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Item does not contain fulltext, Tyrosinemia type 1 (TT1) and phenylketonuria (PKU) are both inborn errors of phenylalanine-tyrosine metabolism. Neurocognitive and behavioral outcomes have always featured in PKU research but received less attention in TT1 research. This study aimed to investigate and compare neurocognitive, behavioral, and social outcomes of treated TT1 and PKU patients. We included 33 TT1 patients (mean age 11.24 years; 16 male), 31 PKU patients (mean age 10.84; 14 male), and 58 age- and gender-matched healthy controls (mean age 10.82 years; 29 male). IQ (Wechsler-subtests), executive functioning (the Behavioral Rating Inventory of Executive Functioning), mental health (the Achenbach-scales), and social functioning (the Social Skills Rating System) were assessed. Results of TT1 patients, PKU patients, and healthy controls were compared using Kruskal-Wallis tests with post-hoc Mann-Whitney U tests. TT1 patients showed a lower IQ and poorer executive functioning, mental health, and social functioning compared to healthy controls and PKU patients. PKU patients did not differ from healthy controls regarding these outcome measures. Relatively poor outcomes for TT1 patients were particularly evident for verbal IQ, BRIEF dimensions "working memory", "plan and organize" and "monitor", ASEBA dimensions "social problems" and "attention problems", and for the SSRS "assertiveness" scale (all p values <0.001). To conclude, TT1 patients showed cognitive impairments on all domains studied, and appeared to be significantly more affected than PKU patients. More attention should be paid to investigating and monitoring neurocognitive outcome in TT1 and research should focus on explaining the underlying pathophysiological mechanism.

Contains fulltext : 286856.pdf (Publisher’s version ) (Open Access), Tyrosinemia type 1 (TT1) and phenylketonuria (PKU) are both inborn errors of phenylalanine-tyrosine metabolism. Neurocognitive and behavioral outcomes have always featured in PKU research but received less attention in TT1 research. This study aimed to investigate and compare neurocognitive, behavioral, and social outcomes of treated TT1 and PKU patients. We included 33 TT1 patients (mean age 11.24 years; 16 male), 31 PKU patients (mean age 10.84; 14 male), and 58 age- and gender-matched healthy controls (mean age 10.82 years; 29 male). IQ (Wechsler-subtests), executive functioning (the Behavioral Rating Inventory of Executive Functioning), mental health (the Achenbach-scales), and social functioning (the Social Skills Rating System) were assessed. Results of TT1 patients, PKU patients, and healthy controls were compared using Kruskal-Wallis tests with post-hoc Mann-Whitney U tests. TT1 patients showed a lower IQ and poorer executive functioning, mental health, and social functioning compared to healthy controls and PKU patients. PKU patients did not differ from healthy controls regarding these outcome measures. Relatively poor outcomes for TT1 patients were particularly evident for verbal IQ, BRIEF dimensions "working memory", "plan and organize" and "monitor", ASEBA dimensions "social problems" and "attention problems", and for the SSRS "assertiveness" scale (all p values <0.001). To conclude, TT1 patients showed cognitive impairments on all domains studied, and appeared to be significantly more affected than PKU patients. More attention should be paid to investigating and monitoring neurocognitive outcome in TT1 and research should focus on explaining the underlying pathophysiological mechanism.

Neoproterozoic iron formations are exposed in the Wadi Hamama area (Egypt) in the northwestern part of the Arabian–Nubian Shield. Mafic and felsic volcanic and volcaniclastic rocks of an intra-oceanic island-arc setting host multiple, thin iron-formation units. Major element compositions of the iron formation confirm a low detrital input, whereas the rare-earth elements and Y data suggest deposition related to an influx of low-temperature hydrothermal fluids. Unlike most Neoproterozoic banded iron formations, but similar to other iron-formation occurrences from the Arabian–Nubian Shield, the Nd isotopic compositions of the Wadi Hamama iron formations are predominantly mantle-like. SIMS U–Pb zircon ages of the host volcaniclastic units indicate that the age of iron-formation deposition is ca. 695 Ma, which is within the Sturtian epoch that is presumed to be a glacial event of global extent. Nevertheless, there is no robust evidence of any influence of Sturtian glaciation in the Arabian–Nubian Shield. Our results rather suggest that the iron formations in the area may have formed as low-temperature exhalites on the floor of an island-arc basin. The iron formations were deposited during periods of volcanic quiescence, with metals having been derived during low-temperature pervasive hydrothermal alteration of volcanic and volcaniclastic rocks exposed at the seafloor–seawater interface. Precipitation took place due to mixing of metal-bearing hydrothermal fluids and cold, oxygenated seawater. There is no need to invoke possible effects of global glaciation to explain the origin of the Sturtian-aged iron formations in the shield. Our study thus suggests that not all Neoproterozoic iron formations are necessarily linked to glacial events as the Hamama deposit represents a non-Rapitan exhalative iron formation.

