A novel mechanism to generate metallic single crystals.

Generally, the evolution of metallic single crystals is based on crystal growth. The single crystal is either produced by growing a seed single crystal or by sophisticated grain selection processes followed by crystal growth. Here, we describe for the first time a fully new mechanism to generate single crystals based on thermo-mechanically induced texture formation during additive manufacturing. The single crystal develops due to two different mechanisms. The first step is a standard grain selection process due to directional solidification, leading to a pronounced fiber texture. The second and new mechanism bases on successive thermo-mechanically induced plastic deformations and texture formation in FCC crystals under compression. During this second step, the columnar grain structure transforms into a single crystal by rotation of individual grains. Thus, the single crystal forms step by step by merging the originally columnar grain structure. This novel, stress induced mechanism opens up completely new perspectives to fabricate single crystalline components and to accurately adjust the orientation according to the load.

Potential efficacy of parent-infant psychotherapy with mothers and their infants from a high-risk population: a randomized controlled pilot trial.

BACKGROUND: Psychotherapy of mother-child dyads is an intervention which was developed to prevent maltreatment and negative children's development. There is a lack of good-quality research investigating psychotherapeutic interventions and social care for mothers at high-risk living in Mother-Child Facilities in Germany. The present randomized controlled pilot trial (RCT) aimed to evaluate the need for parent-infant psychotherapy (PIP) and to explore its impact on the mother-infant relationship. Primary feasibility objectives were recruitment and attrition, with potential efficacy defined as the secondary feasibility objective. METHODS: This pilot RCT focused on (young) mothers with cumulative risk factors and their infants under 7 months of age living in Mother-Child Facilities. N=32 mother-child dyads were randomly allocated to PIP or Care as usual (CAU). Outcomes were assessed at baseline, 3 months, and 6 months of intervention. The primary potential efficacy outcome was maternal sensitivity. Secondary outcomes were maternal mental health problems, reflective functioning, parenting stress, personality organization, infant's development, and attachment. RESULTS: At baseline, all mothers showed low levels of emotional availability, but results revealed improvements in sensitivity, mental health problems, stress, and depressive symptomatology favoring PIP after 6 months. Positive developments in maternal sensitivity, a healthy aspect of mother-child interaction, were only found in the PIP group. Overall attrition was high at 6 months. Some evidence of fewer depressive symptoms and lower maternal distress after 6 months of PIP-intervention exists that did not reach significance. CONCLUSION: Findings revealed improvements in the mother's well-being for both groups, but PIP had a higher impact on the mother-child dyad. In sum, there is some evidence that PIP may represent an effective intervention offer besides the social and pedagogical support in these facilities, but further research is demanded. TRIAL REGISTRATION: DRKS00022485 (retrospectively registered).

Occurrence and determinants of parental psychosocial stress and mental health disorders in parents and their children in early childhood: rationale, objectives, and design of the population-based SKKIPPI cohort study.

PURPOSE: The postnatal period is a vulnerable time for parents and children but epidemiological and health care utilisation data for Germany on parental mental health during early childhood is scarce. This protocol describes the rationale, aim and study design of a population-based cohort study to assess the occurrence and determinants of psychosocial stress and mental health disorders, as well as the use and cost of health care and social services in early childhood. METHODS: As part of the collaborative SKKIPPI project, we will contact a random sample of 30,000 infants listed in the residents' registration offices of three German towns and we expect to include 6,000 mother-child pairs. Both parents are invited to fill out an online screening questionnaire. Mothers with indications of psychosocial stress will be interviewed to assess mental health disorders, regulatory problems of their children, as well as health care and social services utilisation, with a follow-up assessment after 6 months. RESULTS: After description of sociodemographic and health data, we will analyse occurrences, patterns, and potential determinants (maternal age, social status, household factors, migration status etc.) of psychosocial stress and mental health disorders in the mothers and their children in early childhood. CONCLUSIONS: Our study will identify potential risk and protective factors for postnatal mental health and health care utilization of psychosocially burdened families. This will help to improve prevention and treatment strategies to strengthen the parent-child relationship, to reduce persisting vulnerability of children, and to improve health care and social services. TRIAL REGISTRATION: The study has been registered in the German Clinical Trial Registry on February 8th 2019 (DRKS-ID: DRKS00016653).

Nanoscaled eutectic NiAl-(Cr,Mo) composites with exceptional mechanical properties processed by electron beam melting.

