Collaborative evaluation study on 18 candidate diseases for newborn screening in 1.77 million samples.

Analytical and therapeutic innovations led to a continuous but variable extension of newborn screening (NBS) programmes worldwide. Every extension requires a careful evaluation of feasibility, diagnostic (process) quality and possible health benefits to balance benefits and limitations. The aim of this study was to evaluate the suitability of 18 candidate diseases for inclusion in NBS programmes. Utilising tandem mass spectrometry as well as establishing specific diagnostic pathways with second-tier analyses, three German NBS centres designed and conducted an evaluation study for 18 candidate diseases, all of them inherited metabolic diseases. In total, 1 777 264 NBS samples were analysed. Overall, 441 positive NBS results were reported resulting in 68 confirmed diagnoses, 373 false-positive cases and an estimated cumulative prevalence of approximately 1 in 26 000 newborns. The positive predictive value ranged from 0.07 (carnitine transporter defect) to 0.67 (HMG-CoA lyase deficiency). Three individuals were missed and 14 individuals (21%) developed symptoms before the positive NBS results were reported. The majority of tested candidate diseases were found to be suitable for inclusion in NBS programmes, while multiple acyl-CoA dehydrogenase deficiency, isolated methylmalonic acidurias, propionic acidemia and malonyl-CoA decarboxylase deficiency showed some and carnitine transporter defect significant limitations. Evaluation studies are an important tool to assess the potential benefits and limitations of expanding NBS programmes to new diseases.

Investigation of Adverse Reactions in Tattooed Skin through Histological and Chemical Analysis.

BACKGROUND: Just as the number of tattooed people has increased in recent years, so has the number of adverse reactions in tattooed skin. Tattoo colourants contain numerous, partly unidentified substances, which have the potential to provoke adverse skin reactions like allergies or granulomatous reactions. Identification of the triggering substances is often difficult or even impossible. METHODS: Ten patients with typical adverse reactions in tattooed skin were enrolled in the study. Skin punch biopsies were taken and the paraffin-embedded specimens were analysed by standard haematoxylin and eosin and anti-CD3 stainings. Tattoo colourants provided by patients and punch biopsies of patients were analysed with different chromatography and mass spectrometry methods and X-ray fluorescence. Blood samples of 2 patients were screened for angiotensin-converting enzyme (ACE) and soluble interleukin-2 receptor (sIL-2R). RESULTS: Histology showed variable skin reactions such as eosinophilic infiltrate, granulomatous reactions, or pseudolymphoma. CD3+ T lymphocytes dominated the dermal cellular infiltrate. Most patients had adverse skin reactions in red tattoos (n = 7), followed by white tattoos (n = 2). The red tattooed skin areas predominantly contained Pigment Red (P.R.) 170, but also P.R. 266, Pigment Orange (P.O.) 13, P.O. 16, and Pigment Blue (P.B.) 15. The white colourant of 1 patient contained rutile titanium dioxide but also other metals like nickel and chromium and methyl dehydroabietate - known as the main ingredient of colophonium. None of the 2 patients showed increased levels of ACE and sIL-2R related to sarcoidosis. Seven of the study participants showed partial or complete remission after treatment with topical steroids, intralesional steroids, or topical tacrolimus. CONCLUSIONS: The combination of the methods presented might be a rational approach to identify the substances that trigger adverse reactions in tattoos. Such an approach might help make tattoo colourants safer in the future if such trigger substances could be omitted.

Liposome-based high-throughput and point-of-care assays toward the quick, simple, and sensitive detection of neutralizing antibodies against SARS-CoV-2 in patient sera.

