Liver infarctions as the first manifestation of antiphospholipid antibody syndrome in pregnancy: a case report

Background: The differential diagnosis of abdominal pain in pregnant women is broad. Liver diseases as the origin of abdominal pain in pregnancy are rare, and severe forms occur in less than 0.1% of pregnancies. Some disorders, such as hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome and preeclampsia, are unique to pregnancy, while others, such as antiphospholipid antibody syndrome, may manifest in pregnancy but have consequences beyond the current pregnancy. All of them require prompt identification and treatment. Case presentation: A 27-year-old Caucasian woman who was 15+1 weeks pregnant reported to the emergency department twice due to stabbing right-upper-quadrant abdominal pain. Initial laboratory testing revealed mild leukocytosis and slightly elevated liver enzymes. On second presentation, the patient was febrile and had an increased C-reactive protein concentration. Over the course of the next days, nonhemolytic anemia and thrombocytopenia emerged with elevated liver enzymes. Coagulation studies also revealed a prolongation of activated partial thromboplastin time. Magnetic resonance imaging showed nonspecific alterations in the right liver lobe, possibly corresponding to infection or infarction. A hepatic viral infection was ruled out. At that time, the most likely diagnosis was cholangitis with liver abscess formation, and antibiotic therapy was started. Further worsening of the anemia and thrombocytopenia, development of proteinuria, together with a miscarriage on the fourth day of hospitalization resulted in the tentative diagnosis of (triple-positive) antiphospholipid antibody syndrome, which was confirmed 12 weeks after the initial investigation. Treatment consisted of prompt anticoagulation with heparin and later on with a vitamin K antagonist as well as high-dose glucocorticoid therapy. There was no need for intravenous immunoglobulin therapy or plasma exchange, although we suspected a catastrophic form of antiphospholipid antibody syndrome due to infarctions of the liver, placenta, and possibly kidneys (proteinuria). The outcome was favorable. Conclusion: We report a 27-year-old pregnant woman whose abdominal pain was caused by liver infarctions as the first manifestation of catastrophic antiphospholipid antibody syndrome. The antiphospholipid antibody syndrome was possibly secondary to hitherto clinically silent systemic lupus erythematosus since the antinuclear antibodies were increased later on. Hydroxychloroquine therapy was initiated to prevent antiphospholipid antibody syndrome recurrence in a future pregnancy. Keywords: Abortion; Antiphospholipid antibody syndrome; Case report; Hepatopathy; Liver lesions; Pregnancy; Systemic lupus erythematosu

Filling out the gaps – identification of fugralins as products of the PKS2 cluster in Fusarium graminearum

As one of the grain crop pathogenic fungi with the greatest impacts on agricultural economical as well as human health, an elaborate understanding of the life cycle and subsequent metabolome of Fusarium graminearum is of great interest. Throughout the lifetime of the fungus, it is known to produce a wide array of secondary metabolites, including polyketides. One of the F. graminearum polyketides which has remained a mystery until now has been elucidated in this work. Previously, it was suggested that the biosynthetic product of the PKS2 gene cluster was involved in active mycelial growth, the exact mechanism, however, remained unclear. In our work, disruption and overexpression of the PKS2 gene in F. graminearum enabled structural elucidation of a linear and a cyclic tetraketide with a double methyl group, named fugralin A and B, respectively. Further functional characterization showed that the compounds are not produced during infection, and that deletion and overexpression did not affect pathogenicity or visual growth. The compounds were shown to be volatile, which could point to possible functions that can be investigated further in future studies

Motor, cognitive and mobility deficits in 1000 geriatric patients : protocol of a quantitative observational study before and after routine clinical geriatric treatment – the ComOn-study

© The Author(s). 2020 Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: Motor and cognitive deficits and consequently mobility problems are common in geriatric patients. The currently available methods for diagnosis and for the evaluation of treatment in this vulnerable cohort are limited. The aims of the ComOn (COgnitive and Motor interactions in the Older populatioN) study are (i) to define quantitative markers with clinical relevance for motor and cognitive deficits, (ii) to investigate the interaction between both motor and cognitive deficits and (iii) to assess health status as well as treatment outcome of 1000 geriatric inpatients in hospitals of Kiel (Germany), Brescia (Italy), Porto (Portugal), Curitiba (Brazil) and Bochum (Germany). Methods: This is a prospective, explorative observational multi-center study. In addition to the comprehensive geriatric assessment, quantitative measures of reduced mobility and motor and cognitive deficits are performed before and after a two week's inpatient stay. Components of the assessment are mobile technology-based assessments of gait, balance and transfer performance, neuropsychological tests, frailty, sarcopenia, autonomic dysfunction and sensation, and questionnaires to assess behavioral deficits, activities of daily living, quality of life, fear of falling and dysphagia. Structural MRI and an unsupervised 24/7 home assessment of mobility are performed in a subgroup of participants. The study will also investigate the minimal clinically relevant change of the investigated parameters. Discussion: This study will help form a better understanding of symptoms and their complex interactions and treatment effects in a large geriatric cohort.info:eu-repo/semantics/publishedVersio