Eutectic NiAl-(Cr,Mo) composites are promising high temperature materials due to their high melting point, excellent oxidation behavior and low density. To enhance the strength, hardness and fracture toughness, high cooling rates are beneficial to obtain a fine cellular-lamellar microstructure. This can be provided by the additive process of selective electron beam melting. The very high temperature gradient achieved in this process leads to the formation of the finest microstructure that has ever been reported for NiAl-(Cr,Mo) in-situ composites. A very high hardness and fracture toughening mechanisms were observed. This represents a feasibility study towards additive manufacturing of eutectic NiAl-(Cr,Mo) in-situ composites by selective electron beam melting.

Efficacy of Parent-Infant-Psychotherapy with mothers with postpartum mental disorder: study protocol of the randomized controlled trial as part of the SKKIPPI project.

BACKGROUND: After the birth of a child, many mothers and fathers experience postpartum mental disorders like depression, anxiety, obsessive-compulsive disorder, stress or other illnesses. This endangers the establishment of a secure attachment between the children and their primary caregivers. Early problems in parent-child interaction can have adverse long-term effects on the family and the child's well-being. In order to prevent a transgenerational transmission of mental disorders, it is necessary to evaluate psychotherapeutic interventions that target psychologically burdened parents of infants or toddlers. The aim of this trial is to investigate the efficacy of Parent-Infant-Psychotherapy (PIP) for mothers with postpartum mental disorder and their infants (0-12 months). METHODS/DESIGN: In this open, randomized controlled intervention trial 180 mother-infant-dyads will be included and randomly allocated to 12 sessions of PIP or care as usual. The interventions take place either in inpatient adult psychiatric departments or in outpatient settings with home visits. The primary outcome is the change in maternal sensitivity assessed by the Sensitivity subscale of the Emotional Availability Scale (EAS) through videotaped dyadic play-interactions after 6 weeks. Secondary outcomes are maternal psychopathology, stress, parental reflective functioning, infant development and attachment after 6 weeks and 12 months. In addition, maternal attachment (AAI) and reflective functioning (AAI) will be analyzed as potential moderators, and resource usage in the German health system as well as associated costs will be evaluated. DISCUSSION: There is increasing demand for well-controlled studies on psychotherapeutic interventions in the postpartum period that do not only focus on particular risk groups. This randomized controlled trial (RCT) represents one of the first studies to investigate the efficacy of PIP in inpatient psychiatric departments and outpatient care centers in Germany. The results will fill knowledge gaps on the factors contributing to symptom reduction in postpartum mental disorders and improvements in mother-child relationships and help in developing preventive and therapeutic strategies for the fragmented German health care system. TRIAL REGISTRATION: German Register for Clinical Trials, ID: DRKS00016353.

[Concepts in geriatric uro-oncology]. / Uroonkologische Konzepte im Alter.

Uro-oncology is not only concerned with treatment methods themselves but also with therapeutic objectives and decision-making concepts involving algorithms. We discuss whether the latter is applicable to all patients groups or needs to be adapted in order to be suitable for elderly and frail patients with regard to their lifestyle and living situation as well as their altered physiology.

[Patient with a Fontan circulation undergoing caesarean section: Anesthesiological management]. / Sectio caesarea bei einer Patientin mit Fontan-Zirkulation : Anästhesiologisches Management.

Adults suffering from congenital heart diseases (CHD) represent a challenge to anesthesiologists because of the diverse pathologies, complex pathophysiology and special treatment strategies. Due to improved therapeutic options for CHD, patient quality of life and life expectancy is increasing, leaving them as a growing population including pregnant patients with CHD. This article presents the main principles of the pathophysiology and anesthesiological management of pregnant patients living with a Fontan circulation based on a case report, which was complicated by an aortic coarctation and atonic uterine hemorrhage.

Non-reproductive Effects of Anovulation: Bone Metabolism in the Luteal Phase of Premenopausal Women Differs between Ovulatory and Anovulatory Cycles.