The emergence of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) in 2019 caused an increased interest in neutralizing antibody tests to determine the immune status of the population. Standard live-virus-based neutralization assays such as plaque-reduction assays or pseudovirus neutralization tests cannot be adapted to the point-of-care (POC). Accordingly, tests quantifying competitive binding inhibition of the angiotensin-converting enzyme 2 (ACE2) receptor to the receptor-binding domain (RBD) of SARS-CoV-2 by neutralizing antibodies have been developed. Here, we present a new platform using sulforhodamine B encapsulating liposomes decorated with RBD as foundation for the development of both a fluorescent, highly feasible high-throughput (HTS) and a POC-ready neutralizing antibody assay. RBD-conjugated liposomes are incubated with serum and subsequently immobilized in an ACE2-coated plate or mixed with biotinylated ACE2 and used in test strip with streptavidin test line, respectively. Polyclonal neutralizing human antibodies were shown to cause complete binding inhibition, while S309 and CR3022 human monoclonal antibodies only caused partial inhibition, proving the functionality of the assay. Both formats, the HTS and POC assay, were then tested using 20 sera containing varying titers of neutralizing antibodies, and a control panel of sera including prepandemic sera and reconvalescent sera from respiratory infections other than SARS-CoV-2. Both assays correlated well with a standard pseudovirus neutralization test (r = 0.847 for HTS and r = 0.614 for POC format). Furthermore, excellent correlation (r = 0.868) between HTS and POC formats was observed. The flexibility afforded by liposomes as signaling agents using different dyes and sizes can hence be utilized in the future for a broad range of multianalyte neutralizing antibody diagnostics.

Free carnitine concentrations and biochemical parameters in medium-chain acyl-CoA dehydrogenase deficiency: Genotype-phenotype correlation.

Biallelic variants in the ACADM gene cause medium-chain acyl-CoA dehydrogenase deficiency (MCADD). This study reports on differences in the occurrence of secondary free carnitine (C0) deficiency and different biochemical phenotypes related to genotype and age in 109 MCADD patients followed-up at a single tertiary care center during 22 years. C0 deficiency occurred earlier and more frequently in c.985A>G homozygotes (genotype A) compared to c.985A>G compound heterozygotes (genotype B) and individuals carrying variants other than c.985A>G and c.199C>T (genotype D) (median age 4.2 vs. 6.6 years; p < 0.001). No patient carrying c.199C>T (genotype C) developed C0 deficiency. A daily dosage of 20-40 mg/kg carnitine was sufficient to maintain normal C0 concentrations. Compared to genotype A as reference group, octanoylcarnitine (C8) was significantly lower in genotypes B and C, whereas C0 was significantly higher by 8.28 µmol/L in genotype C (p < 0.05). In conclusion, C0 deficiency is mainly found in patients with pathogenic genotypes associated with high concentrations of presumably toxic acylcarnitines, while individuals carrying the variant c.199C>T are spared and show consistently mild biochemical phenotypes into adulthood. Low-dose carnitine supplementation maintains normal C0 concentrations. However, future studies need to evaluate clinical benefits on acute and chronic manifestations of MCADD.

Does the medium matter? Comparing the effectiveness of videos, podcasts and online articles in nutrition communication.

Videos and podcasts have become popular in nutrition communication. However, it is unclear whether they are more effective than online texts in conveying knowledge and promoting behavioural intentions. Based on the Cognitive Theory of Multimedia Learning, it was hypothesised that videos are more effective than podcasts or texts in communicating nutrition-related information. In addition, differences in behaviour change intentions were explored. The pre-registered online experiment used a 3 (medium: video, podcast and text) × 3 (topic: diet and climate change, sugar content, and nudging) between-subjects design with 320 participants who were randomly assigned to the conditions. After receiving the respective content, the participants' intention to change their behaviour accordingly and their knowledge about all topics were assessed. A mixed Analysis of Variance revealed a significant interaction of topic and knowledge, indicating that knowledge was higher for the topic that participants were assigned to, compared to the two topics they received no information about. There were no differences in knowledge or intention for the three media. Videos, podcasts and texts are equally suitable for conveying nutrition knowledge and may also be equally beneficial for promoting intention. Communicators may thus base their choice of medium on considerations like available resources and preferences of the target group.

