.1 ppm [13C2H2]-formaldehyde using liquid chromatography-coupled tandem mass spectrometry. Exogenous N6-formyllysine was detected in the nasal epithelium, with concentration-dependent formation in total as well as fractionated (cytoplasmic, membrane, nuclear) proteins, but was not detected in the lung, liver, or bone marrow. Endogenous adducts dominated at all exposure conditions, with a 6 h 9.1 ppm formaldehyde exposure resulting in one-third of the total load of N6-formyllysine being derived from exogenous sources. The results parallel previous studies of formaldehyde-induced DNA adducts

Quantitative Analysis of Histone Modifications: Formaldehyde Is a Source of Pathological N6-Formyllysine That Is Refractory to Histone Deacetylases

Aberrant protein modifications play an important role in the pathophysiology of many human diseases, in terms of both dysfunction of physiological modifications and the formation of pathological modifications by reaction of proteins with endogenous electrophiles. Recent studies have identified a chemical homolog of lysine acetylation, N[superscript 6]-formyllysine, as an abundant modification of histone and chromatin proteins, one possible source of which is the reaction of lysine with 3′-formylphosphate residues from DNA oxidation. Using a new liquid chromatography-coupled to tandem mass spectrometry method to quantify all N[superscript 6]-methyl-, -acetyl- and -formyl-lysine modifications, we now report that endogenous formaldehyde is a major source of N[superscript 6]-formyllysine and that this adduct is widespread among cellular proteins in all compartments. N[superscript 6]-formyllysine was evenly distributed among different classes of histone proteins from human TK6 cells at 1–4 modifications per 10[superscript 4] lysines, which contrasted strongly with lysine acetylation and mono-, di-, and tri-methylation levels of 1.5-380, 5-870, 0-1400, and 0-390 per 10[superscript 4] lysines, respectively. While isotope labeling studies revealed that lysine demethylation is not a source of N[superscript 6]-formyllysine in histones, formaldehyde exposure was observed to cause a dose-dependent increase in N[superscript 6]-formyllysine, with use of [[superscript 13]C,[superscript 2]H[subscript 2]]-formaldehyde revealing unchanged levels of adducts derived from endogenous sources. Inhibitors of class I and class II histone deacetylases did not affect the levels of N[superscript 6]-formyllysine in TK6 cells, and the class III histone deacetylase, SIRT1, had minimal activity (<10%) with a peptide substrate containing the formyl adduct. These data suggest that N[superscript 6]-formyllysine is refractory to removal by histone deacetylases, which supports the idea that this abundant protein modification could interfere with normal regulation of gene expression if it arises at conserved sites of physiological protein secondary modification

Estimation of the Logit model for the online contraflow problem

Contraflow or lane reversal is an efficient way for increasing the outbound capacity of a network by reversing the direction of in-bound roads during evacuations. Hence, it can be considered as a potential remedy for solving congestion problems during evacuation in the context of homeland security, natural disasters and urban evacuations, especially in response to an expected disaster. Most of the contraflow studies are performed offline, thus strategies are generated beforehand for future implementation. Online contraflow models, however, would be often computationally demanding and time-consuming. This study contributes to the state of the art of contraflow modelling in two regards. First, it focuses on the calibration of a Logit choice model which predicts the online contraflow directions of strategic lanes based on the set of directions obtained from offline scenarios. This is the first effort to adjust offline results to be applied for an online case. The second contribution of this paper is the generation of calibration data set from a novel approach through simulation. The calibrated Logit model is then tested for the network of the City of Fort Worth, Texas. The results show a high performance of this approach to generating beneficial strategies, including an increase in up to 16% in throughput compared to no contraflow case