Regulation of a novel Fusarium cytokinin in Fusarium pseudograminearum

Fusarium pseudograminearum is an agronomically important fungus, which infects many crop plants, including wheat, where it causes Fusarium crown rot. Like many other fungi, the Fusarium genus produces a wide range of secondary metabolites of which only few have been characterized. Recently a novel gene cluster was discovered in F. pseudograminearum, which encodes production of cytokinin-like metabolites collectively named Fusarium cytokinins. They are structurally similar to plant cytokinins and can activate cytokinin signalling in vitro and in planta. Here, the regulation of Fusarium cytokinin production was analysed in vitro. This revealed that, similar to deoxynivalenol (DON) production in Fusarium graminearum, cytokinin production can be induced in vitro by specific nitrogen sources in a pH-dependent manner. DON production was also induced in both F. graminearum and F. pseudograminearum in cytokinin-inducing conditions. In addition, microscopic analyses of wheat seedlings infected with a F. pseudograminearum cytokinin reporter strain showed that the fungus specifically induces its cytokinin production in hyphae, which are in close association with the plant, suggestive of a function of Fusarium cytokinins during infection

H3K27me3 is vital for fungal development and secondary metabolite gene silencing, and substitutes for the loss of H3K9me3 in the plant pathogen Fusarium proliferatum.

Facultative heterochromatin marked by histone H3 lysine 27 trimethylation (H3K27me3) is an important regulatory layer involved in secondary metabolite (SM) gene silencing and crucial for fungal development in the genus Fusarium. While this histone mark is essential in some (e.g., the rice pathogen Fusarium fujikuroi), it appears dispensable in other fusaria. Here, we show that deletion of FpKMT6 is detrimental but not lethal in the plant pathogen Fusarium proliferatum, a member of the Fusarium fujikuroi species complex (FFSC). Loss of FpKmt6 results in aberrant growth, and expression of a large set of previously H3K27me3-silenced genes is accompanied by increased H3K27 acetylation (H3K27ac) and an altered H3K36me3 pattern. Next, H3K9me3 patterns are affected in Δfpkmt6, indicating crosstalk between both heterochromatic marks that became even more obvious in a strain deleted for FpKMT1 encoding the H3K9-specific histone methyltransferase. In Δfpkmt1, all H3K9me3 marks present in the wild-type strain are replaced by H3K27me3, a finding that may explain the subtle phenotype of the Δfpkmt1 strain which stands in marked contrast to other filamentous fungi. A large proportion of SM-encoding genes is allocated with H3K27me3 in the wild-type strain and loss of H3K27me3 results in elevated expression of 49% of them. Interestingly, genes involved in the biosynthesis of the phytohormones gibberellins (GA) are among the most upregulated genes in Δfpkmt6. Although several FFSC members harbor GA biosynthetic genes, its production is largely restricted to F. fujikuroi, possibly outlining the distinct lifestyles of these notorious plant pathogens. We show that H3K27me3 is involved in GA gene silencing in F. proliferatum and at least one additional FFSC member, and thus, may serve as a regulatory layer for gene silencing under non-favoring conditions

Fusaoctaxin A, an Example of a Two-Step Mechanism for Non-Ribosomal Peptide Assembly and Maturation in Fungi

Fungal non-ribosomal peptide synthetase (NRPS) clusters are spread across the chromosomes, where several modifying enzyme-encoding genes typically flank one NRPS. However, a recent study showed that the octapeptide fusaoctaxin A is tandemly synthesized by two NRPSs in Fusarium graminearum. Here, we illuminate parts of the biosynthetic route of fusaoctaxin A, which is cleaved into the tripeptide fusatrixin A and the pentapeptide fusapentaxin A during transport by a cluster-specific ABC transporter with peptidase activity. Further, we deleted the histone H3K27 methyltransferase kmt6, which induced the production of fusaoctaxin A

Fusaoctaxin A, an Example of a Two-Step Mechanism for Non-Ribosomal Peptide Assembly and Maturation in Fungi

Fungal non-ribosomal peptide synthetase (NRPS) clusters are spread across the chromosomes, where several modifying enzyme-encoding genes typically flank one NRPS. However, a recent study showed that the octapeptide fusaoctaxin A is tandemly synthesized by two NRPSs in Fusarium graminearum. Here, we illuminate parts of the biosynthetic route of fusaoctaxin A, which is cleaved into the tripeptide fusatrixin A and the pentapeptide fusapentaxin A during transport by a cluster-specific ABC transporter with peptidase activity. Further, we deleted the histone H3K27 methyltransferase kmt6, which induced the production of fusaoctaxin A