Serum glial fibrillary acidic protein and neurofilament light chain in patients with early treated phenylketonuria.

To pave the way for healthy aging in early treated phenylketonuria (ETPKU) patients, a better understanding of the neurological course in this population is needed, requiring easy accessible biomarkers to monitor neurological disease progression in large cohorts. The objective of this pilot study was to investigate the potential of glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) as blood biomarkers to indicate changes of the central nervous system in ETPKU. In this single-center cross-sectional study, GFAP and NfL concentrations in serum were quantified using the Simoa® multiplex technology in 56 ETPKU patients aged 6-36 years and 16 age matched healthy controls. Correlation analysis and hierarchical linear regression analysis were performed to investigate an association with disease-related biochemical parameters and retinal layers assessed by optical coherence tomography. ETPKU patients did not show significantly higher GFAP concentrations (mean 73 pg/ml) compared to healthy controls (mean 60 pg/ml, p = 0.140). However, individual pediatric and adult ETPKU patients had GFAP concentrations above the healthy control range. In addition, there was a significant association of GFAP concentrations with current plasma tyrosine concentrations (r = -0.482, p = 0.036), a biochemical marker in phenylketonuria, and the retinal inner nuclear layer volume (r = 0.451, p = 0.04). There was no evidence of NfL alterations in our ETPKU cohort. These pilot results encourage multicenter longitudinal studies to further investigate serum GFAP as a complementary tool to better understand and monitor neurological disease progression in ETPKU. Follow-up investigations on aging ETPKU patients are required to elucidate the potential of serum NfL as biomarker.

microRNA Expression Profile of Purified Alveolar Epithelial Type II Cells.

Alveolar type II (ATII) cells are essential for the maintenance of the alveolar homeostasis. However, knowledge of the expression of the miRNAs and miRNA-regulated networks which control homeostasis and coordinate diverse functions of murine ATII cells is limited. Therefore, we asked how miRNAs expressed in ATII cells might contribute to the regulation of signaling pathways. We purified "untouched by antibodies" ATII cells using a flow cytometric sorting method with a highly autofluorescent population of lung cells. TaqMan® miRNA low-density arrays were performed on sorted cells and intersected with miRNA profiles of ATII cells isolated according to a previously published protocol. Of 293 miRNAs expressed in both ATII preparations, 111 showed equal abundances. The target mRNAs of bona fide ATII miRNAs were used for pathway enrichment analysis. This analysis identified nine signaling pathways with known functions in fibrosis and/or epithelial-to-mesenchymal transition (EMT). In particular, a subset of 19 miRNAs was found to target 21 components of the TGF-ß signaling pathway. Three of these miRNAs (miR-16-5p, -17-5p and -30c-5p) were down-modulated by TGF-ß1 stimulation in human A549 cells, and concomitant up-regulation of associated mRNA targets (BMPR2, JUN, RUNX2) was observed. These results suggest an important role for miRNAs in maintaining the homeostasis of the TGF-ß signaling pathway in ATII cells under physiological conditions.

Strategic pheromone signalling by mate searching females of the sexually cannibalistic spider Argiope bruennichi.

Reproduction often requires finding a mating partner. To this end, females of many arthropods advertise their presence to searching males via volatile chemical signals. Such pheromones are considered low-cost signals, although this notion is based on little evidence and has recently been challenged. Even when using comparatively low-cost signals, females should signal as little as possible to minimize costs while still ensuring mate attraction. Here, we test the strategic-signalling hypothesis using Argiope bruennichi. In this orb-weaving spider, egg maturation commences with adult moult, and females that do not attract a male in time will lay a large batch of unfertilized eggs approximately three weeks after maturation. Using GC-MS analyses, we show that virgin females enhance their signalling effort, i.e. pheromone quantity per unit body mass, with increasing age and approaching oviposition. We further demonstrate that pheromone release is condition dependent, suggesting the occurrence of physiological costs. Mate choice assays revealed that pheromone quantity is the only predictor of female attractiveness for males. In support of the strategic-signalling hypothesis, pheromone signals by female A. bruennichi become stronger with increased need as well as body condition, and might thus qualify as an honest signal of female quality.

