Longterm course of neuropsychological symptoms and ME/CFS after SARS-CoV-2-infection: a prospective registry study.

A significant proportion of patients after SARS-CoV-2 infection suffer from long-lasting symptoms. Although many different symptoms are described, the majority of patients complains about neuropsychological symptoms. Additionally, a subgroup of patients fulfills diagnostic criteria for ME/CFS. We analyzed a registry of all patients presenting in the out-patients clinic at a German university center. For patients with more than one visit, changes in reported symptoms from first to second visit were analyzed. A total of 1022 patients were included in the study, 411 of them had more than one visit. 95.5% of the patients reported a polysymptomatic disease. At the first visit 31.3% of the patients fulfilled ME/CFS criteria after a median time of 255 days post infection and and at the second visit after a median of 402 days, 19.4% still suffered from ME/CFS. Self-reported fatigue (83.7-72.7%) and concentration impairment (66.2-57.9%) decreased from first to second visit contrasting non-significant changes in the structured screening. A significant proportion of SARS-CoV-2 survivors presenting with ongoing symptoms present with ME/CFS. Although the proportion of subjective reported symptoms and their severity reduce over time, a significant proportion of patients suffer from long-lasting symptoms necessitating new therapeutic concepts.

[Online information for relatives of critically ill patients : Pilot test of the usability of an ICU families website]. / Onlineinformation für Angehörige von kritisch Kranken : Pilottestung zur Nutzbarkeit der ICU Families Website.

BACKGROUND: Relatives of intensive care patients have a very high need for information. This is due to the acute and serious, often life-threatening illness of the patients and the very complex and technical environment of an intensive care unit (ICU). Unmet needs for information can increase anxiety, sleep disorders, stress, and depressive symptoms in the relatives. OBJECTIVES: The potential of the ICU families website in terms of usability and functionality during real-time testing were evaluated. METHODS: The ICU families project created a dynamic online information platform in the form of a password-protected website. It contains pictures, written explanations, 5 movies, a forum and a diary function. The usability of the website was tested among 10 lay people and 10 experts (7 nurses and 3 physicians) according to the Think Aloud Method. RESULTS: The outcome is qualitative feedback based on video documentation by laypeople and suggestions by experts. Criticisms mentioned by the test subjects were insufficient image material, small size of the operator contact link and lack of a home button. With a mean of 9.1 (rating scale, 0 = very poor, 10 = very good), the website was almost universally recommended by the experts. CONCLUSIONS: This usability test of a website for relatives of ICU patients conducted among 20 test subjects showed the biggest challenges related to solving individual test scenarios and provided valuable hints for improving website usability. Features of the website highlighted as positive were the clear layout, the symbols, the diary and the consideration of children. This information was used to improve the site for subsequent roll-out in a randomized, controlled and multicentre study.

Gut microbiota, dietary intakes and intestinal permeability reflected by serum zonulin in women.

PURPOSE: Increased gut permeability causes the trespass of antigens into the blood stream which leads to inflammation. Gut permeability reflected by serum zonulin and diversity of the gut microbiome were investigated in this cross-sectional study involving female study participants with different activity and BMI levels. METHODS: 102 women were included (BMI range 13.24-46.89 kg m-2): Anorexia nervosa patients (n = 17), athletes (n = 20), normal weight (n = 25), overweight (n = 21) and obese women (n = 19). DNA was extracted from stool samples and subjected to 16S rRNA gene analysis (V1-V2). Quantitative Insights Into Microbial Ecology (QIIME) was used to analyze data. Zonulin was measured with ELISA. Nutrient intake was assessed by repeated 24-h dietary recalls. We used the median of serum zonulin concentration to divide our participants into a "high-zonulin" (> 53.64 ng/ml) and "low-zonulin" (< 53.64 ng/ml) group. RESULTS: The alpha-diversity (Shannon Index, Simpson Index, equitability) and beta-diversity (unweighted and weighted UniFrac distances) of the gut microbiome were not significantly different between the groups. Zonulin concentrations correlated significantly with total calorie-, protein-, carbohydrate-, sodium- and vitamin B12 intake. Linear discriminant analysis effect size (LEfSe) identified Ruminococcaceae (LDA = 4.163, p = 0.003) and Faecalibacterium (LDA = 4.151, p = 0.0002) as significantly more abundant in the low zonulin group. CONCLUSION: Butyrate-producing gut bacteria such as Faecalibacteria could decrease gut permeability and lower inflammation. The diversity of the gut microbiota in women does not seem to be correlated with the serum zonulin concentration. Further interventional studies are needed to investigate gut mucosal permeability and the gut microbiome in the context of dietary factors.

Impaired probabilistic classification learning with feedback in patients with major depression.

