Application of an NGS‐based 28‐gene panel in myeloproliferative neoplasms reveals distinct mutation patterns in essential thrombocythaemia,primary myelofibrosis and polycythaemia vera

Molecular routine diagnostics for BCR‐ABL1‐negative myeloproliferative neoplasms (MPN) currently focusses on mutations in JAK2, CALR and MPL. In recent years, recurrent mutations in MPNs have been identified in several other genes. We here present the validation of a next generation sequencing (NGS)‐based 28‐gene panel and its use in MPN. We analysed the mutation status of 28 genes in 100 MPN patients [40 essential thrombocythaemia (ET), 30 primary myelofibrosis (PMF), 30 polycythaemia vera (PV)] and found two or more mutated genes in 53 patients. Moreover, significantly more mutated splicing genes (SF3B1, SRSF2 and U2AF1) were present in PMF (0·60 mutated genes/patient) compared to ET (0·15) while no mutations in splicing genes were found in PV. Additionally, chromatin modification genes (ASXL1 and EZH2) were frequently mutated in PMF patients (0·50) and, to a significantly lesser extent, in ET (0·13) and PV (0·07). Contrarily, DNA methylation genes (DNMT3A, IDH1, IDH2 and TET2) were mutated most often in PV (0·5) and less frequently in ET (0·23) and PMF (0·20), but without reaching statistical significance. Our results demonstrate the feasibility and utility of NGS‐based panel diagnostics for MPN. With 53% of the patients bearing two or more mutated genes, their prognostic relevance needs further studies.     

Dissociation between the procedural learning of letter names and motor sequences in developmental dyslexia

Motor sequence learning has been studied extensively in Developmental dyslexia (DD). The purpose of the present research was to examine procedural learning of letter names and motor sequences in individuals with DD and control groups. Both groups completed the Serial Search Task which enabled the assessment of learning of letter names and motor sequences independently of each other. Control participants learned both the letter names as well as the motor sequence. In contrast, individuals with DD were impaired in learning of the letter names sequence and showed a reliable transfer of the motor sequence. Previous studies proved that motor sequence learning is impaired in DD. The present study demonstrated that this deficit is more pronounced when the task to be learned involves linguistic units. This result implies that the procedural learning system of language is more deficient than the motor procedural learning system in individuals with DD. The dissociation between motor and letter names sequence learning in those with DD also implies that the systems underlying these two tasks are separable.     

Type I IL-1 receptor mediates IL-1 and intracellular IL-1 receptor antagonist effects in skin inflammation

The IL-1 system plays a key role in skin physiology and pathology. In this study, we used mutant mice lacking the type I IL-1 receptor (IL-1RI), lacking IL-1 receptor antagonist (IL-1Ra), or overexpressing the human intracellular (ic) IL-1Ra1 isoform, as well as combinations thereof, to dissect the role of the IL-1 system in phorbol 13-myristate 12-acetate (PMA)-induced skin inflammation. In wild-type (WT) mice, PMA application induced epidermal thickening and dermal inflammation. Skin IL-1alpha production and circulating levels of the acute-phase protein serum amyloid A (SAA) were elevated. In mice lacking IL-1RI or overexpressing icIL-1Ra1, PMA induced similar epidermal thickening as in WT mice, but dermal inflammation was partially prevented. Skin IL-1alpha mRNA expression was similar in PMA-treated IL-1RI-/- and WT mice, whereas the increase in serum SAA was suppressed in IL-1RI-/- mice. Interestingly, PMA-induced IL-1alpha mRNA expression was further enhanced by icIL-1Ra1 overexpression in an IL-1RI-dependent manner. Finally, IL-1Ra-/- mice spontaneously displayed skin lesions characterized by high IL-1beta, but not IL-1alpha, expression. In conclusion, PMA-induced epidermal thickening and skin IL-1alpha expression were independent of IL-1 signaling, in contrast to dermal inflammation and systemic inflammatory response.     

The association between personal care products and lung function

PurposeChemical exposures are important determinants of respiratory health. The objective of the present study was to determine the association between the use of personal care products, which may contain respirable components, and lung function.MethodsUsing questionnaire and spirometry data collected during the Canadian Health Measures population survey, the association was tested between 1-second forced expiratory volume (FEV_l) and forced vital capacity (FVC) expressed as a percentage of predicted, and the frequency of use of personal care products categorized as eye makeup, fragrances, hairstyle products, lipstick, and scented body products.ResultsFive thousand sixteen of the 5604 participants in the survey reported using at least one personal care product in the past 3 months. Among men and women, an interquartile increase in hairstyle products was associated with an approximate 2% decrease in both FEV₁ and FVC (P < .05). Among women, each product category was associated with a significant decrease in lung function with the largest observed effect being a 4.08% (95% confidence interval, 7.71–0.45) decrease in FVC associated with an interquartile range increase in the frequency of use of scented body products.ConclusionsThis study provides data suggesting that using personal care products may have a small adverse effect on lung function. Further research is warranted to investigate this possibility.     

The effect of ultrafast fiber laser application on the bond strength of resin cement to titanium

The purpose of this study was to investigate the effect of ultrafast fiber laser treatment on the bond strength between titanium and resin cement. A total of 60 pure titanium discs (15 mm × 2 mm) were divided into six test groups (n = 10) according to the surface treatment used: group (1) control, machining; group (2) grinding with a diamond bur; group (3) ultrafast fiber laser application; group (4) resorbable blast media (RBM) application; group (5) electro-erosion with copper; and group (6) sandblasting. After surface treatments, resin cements were applied to the treated titanium surfaces. Shear bond strength testing of the samples was performed with a universal testing machine after storing in distilled water at 37 °C for 24 h. One-way ANOVA and Tukey’s HSD post hoc test were used to analyse the data (P < 0.05). The highest bond strength values were observed in the laser application group, while the lowest values were observed in the grinding group. Sandblasting and laser application resulted in significantly higher bond strengths than control treatment (P < 0.05). Ultrafast fiber laser treatment and sandblasting may improve the bond strength between resin cement and titanium.