Introduction: Several authors have linked subclinical ovulatory disturbances in normal length menstrual cycles to premenopausal fracture risk and bone changes. This study systematically examined the influence of ovulation and anovulation on the bone metabolism of premenopausal women. Participants and Methods: In 176 cycles in healthy premenopausal women, FSH, 17ß-estradiol (E2) and progesterone (P4) as well as bone alkalic phosphatase (BAP), pyridinoline (PYD) and C-terminal crosslinks (CTX) were measured during the follicular and during the luteal phase. The probability and timing of ovulation was self-assessed by a monitoring device. In addition, bone density of the lumbar spine was measured by quantitative computed tomography (QCT) at baseline and at the end of the study. Analysis was restricted to blood samples taken more than three days before the following menstruation. Results: 118 cycles out of the 176 collected cycles were complete with blood samples taken within the correct time interval. Of these, 56.8 % were ovulatory by two criteria (ovulation symbol shown on the monitor display and LP progesterone > 6 ng/ml), 33.1 % were possibly ovulatory by one criterion (ovulation symbol shown on the monitor display or LP progesterone > 6 ng/ml), and 10.2 % were anovulatory by both criteria). Ovulation in the previous cycle and in the same cycle did not significantly influence the mean absolute concentrations of the bone markers. However, bone formation (BAP) was higher in the luteal phase of ovulatory cycles than in anovulatory cycles (n. s.) and the relative changes within one cycle were significantly different for bone resorption (CTX) during ovulatory vs. anovulatory cycles (p < 0.01). In 68 pairs of cycles following each other directly, both ovulation in the previous cycle and ovulation in the present cycle influenced CTX, but not the differences of other bone markers. Conclusion: Ovulatory cycles reduce bone resorption in their luteal phase and that of the following cycle. The interaction between ovulation and bone metabolism is complex. Since anovulation may occur in low estrogen states such as pre-anorexic dietary restraint, as well as with high estrogenic circumstances e.g. from functional perimenopausal ovarian cysts, the association with bone changes has been variable in the literature. Accumulating physiological and clinical evidence however point towards a role for ovulation in enhancing bone formation and limiting bone resorption.

[Anesthesiology: partner or competitor?]. / Anästhesie: Partner oder Konkurrent?

Surgery and anesthesiology have always been closely connected. Within the increasing complexity of therapies and technical capabilities both subjects overlap in certain areas. This article deals with the question whether anesthesiology is acting as a partner or competitor in the cooperation with the various operative specialties. In several studies it has been shown that the outcome of surgical patients can be improved by communication and interaction with anesthesiology and that forming multidisciplinary teams will be highly beneficial for patients in intensive care units.

Unrestricted quality of seeds in European broad-leaved tree species growing at the cold boundary of their distribution.

BACKGROUND AND AIMS: The low-temperature range limit of tree species may be determined by their ability to produce and disperse viable seeds. Biological processes such as flowering, pollen transfer, pollen tube growth, fertilization, embryogenesis and seed maturation are expected to be affected by cold temperatures. The aim of this study was to assess the quality of seeds of nine broad-leaved tree species close to their elevational limit. METHODS: We studied nine, mostly widely distributed, European broad-leaved tree species in the genera Acer, Fagus, Fraxinus, Ilex, Laburnum, Quercus, Sorbus and Tilia. For each species, seeds were collected from stands close to optimal growth conditions (low elevation) and from marginal stands (highest elevation), replicated in two regions in the Swiss Alps. Measurements included seed weight, seed size, storage tissue quality, seed viability and germination success. KEY RESULTS: All species examined produced a lot of viable seeds at their current high-elevation range limit during a summer ranked 'normal' by long-term temperature records. Low- and high-elevation seed sources showed hardly any trait differences. The concentration of non-structural carbohydrates tended to be higher at high elevation. Additionally, in one species, Sorbus aucuparia, all measured traits showed significantly higher seed quality in high-elevation seed sources. CONCLUSIONS: For the broad-leaved tree taxa studied, the results are not in agreement with the hypothesis of reduced quality of seeds in trees at their high-elevation range limits. Under the current climatic conditions, seed quality does not constitute a serious constraint in the reproduction of these broad-leaved tree species at their high-elevation limit.

[Ex-vivo-chemoresponse testing of head and neck cancer: an old hat?]. / Ex-vivo-Chemoresponsetestung von Kopf-Hals-Tumoren: Ein alter Hut?