BACKGROUND: The function of basal ganglia (BG) in the pathophysiology of major depression (MD) is still unclear. Recent research found changes in BG regarding size, structure and cerebral perfusion in patients with MD. Neuroimaging shows recruitment of the striatum during feedback (FB) based incidental learning of probabilistic classification learning, while the medial temporal lobe (MTL) is associated with paired associate (PA) based incidental learning. The purpose of this study was to evaluate whether FB-based incidental learning is affected in MD. METHODS: The FB and PA versions of the weather prediction task (WPT), a task of incidental probabilistic classification learning, were completed by patients with MD (n=44) and healthy controls (n=44). In FB-learning the participants received either a "thumbs-up" or "thumbs-down" message according to their right or wrong classification of cards to a certain kind of weather (either rainy or fine), while in PA learning no classification was required. Severity of MD was rated on the Beck Depression Inventory and Hamilton Rating Scale for depression. RESULTS: Patients with MD were selectively impaired on the FB task relative to controls (p<0.05), while no significant difference was found for PA learning between the two groups. Furthermore, there were no significant differences between FB and PA-learning within the patient and control groups. CONCLUSION: Our results indicate a distinct impairment on the FB-based version of the weather prediction task. These findings implicate disturbed reinforcement learning in this group of patients.

[Predictors of mental and physical quality of life in Huntington's disease]. / Prädiktoren der psychischen und physischen Lebensqualität beim Morbus Huntington.

BACKGROUND: The assessment of health-related quality of life (hrQoL) is an important tool in therapy studies and in the treatment of patients with Huntington's disease (HD). In the absence of causal interventions, HD therapy targets the alleviation of symptoms aiming to improve impaired hrQoL. The aim of this study was to determine the impact of disease characteristics on hrQoL in HD. METHODS: A total of 80 genetically confirmed HD patients underwent an assessment using the Unified Huntington's Disease Rating Scale, the Beck Depression Inventory, the Hamilton Rating Scale and the SF-36, a scale for the assessment of physical and mental QoL. RESULTS: Multiple regression analysis revealed that health-related physical and mental QoL was considerably influenced by the functional capacity. The mental QoL also correlated with the degree of depressive symptoms, age and the number of CAG repeats. However, there was no statistical relation between QoL and motor and cognitive abilities. DISCUSSION: This study underlines the relationship between function capacity and depressive symptoms with mental and physical QoL. This is the first time that hrQoL has been investigated in a German speaking cohort. The results are in accordance with previous studies of hrQoL in HD.

[Verbal memory in patients with major depression]. / Das verbale Gedächtnis bei depressiven Patienten.

INTRODUCTION: Patients with major depression commonly report memory deficits but studies on this topic have shown inconsistent results. The aim of this study was to determine whether patients with major depression showed any differences in explicit verbal memory compared to healthy controls. MATERIAL AND METHODS: We used the California verbal learning test (CVLT) in order to compare the explicit verbal memory of 30 patients (21 women and 9 men) to a healthy control group (23 women and 10 men). RESULTS: The results showed no significant differences between verbal memory performance of patients with major depression and healthy controls. DISCUSSION: Verbal memory of depressive patients with antidepressant pharmacotherapy showed no significant differences compared to a healthy control group. It can be assumed that verbal memory in depression depends on variable parameters (e.g. age, severity and duration of depression and medication). More studies with a larger number of patients should be conducted to obtain reliable results about explicit verbal memory in depression.

Plasmon resonance in warm dense matter.

Collective Thomson scattering with extreme ultraviolet light or x rays is shown to allow for a robust measurement of the free electron density in dense plasmas. Collective excitations like plasmons appear as maxima in the scattering signal. Their frequency position can directly be related to the free electron density. The range of applicability of the standard Gross-Bohm dispersion relation and of an improved dispersion relation in comparison to calculations based on the dielectric function in random phase approximation is investigated. More important, this well-established treatment of Thomson scattering on free electrons is generalized in the Born-Mermin approximation by including collisions. We show that, in the transition region from collective to noncollective scattering, the consideration of collisions is important.

Observations of plasmons in warm dense matter.

We present the first collective x-ray scattering measurements of plasmons in solid-density plasmas. The forward scattering spectra of a laser-produced narrow-band x-ray line from isochorically heated beryllium show that the plasmon frequency is a sensitive measure of the electron density. Dynamic structure calculations that include collisions and detailed balance match the measured plasmon spectrum indicating that this technique will enable new applications to determine the equation of state and compressibility of dense matter.

Lethal brain abscess due to the fungus Scedosporium apiospermum (teleomorph Pseudallescheria boydii) after a near-drowning incident: case report and review of the literature.

