The influence of the SARS-CoV-2 lockdown on patients with inflammatory rheumatic diseases on their adherence to immunomodulatory medication: a cross sectional study over 3 months in Germany.

OBJECTIVES: To evaluate the influence of the SARS-CoV-2 pandemic on the adherence of patients with inflammatory rheumatic diseases (IRD) to their immunomodulatory medication during the three-month lockdown in Germany. METHODS: From 16th March until 15th June 2020, IRD patients from private practices and rheumatology departments were asked to answer a questionnaire addressing their behaviour with respect to their immunomodulating therapy. Eight private practices and nine rheumatology departments that included rheumatology primary care centres and university hospitals participated. A total of 4252 questionnaires were collected and evaluated. RESULTS: The majority of patients (54%) were diagnosed with RA, followed by psoriatic arthritis (14%), ankylosing spondylitis (10%), connective tissue diseases (12%) and vasculitides (6%). Most of the patients (84%) reported to continue their immunomodulatory therapy. Termination of therapy was reported by only 3% of the patients. The results were independent from the type of IRD, the respective immunomodulatory therapy and by whom the patients were treated (private practices vs rheumatology departments). Younger patients (<60 years) reported just as often as older patients to discontinue their therapy. CONCLUSION: The data show that most of the patients continued their therapy in spite of the pandemic. A significant change in behaviour with regard to their immunomodulatory therapy was not observed during the three months of observation. The results support the idea that the immediate release of recommendations of the German Society of Rheumatology were well received, supporting the well-established physician-patient relationship in times of a crisis.

[Osteoporosis detection using cone-beam computed tomography]. / Osteoporoseerkennung mittels digitaler Volumentomographie.

BACKGROUND: Osteoporosis is still underdiagnosed in Germany. OBJECTIVES: Is it possible to detect osteoporosis on the basis of a cone-beam computed tomography image of the mandible and several measuring methods? MATERIALS AND METHODS: Sixteen cone-beam computed tomography (CBCT) images from patients of the dental clinic at the University of Ulm were reinvestigated. When the CBCT images were processed the subjects were at least 55 years old, and the mandible was completely mapped on the image. Furthermore, a dual-energy X­ray absorptiometry scan or a CT bone mineral density test was required for every subject. The subjects were divided into an osteoporosis group and a control group. The computed tomography mental index (CTMI), the computed tomography mandibular index superior (CTI[S]) and the computed tomography mandibular index inferior (CTI[I]) were deployed for comparison of the groups. In the first instance a comparison of the osteoporosis and control groups was made for both male and female subjects. Subsequently, only the images of the female subjects were compared to each other. RESULTS: A possibility for osteoporosis can be expressed at CTMI values located < 3.0 mm. As well for CTI(S) < 0.18 and CTI(I) < 0.23. There arises a 66.7 % sensitivity and 70 % specificity for the mixed subject group and an 80 % sensitivity and 57.1 % specificity for the female subject group for CTMI and CTI(S). Furthermore, there are 50.0 % sensitivity and 70 % specificity for the mixed subject group and 60.0 % sensitivity and 57.1 % specificity for the female subject group for the CTI(I). CONCLUSION: CTMI, CTI(S) and CTI(I) are only suitable for osteoporosis detection to a limited extent.

Dynamics and gravitational wave signature of collapsar formation.

We perform 3+1 general relativistic simulations of rotating core collapse in the context of the collapsar model for long gamma-ray bursts. We employ a realistic progenitor, rotation based on results of stellar evolution calculations, and a simplified equation of state. Our simulations track self-consistently collapse, bounce, the postbounce phase, black hole formation, and the subsequent early hyperaccretion phase. We extract gravitational waves from the spacetime curvature and identify a unique gravitational wave signature associated with the early phase of collapsar formation.

Progressive secondary exo-focal dopaminergic neurodegeneration occurs in not directly connected midbrain nuclei after pure motor-cortical stroke.