Identification of Cuticular and Web Lipids of the Spider Argiope bruennichi.

Emerging evidence shows that the cuticular and silk lipids of spiders are structurally more diverse than those of insects, although only a relatively low number of species have been investigated so far. As in insects, such lipids might play a role as signals in various contexts. The wasp spider Argiope bruennichi has probably the best investigated chemical communication system within spiders, including the known structure of the female sex pheromone. Recently we showed that kin-recognition in A. bruennichi could be mediated through the cuticular compounds consisting of hydrocarbons and, to a much larger proportion, of wax esters. By use of mass spectrometry and various derivatization methods, these were identified as esters of 2,4-dimethylalkanoic acids and 1-alkanols of varying chain lengths, such as tetradecyl 2,4-dimethylheptadecanoate. A representative enantioselective synthesis of this compound was performed which proved the identifications and allowed us to postulate that the natural enantiomer likely has the (2R,4R)-configuration. Chemical profiles of the silk and cuticular lipids of females were similar, while male cuticular profiles differed from those of females. Major components of the male cuticular lipids were tridecyl 2,4-dimethyl-C17-19 alkanoates, whereas those of females were slightly longer, comprising tridecyl 2,4-dimethyl-C19-21 alkanoates. In addition, minor female-specific 4-methylalkyl esters were detected.

Optical Coherence Tomography to Assess Neurodegeneration in Phenylalanine Hydroxylase Deficiency.

In phenylalanine hydroxylase (PAH) deficiency, an easily feasible method to access the progression of neurodegeneration is warranted to contribute to current discussions on treatment indications and targets. The objective of the present study was to investigate whether optical coherence tomography (OCT) measures as markers of neurodegeneration differ between patients with PAH deficiency and healthy controls (HCs) according to phenotype and metabolic control. In this single-center cross-sectional study, 92 patients with different phenotypes of PAH deficiency [PAH deficiency not requiring treatment, early treated phenylketonuria (ETPKU), and late-diagnosed phenylketonuria (PKU)] compared with 76 HCs were examined using spectral-domain OCT. Indices of phenylalanine elevation and variability were correlated with OCT parameters. Late-diagnosed PKU patients showed reduced peripapillary retinal nerve fiber layer (pRNFL) thickness and combined ganglion cell and inner plexiform layer (GCIPL) volume. Adult ETPKU patients were found to have lower GCIPL volume (p = 0.016), which correlated with the indices of phenylalanine control. In pediatric ETPKU patients with poor metabolic control, pRNFL was significantly reduced (p = 0.004). Patients with PAH deficiency not requiring treatment did not exhibit retinal degeneration. Inner nuclear layer (INL) was significantly increased in the pediatric ETPKU patients, driven by those with current poor metabolic control (p = 0.006). Our data provide evidence of retinal neuroaxonal degeneration and INL swelling, depending on the phenotype, current age, and metabolic control. These findings suggest that OCT is suitable to investigate neurodegeneration in PKU and we propose OCT as a sensitive, reliable, safe, low-burden, and low-cost examination for future multicenter studies.

Family-specific chemical profiles provide potential kin recognition cues in the sexually cannibalistic spider Argiope bruennichi.