A 39-year-old healthy man developed a brain abscess weeks after a near-drowning incident. Scedosporium apiospermum, the anamorph of Pseudallescheria boydii, was isolated from the abscess. The patient died 153 days after the accident despite antifungal therapy. We discuss the role of antifungals and review the literature for comparable cases.

Ictal dystonic posturing in mesial versus neocortical temporal lobe seizures.

PURPOSE: Ictal contralateral dystonic posturing is a frequently observed clinical feature in temporal lobe seizures. It is generally interpreted as the result of spread of the ictal discharge into basal ganglia structure. In previous reports, analysing ictal behavior, a precise definition and description of the upper limb ictal dystonia is often lacking or contradictory. In our study we aimed to determine whether different subtypes of dystonia and their latency from the clinical onset of seizure might be of value for the differentiation between mesial temporal lobe epilepsy (MTLE) and neocortical temporal lobe epilepsy (NTLE). METHODS: Eighty seizures (51 MTLE and 29 NTLE) and 30 patients (20 MTLE and 10 NTLE) were analyzed with regard to dystonic posturing of the upper limb. Ictal dystonia was subdivided into different subtypes according to distinct clinical features. Their frequency and latency from the clinical onset of seizure were assessed. RESULTS: Frequencies of all subtypes were similar in MTLE and NTLE. Concerning the latencies contralateral dystonic posturing characterized by sustained muscle contractions with flexion of the wrist and fist closure, a frequently appearing feature, occurred significantly earlier in NTLE than in MTLE seizures. CONCLUSIONS: This difference between the two groups may provide a differentiation between an epileptic focus of mesial from neocortical temporal lobe origin.

Future aspects of the presurgical evaluation in epilepsy.

Epilepsy surgery is a successful therapeutic approach in patients with medically intractable epilepsy. The presurgical evaluation aims to detect the epileptogenic brain area by use of different diagnostic techniques. In this review article the current diagnostic procedures applied for this purpose are described. The diagnostic armamentarium can be divided conceptually into three different groups: assessment of function/dysfunction, structural/morphologic imaging methods and functional neuroimaging techniques. Properties, diagnostic power and limits of all diagnostic tools used in the diagnostic evaluation are discussed. In addition, future perspectives and the diagnostic value of new technologies are mentioned. Some are increasingly gaining acceptance in the routine preoperative diagnostic procedure like MR volumetry or MR spectroscopy of the hippocampus in patients with temporal lobe epilepsy. Some, on the other hand, like MEG and 11C-flumazenil PET, still remain experimental diagnostic tools as they are technically demanding and cost intensive. Besides the refinement of established techniques, co-registration of different modalities like spike-triggered functional MRI will play an important role in the non-invasive detection of the epileptic seizure focus and may change the regimen of the preoperative diagnostic work up of epilepsy patients in the future.

Replication of the linear chromosomal DNA from the centrally located oriC of Streptomyces ambofaciens revealed by PFGE gene dosage analysis.

From a cosmid clone of Streptomyces ambofaciens containing the dnaA and gyrAB genes, a 2.7-kb self-replicating DNA fragment containing the chromosome replication origin oriC was isolated. This cosmid was previously maped physically to a region near the middle of the 8-Mb linear chromosomal DNA. A pulsed-field gel electrophoresis time-course analysis revealed that sequences flanking oriC were overrepresented relative to the rest of the chromosomal DNA during rapid growth, indicating that this origin is active. In addition, the terminal regions of the chromosomal DNA showed a slight overrepresentation at the onset of stationary phase.

Characterization of two Streptomyces ambofaciens recA mutants: identification of the RecA protein by immunoblotting.

The recA gene was isolated from Streptomyces ambofaciens DSM40697. Its nucleotide sequence predicted a protein of 372 residues. Two recA mutants, NSAR1001 and NSAR57, obtained by gene disruption encoded a RecA protein lacking respectively 30 and at least 62 amino acids from the C-terminal end. NSAR1001 showed a wild-type sensitivity to UV light and oxolinic acid. In contrast, NSAR57 was highly sensitive to these agents and the loss of the inserted DNA restored the wild-type phenotype. Western blot analysis using antiserum to Escherichia coli RecA showed that overproduction of RecA was correlated with overtranscription of recA in an S. ambofaciens amplified mutant derived from genetic instability.

An amplifiable and deletable locus of Streptomyces ambofaciens RP181110 contains a very large gene homologous to polyketide synthase genes.