Transsynaptic anterograde and retrograde degeneration of neurons and neural fibers are assumed to trigger local excitotoxicity and inflammatory processes. These processes in turn are thought to drive exo-focal neurodegeneration in remote areas connected to the infarcted tissue after ischemic stroke. In the case of middle cerebral artery occlusion (MCAO), in which striato-nigral connections are affected, the hypothesis of inflammation-induced remote neurodegeneration is based on the temporal dynamics of an early appearance of inflammatory markers in midbrain followed by dopaminergic neuronal loss. To test the hypothesis of a direct transsynaptic mediation of secondary exo-focal post-ischemic neurodegeneration, we used a photochemical induction of a stroke (PTS) in Sprague-Dawley rats restricted to motor cortex (MC), thereby sparing the striatal connections to dopaminergic midbrain nuclei. To dissect the temporal dynamics of post-ischemic neurodegeneration, we analyzed brain sections harvested at day 7 and 14 post stroke. Here, an unexpectedly pronounced and widespread loss of dopaminergic neurons occurred 14 days after stroke also affecting dopaminergic nuclei that are not directly coupled to MC. Since the pattern of neurodegeneration in case of a pure motor stroke is similar to a major stroke including the striatum, it is unlikely that direct synaptic coupling is a prerequisite for delayed secondary exo-focal post ischemic neurodegeneration. Furthermore, dopaminergic neurodegeneration was already detected by Fluoro-Jade C staining at day 7, coinciding with a solely slight inflammatory response. Thus, inflammation cannot be assumed to be the primary driver of exo-focal post-ischemic cell death. Moreover, nigral substance P (SP) expression indicated intact striato-nigral innervation after PTS, whereas opposing effects on SP expression after striatal infarcts argue against a critical role of SP in neurodegenerative or inflammatory processes during exo-focal neurodegeneration.

Cloning and DNA sequence analysis of a polygalacturonase cDNA from Aspergillus niger RH5344.

A 1319 bp long cDNA encoding for a polygalacturonase (EC 3.2.1.15) from Aspergillus niger RH5344 comprises a single open reading frame of 1089 bp which includes the mature protein of 362 amino acids and an NH2-terminal signal peptide of 27 amino acids. The directly determined peptides of the mature polygalacturonase confirmed the sequence information deduced from the cDNA.

Identification of 4-chlorobenzoyl-coenzyme A as intermediate in the dehalogenation catalyzed by 4-chlorobenzoate dehalogenase from Pseudomonas sp. CBS3.

The intermediate in the reaction catalyzed by 4-chlorobenzoate dehalogenase from Pseudomonas sp. CBS3 was identified as 4-chlorobenzoyl-CoA. One component of 4-chlorobenzoate dehalogenase worked as a a 4-chlorobenzoyl-CoA ligase catalyzing the formation of 4-chlorobenzoyl-CoA from 4-chlorobenzoate, coenzyme A and ATP. This intermediate was detected spectrophotometrically and by HPLC. 4-chlorobenzoyl-CoA was the substrate for the dehalogenase component, which catalyzed the conversion to 4-hydroxybenzoate with concomitant release of coenzyme A.

Tetrodotoxin-sensitive ion channels characterized in glial and neuronal cells from rat brain.

Ion channels were studied in primary neuronal and in primary glial cultures from rat brain by measuring the uptake of guanidinium, an ion that can permeate the Na+ channel. Neuronal cells exhibit a veratridine-stimulated (EC50 30 microM) guanidinium uptake, which is blocked by tetrodotoxin (IC50 30nM). This demonstrates the presence of a voltage-dependent Na+ channel. In glial cells veratridine + scorpion toxin, but not veratridine or scorpion toxin alone can stimulate a tetrodotoxin-sensitive ion uptake, thus indicating a 'silent' Na+ channel in the glial cells. Phentolamine, propranolol and various local anesthetic drugs (e.g. tetracaine, dibucaine) blocked the two different kinds of Na+ channels in the two cell populations investigated.

Immunological cross-reactivity of cultured rat hippocampal neurons with goldfish brain proteins synthesized during memory consolidation.

