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Since the properties of functional materials are highly dependent on their specific structure, and since the structural changes, for example during crystallization, induced by coating and annealing processes are significant, the study of structure and its formation is of interest for fundamental and applied science. However, structure analysis is often limited to ex situ determination of final states due to the lack of specialized sample cells that enable real‐time investigations. The lack of such cells is mainly due to their fairly complex design and geometrical restrictions defined by the beamline setups. To overcome this obstacle, an advanced sample cell has been designed and constructed; it combines automated doctor blading, solvent vapor annealing and sample hydration with real‐time grazing‐incidence wide‐ and small‐angle scattering (GIWAXS/GISAXS) and X‐ray reflectivity (XRR). The sample cell has limited spatial requirements and is therefore widely usable at beamlines and laboratory‐scale instruments. The cell is fully automatized and remains portable, including the necessary electronics. In addition, the cell can be used by interested scientists in cooperation with the Institute for Crystallography and Structural Physics and is expandable with regard to optical secondary probes. Exemplary research studies are presented, in the form of coating of P3HT:PC61PM thin films, solvent vapor annealing of DRCN5T:PC71BM thin films, and hydration of supported phospholipid multilayers, to demonstrate the capabilities of the in situ cell. A description of a flexible sample cell for time‐resolved grazing‐incidence X‐ray scattering and X‐ray reflectivity measurements is presented. The cell is especially designed for studying drying kinetics, solvent vapor annealing and hydration processes. [ABSTRACT FROM AUTHOR]

Pathogenic variants in the DHCR7 gene cause Smith-Lemli-Opitz syndrome (SLOS), a defect of cholesterol biosynthesis resulting in an autosomal recessive congenital metabolic malformation disorder. In approximately 4% of patients, the second mutation remains unidentified. In this study, 12 SLOS patients diagnosed clinically and/or by elevated 7-dehydrocholesterol (7-DHC) have been investigated by customized multiplex ligation-dependent probe amplification (MLPA) analysis, because only one DHCR7 sequence variant has been detected. Two unrelated patients of this cohort carry different large deletions in the DHCR7 gene. One patient showed a deletion of exons 3-6. The second patient has a deletion of exons 1 and 2 (non-coding) and lacks the major part of the promoter. These two patients show typical clinical and biochemical phenotypes of SLOS. Second disease-causing mutations are p.(Arg352Trp) and p.(Thr93Met), respectively. Deletion breakpoints were characterized successfully in both cases. Such large deletions are rare in the DHCR7 gene but will resolve some of the patients in whom a second mutation has not been detected. [ABSTRACT FROM AUTHOR]

Human leukocyte antigen B (HLA-B) is responsible for presenting peptides to immune cells and plays a critical role in normal immune recognition of pathogens. A variant allele, HLA-B*57:01, is associated with increased risk of a hypersensitivity reaction to the anti-HIV drug abacavir. In the absence of genetic prescreening, hypersensitivity affects ~6% of patients and can be life-threatening with repeated dosing. We provide recommendations (updated periodically at http://www.pharmkgb.org) for the use of abacavir based on HLA-B genotype. [ABSTRACT FROM AUTHOR]

The article offers information about the computer program named ANKAphase which processes X-ray inline phase-contrast radiographs. The authors state that the program uses a single-distance non-iterative phase-retrieval described by David Paganin and his colleagues. They state that it is valid only for monochromatic illumination and single-material objects and is designed to be applied to tomography data.

The content of coenzyme Q10 (CoQ(10)) was examined in skin fibroblasts of 10 patients with mevalonic aciduria (MVA) and of 22 patients with methylmalonic aciduria (MMA). Patients with these inborn errors of metabolism are thought to be at risk for CoQ(10) depletion either by direct inhibition of the proximal pathway of CoQ(10) synthesis (MVA) or indirectly by inhibition of mitochondrial energy metabolism (MMA). We demonstrated that CoQ(10) concentrations were not significantly different from controls in MVA patients, suggesting that there may be upregulatory effects. On the other hand the CoQ(10) content in fibroblasts of patients with MMA was significantly reduced. [ABSTRACT FROM AUTHOR]

