Ambient pressure X-ray photoelectron spectroscopy study of room-temperature oxygen adsorption on Cu(1 0 0) and Cu(1 1 1)

We investigated the room-temperature chemisorption of oxygen on Cu(1 0 0) and Cu(1 1 1) using ambient-pressure X-ray photoelectron spectroscopy (APXPS). A shoulder-to-shoulder comparison between the oxygen-gas titration on the two surfaces reveals that Cu(1 0 0) is the more active for oxygen dissociative chemisorption when the surfaces are clean. The (2 √ 2 × √ 2 )R45o missing-row reconstruction appears in Cu(1 0 0)’s LEED image after about 104 Langmuir of oxygen exposure, whereas on Cu(1 1 1), no long-range ordering was observed throughout the whole experiment. An oxide layer consisting of cuprous and cupric oxide shows up on Cu(1 1 1) at an oxygen exposure that is significantly lower than for Cu(1 0 0). This observation suggests that the presence of (2 √ 2 × √ 2 )R45o missing-row reconstruction layer slows down Cu(1 0 0) oxidation. Literature has widely reported that surface morphology influences the copper oxidation process. This study provides an XPS demonstration that copper surface oxide formation in O2 at room temperature depends on the surface crystallographic orientation

Preventive use of nitisinone in alkaptonuria

Abstract Alkaptonuria (AKU, OMIM 203500) is a rare congenital disorder caused by a deficiency of the enzyme homogentisate-1,2,-dioxygenase. The long-term consequences of AKU are joint problems, cardiac valve abnormalities and renal problems. Landmark intervention studies with nitisinone 10 mg daily, suppressing an upstream enzyme activity, demonstrated its beneficial effects in AKU patients with established complications, which usually start to develop in the fourth decade. Lower dose of nitisinone in the range of 0.2–2 mg daily will already reduce urinary homogentisic acid (uHGA) excretion by > 90%, which may prevent AKU-related complications earlier in the course of the disease while limiting the possibility of side-effects related to the increase of plasma tyrosine levels caused by nitisinone. Future preventive studies should establish the lowest possible dose for an individual patient, the best age to start treatment and also collect evidence to which level uHGA excretion should be reduced to prevent complications

3-Dimensional Imaging of Biological Structures by High Resolution Confocal Scanning Laser Microscopy

Imaging in confocal microscopy is characterized by the ability to make a selective image of just one plane inside a specimen, virtually unaffected -within certain limits-by the out-of-focus regions above and below it. This property, called optical sectioning, is accompanied by improved imaging transverse to the optical axis. We have coupled a confocal microscope to a computer system, making the combination of both an excellent instrument for mapping the 3-dimensional structure of extended specimens into a computer memory/data array. We measured that the volume element contributing to each data point has, under typical fluorescence conditions, a size of 0.2 x 0.2 x 0.72 μm. The data can be analysed and represented in various ways, i.e., stereoscopical views from any desired angle. After a description of the experimental arrangement, we show various examples of biological and food-structural studies. The microscope can be operated either in reflection or in fluorescence. In the latter mode a spectral element allows selection of the wavelength band of fluorescence light contributing to the image. In this way, we can distinguish various structures inside the cell and study their 3-dimensional relationships. Various applications in biology and the study of food structure are presented

Hydrogen migration at restructuring palladium-silver oxide boundaries dramatically enhances reduction rate of silver oxide.

Heterogeneous catalysts are complex materials with multiple interfaces. A critical proposition in exploiting bifunctionality in alloy catalysts is to achieve surface migration across interfaces separating functionally dissimilar regions. Herein, we demonstrate the enhancement of more than 104 in the rate of molecular hydrogen reduction of a silver surface oxide in the presence of palladium oxide compared to pure silver oxide resulting from the transfer of atomic hydrogen from palladium oxide islands onto the surrounding surface formed from oxidation of a palladium-silver alloy. The palladium-silver interface also dynamically restructures during reduction, resulting in silver-palladium intermixing. This study clearly demonstrates the migration of reaction intermediates and catalyst material across surface interfacial boundaries in alloys with a significant effect on surface reactivity, having broad implications for the catalytic function of bimetallic materials

Studying surface chemistry of mixed conducting perovskite oxide electrodes with synchrotron-based soft X-rays