Ependymins are goldfish brain glycoproteins exhibiting a specifically enhanced rate of synthesis when the animals adopt a new pattern of swimming behavior. With specific antisera against ependymins it has become possible to look for ependymin-like immunoreactivity in other animal species, both qualitatively by immunofluorescence staining and quantitatively by radioimmunoassay. Ependymin-like immunoreactivity was detected not only in other fish but also in rat brain. In the rat radioimmunoassay measurements were highest for the hippocampal formation and for cultured neurons derived from the embryonic hippocampus. Immunofluorescence staining was performed on various cell culture systems derived from rat brain, in order to establish which cell type contains the antigen. Only neuronal cell populations reacted with the anti-ependymin antisera. Cells derived from embryonic rat brain hippocampus which resembled pyramidal neurons stained particularly bright for ependymin-like immunoreactivity. The antigenic material was distributed throughout the cytoplasm including the neuronal extensions. Various neuron-specific antisera have been used to counterstain the cells containing ependymin-like immunoreactivity.

Selective increase of R-I subunit of cyclic AMP-dependent protein kinase in glia-rich primary cultures upon treatment with dibutyryl cyclic AMP.

Levels of cyclic GMP-dependent protein kinase and of the subunits (R-I, R-II and C) of cyclic AMP-dependent protein kinase were determined in two types of neural primary cell cultures that were either treated or not treated with dibutyryl cyclic AMP. Astroglia-rich cell cultures from newborn rat brain responded to exposure to dibutyryl cyclic AMP by a 2-3-fold increase in the level of R-I subunit, as demonstrated by two radioimmunological procedures, while the levels of the other subunits (R-II and C) and of cyclic GMP-dependent protein kinase remained unaffected. In contrast, neuron-rich cell cultures from embryonic rat brain did not display such a change in the level of R-I subunit. Thus, the elevation in the level of R-I elicited by dibutyryl cyclic AMP in normal non-malignant neural cells in culture was restricted to glial rather than neuronal cells.

Detecting nitrous oxide reductase (NosZ) genes in soil metagenomes: method development and implications for the nitrogen cycle.

UNLABELLED: Microbial activities in soils, such as (incomplete) denitrification, represent major sources of nitrous oxide (N2O), a potent greenhouse gas. The key enzyme for mitigating N2O emissions is NosZ, which catalyzes N2O reduction to N2. We recently described "atypical" functional NosZ proteins encoded by both denitrifiers and nondenitrifiers, which were missed in previous environmental surveys (R. A. Sanford et al., Proc. Natl. Acad. Sci. U. S. A. 109:19709-19714, 2012, doi:10.1073/pnas.1211238109). Here, we analyzed the abundance and diversity of both nosZ types in whole-genome shotgun metagenomes from sandy and silty loam agricultural soils that typify the U.S. Midwest corn belt. First, different search algorithms and parameters for detecting nosZ metagenomic reads were evaluated based on in silico-generated (mock) metagenomes. Using the derived cutoffs, 71 distinct alleles (95% amino acid identity level) encoding typical or atypical NosZ proteins were detected in both soil types. Remarkably, more than 70% of the total nosZ reads in both soils were classified as atypical, emphasizing that prior surveys underestimated nosZ abundance. Approximately 15% of the total nosZ reads were taxonomically related to Anaeromyxobacter, which was the most abundant genus encoding atypical NosZ-type proteins in both soil types. Further analyses revealed that atypical nosZ genes outnumbered typical nosZ genes in most publicly available soil metagenomes, underscoring their potential role in mediating N2O consumption in soils. Therefore, this study provides a bioinformatics strategy to reliably detect target genes in complex short-read metagenomes and suggests that the analysis of both typical and atypical nosZ sequences is required to understand and predict N2O flux in soils. IMPORTANCE: Nitrous oxide (N2O) is a potent greenhouse gas with ozone layer destruction potential. Microbial activities control both the production and the consumption of N2O, i.e., its conversion to innocuous dinitrogen gas (N2). Until recently, consumption of N2O was attributed to bacteria encoding "typical" nitrous oxide reductase (NosZ). However, recent phylogenetic and physiological studies have shown that previously uncharacterized, functional, "atypical" NosZ proteins are encoded in genomes of diverse bacterial groups. The present study revealed that atypical nosZ genes outnumbered their typical counterparts, highlighting their potential role in N2O consumption in soils and possibly other environments. These findings advance our understanding of the diversity of microbes and functional genes involved in the nitrogen cycle and provide the means (e.g., gene sequences) to study N2O fluxes to the atmosphere and associated climate change.