Objective:: Alkaptonuria (AKU) is a rare inborn error of metabolism of aromatic amino acids and considered to be an autosomal recessive trait caused by mutations in the homogentisate 1,2-dioxygenase ( HGD) gene. A dominant pattern of inheritance has been reported but was attributed to extended consanguinity in many cases. However, we have observed a non-consanguineous family segregating AKU in a dominant manner over three generations. Results:: All affected individuals presented with typical features of AKU including darkening of the urine, ochronosis, arthropathy, and elevated urinary excretion of homogentisic acid. Sequence analysis of the HGD gene from genomic DNA of two affected individuals, uncle and niece, revealed a heterozygous missense mutation (M368V) in the uncle that was not present in his niece. Microsatellite genotyping demonstrated that both were heterozygous at the HGD locus and shared one haplotype. This haplotype did not contain a detectable HGD mutation. The haplotype was also found in a healthy son of the niece, making a dominant HGD mutation unlikely. Moreover, sequencing of cDNA from lymphoblastoid cells of the niece did not reveal an HGD mRNA with a potentially dominant-negative effect. Conclusion:: Rare causes of the uncommon AKU inheritance in this family have to be considered, ranging from the coincidence of undetectable HGD mutations to a dominant mutation of a second, hitherto unknown AKU gene. [ABSTRACT FROM AUTHOR]

Fungi, above all filamentous fungi, can occur almost everywhere, even in water. They can grow in such a quantity in water that they can affect the health of the population or have negative effects on food production. There are several reports of fungal growth in water from different countries, but to our knowledge none from Austria so far. The aim of this study was to gain an overview of the spectrum of filamentous fungi and yeasts in drinking water systems. Thirty-eight water samples from drinking water and groundwater were analysed. Fungi were isolated by using membrane filtration and plating method with subsequent cultivation on agar plates. The different taxa of fungi were identified using routine techniques as well as molecular methods. Fungi were isolated in all water samples examined. The mean value for drinking water was 9.1 CFU per 100 ml and for groundwater 5400 CFU per 100 ml. Altogether 32 different taxa of fungi were found. The taxa which occurred most frequently were Cladosporium spp., Basidiomycetes and Penicillium spp. (74.6%, 56.4% and 48.7%, respectively). This study shows that drinking water can be a reservoir for fungi, among them opportunists, which can cause infections in immunosuppressed patients. [ABSTRACT FROM AUTHOR]

The diagnostic biochemical hallmarks of Smith–Lemli–Opitz syndrome (SLOS) are elevated concentrations of the cholesterol precursors 7- and 8dehydrocholesterol (7- and 8-DHC). We describe a patient with classical SLOS phenotype and oesophageal achalasia, which has not been reported in SLOS patients before. Plasma 7-DHC and 8-DHC were only marginally elevated. The diagnosis was confirmed by sterol analysis in cultured skin fibroblasts and mutation analysis. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To describe biochemical findings and the spectrum of mevalonate kinase (MVK) gene mutations as well as an associated TNFRSF1A low-penetrance variant in a series of patients with clinical features of the hyperimmunoglobulinemia D with periodic fever syndrome (HIDS). METHODS: The MVK gene was sequenced in 8 children and 1 adult (including 2 siblings) fulfilling the clinical criteria for HIDS. In addition, sequencing of exons 2, 3, 4, and 6 of the TNFRSF1A gene was performed in patients with only one or no MVK mutation. Mevalonate kinase (MK) enzyme activity in leukocytes and renal excretion of mevalonic acid were also measured. RESULTS: Mutations in the coding region of the MVK gene were detected in 6 patients, and the most common mutation was V377I. Among these patients were 2 novel mutations, both of which were located in exon 6. These novel mutations resulted in the substitution of tryptophan (TGG) by a stop codon (TGA) at amino acid position 188 (W188X) and in the exchange of valine (GTG) for alanine (GCG) at amino acid position 203 (V203A). In 1 patient, a combination of one MVK (V377I) mutation and one TNFRSF1A (R92Q) mutation was present. The patient's clinical phenotype resembled a mixture of variant-type HIDS and tumor necrosis factor receptor-associated periodic syndrome (TRAPS). Her IgD values varied between normal and slightly increased, and the MK activity was in the low-normal range, while urinary mevalonate concentrations were always normal. CONCLUSION: The genotype findings indicate that a relatively small number of genes may be involved in the clinical manifestation of HIDS, with low-penetrance TNFRSF1A variants possibly influencing the HIDS phenotype or MVK mutations contributing to TRAPS. [ABSTRACT FROM AUTHOR]