Reliable prediction of the chance of a successful treatment of head and neck squamous cell carcinoma by cytostatics and targeting therapies would be very valuable, since HNSCC due to their heterogenic biology mostly respond non-uniformly and moreover with low response rates. To raise the prospect of chemotherapy by using multimodal therapies usually goes hand in hand with a higher incidence of severe adverse events and acute toxicity but also chemo-associated increased cancer risk following successful treatment. In addition, the increasing numbers of treatment options without availability of reliable prognostic biomarkers for a probably successful outcome make the decision for one or the other medication to something rather like gambling. Therefore, quite early a pre-therapeutic predictive exvivo chemoresponse testing of bioptic specimens was intended. However, the results gained mostly were disillusioning and allowed not for reliable prediction of chance of successful outcome of treatment with tolerable doses of the pharmaceuticals and in particular their combinations. Predictive testing, hence, was belittled as improper for the clinical context. Based on advanced methods, some working groups reassume this subject. This review describes recent advances in ex-vivo chemoresponse testing, discusses pre-requisites which have to be fulfilled before their inclusion into decision-making, and outlines why ex-vivo chemoresponse testing probably is not an old hat.

Water relations of climbing ivy in a temperate forest.

Ivy (Hedera helix) is the most important liana in temperate European forests. We studied water relations of adult ivy in a natural, 35 m tall mixed deciduous forest in Switzerland using a construction crane to access the canopy. Predawn leaf water potential at the top of climbing ivy ranged from -0.4 to -0.6 MPa, daily minima ranged from -1.3 to -1.7 MPa. Leaf water potentials as well as relative sap flow were held surprisingly constant throughout different weather conditions, suggesting a tendency to isohydric behaviour. Maximum stomatal conductance was 200 mmol m⁻² s⁻¹. The use of a potometer experiment allowed us to measure absolute transpiration rates integrated over a whole plant of 0.23 mmol m⁻² s⁻¹. Nightly sap flow of ivy during warm, dry nights accounted for up to 20% of the seasonal maximum. Maximum sap flow rates were reached at ca. 0.5 kPa vpd. On the other hand, the host trees showed a less conservative stomatal regulation, maximum sap flow rates were reached at vpd values of ca. 1 kPa. Sap flow rates of ivy decreased by ca. 20% in spring after bud break of trees, suggesting that ivy profits strongly from warm sunny days in early spring before budbreak of the host trees and from mild winter days. This species may benefit from rising winter temperatures in Europe and thus become a stronger competitor against its host trees.

Correlation of enzyme activity and clinical phenotype in POMT1-associated dystroglycanopathies.

BACKGROUND: Mutations in protein O-mannosyltransferases (POMTs) cause a heterogeneous group of muscular dystrophies with abnormal glycosylation of alpha-dystroglycan (dystroglycanopathies). The wide spectrum of clinical severities ranges from Walker-Warburg syndrome (WWS), associated with brain and eye abnormalities, to mild forms of limb girdle muscular dystrophy (LGMD). OBJECTIVE: The aim of this study was to elucidate the impact of mutations in POMT1 on the clinical phenotype. METHODS: We examined 2 patients with POMT1-associated alpha-dystroglycanopathy, 1 displaying a LGMD2K and 1 with a WWS phenotype. Using dermal fibroblasts, we analyzed the influence of the POMT1 mutations on the glycosylation status of alpha-dystroglycan, protein O-mannosyltransferase activity, and the stability of the mutant POMT1 protein. RESULTS: We report on novel compound heterozygous mutations in POMT1 (p.L171A and p.A589VfsX38) that result in LGMD2K. We further demonstrate that a homozygous splice site mutation of a recently identified WWS patient results in POMT1 p.del77-93. Using dermal fibroblasts, we show that mannosyltransferase activity is reduced in the patients and that stability of POMT1 mutant proteins p.A589VfsX38 and p.del77-93 is significantly decreased. CONCLUSIONS: Our results suggest that dermal fibroblasts can be applied to facilitate the diagnostic analysis of dystroglycanopathy patients as well as to study the pathogenic mechanism of POMT mutations. Characterization of the POMT1 substrate protein alpha-dystroglycan and POMT in vitro mannosyltransferase activity shows that the severity of the clinical phenotype of the patients analyzed is inversely correlated with POMT activity.

Interactive effects of plant species diversity and elevated CO2 on soil biota and nutrient cycling.