The chimeric genome of Sphaerochaeta: nonspiral spirochetes that break with the prevalent dogma in spirochete biology.

UNLABELLED: Spirochaetes is one of a few bacterial phyla that are characterized by a unifying diagnostic feature, namely, the helical morphology and motility conferred by axial periplasmic flagella. Their unique morphology and mode of propulsion also represent major pathogenicity factors of clinical spirochetes. Here we describe the genome sequences of two coccoid isolates of the recently described genus Sphaerochaeta which are members of the phylum Spirochaetes based on 16S rRNA gene and whole-genome phylogenies. Interestingly, the Sphaerochaeta genomes completely lack the motility and associated signal transduction genes present in all sequenced spirochete genomes. Additional analyses revealed that the lack of flagella is associated with a unique, nonrigid cell wall structure hallmarked by a lack of transpeptidase and transglycosylase genes, which is also unprecedented in spirochetes. The Sphaerochaeta genomes are highly enriched in fermentation and carbohydrate metabolism genes relative to other spirochetes, indicating a fermentative lifestyle. Remarkably, most of the enriched genes appear to have been acquired from nonspirochetes, particularly clostridia, in several massive horizontal gene transfer events (>40% of the total number of genes in each genome). Such a high level of direct interphylum genetic exchange is extremely rare among mesophilic organisms and has important implications for the assembly of the prokaryotic tree of life. IMPORTANCE: Spiral shape and motility historically have been the unifying hallmarks of the phylum Spirochaetes. These features also represent important virulence factors of highly invasive pathogenic spirochetes such as the causative agents of syphilis and Lyme disease. Through the integration of genome sequencing, microscopy, and physiological studies, we conclusively show that the spiral morphology and motility of spirochetes are not universal morphological properties. In particular, we found that the genomes of the members of the recently described genus Sphaerochaeta lack the genes encoding the characteristic flagellar apparatus and, in contrast to most other spirochetes, have acquired many metabolic and fermentation genes from clostridia. These findings have major implications for the isolation and study of spirochetes, the diagnosis of spirochete-caused diseases, and the reconstruction of the evolutionary history of this important bacterial phylum. The Sphaerochaeta sp. genomes offer new avenues to link ecophysiology with the functionality and evolution of the spirochete flagellar apparatus.

Quality analysis of selective microparticle deposition on electrically programmable surfaces.

Image processing and pattern analysis can evaluate the deposition quality of triboelectrically charged microparticles on charged surfaces. The image processing method presented in this paper aims at controlling the quality of peptide arrays generated by particle based solid phase Merrifield combinatorial peptide synthesis. Incorrectly deposited particles are detected before the amino acids therein are coupled to the growing peptide. The calibration of the image acquisition is performed in a supervised training step in which all parameters of the quality analyzing algorithm are learnt given one representative image. Then, the correct deposition pattern is determined by a linear support vector machine. Knowing the pattern, contaminated areas can be detected by comparing the pattern with the actual deposition. Taking into account the resolution of the image acquisition system and its magnification factor, the number and size of contaminating particles can be calculated out of the number of connected foreground pixels.

[Lung edema as a complication of tocolysis in twin pregnancy]. / Lungenödem als Tokolysekomplikation bei Geminischwangerschaft.

It was reported about a case of acute pulmonary oedema during tocolytic therapy with beta 2-stimulator Fenoterol. The aetiologic factors of the isotonic hyperhydration by beta-mimetic drugs, medicamentous influences and favoured factors have been discussed. Diagnostic and therapeutic consequences have been concluded.