Anaerobic growth of Pseudomonas aeruginosa on nitrate or arginine requires the anr gene, which codes for a positive control element (ANR) capable of functionally complementing an fnr mutation in Escherichia coli. The anr gene was sequenced; it showed 51% identity with the fnr gene at the amino acid sequence level. Four cysteine residues known to be essential in the FNR protein are conserved in ANR. The anr gene product (deduced M, 27129) was visualized by the maxicell method and migrated like a 32 kDa protein in gel electrophoresis under denaturing conditions. An anr mutant of P. aeruginosa constructed by gene replacement was defective in nitrate respiration, arginine deiminase activity, and hydrogen cyanide biosynthesis, underscoring the diverse metabolic functions of ANR during oxygen limitation. Pseudomonas fluorescens, Pseudomonas putida, Pseudomonas syringae, and Pseudomonas mendocina all had a functional analogue of ANR, indicating that similar anaerobic control mechanisms exist in these bacteria. [ABSTRACT FROM AUTHOR]

Introduction of the recombinant cosmid pME3090 into Pseudomonas fluorescens strain CHA0, a good biocontrol agent of various diseases caused by soilborne pathogens, increased three- to five-fold the production of the antibiotic metabolites pyoluteorin (Plt) and 2,4-diacetylphloroglucinol (Phl) in vitro. Strain CHA0/pME3090 also overproduced Plt and Phl in the rhizosphere of wheat infected or not infected with Pythium ultimum. The biocontrol activity of the wild-type and recombinant strains was compared using various plant pathogen-host combinations in a gnotobiotic system. Antibiotic overproduction affected neither the protection of wheat against P. ultimum and Gaeumannomyces graminis var. tritici nor the growth of wheat plants. In contrast strain CHA0/pME3090 showed an increased capacity to protect cucumber against Fusarium oxysporum f.sp. cucumerinum and Phomopsis sclerotioides compared with the wild-type strain CHA0. The antibiotic overproducing strain protected tobacco roots significantly better against Thielaviopsis basicola than the wild-type strain but drastically reduced the growth of tobacco plants and was also toxic to the growth of sweet corn. On King's B agar and on malt agar, the recombinant strain CHA0/pME3090 inhibited all pathogens more than did the parental strain CHA0. Synthetic Plt and Phl were toxic to all fungi tested. Tobacco and sweet corn were more sensitive to synthetic Plt and Phl than were cucumber and wheat. There was no correlation between the sensitivity of the pathogens to the synthetic antibiotics and the degree of disease suppression by strain CHA0-pME3090. However, there was a correlation between the sensitivity of the plants and the toxicity of the recombinant strain. We conclude that the plant species rather than the pathogen determines whether cosmid pME3090 in P. fluorescens strain CHA0 leads to improved disease suppression. [ABSTRACT FROM AUTHOR]

Interestingly, the subgroup analysis found that only women receiving oral progestogen, and not those receiving vaginal progestogen, had a higher LBR. The secondary outcome of miscarriage was consistent with the LBR results, with vaginal progestogen again providing no benefit, although oral progestogen did decrease the miscarriage risk. Four of the five studies that evaluated oral progestogen used a synthetic progestin, dydrogesterone, which is not available in the USA or potentially other countries. [Extracted from the article]

Summary: Deficiency of succinic semialdehyde dehydrogenase (SSADH) is a rare neurometabolic disorder with accumulation of 4-hydroxybutyric acid (4-HBA) as a biochemical hallmark. We present a boy with an unresolved severe neurological disorder and intermittent elevation of 4-HBA in serum and CSF which was later shown to result from iatrogenic administration of 4-HBA for sedation purposes. [ABSTRACT FROM AUTHOR]

The article offers information on different methods of induction of labour, ranging from mechanical to pharmacological. Topics discussed women in the oral misoprostol group received an average of 5.5 doses; highlights the need to rigorously test new medications and technologies; and slow-release misoprostol vaginal insert (MVI) with the WHO.

The article offers information on the study on the importance of cost considerations in preterm birth trials. It mentions the study presents a planned secondary analysis of the APOSTEL III trial comparing nifedipine and atosiban as tocolytics for women with threatened preterm birth; and also mentions the societal costs of lost productivity of the newborns who died were not taken into account.

The Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for HLA-B Genotype and Abacavir Dosing were originally published in April 2012. We reviewed recent literature and concluded that none of the evidence would change the therapeutic recommendations in the original guideline; therefore, the original publication remains clinically current. However, we have updated the Supplementary Material online and included additional resources for applying CPIC guidelines to the electronic health record. Up-to-date information can be found at PharmGKB (http://www.pharmgkb.org). [ABSTRACT FROM AUTHOR]

The majority of pregnant women take prescription drugs during their pregnancy. Given the multitude of physiologic changes incumbent in pregnancy, accurate clinical trial data on drugs in pregnancy are crucial. This report summarizes the 264 registered clinical trials in the past two years. With many of these drug trials being pharmacokinetic and placebo-controlled studies, therapeutic drug trials are becoming more common. [ABSTRACT FROM AUTHOR]

An equation in the paper by Weitkamp et al. [(2011), J.Synchrotron Rad.18, 617629] is corrected. [ABSTRACT FROM AUTHOR]

Left ventricular assist device (LVAD) candidacy screening includes evaluation for peripheral arterial disease (PAD). However, given current evidence, the impact of PAD on post-LVAD complications remains unknown. The National Inpatient Sample (NIS) database (2002-2017) was utilized to identify all LVAD cases. The in-hospital safety endpoints included major cardiovascular adverse events and its components. A propensity-matched analysis was used to obtain adjusted odds ratios (aOR). A subgroup analysis of patients with diabetes mellitus (DM) with PAD was also performed. A total of 27 424 patients with LVAD implantation (PAD: 516 [1.8%] and no-PAD 26 908 [98.2%]) were included. There were significant intergroup differences in the demographics and baseline comorbidities. A weighted sample of 1053 (no-PAD 537, PAD 516) propensity-matched population was selected. The adjusted odds for in-hospital mortality (aOR 1.7; 95% CI, 1.2-2.44, P = .004) were found to be significantly higher for LVAD-patients with PAD. There was no significant difference in the adjusted odds of MACE (aOR 1.16, 95% CI 0.87-1.5), postprocedure bleeding (aOR 0.88, 95% CI 0.62-1.26, P = .54) and risk of pneumonia (aOR 0.67, 95% CI 0.44-1.15, P = .63) between the two groups. A selected cohort of DM-only population (7339) consistently showed a higher adjusted mortality rate in PAD patients with LVAD implantation (aOR 2.3, 95% CI 1.2-4.47, P = .01). The rate of MACE (P = .17), myocardial infarction (P = .12), stroke (P = .60), postprocedural (0.10), and major bleeding (P = .51) remained identical between patients with PAD and those with no-PAD. PAD confers an increased risk of in-hospital all-cause mortality in patients undergoing LVAD implantation. This risk increases further in patients with a concomitant diagnosis of DM., (© 2021 International Center for Artificial Organs and Transplantation and Wiley Periodicals LLC.)

Smith-Lemli-Opitz (SLOS), or RSH syndrome, is an autosomal recessive deficiency of 7-dehydrocholesterol reductase (DHCR7) resulting in an accumulation of 7- and 8-dehydrocholesterol (7- and 8-DHC) in tissues and body fluids. At birth patients have variable malformations of CNS, heart, kidney, genitalia, and limbs, which may be life-limiting. In later course, psychomotor and mental retardation and behavior abnormalities become evident. Prenatally SLOS can be suspected on the basis of malformations and intrauterine growth retardation (IUGR) in prenatal ultrasonography and reduced maternal free estriol in serum. The diagnosis is confirmed by sterol analysis in a chorionic villus biopsy or amniotic fluid (AF). In this study, we evaluated the predictive value of the above mentioned criteria in combination with family history by quantification of sterols in AF in pregnancies with either a family history, ultrasonographical abnormalities typical for SLOS, or reduced maternal serum unconjugated estriol (MSuE3). The relative frequency of SLOS in fetuses with an affected sibling was 0.23, as to be expected for an autosomal recessive disease. The probability for SLOS was <0.6% when neither an affected sib nor more than one typical SLOS malformation was present. For safety reasons and for cost-effectiveness we recommend careful evaluation of history, MSuE3, and clinical presentation before determining sterols in AF., (Copyright © 2013 Wiley Periodicals, Inc.)

Holoprosencephaly (HPE) is the most common structural malformation of the developing forebrain in humans. The HPE phenotype is extremely variable and the etiology is heterogeneous. Among a variety of embryological toxins that can induce HPE, inhibitors, and other pertubations of cholesterol biosynthesis have been shown to be important factors, most likely because cholesterol is required in the Sonic hedgehog signaling cascade. Decreased levels of maternal cholesterol during pregnancy increase the risk for preterm delivery, but they are not associated with congenital malformations. However, if the fetus is affected by an inborn error of endogenous cholesterol synthesis, a reduction of maternal cholesterol concentration and cholesterol transport over the placenta aggravates the phenotypic expression. Exposure to lipophilic statins in early pregnancy may be associated with a substantial risk for structural CNS defects., (2010 Wiley-Liss, Inc.)