Kin recognition, the ability to detect relatives, is important for cooperation, altruism and also inbreeding avoidance. A large body of research on kin recognition mechanisms exists for vertebrates and insects, while little is known for other arthropod taxa. In spiders, nepotism has been reported in social and solitary species. However, there are very few examples of kin discrimination in a mating context, one coming from the orb-weaver Argiope bruennichi. Owing to effective mating plugs and high rates of sexual cannibalism, both sexes of A. bruennichi are limited to a maximum of two copulations. Males surviving their first copulation can either re-mate with the current female (monopolizing paternity) or leave and search for another. Mating experiments have shown that males readily mate with sisters but are more likely to leave after one short copulation as compared with unrelated females, allowing them to search for another mate. Here, we ask whether the observed behaviour is based on chemical cues. We detected family-specific cuticular profiles that qualify as kin recognition cues. Moreover, correlations in the relative amounts of some of the detected substances between sexes within families indicate that kin recognition is likely based on subsets of cuticular substances, rather than entire profiles.

Newborn screening for carnitine transporter defect in Bavaria and the long-term follow-up of the identified newborns and mothers: Assessing the benefit and possible harm based on 19 ½ years of experience.

Carnitine transporter defect (CTD) is a potentially life-threatening disorder causing acute metabolic decompensation, cardiac arrhythmia, and cardiac and skeletal myopathies. CTD is included in many newborn screening (NBS) programs. The screening parameter free carnitine, however, is influenced by maternal conditions due to placental transfer. This study reviewed the NBS results for CTD as part of a pilot study in Bavaria, Germany, and the long-term follow-up of the identified patients treated in our center between January 1999 and June 2018. Among 1,816,000 Bavarian NBS samples, six newborns were diagnosed with CTD (incidence of 1:302,667; positive predictive value (PPV) of 1.63% from 2008 to 2018). In the 24 newborns presented to our center for confirmatory testing, we detected four newborns and six mothers with CTD, one newborn and three mothers in whom CTD was presumed but not genetically confirmed, and one mother with glutaric aciduria type I. In 11 newborns, no indication for an inborn error of metabolism was found. The newborns and mothers with CTD had no serious cardiac adverse events or relevant muscular symptoms at diagnosis and during treatment for up to 14 years. Three mothers were lost to follow-up. Revealing a lower incidence than expected, our data confirm that NBS for CTD most likely misses newborns with CTD. It rather produces high numbers of false-positives and a low PPV picking up asymptomatic mothers with a diagnosis of uncertain clinical significance. Our data add to the growing evidence that argues against an implementation of CTD in NBS programs.

Tattoos - more than just colored skin? Searching for tattoo allergens.

During tattooing, a high amount of ink is injected into the skin. Tattoo inks contain numerous substances such as the coloring pigments, impurities, solvents, emulsifiers, and preservatives. Black amorphous carbon particles (carbon black), white titanium dioxide, azo or polycyclic pigments create all varieties of color shades in the visible spectrum. Some ingredients of tattoo inks might be hazardous and allergenic chemicals of unknown potential. In Germany, about 20 % of the general population is tattooed and related adverse reactions are increasingly reported. Since tattoo needles inevitably harm the skin, microorganisms can enter the wound and may cause infections. Non-allergic inflammatory reactions (for example cutaneous granuloma and pseudolymphoma) as well as allergic reactions may emerge during or after wound healing. Especially with allergies occurring after weeks, months or years, it remains difficult to identify the specific ingredient(s) that trigger the reaction. This review summarizes possible adverse effects related to tattooing with a focus on the development of tattoo-mediated allergies. To date, relevant allergens were only identified in rare cases. Here we present established methods and discuss current experimental approaches to identify culprit allergens in tattoo inks - via testing of the patient and in vitro approaches.

Subcutaneous vitamin B12 administration using a portable infusion pump in cobalamin-related remethylation disorders: a gentle and easy to use alternative to intramuscular injections.

