Central precocious puberty in a 3 year-old girl with Phenylketonuria: a rare association?

Background Central precocious puberty (CPP) and phenylketonuria (PKU) are two rare conditions, the latter being the rarer. To date, only one case featuring both these conditions has been reported, and hyperphenylalaninemia was assumed triggering CPP. Case presentation We present a 3.2 years old girl referred with a 12 months history of breast and pubic hair development, and vaginal discharge. Hyperphenylalaninemia had been identified by newborn screening and PKU subsequently confirmed by plasma amino acid and genetic analysis. Early dietary control of plasma phenylalanine had been excellent afterwards, resulting in phenylalanine concentrations consistently within the recommended range. Clinical scenario, hormonal assessment and imaging were in keeping with true idiopathic central precocious puberty. Treatment with long lasting gonadotropin-releasing hormone analogue led to regression of secondary sexual characteristics. Conclusion We describe for the first time CPP in a girl affected with PKU but with persistently well controlled blood phenylalanine concentrations. This finding is in contrast to a previous report which suggested persistently high phenylalaninemia levels as potential trigger for CPP in PKU patients. Our report, together with the lack of evidence in published cohort studies of children with PKU, strongly suggests this rare association is coincidental and independent of the presence of severe hyperphenylalaninemia.</p

Self-assembling behavior in decane solution of potential wax crystal nucleators based on poly(co-olefins)

The control of the precipitation and gelation of long chain paraffins from oil remains an enduring technological challenge regarding the processing and recovery of refined fuels and waxy crudes. Wax crystal modifiers based on polyethylene -poly(ethylene-propylene) (PE-PEP) diblock copolymers function as efficient nucleators for wax crystals in middle distillate fuels. These diblock polymers self-assemble in oil to form expansive platelike aggregates consisting of a PE core cloaked behind the amorphous PEP brush layer. The PE core thus promotes nucleation of solubilized long chain alkanes. Additional candidate structures for wax crystal nucleators include linear and star copolyolefins where the composition variation signals the alteration between crystalline and amorphous segments. This study focuses upon the self-assembling behavior in solution of these materials. The characteristics of the single chains and the aggregates formed at lower temperatures were determined via small-angle neutron scattering. Both plates and needlelike structures were found. The placement of the amorphous and crystalline blocks in the arms of the star shaped polymers was found to influence the architecture of the self-assembled micelles. As a point of comparison a commercial copolymer of ethylene-vinyl acetate (EVA) was also investigated. The EVA material was found to be relatively "undisciplined" in comparison to the structurally more uniform anionically prepared counterparts

Impact of Genetic Polymorphisms on the Smoking-related Risk of Periodontal Disease: the Population-based Study SHIP

Periodontitis is a bacterial inflammatory disease leading to attachment loss with the consequence of tooth loss. There exists a multifactorial risk pattern including bacterial challenge, smoking, age, sex, diabetes, socio-economic and genetic factors. Smoking has the highest impact on the course of the disease modulated by all the other factors. Here, we report the relationship between smoking and the polymorphisms of genetic polymorphisms inflicted in the pathogenesis

Cystathionine beta synthase deficiency and brain edema associated with methionine excess under betaine supplementation: Four new cases and a review of the evidence.

CBS deficient individuals undergoing betaine supplementation without sufficient dietary methionine restriction can develop severe hypermethioninemia and brain edema. Brain edema has also been observed in individuals with severe hypermethioninemia without concomitant betaine supplementation. We systematically evaluated reports from 11 published and 4 unpublished patients with CBS deficiency and from additional four cases of encephalopathy in association with elevated methionine. We conclude that, while betaine supplementation does greatly exacerbate methionine accumulation, the primary agent causing brain edema is methionine rather than betaine. Clinical signs of increased intracranial pressure have not been seen in patients with plasma methionine levels below 559 μmol/L but occurred in one patient whose levels did not knowingly exceed 972 μmol/L at the time of manifestation. While levels below 500 μmol/L can be deemed safe it appears that brain edema can develop with plasma methionine levels close to 1000 μmol/L. Patients with CBS deficiency on betaine supplementation need to be regularly monitored for concordance with their dietary plan and for plasma methionine concentrations. Recurrent methionine levels above 500 μmol/L should alert clinicians to check for clinical signs and symptoms of brain edema and review dietary methionine intake. Levels approaching 1000 μmol/L do increase the risk of complications and levels exceeding 1000 μmol/L, despite best dietetic efforts, should be acutely addressed by reducing the prescribed betaine dose

Severe methylenetetrahydrofolate reductase deficiency: Clinical clues to a potentially treatable cause of adult-onset hereditary spastic paraplegia

IMPORTANCE: Hereditary spastic paraplegia is a highly heterogeneous group of neurogenetic disorders with pure and complicated clinical phenotypes. No treatment is available for these disorders. We identified 2 unrelated families, each with 2 siblings with severe methylenetetrahydrofolate reductase (MTHFR) deficiency manifesting a complicated form of adult-onset hereditary spastic paraparesis partially responsive to betaine therapy. OBSERVATIONS: Both pairs of siblings presented with a similar combination of progressive spastic paraparesis and polyneuropathy, variably associated with behavioral changes, cognitive impairment, psychosis, seizures, and leukoencephalopathy, beginning between the ages of 29 and 50 years. By the time of diagnosis a decade later, 3 patients were ambulatory and 1 was bedridden. Investigations have revealed severe hyperhomocysteinemia and hypomethioninemia, reduced fibroblast MTHFR enzymatic activity (18%-52%of control participants), and 3 novel pathogenic MTHFR mutations, 2 as compound heterozygotes in one family and 1 as a homozygous mutation in the other family. Treatment with betaine produced a rapid decline of homocysteine by 50% to 70%in all 4 patients and, over 9 to 15 years, improved the conditions of the 3 ambulatory patients. CONCLUSIONS AND RELEVANCE: Although severe MTHFR deficiency is a rare cause of complicated spastic paraparesis in adults, it should be considered in select patients because of the potential therapeutic benefit of betaine supplementation. Copyright 2014 American Medical Association. All rights reserved

Human Mitochondrial HMG-CoA Synthase Deficiency: Role of Enzyme Dimerization Surface and Characterization of Three New Patients.

Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency (mitochondrial HMG-CoA synthase deficiency or mHS deficiency, OMIM #605911) is an inborn error of metabolism that affects ketone body synthesis. Acute episodes include vomiting, lethargy, hepatomegaly, hypoglycemia and dicarboxylic aciduria. The diagnosis is difficult due to the relatively unspecific clinical and biochemical presentation, and fewer than 30 patients have been described. This work describes three new patients with mHS deficiency and two missense mutations c.334C>T (p.R112W) and c.430G>T (p.V144L) previously not reported. We developed a new method to express and measure the activity of the enzyme and in this work the study is extended to ten new missense variants including those of our patients. Enzymatic assays showed that three of the mutant proteins retained some but seven completely lacked activity. The identification of a patient homozygous for a mutation that retains 70% of enzyme activity opens the door to a new interpretation of the disease by demonstrating that a modest impairment of enzyme function can actually produce symptoms. This is also the first study employing molecular dynamics modelling of the enzyme mutations. We show that the correct maintenance of the dimerization surface is crucial for retaining the structure of the active center and therefore the activity of the enzyme.post-print1746 K

Improving polymeric microemulsions with block copolymer polydispersity

Recent experiments have demonstrated that block copolymers are capable of stabilizing immiscible homopolymer blends producing bicontinuous microemulsion. The stability of these polymeric alloys requires the copolymer to form flexible, nonattractive monolayers along the homopolymer interfaces. We predict that copolymer polydispersity can substantially and simultaneously improve the monolayers in both of these respects. Furthermore, polydispersity should provide similar improvements in systems, such as colloidal suspensions and polymer/clay composites, that utilize polymer brushes to suppress attractive interactions

Multi-method study of the Middle Pleistocene loess–palaeosol sequence of Köndringen, SW Germany

Loess–palaeosol sequences (LPSs) remain poorly investigated in the southern part of the Upper Rhine Graben but represent an important element to understand the environmental context controlling sediment dynamics in the area. A multi-method approach applied to the LPS at Köndringen reveals that its formation occurred during several glacial–interglacial cycles. Field observations, as well as colour, grain size, magnetic susceptibility, organic carbon, and carbonate content measured in three profiles at 5 cm resolution, provide detailed stratigraphical information. Only minor parts of the LPS are made up of loess sediment, whereas the major parts are polygenetic palaeosols and pedosediments of varying development that are partly intersected, testifying to a complex local geomorphic evolution. The geochronological framework is based on 10 cm resolution infrared-stimulated luminescence (IRSL) screening combined with 18 multi-elevated-temperature post-IR IRSL ages. The luminescence ages indicate that two polygenetic, truncated Luvisols formed during marine isotope stages (MISs) 9(–7?) and MIS 5e, whereas unaltered loess units correspond to the last glacial (MISs 5d–2) and MIS 8. The channel-like structure containing the two truncated Luvisols cuts into &gt; 2 m thick pedosediments apparently deposited during MIS 12. At the bottom of the LPS, a horizon with massive carbonate concretions (loess dolls) occurs, which may correspond to at least one older interglacial.</p

Bulk and Boundary Critical Behavior at Lifshitz Points

Lifshitz points are multicritical points at which a disordered phase, a homogeneous ordered phase, and a modulated ordered phase meet. Their bulk universality classes are described by natural generalizations of the standard $\phi^4$ model. Analyzing these models systematically via modern field-theoretic renormalization group methods has been a long-standing challenge ever since their introduction in the middle of the 1970s. We survey the recent progress made in this direction, discussing results obtained via dimensionality expansions, how they compare with Monte Carlo results, and open problems. These advances opened the way towards systematic studies of boundary critical behavior at $m$-axial Lifshitz points. The possible boundary critical behavior depends on whether the surface plane is perpendicular to one of the $m$ modulation axes or parallel to all of them. We show that the semi-infinite field theories representing the corresponding surface universality classes in these two cases of perpendicular and parallel surface orientation differ crucially in their Hamiltonian's boundary terms and the implied boundary conditions, and explain recent results along with our current understanding of this matter.Comment: Invited contribution to STATPHYS 22, to be published in the Proceedings of the 22nd International Conference on Statistical Physics (STATPHYS 22) of the International Union of Pure and Applied Physics (IUPAP), 4--9 July 2004, Bangalore, Indi

Clearance of materials from accelerator facilities

A new Technical Standard that supports the clearance of materials and equipment (personal property) from U.S. Department of Energy (DOE) accelerator facilities has been developed. The Standard focuses on personal property that has the potential to be radiologically impacted by accelerator operations. It addresses material clearance programs and protocols for off-site releases without restriction on use. Common metals with potential volumetric activation are of main interest with technical bases provided in Appendices of the Standard. The clearance protocols in the Standard include three elements: 1) clearance criteria, 2) process knowledge, and 3) measurement methods. This paper presents the technical aspects of the new Standard, discusses operational experience gained in clearance of materials and equipment from several accelerator facilities at SLAC and examples as to how this Standard can be applied to benefit the entirety of the DOE Accelerator Complex