[Sonographic studies of physiologic involution of the uterus in the puerperium]. / Sonographische Untersuchungen der physiologischen Involution des Uterus im Wochenbett.

141 sonographic investigations were performed in a group of 52 patients between the first and eighth day after normal delivery for supervision of physiologic involution of the uterus. There were examined position of the uterus, size of cervix and corpus and thickness of anterior and posterior uterine wall. The results were examined statistically concerning correlations to birth weight of the newborn.

[Sonographically evident changes in placental structures in pregnancy. 1]. / Sonographisch nachweisbare Veränderungen plazentarer Strukturen während der Schwangerschaft. 1. Mitteilung.

During the routine prenatal care a sonographical valuation of the placental tissue structure is performed. It could be proved at 657 gravids (1436 examinations) that the placental tissue structure is changing the course of pregnancy. The results were graduated in three stages from 0 to 3. Stage 0 represents the placenta in the first and second trimester and Stage 3 is used for the ripe placenta. The practical use of the placental tissue structure diagnosis is discussed.

Purification and properties of 4-halobenzoate-coenzyme A ligase from Pseudomonas sp. CBS3.

The bacterial strain Pseudomonas sp. CBS3 possesses a multi component enzyme system which converts 4-chlorobenzoate to 4-hydroxybenzoate. In the first step 4-chlorobenzoate is activated in a coenzyme A, ATP and Mg(2+)-dependent reaction to 4-chlorobenzoyl-coenzyme A. ATP is cleaved thereby into AMP and pyrophosphate. The involved 4-chlorobenzoate-coenzyme A ligase was purified to apparent homogeneity by a 6-step purification procedure. The native enzyme had an apparent molecular mass of 115000 Da and was composed of two identical polypeptide subunits of 57 kDa. The enzyme displayed an isoelectric point of 5.3. The maximal initial rate of catalysis was achieved in 100mM Tris/HCl or Tricine/NaOH buffer, pH 8.4, at 35 degrees C. Under these conditions the apparent Km values for ATP, coenzyme A and 4-chlorobenzoate were 2.4 to 3.5 mM, 0.11 to 0.19mM and 0.05 to 0.065mM, respectively. Vmax was 111.6 mumol/(min x mg protein). The N-terminal amino-acid sequence was determined. 4-Halobenzoates were preferentially converted to the corresponding thioesters. Therefore, the enzyme was named 4-halobenzoate-coenzyme A ligase.

[Thanatophoric dwarfism]. / Thanatophorer Zwergwuchs.

The thanatophoric dwarfism is a relatively rare disease. The course of a pregnancy with this in every case lethal syndrome is demonstrated in one case. The possible ultrasonographic suspected diagnosis is discussed. If the diagnosis is certain termination of pregnancy is indicated.

Dehalogenation of 4-chlorobenzoate by 4-chlorobenzoate dehalogenase from pseudomonas sp. CBS3: an ATP/coenzyme A dependent reaction.

Pseudomonas sp. CBS3 was grown with 4-chlorobenzoate as sole source of carbon and energy. Freshly prepared cell-free extracts converted 4-chlorobenzoate to 4-hydroxybenzoate. After storage for 16 hours at 25 degrees C only about 50% of the initial activity was left. Treatment at 55 degrees C for 10 minutes, dialysis or desalting of the extracts by gel filtration caused a total loss of the activity of the 4-chlorobenzoate dehalogenase. The activity could be restored by the addition of ATP, coenzyme A and Mg2+. If one of these cofactors was missing, no dehalogenating activity was detectable. The amount of 4-hydroxybenzoate formed was proportional to the amount of ATP available in the test system whereas CoA served as a real coenzyme. A novel ATP/coenzyme A dependent reaction mechanism for the dehalogenation of 4-chlorobenzoate by 4-chlorobenzoate dehalogenase from Pseudomonas sp. CBS3 is proposed.