Streptomyces ambofaciens RP181110 produces the macrolide polyketide spiramycin. Like many other Streptomyces species, the RP181110 strain is prone to genetic instability involving genomic rearrangements (deletions and/or amplifications) in the large unstable region of the genome. It has previously been demonstrated that the amplification of a particular locus (AUD205) affects spiramycin biosynthesis and, conversely, the loss of this amplification is correlated with the restoration of antibiotic production. This report focuses on a 0.93 kb reiterated fragment specific for the AUD205 locus. Sequencing of 3596 bp including this reiteration revealed the presence of an ORF (orfPS) whose potential product was highly homologous to the EryA and Raps proteins, responsible for the biosynthesis of erythromycin in Saccharopolyspora erythraea and rapamycin in Streptomyces hygroscopicus, respectively. orfPS encodes a protein with at least four successive domains: ketoacyl synthase, acyltransferase, ketoreductase and acyl carrier protein. This organization is very similar to most eryA and rap modules. The reiterated sequence corresponds to the acyltransferase domain. orfPS was transcribed during rapid growth and stationary phase in RP181110 and overtranscribed in the amplified mutant. Both these results suggest that the gene encodes a type I polyketide synthase and its reorganization is responsible for the loss of spiramycin production in the amplified strains.

Characterization of the gor gene of the lactic acid bacterium Streptococcus thermophilus CNRZ368.

Cloning and characterization of the gor gene of the lactic acid bacterium Streptococcus thermophilus, encoding glutathione reductase, are described in this paper. This enzyme is a part of the enzymatic defences against oxidative stress in eukaryotic cells and in Gram-negative bacteria, but was never found in Gram-positive bacteria before this study. The amino acid sequence shares extensive similarities with glutathione reductases from other organisms, e.g. 62% amino acid identity with Escherichia coli protein. Northern blot analysis and glutathione reductase enzyme assays gave evidence that the gene is expressed in aerobically growing cells.

Preparation of two plasma membrane fractions from ascites tumour cells by gel chromatography on Sephacryl S-1000.

Two plasma membrane fractions from ascites tumour cells with differences in vesicle size were isolated by gel-exclusion chromatography on Sephacryl S-1000. Fraction 1 appeared in the void volume and had a vesicle diameter in the range 300-400 nm. Fraction 3, with an equilibrium constant (Kd) of 0.58, consisted of vesicles between 100 and 200 nm in diameter as measured by routine size analysis with the electron microscope and by calibration of the column with latex beads. The appearance of two plasma membrane fractions could also be confirmed by iodination of the surface membrane prior to fractionation. This gel chromatographic procedure represents a rapid and convenient method for the isolation of membrane material, which was enriched between five- and fourteen-fold based on the specific activity of the membrane-bound marker enzymes. Fraction 1 contained small amounts of lysosomal and Golgi membranes, and fraction 3 some material of the Golgi apparatus and the endoplasmic reticulum. The major portion of the contaminating membraneous material remained on the column and could be eluted with high salt buffer. The two plasma membrane fractions revealed some differences in 5'-nucleotidase specific activity and in the protein pattern, especially in the higher molecular weight range, as shown by sodium dodecyl sulphate gel electrophoresis.

Comparison of 5'-nucleotidase activities of isolated plasma membranes of two ascites cell variants.

The glycogen-containing ascites cell line was found to have a 3-5 times higher 5'-nucleotidase specific activity than the glycogen-free variant, resulting in different substrate affinity constants of Km = 0.14 mM and Km = 0.69 mM respectively. These activity differences were due to true 5'-nucleotidase as shown by its inactivation through specific inhibitors such as concanavalin A and alpha, beta-methylene adenosine diphosphate. Substrate specificity of the enzyme was similar in both cell lines, but differences were observed with respect to the pH optimum and stability.

Marking of olfactory axons of fishes by intravital staining with Procion brilliant yellow.

Olfactory axons of fishes can be traced after vital staining of the olfactory surface with the fluorescent dye Procion brilliant yellow M 4-RAN. Following selective accumulation by the receptor dendrites and perikarya the dye migrates intra-axonally over distances of more than 200 micrometer. Fluorescence microscope observation of formaldehyde fixed and paraffin sectioned preparations of the olfactory organ demonstrate clearly the system of intraepithelial axons and their first order bundles running toward the olfactory nerve.

[Selective staining by procion dyes of olfactory sensory neurons in the catfish Ictalurus nebulosus (author's transl)]. / Selektivdarstellung der Riechsinneszellen des Zwergwelses Ictalurus nebulosus mit Procionfarbstoffen.

Procion Brilliant Yellow M4RAN and Procion Yellow M4R applied to the catfish olfactory mucosa stain intravitally and enter the olfactory receptors by their dendrites. The dye invades the receptor pericaryon and subsequently migrates within the axon in distal direction. Fluorescence microscopy of aldehyd fixed and paraffin sectioned preparations reveals clear selective staining of the sensory neurons in yellow colour.