Assessment of plasma chitotriosidase activity, CCL18/PARC concentration and NP-C suspicion index in the diagnosis of Niemann-Pick disease type C: A prospective observational study

Background: Niemann-Pick disease type C (NP-C) is a rare, autosomal recessive neurodegenerative disease caused by mutations in either the NPC1 or NPC2 genes. The diagnosis of NP-C remains challenging due to the non-specific, heterogeneous nature of signs/symptoms. This study assessed the utility of plasma chitotriosidase (ChT) and Chemokine (C-C motif) ligand 18 (CCL18)/pulmonary and activation-regulated chemokine (PARC) in conjunction with the NP-C suspicion index (NP-C SI) for guiding confirmatory laboratory testing in patients with suspected NP-C. Methods: In a prospective observational cohort study, incorporating a retrospective determination of NP-C SI scores, two different diagnostic approaches were applied in two separate groups of unrelated patients from 51 Spanish medical centers (n = 118 in both groups). From Jan 2010 to Apr 2012 (Period 1), patients with =2 clinical signs/symptoms of NP-C were considered ''suspected NP-C'' cases, and NPC1/NPC2 sequencing, plasma chitotriosidase (ChT), CCL18/PARC and sphingomyelinase levels were assessed. Based on findings in Period 1, plasma ChT and CCL18/PARC, and NP-C SI prediction scores were determined in a second group of patients between May 2012 and Apr 2014 (Period 2), and NPC1 and NPC2 were sequenced only in those with elevated ChT and/or elevated CCL18/PARC and/or NP-C SI =70. Filipin staining and 7-ketocholesterol (7-KC) measurements were performed in all patients with NP-C gene mutations, where possible. Results: In total across Periods 1 and 2, 10/236 (4%) patients had a confirmed diagnosis o NP-C based on gene sequencing (5/118 4.2%] in each Period): all of these patients had two causal NPC1 mutations. Single mutant NPC1 alleles were detected in 8/236 (3%) patients, overall. Positive filipin staining results comprised three classical and five variant biochemical phenotypes. No NPC2 mutations were detected. All patients with NPC1 mutations had high ChT activity, high CCL18/PARC concentrations and/or NP-C SI scores =70. Plasma 7-KC was higher than control cut-off values in all patients with two NPC1 mutations, and in the majority of patients with single mutations. Family studies identified three further NP-C patients. Conclusion: This approach may be very useful for laboratories that do not have mass spectrometry facilities and therefore, they cannot use other NP-C biomarkers for diagnosis

Changes in lipid content, fatty acid composition and lipid class composition of eggs and developing larvae (0-40 days old) of cultured common dentex (Dentex dentex Linnaeus 1758)

Total lipid content, fatty acid (FA) composition and lipid class composition of common dentex eggs spawned at different times and larvae reared under different culture conditions until 40 days posthatch (dph) were analysed to get a general pattern of lipid composition during larval development. Two groups of larvae were kept under starvation to compare their FA composition with that obtained from normally fed larvae. To compare FA use or accumulation during larval development, results were grouped according to the developmental stage of the larvae instead of age in days posthatch. Saturated and monounsaturated FAs decreased along larval development, while polyunsaturated fatty acid (PUFA) content increased. The ratio of docosahexaenoic acid (DHA)/eicosapentaenoic acid shifted from 4 to 5 in early developmental stages to lower than 1 after metamorphosis. Arachidonic acid levels remained constant along larval development. Larvae kept 6 days under starvation consumed most of their n-3 PUFA while conserving the DHA to values at day 0. The results presented here are useful for the design of nutritional experiments, because there were differences detected in terms of lipid and FA composition between developmental stages with higher differences mainly found in first-feeding larvae and early developmental stages

Quasi-periodic Pulsations in Solar and Stellar Flares: An Overview of Recent Results (Invited Review)

Quasi-periodic pulsations (or QPPs) are periodic intensity variations in the flare emission that occur across all wavelength bands. In this article, we review the observational and modelling achievements since the previous review on this topic by Nakariakov and Melnikov (Space Sci. Rev.149, 119, 2009). In recent years, it has become clear that QPPs are an inherent feature of solar flares because almost all flares exhibit QPPs. Moreover, it is now firmly established that QPPs often show multiple periods. We also review possible mechanisms for generating QPPs. Up to now, it has not been possible to conclusively identify the triggering mechanism or cause of QPPs. The lack of this identification currently hampers possible seismological inferences of flare plasma parameters. QPPs in stellar flares have been detected for a long time, and the high-quality data of the Kepler mission allows studying the QPP more systematically. However, it has not been conclusively shown whether the timescales of stellar QPPs are different or the same as those in solar flares