BACKGROUND: Cobalamin (cbl)-related remethylation disorders are a heterogeneous group of inherited disorders comprising the remethylation of homocysteine to methionine and affecting multiple organ systems, most prominently the nervous system and the bone marrow. To date, the parenteral, generally intramuscular, lifelong administration of hydroxycobalamin (OHCbl) is the mainstay of therapy in these disorders. The dosage and frequency of OHCbl is titrated in each patient to the minimum effective dose in order to account for the painful injections. This may result in undertreatment, a possible risk factor for disease progression and disease-related complications. RESULTS: We describe parenteral administration of OHCbl using a subcutaneous catheter together with a portable infusion pump in a home therapy setting in four pediatric patients with remethylation disorders, two patients with cblC, one patient with cblG, and one patient with cblE deficiency, in whom intramuscular injections were not or no longer feasible. The placement of the subcutaneous catheters and handling of the infusion pump were readily accomplished and well accepted by the patients and their families. No adverse events occurred. The use of a small, portable syringe driver pump allowed for a most flexible administration of OHCbl in everyday life. The concentrations of total homocysteine levels were determined at regular patient visits and remained within the therapeutic target range. This approach allowed for the continuation of OHCbl therapy or the adjustment of therapy required to improve metabolic control in our patients. CONCLUSIONS: Subcutaneous infusion using a subcutaneous catheter system and a portable pump for OHCbl administration in combined and isolated remethylation disorders is safe, acceptable, and effective. It decreases disease burden in preventing frequent single injections and providing patient independence. Thus, it may promote long-term adherence to therapy in patients and parents.

Diagnostic Challenges Using a 2-Tier Strategy for Methylmalonic Acidurias: Data from 1.2 Million Dried Blood Spots.

BACKGROUND: The detection of methylmalonic acid (MMA) by second-tier analysis has been shown to reduce the number of false positives in newborn screening (NBS) for genetically determined methylmalonic acidurias (MMAuria). In addition to genetic conditions, MMA is an indicator of vitamin B12 status, thus applicable to detect maternal vitamin B12 deficiency in the newborns screened. METHODS: Biochemical and clinical follow-up data of a 7.5-year pilot study with 1.2 million newborns screened were reviewed. RESULTS: Among 1,195,850 NBS samples, 3,595 (0.3%) fulfilled criteria for second-tier analysis of MMA. In 37 (0.003%; 1/32,000) samples, elevated concentrations of MMA were detected, resulting in diagnostic workup at a metabolic center in 21 newborns. In 6 infants (1/199,000), genetic conditions were established, 1 infant with cobalamin C deficiency (CblC) showed only a moderate elevation of MMA. The remaining 15 newborns (1/79,000) displayed significantly lower concentrations of MMA and were evaluated for maternal vitamin B12 deficiency. In 9 mothers, vitamin B12 deficiency was verified, and 6 showed no indication for vitamin B12 deficiency. Treatment with vitamin B12 normalized biochemical parameters in all 15 infants. CONCLUSIONS: Applying a 2-tier strategy measuring MMA in NBS identified genetic conditions of MMAuria. It was possible to separate severe, early-onset phenotypes from maternal vitamin B12 deficiency. However, the detection of CblC deficiency with mildly elevated MMA interferes with impaired vitamin B12 status of unknown relevance and thus burdens possibly healthy newborns. Regarding maternal vitamin B12 deficiency, testing and supplementing mothers-to-be is preferable. This might decrease straining follow-up of newborns and improve quality and overall perception of NBS.

[Dietary treatment of inborn errors of metabolism-a balancing act between indulgence and therapy]. / Ernährung bei angeborenen Stoffwechselerkrankungen ­ ein Spagat zwischen Genuss und Therapie.

