Results after two years of follow-up with an adult team

Funding: This article was supported by National Funds through FCT-Fundação para a Ciência e a Tecnologia, I.P., within CINTESIS, R&D Unit (reference UIDB/4255/2020).We aimed to report the implementation of a phenylketonuria (PKU) transition program and study the effects of follow-up with an adult team on metabolic control, adherence, and loss of follow-up. Fifty-five PKU patients were analysed in the study periods (SP): 2 years before (SP1) and after the beginning of adult care (SP2). Retrospective data on metabolic control and number of clinic appointments were collected for each SP, and protein intakes were analysed. In SP2, three patients (6%) were lost to follow-up. There was a small but statistically significant increase in median number of annual blood spots from SP1 to SP2: 11 (7–15) vs. 14 (7–20); p = 0.002. Mean ± SD of median blood Phe remained stable (525 ± 248 µmol/L vs. 552 ± 225 µmol/L; p = 0.100); median % of blood Phe < 480 µmol/L decreased (51 (4–96)% vs. 37 (5–85)%; p = 0.041) and median number of clinic appointments increased from SP1 to SP2: (5 (4–6) vs. 11 (8–13); p < 0.001). No significant differences were found regarding any parameter of protein intake. Our results suggest that the implementation of an adult service was successful as impact on metabolic control was limited and attendance remained high. Continuous dietetic care likely contributed to these results by keeping patients in fol-low-up and committed to treatment.publishersversionpublishe

Hypothyroidism modifies lipid composition of polymorphonuclear leukocytes

Thyroid hormones are important regulators of lipid metabolism. Polymorphonuclear leukocytes (PMN) are essential components of innate immune response. Our goal was to determine whether hypothyroidism affects lipid metabolism in PMN cells. Wistar rats were made hypothyroid by administrating 0.1 g/L 6-propyl-2-thiouracil (PTU) in drinking water during 30 days. Triacylglycerides (TG), cholesterol and phospholipids were determined in PMN and serum by conventional methods. The mRNA expression of LDL receptor (LDL-R), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCoAR), sterol regulatory element binding protein 2 (SREBP-2), and diacylglycerol acyltransferase 2 (DGAT-2) were quantified by Real-Time PCR. Cellular neutral lipids were identified by Nile red staining. We found hypothyroidism decreases serum TG whereas it increases them in PMN. This result agrees with those observed in Nile red preparations, however DAGT-2 expression was not modified. Cholesterol synthesizing enzyme HMGCoAR mRNA and protein was reduced in PMN of hypothyroid rats. As expected, cholesterol content decreased in the cells although it increased in serum. Hypothyroidism also reduced relative contents of palmitic, stearic, and arachidonic acids, whereas increased the myristic, linoleic acids, and the unsaturation index in PMN. Thus, hypothyroidism modifies PMN lipid composition. These findings would emphasize the importance of new research to elucidate lipid-induced alterations in specific function(s) of PMN.Facultad de Ciencias Médica

Hypothalamic miR-30 regulates puberty onset via repression of the puberty-suppressing factor, Mkrn3.

Mkrn3, the maternally imprinted gene encoding the makorin RING-finger protein-3, has recently emerged as putative pubertal repressor, as evidenced by central precocity caused by MKRN3 mutations in humans; yet, the molecular underpinnings of this key regulatory action remain largely unexplored. We report herein that the microRNA, miR-30, with three binding sites in a highly conserved region of its 3' UTR, operates as repressor of Mkrn3 to control pubertal onset. Hypothalamic miR-30b expression increased, while Mkrn3 mRNA and protein content decreased, during rat postnatal maturation. Neonatal estrogen exposure, causing pubertal alterations, enhanced hypothalamic Mkrn3 and suppressed miR-30b expression in female rats. Functional in vitro analyses demonstrated a strong repressive action of miR-30b on Mkrn3 3' UTR. Moreover, central infusion during the juvenile period of target site blockers, tailored to prevent miR-30 binding to Mkrn3 3' UTR, reversed the prepubertal down-regulation of hypothalamic Mkrn3 protein and delayed female puberty. Collectively, our data unveil a novel hypothalamic miRNA pathway, involving miR-30, with a prominent role in the control of puberty via Mkrn3 repression. These findings expand our current understanding of the molecular basis of puberty and its disease states

Upper limit for gamma-ray emission above 140 GeV from the dwarf spheroidal galaxy Draco

The nearby dwarf spheroidal galaxy Draco with its high mass to light ratio is one of the most auspicious targets for indirect dark matter searches. Annihilation of hypothetical DM particles can result in high-energy gamma-rays, e.g. from neutralino annihilation in the supersymmetric framework. With the MAGIC telescope a search for a possible DM signal originating from Draco was performed during 2007. The analysis of the data results in a flux upper limit of 1.1x10^-11 photons cm^-2 sec^-1 for photon energies above 140 GeV, assuming a point like source. Furthermore, a comparison with predictions from supersymmetric models is given. While our results do not constrain the mSUGRA phase parameter space, a very high flux enhancement can be ruled out.Comment: Accepted for publication by Astrophysical Journa