Differentiation of microglial cells is characterized by transformation from ameboid into ramified cell shape and up-regulation of K+ channels. The processes of microglial differentiation are controlled by astrocytic factors. The mechanisms by which astrocytes cause developmental changes in morphological and electrophysiological properties of microglia have remained unclear. We show here that the cytokines transforming growth factor-beta (TGF-beta), macrophage colony-stimulating factor (M-CSF) and granulocyte/macrophage colony-stimulating factor (GM-CSF) are released by astrocytes at concentrations sufficient to induce ramification and up-regulation of delayed rectifier (DR) K+ channels in microglia. Transformation from ameboid into ramified morphology induced in microglia by exposure to astrocyte-conditioned medium (ACM) was inhibited by neutralizing antibodies against TGF-beta, M-CSF or GM-CSF, whilst ACM-induced DR channel expression was exclusively inhibited by antibodies against TGF-beta. Although both ramification and DR channel up-regulation occurred simultaneously, DR channel blockade by charybdotoxin failed to inhibit microglial ramification. The ACM-induced ramification of microglia was inhibited by the tyrosine kinase inhibitor genistein, whereas DR channel up-regulation did not occur in the presence of the serine/threonine kinase inhibitor H7. Our data suggest that astrocytes modulate processes of microglial differentiation in parallel but via distinct signalling pathways.

Morphological, immunophenotypical and electrophysiological properties were investigated in isolated cultured murine microglia before and after exposure to astrocyte-conditioned medium (ACM). Following application of ACM, microglial cells underwent a dramatic shape transformation from an amoeboid appearance to a ramified morphology. In parallel to morphological changes, a downregulation of macrophage surface antigens was observed in microglia exposed to ACM. Staining intensities for major histocompatibility complex (MHC) class II molecules and for the adhesion molecules leukocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) were significantly decreased in ramified microglia 5 days after exposure to ACM. In microglial cells treated daily with ACM over a period of 5 days, the smallest staining intensities for all surface antigens as well as the smallest ramification index as a measure for the highest degree of ramification were determined. In addition, upregulation of delayed rectifier K + currents was observed in microglia exposed to ACM for 1 day or treated daily with ACM for 5 days. In contrast, untreated amoeboid microglia or ramified microglia analysed 5 days after exposure to ACM did not express delayed rectifier K + currents. Analyses of the resting membrane potential and expression levels and properties of inward rectifier K + currents did not reveal any differences between untreated and ACM-treated microglia. It is suggested that electrophysiological properties of microglia do not strongly correlate with the morphology or the immunophenotype of microglial cells.

The aim of this study was to analyse microglial reactions to excitotoxic N-methyl-D-aspartic acid (NMDA)-induced degeneration of rat dentate and hippocampal neurons in vitro. We used a migration model combining the techniques of microglial single cell culture and organotypic hippocampal slice culture (OHSC). Site-specific oxidative damage in OHSCs was induced by pretreatment with 50 microM NMDA. Neuronal injury determined by propidium iodide (PI) uptake included the hippocampal cell layers of the dentate gyrus (DG) and the cornu ammonis (CA). Fluorescence-prelabelled microglial cells with ameboid morphology were transferred onto the OHSC and migrated predominantly to the prelesioned cell layers of DG and CA when compared with unlesioned areas of the OHSC. In NMDA pretreated slices, microglial cells clustered around degenerating granule cells in the DG and pyramidal cells in the CA. This effect was significantly inhibited in unlesioned slice cultures and in NMDA-exposed cultures that were pretreated with the NMDA-antagonist MK-801. Our observations suggest that microglia -- attracted by the presence of stimuli provided by NMDA-induced neuronal death -- migrate specifically towards these lesioned neurons.

Microglial cells with their characteristic ramified morphology are exclusively found in healthy CNS tissue, whereas various pathologies are associated with the occurrence of amoeboid, macrophage-like cells. It is still a matter of discussion whether amoeboid cells are blood-derived macrophages, or whether a characteristic change in morphology, reflecting activation of previously ramified microglia, takes place. Cells in dissociated microglia culture obtained from healthy rat brains, inevitably developing this amoeboid morphology, were labelled with a fluorescent dye and transferred onto organotypic hippocampal slice cultures. Prelabelled cells with amoeboid morphology invaded these slice cultures and had, after 9 days in vitro, gradually transformed into highly ramified cells. Our findings strengthen the hypothesis that the observed amoeboid and ramified cells belong to a single population of microglia, appearing with different morphologies depending on the presence of stimuli provided by the CNS microenvironment. Microglial cells obviously appear in different shapes and can switch from immunologically resting to activated modes and vice versa.