Terrestrial ecosystems consist of mutually dependent producer and decomposer subsystems, but not much is known on how their interactions are modified by plant diversity and elevated atmospheric CO2 concentrations. Factorially manipulating grassland plant species diversity and atmospheric CO2 concentrations for five years, we tested whether high diversity or elevated CO2 sustain larger or more active soil communities, affect soil aggregation, water dynamics, or nutrient cycling, and whether plant diversity and elevated CO2 interact. Nitrogen (N) and phosphorus (P) pools, symbiotic N2 fixation, plant litter quality, soil moisture, soil physical structure, soil nematode, collembola and acari communities, soil microbial biomass and microflora community structure (phospholipid fatty acid [PLFA] profiles), soil enzyme activities, and rates of C fluxes to soils were measured. No increases in soil C fluxes or the biomass, number, or activity of soil organisms were detected at high plant diversity; soil H2O and aggregation remained unaltered. Elevated CO2 affected the ecosystem primarily by improving plant and soil water status by reducing leaf conductance, whereas changes in C cycling appeared to be of subordinate importance. Slowed-down soil drying cycles resulted in lower soil aggregation under elevated CO2. Collembola benefited from extra soil moisture under elevated CO2, whereas other faunal groups did not respond. Diversity effects and interactions with elevated CO2 may have been absent because soil responses were mainly driven by community-level processes such as rates of organic C input and water use; these drivers were not changed by plant diversity manipulations, possibly because our species diversity gradient did not extend below five species and because functional type composition remained unaltered. Our findings demonstrate that global change can affect soil aggregation, and we advocate that soil aggregation should be considered as a dynamic property that may respond to environmental changes and feed back on other ecosystem functions.

The normal phenotype of Pmm1-deficient mice suggests that Pmm1 is not essential for normal mouse development.

Phosphomannomutases (PMMs) are crucial for the glycosylation of glycoproteins. In humans, two highly conserved PMMs exist: PMM1 and PMM2. In vitro both enzymes are able to convert mannose-6-phosphate (mannose-6-P) into mannose-1-P, the key starting compound for glycan biosynthesis. However, only mutations causing a deficiency in PMM2 cause hypoglycosylation, leading to the most frequent type of the congenital disorders of glycosylation (CDG): CDG-Ia. PMM1 is as yet not associated with any disease, and its physiological role has remained unclear. We generated a mouse deficient in Pmm1 activity and documented the expression pattern of murine Pmm1 to unravel its biological role. The expression pattern suggested an involvement of Pmm1 in (neural) development and endocrine regulation. Surprisingly, Pmm1 knockout mice were viable, developed normally, and did not reveal any obvious phenotypic alteration up to adulthood. The macroscopic and microscopic anatomy of all major organs, as well as animal behavior, appeared to be normal. Likewise, lectin histochemistry did not demonstrate an altered glycosylation pattern in tissues. It is especially striking that Pmm1, despite an almost complete overlap of its expression with Pmm2, e.g., in the developing brain, is apparently unable to compensate for deficient Pmm2 activity in CDG-Ia patients. Together, these data point to a (developmental) function independent of mannose-1-P synthesis, whereby the normal knockout phenotype, despite the stringent conservation in phylogeny, could be explained by a critical function under as-yet-unidentified challenge conditions.

CDG-Id caused by homozygosity for an ALG3 mutation due to segmental maternal isodisomy UPD3(q21.3-qter).

We report on a patient with a congenital disorder of glycosylation type Id (CDG-Id) caused by a homozygous mutation in the ALG3 gene, which results from a de novo mutation in combination with a segmental maternal uniparental isodisomy (UPD). The patient presented with severe psychomotor delay, primary microcephaly, and opticus atrophy, compatible with a severe form of CDG. Isoelectric focusing of transferrin showed a type I pattern and lipid-linked oligosaccharide analysis showed an accumulation of dol-PP-GlcNAc2Man5 in patient's fibroblasts suggesting a defect in the ALG3 gene. A homozygous ALG3 missense mutation p.R266C (c.796C > T) was identified. Further evaluation revealed that neither the mother nor the father were carrier of the p.R266C mutation. Marker analysis revealed a segmental maternal isodisomy for the chromosomal region 3q21.3-3qter. UPD for this region has not been described before. More important, the combination of UPD with a de novo mutation is an exceptional coincidence and an extraordinary observation.

No down-regulation of leaf photosynthesis in mature forest trees after three years of exposure to elevated CO2.