Observation of Pulsed Gamma-rays Above 25 GeV from the Crab Pulsar with MAGIC

One fundamental question about pulsars concerns the mechanism of their pulsed electromagnetic emission. Measuring the high-end region of a pulsar's spectrum would shed light on this question. By developing a new electronic trigger, we lowered the threshold of the Major Atmospheric gamma-ray Imaging Cherenkov (MAGIC) telescope to 25 GeV. In this configuration, we detected pulsed gamma-rays from the Crab pulsar that were greater than 25 GeV, revealing a relatively high cutoff energy in the phase-averaged spectrum. This indicates that the emission occurs far out in the magnetosphere, hence excluding the polar-cap scenario as a possible explanation of our measurement. The high cutoff energy also challenges the slot-gap scenario.Comment: Slight modification of the analysis: Fitting a more general function to the combined data set of COMPTEL, EGRET and MAGIC. Final result and conclusion is unchange

Evaluation of the potential association of SOHLH2 polymorphisms with non-obstructive azoospermia susceptibility in a large European population

Non-obstructive azoospermia (NOA) or spermatogenic failure is a complex disease with an important genetic component that causes infertility in men. Known genetic factors associated with NOA include AZF microdeletions of the Y chromosome or karyotype abnormalities; however, most causes of NOA are idiopathic. During the last decade, a large list of associations between single-nucleotide polymorphisms (SNP) and NOA have been reported. However, most of the genetic studies have been performed only in Asian populations. We aimed to evaluate whether the previously described association in Han Chinese between NOA and two SNPs of the SOHLH2 gene (involved in the spermatogenesis process) may also confer risk for NOA in a population of European ancestry. We genotyped a total of 551 NOA patients (218 from Portugal and 333 from Spain) and 1,050 fertile controls (226 from Portugal and 824 from Spain) for the genetic variants rs1328626 and rs6563386 using TaqMan assays. To test for association, we compared the allele and genotype frequencies between cases and controls using an additive model. A haplotype analysis and a meta-analysis using the inverse variance method with our data and those of the original Asian study were also performed. No statistically significant differences were observed in any of the analyses described above. Therefore, considering the high statistical power of our study, it is not likely that the two analysed SOHLH2 genetic variants are related with an increase susceptibility to NOA in the European population.info:eu-repo/semantics/publishedVersio

First bounds on the high-energy emission from isolated Wolf-Rayet binary systems

High-energy gamma-ray emission is theoretically expected to arise in tight binary star systems (with high mass loss and high velocity winds), although the evidence of this relationship has proven to be elusive so far. Here we present the first bounds on this putative emission from isolated Wolf-Rayet (WR) star binaries, WR 147 and WR 146, obtained from observations with the MAGIC telescope.Comment: (Authors are the MAGIC Collaboration.) Manuscript in press at The Astrophysical Journal Letter

MAGIC Upper Limits for two Milagro-detected, Bright Fermi Sources in the Region of SNR G65.1+0.6

We report on the observation of the region around supernova remnant G65.1+0.6 with the stand-alone MAGIC-I telescope. This region hosts the two bright GeV gamma-ray sources 1FGL J1954.3+2836 and 1FGL J1958.6+2845. They are identified as GeV pulsars and both have a possible counterpart detected at about 35 TeV by the Milagro observatory. MAGIC collected 25.5 hours of good quality data, and found no significant emission in the range around 1 TeV. We therefore report differential flux upper limits, assuming the emission to be point-like (<0.1 deg) or within a radius of 0.3 deg. In the point-like scenario, the flux limits around 1 TeV are at the level of 3 % and 2 % of the Crab Nebula flux, for the two sources respectively. This implies that the Milagro emission is either extended over a much larger area than our point spread function, or it must be peaked at energies beyond 1 TeV, resulting in a photon index harder than 2.2 in the TeV band.Comment: 8 pages, 3 figures, 1 tabl

Simultaneous multi-frequency observation of the unknown redshift blazar PG 1553+113 in March-April 2008

The blazar PG 1553+113 is a well known TeV gamma-ray emitter. In this paper, we determine its spectral energy distribution using simultaneous multi-frequency data in order to study its emission processes. An extensive campaign was carried out between March and April 2008, where optical, X-ray, high-energy (HE) gamma-ray, and very-high-energy (VHE) gamma-ray data were obtained with the KVA, Abastumani, REM, RossiXTE/ASM, AGILE and MAGIC telescopes, respectively. This is the first simultaneous broad-band (i.e., HE+VHE) gamma-ray observation, though AGILE did not detect the source. We combine data to derive source's spectral energy distribution and interpret its double peaked shape within the framework of a synchrotron self compton modelComment: 5 pages, 2 figures, publishe