The South Um Mongul prospect is a Cu-Mo-Au porphyry system. It is covered by porphyritic dacite and hornblende gabbro. Both units are intruded by monzogranite, which encloses xenoliths of both units. Using LA-ICP-MS U-Pb zircon method, the dacite is dated at ca. 773 ± 6.9 Ma, while the gabbro and the monzogranite are dated at 603 ± 3.5 and 558 ± 4.6 Ma, respectively. The dacite age is consistent with the mid-Cryogenian subduction-related magmatic stage and the gabbro-monzogranite age is comparable to the Ediacaran post-collisional magmatic stage during the evolution of the Arabian-Nubian Shield. The dacite is akin to high-K I-type granitoids and its primitive mantle-normalized trace element patterns show negative Nb anomalies and enrichment in LILE (large ion lithophile elements), Th and U over HFSE. These geochemical characteristics are similar to those of felsic magma formed in a subduction-related tectonic setting. The high La/Ybcn (7.2–30.9), Nb/Yb (2.63–4.41) and Th/Yb (2.07–3.04) ratios of the dacite are comparable to continental rather than oceanic arc systems. Its low Sm/Yb ratios (1.84–3.13) support the primitive nature of the crust beneath the continental arc and derivation from a garnet-free lower crustal source. The dacite has low Sr/Y ratios (5–9) and its Eu/Eu⁎ ratios range from 0.66 to 0.83. Similar to dacite, the primitive mantle-normalized trace element patterns of the post-collisional suite show a subduction-related geochemical signature. However, the gabbro is characterized by Th/Ta ratios (3.4–14.8), which are comparable with the within-plate tectonic setting. The subduction-related geochemical signature is inherited from long subduction history beneath the Arabian-Nubian Shield. Both the gabbro and monzogranite are characterized by high Ba (404–590 ppm and 936–1590 ppm, respectively) and Sr (611–708 ppm and 624–793 ppm, respectively) contents, which make them analogous to the Caledonian appinite-high Ba-Sr granite assemblage. The formation of th

The purpose of this study was to determine if immune mechanisms in GAD positive patients' contribute to the pathogenesis of a specific sub-type of Type 2 diabetes. GAD positive (n = 8) and GAD negative (n = 8) subjects diagnosed with Type 2 diabetes were matched for age, gender, body mass index, duration of diabetes and glycaemic control. All subjects underwent an insulin-modified frequently sampled intravenous glucose tolerance test to measure insulin sensitivity and insulin secretory function with minimal model analysis. In addition, BRIN-BD11 clonal ß-cells were supplemented with patients' sera to determine basal and alanine-stimulated insulin secretion and terminal complement complex (TCC) formation. Both groups were severely insulin resistant (0.56 ± 0.17 vs. 0.99 ± 0.33 10-4 min-1/(µU ml-1) for GADneg and GADpos, respectively) but the GAD negative subjects had a higher basal (87 ± 11 vs. 58 ± 14 pmol l-1, p < 0.05) and glucose-stimulated insulin secretion (?AUCins 0.96 ± 0.12 vs. 0.60 ± 0.12 pmol/(l-1 min), p < 0.05). In vivo measures of insulin secretion were negatively correlated with TCC formation, independent of antibody status. In conclusion, GAD positive subjects initially diagnosed with Type 2 diabetes are unable to compensate for insulin resistance due to more pronounced ß-cell impairment. TCC formation may be partly responsible for the insulin secretory dysfunction associated with this specific sub-type of Type 2 diabetes. © 2007 Elsevier Ireland Ltd. All rights reserved.