A fundamental understanding of the electrochemical reactions and surface chemistry at the solid–gas interface in situ and operando is critical for electrode materials applied in electrochemical and catalytic applications. Here, the surface reactions and surface composition of a model of mixed ionic and electronic conducting (MIEC) perovskite oxide, (La0.8Sr0.2)0.95Cr0.5Fe0.5O3-δ (LSCrF8255), were investigated in situ using synchrotron-based near-ambient pressure (AP) X-ray photoelectron spectroscopy (XPS) and near-edge X-ray absorption fine-structure spectroscopy (NEXAFS). The measurements were conducted with a surface temperature of 500 °C under 1 mbar of dry oxygen and water vapor, to reflect the implementation of the materials for oxygen reduction/evolution and H2O electrolysis in the applications such as solid oxide fuel cell (SOFC) and electrolyzers. Our direct experimental results demonstrate that, rather than the transition metal (TM) cations, the surface lattice oxygen is the significant redox active species under both dry oxygen and water vapor environments. It was proven that the electron holes formed in dry oxygen have a strong oxygen character. Meanwhile, a relatively higher concentration of surface oxygen vacancies was observed on the sample measured in water vapor. We further showed that in water vapor, the adsorption and dissociation of H2O onto the perovskite surface were through forming hydroxyl groups. In addition, the concentration of Sr surface species was found to increase over time in dry oxygen due to Sr surface segregation, with the presence of oxygen holes on the surface serving as an additional driving force. Comparatively, less Sr contents were observed on the sample in water vapor, which could be due to the volatility of Sr(OH)2. A secondary phase was also observed, which exhibited an enrichment in B-site cations, particularly in Fe and relatively in Cr, and a deficiency in A-site cation, notably in La and relatively in Sr. The findings and methodology of this study allow for the quantification of surface defect chemistry and surface composition evolution, providing crucial understanding and design guidelines in the electrocatalytic activity and durability of electrodes for efficient conversions of energy and fuels

Occurrence of subdural hematomas in Dutch glutaric aciduria type 1 patients

Patients with glutaric aciduria type 1 (GA1), a rare inherited metabolic disorder, have an increased risk for subdural hematomas (SDHs). GA1 is therefore generally included in the differential diagnosis of children presenting with SDHs. This retrospective cohort study reviews all 25 registered, in the Dutch Diagnosis Registration for Metabolic Disorders, GA1 patients in the Netherlands. This was done between May 2014 and November 2014 to determine the lifetime incidence of SDHs in this population. Seventeen patients were diagnosed either due to clinical symptoms or because of family members with GA1. One out of these 17 had a SDH. This patient showed widened Sylvian fissures on MRI, characteristic for GA1. Eight patients were diagnosed by newborn screening. Three of them had neuroimaging results, and none of them had SDHs. This study shows an overall lower incidence (4.0 %) of SDHs in patients with GA1 than reported in the literature (20–30 %). Conclusion: This finding, in combination with the fact that SDHs in GA1 appear to occur only in the presence of characteristic brain abnormalities on imaging, we recommend that GA1 should not routinely be a part of the differential diagnosis of children with unexplained SDHs in the absence of imaging characteristics suggestive of GA1. What is known:• Glutaric aciduria type 1 is a rare metabolic disorder predisposing children to subdural hematoma development due to brain abnormalities.• Because of these subdural hematomas, glutaric aciduria type 1 testing is part of abusive head trauma work-up.What is new:• The overall subdural hematoma incidence in glutaric aciduria type 1 patients is much lower than previously reported and only occurs in case of predisposing brain abnormalities

Computational flow cytometry as a diagnostic tool in suspected-myelodysplastic syndromes

The diagnostic work-up of patients suspected for myelodysplastic syndromes is challenging and mainly relies on bone marrow morphology and cytogenetics. In this study, we developed and prospectively validated a fully computational tool for flow cytometry diagnostics in suspected-MDS. The computational diagnostic workflow consists of methods for pre-processing flow cytometry data, followed by a cell population detection method (FlowSOM) and a machine learning classifier (Random Forest). Based on a six tubes FC panel, the workflow obtained a 90% sensitivity and 93% specificity in an independent validation cohort. For practical advantages (e.g., reduced processing time and costs), a second computational diagnostic workflow was trained, solely based on the best performing single tube of the training cohort. This workflow obtained 97% sensitivity and 95% specificity in the prospective validation cohort. Both workflows outperformed the conventional, expert analyzed flow cytometry scores for diagnosis with respect to accuracy, objectivity and time investment (less than 2 min per patient)

Long-Term Outcomes and Practical Considerations in the Pharmacological Management of Tyrosinemia Type 1