For many inborn metabolic diseases, a lifelong diet is a crucial part of the therapy since pharmacological therapy is available for only a few conditions and patients. The implementation of a low natural protein diet with a reduced intake of natural protein and the complementary use of synthetic amino acid mixtures is described using the examples of phenylketonuria and urea cycle disorders focusing on children and adolescents. For phenylketonuria, the amino acid supplement is free of phenylalanine whereas for urea cycle disorders, it exclusively consists of essential amino acids. The dietary treatment aims to maintain metabolic stability and to prevent accumulation of toxic metabolites. At the same time, the nutritional requirements to ensure growth and development must be met. Therefore, patients need to follow strict rules regarding the choice of food products. This restrictive therapy interferes with the desire for autonomy and the joy of eating and often results in a reduced quality of life.Following the diet is crucial for a favorable outcome. To meet its requirements, patients and their families are provided with training. It is a great challenge not only to support the patients and their families in all practical aspects of dietary management, but also to motivate them to lifelong adherence in order to ensure the best possible outcome.

Exogeneous Spatial Cueing beyond the Near Periphery: Cueing Effects in a Discrimination Paradigm at Large Eccentricities.

Although visual attention is one of the most thoroughly investigated topics in experimental psychology and vision science, most of this research tends to be restricted to the near periphery. Eccentricities used in attention studies usually do not exceed 20° to 30°, but most studies even make use of considerably smaller maximum eccentricities. Thus, empirical knowledge about attention beyond this range is sparse, probably due to a previous lack of suitable experimental devices to investigate attention in the far periphery. This is currently changing due to the development of temporal high-resolution projectors and head-mounted displays (HMDs) that allow displaying experimental stimuli at far eccentricities. In the present study, visual attention was investigated beyond the near periphery (15°, 30°, 56° Exp. 1) and (15°, 35°, 56° Exp. 2) in a peripheral Posner cueing paradigm using a discrimination task with placeholders. Interestingly, cueing effects were revealed for the whole range of eccentricities although the inhomogeneity of the visual field and its functional subdivisions might lead one to suspect otherwise.

Management of three preterm infants with phenylketonuria.

Providing adequate amounts of protein in preterm infants suffering from a metabolic disease that requires a reduced intake of natural protein is challenging. Phenylketonuria (PKU) is an inborn error of metabolism affecting the enzymatic conversion of phenylalanine to tyrosine. The dietary treatment of PKU aims to lower phenylalanine concentrations in the blood by implementing a low-phenylalanine diet restrictive in natural protein. We describe the nutritional management of three preterm infants, two with very low birth weight, with PKU detected by newborn screening. All three infants tolerated high amounts of phenylalanine; two were breastfed unrestrictedly during late prematurity. We show that nutrition of preterm infants with PKU according to recommendations of early and intensive nutrition with a high intake of protein is feasible even in infants with impaired enteral feeding. Due to a high phenylalanine tolerance of PKU infants during prematurity, there is no need for a phenylalanine-free parenteral amino acid mixture. During the catabolic state of prematurity preterm infants with PKU have phenylalanine requirements comparable to healthy preterm infants.

Feature prediction across eye movements is location specific and based on retinotopic coordinates.

With each saccadic eye movement, internal object representations change their retinal position and spatial resolution. Recently, we suggested that the visual system deals with these saccade-induced changes by predicting visual features across saccades based on transsaccadic associations of peripheral and foveal input (Herwig & Schneider, 2014). Here we tested the specificity of feature prediction by asking (a) whether it is spatially restricted to the previous learning location or the saccade target location, and (b) whether it is based on retinotopic (eye-centered) or spatiotopic (world-centered) coordinates. In a preceding acquisition phase, objects systematically changed their spatial frequency during saccades. In the following test phases of two experiments, participants had to judge the frequency of briefly presented peripheral objects. These objects were presented either at the previous learning location or at new locations and were either the target of a saccadic eye movement or not (Experiment 1). Moreover, objects were presented either in the same or different retinotopic and spatiotopic coordinates (Experiment 2). Spatial frequency perception was biased toward previously associated foveal input indicating transsaccadic learning and feature prediction. Importantly, while this pattern was not bound to the saccade target location, it was seen only at the previous learning location in retinotopic coordinates, suggesting that feature prediction probably affects low- or mid-level perception.