The photosynthetic responses of six species of mature forest trees to long-term exposure to elevated CO2 (ca. 530 ppm) were determined at the Swiss Canopy Crane (SCC) site near Basel, Switzerland. In the third year of growth in elevated CO2, using web-FACE technology, net photosynthesis (As) in fully sunlit, upper canopy foliage was stimulated by ca. 40% compared to ambient controls. This enhancement did not differ from the instantaneous increase in As found in ambient-grown leaves that were temporarily measured at elevated CO2. A complete lack of down-regulation of photosynthesis was found in all species and in both the early and the late growing season. Neither was leaf nitrogen content significantly affected by long-term exposure to elevated CO2. Our results document a persistent enhancement in leaf level photosynthesis in response to elevated CO2 in mature forest trees over a period of three years. Circumstantial evidence suggests that the additional assimilates feed into large sinks other than stem and shoot growth.

Water relations in grassland and desert ecosystems exposed to elevated atmospheric CO2.

Atmospheric CO2 enrichment may stimulate plant growth directly through (1) enhanced photosynthesis or indirectly, through (2) reduced plant water consumption and hence slower soil moisture depletion, or the combination of both. Herein we describe gas exchange, plant biomass and species responses of five native or semi-native temperate and Mediterranean grasslands and three semi-arid systems to CO2 enrichment, with an emphasis on water relations. Increasing CO2 led to decreased leaf conductance for water vapor, improved plant water status, altered seasonal evapotranspiration dynamics, and in most cases, periodic increases in soil water content. The extent, timing and duration of these responses varied among ecosystems, species and years. Across the grasslands of the Kansas tallgrass prairie, Colorado shortgrass steppe and Swiss calcareous grassland, increases in aboveground biomass from CO2 enrichment were relatively greater in dry years. In contrast, CO2-induced aboveground biomass increases in the Texas C3/C4 grassland and the New Zealand pasture seemed little or only marginally influenced by yearly variation in soil water, while plant growth in the Mojave Desert was stimulated by CO2 in a relatively wet year. Mediterranean grasslands sometimes failed to respond to CO2-related increased late-season water, whereas semiarid Negev grassland assemblages profited. Vegetative and reproductive responses to CO2 were highly varied among species and ecosystems, and did not generally follow any predictable pattern in regard to functional groups. Results suggest that the indirect effects of CO2 on plant and soil water relations may contribute substantially to experimentally induced CO2-effects, and also reflect local humidity conditions. For landscape scale predictions, this analysis calls for a clear distinction between biomass responses due to direct CO2 effects on photosynthesis and those indirect CO2 effects via soil moisture as documented here.

Improvement of CDG diagnosis by combined examination of several glycoproteins.

Congenital disorders of glycosylation (CDG) represent a family of genetic diseases with broad clinical presentation. Initial diagnosis is currently mainly based on the identification of hyposialylated serum transferrin (TF) by isoelectric focusing (IEF). To improve the diagnosis of known CDG types and to identify so far unknown CDG cases, additional glycoproteins, alpha1-antitrypsin titrypsin (alpha1-AT) and alpha1-antichymotrypsin (alpha1-ACT), were studied. According to the patterns of transferrin, enzyme assays and mutation analysis, 16 patients with various clinical symptoms suspicious for CDG were divided into three groups: group A (n = 6) with confirmed CDG; group B (n = 4) with clear abnormal TF-IEF patterns of unknown origin (all known CDG types were excluded) and group C (n = 6) with borderline TF-IEF patterns; 164 samples served as a control group. Automated IEF of TF, alpha1-AT and alpha1-ACT was carried out using a PhastSystem. CDG patients with glycosylation defects of known origin (group A) and patients with abnormal TF-IEF patterns due to glycosylation defects of as yet unknown origin (group B) showed abnormal IEF patterns of all three glycoproteins. These results confirmed generalized defects of glycosylation. Furthermore, the IEF pattern of alpha1-ACT seems to allow a differentiation between CDG Ia and CDG Ic. However, patients with borderline TF-IEF pattern (group C) showed a normal alpha1-AT-IEF pattern. Four of these six patients also showed a normal alpha1-ACT-IEF pattern; this constellation suggests that CDG can most likely be excluded. In the two remaining patients of group C with a borderline TF-IEF pattern an abnormal pattern of alpha1-ACT-IEF was obtained which needs further investigations. We conclude that the combined investigation of three glycoproteins provides additional information in the diagnostic work-up of patients with possible CDG. The suspicion of CDG in patients with apparent glycosylation defects of unknown origin or borderline TF-IEF pattern can be either substantiated or weakened.