Tyrosinemia type 1 (TT1) is a rare metabolic disease caused by a defect in tyrosine catabolism. TT1 is clinically characterized by acute liver failure, development of hepatocellular carcinoma, renal and neurological problems, and consequently an extremely poor outcome. This review showed that the introduction of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) in 1992 has revolutionized the outcome of TT1 patients, especially when started pre-clinically. If started early, NTBC can prevent liver failure, renal problems, and neurological attacks and decrease the risk for hepatocellular carcinoma. NTBC has been shown to be safe and well tolerated, although the long-term effectiveness of treatment with NTBC needs to be awaited. The high tyrosine concentrations caused by treatment with NTBC could result in ophthalmological and skin problems and requires life-long dietary restriction of tyrosine and its precursor phenylalanine, which could be strenuous to adhere to. In addition, neurocognitive problems have been reported since the introduction of NTBC, with hypothesized but as yet unproven pathophysiological mechanisms. Further research should be done to investigate the possible relationship between important clinical outcomes and blood concentrations of biochemical parameters such as phenylalanine, tyrosine, succinylacetone, and NTBC, and to develop clear guidelines for treatment and follow-up with reliable measurements. This all in order to ultimately improve the combined NTBC and dietary treatment and limit possible complications such as hepatocellular carcinoma development, neurocognitive problems, and impaired quality of life

Food or medicine? A European regulatory perspective on nutritional therapy products to treat inborn errors of metabolism

Dietary or nutritional management strategies are the cornerstone of treatment for many inborn errors of metabolism (IEMs). Though a vital part of standard of care, the products prescribed for this are often not formally registered as medication. Instead, they are regulated as food or as food supplements, impacting the level of oversight as well as reimbursed policies. This scoping literature review explores the European regulatory framework relevant to these products and its implications for current clinical practice. Searches of electronic databases (PubMed, InfoCuria) were carried out, supplemented by articles identified by experts, from reference lists, relevant guidelines and case-law by the European Court of Justice. In the European Union (EU), nutritional therapy products are regulated as food supplements, food for special medical purposes (FSMPs) or medication. The requirements and level of oversight increase for each of these categories. Relying on lesser-regulated food products to treat IEMs raises concerns regarding product quality, safety, reimbursement and patient access. In order to ascertain whether a nutritional therapy product functions as medication and thus could be classified as such, we developed a flowchart to assess treatment characteristics (benefit, pharmacological attributes, and safety) with a case-based approach. Evaluating nutritional therapy products might reveal a justifiable need for a pharmaceutical product. A flowchart can facilitate systematically distinguishing products that function medication-like in the management of IEMs. Subsequently, finding and implementing appropriate solutions for these products might help improve the quality, safety and accessibility including reimbursement of treatment for IEMs.</p

Long-term dietary intervention with low Phe and/or a specific nutrient combination improve certain aspects of brain functioning in phenylketonuria (PKU)

Introduction In phenylketonuria (PKU), a gene mutation in the phenylalanine metabolic pathway causes accumulation of phenylalanine (Phe) in blood and brain. Although early introduction of a Phe-restricted diet can prevent severe symptoms from developing, patients who are diagnosed and treated early still experience deficits in cognitive functioning indicating shortcomings of current treatment. In the search for new and/or additional treatment strategies, a specific nutrient combination (SNC) was postulated to improve brain function in PKU. In this study, a long-term dietary intervention with a low-Phe diet, a specific combination of nutrients designed to improve brain function, or both concepts together was investigated in male and female BTBR PKU and WT mice. Material & methods 48 homozygous wild-types (WT, +/+) and 96 PKU BTBRPah2 (-/-) male and female mice received dietary interventions from postnatal day 31 till 10 months of age and were distributed in the following six groups: high Phe diet (WT C-HP, PKU C-HP), high Phe plus specific nutrient combination (WT SNC-HP, PKU SNC-HP), PKU low-Phe diet (PKU C-LP), and PKU low-Phe diet plus specific nutrient combination (PKU SNC- LP). Memory and motor function were tested at time points 3, 6, and 9 months after treatment initiation in the open field (OF), novel object recognition test (NOR), spatial object recognition test (SOR), and the balance beam (BB). At the end of the experiments, brain neurotransmitter concentrations were determined. Results In the NOR, we found that PKU mice, despite being subjected to high Phe conditions, could master the task on all three time points when supplemented with SNC. Under low Phe conditions, PKU mice on control diet could master the NOR at all three time points, while PKU mice on the SNC supplemented diet could master the task at time points 6 and 9 months. SNC supplementation did not consistently influence the performance in the OF, SOR or BB in PKU mice. The low Phe diet was able to normalize concentrations of norepinephrine and serotonin; however, these neurotransmitters were not influenced by SNC supplementation. Conclusion This study demonstrates that both a long-lasting low Phe diet, the diet enriched with SNC, as well as the combined diet was able to ameliorate some, but not all of these PKU-induced abnormalities. Specifically, this study is the first long-term intervention study in BTBR PKU mice that shows that SNC supplementation can specifically improve novel object recognition