Gender associated developmental trajectories of SDQ-dysregulation profile and its predictors in children.

BACKGROUND: Severe mood dysregulation is common in childhood and can be highly impairing. The Dysregulation Profile (DP) can be considered as a broader phenotype of emotional dysregulation, including affect, cognition and behaviour. Since mood dysregulation may persist, but differently in boys and girls, the gender associated course needs to be considered longitudinally to gain a better insight in order to support the children more adequately. This study is focusing on gender associated subgroup trajectories of the Strengths and Difficulties Questionnaire-Dysregulation Profile (SDQ-DP) in middle childhood (9-13 years of age) and includes the potential impact of clinical and psychosocial characteristics. METHOD: The data set was available from the BELLA study on mental health and well-being in children and adolescents, which is the mental health module of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS). A representative epidemiological sample of 564 children living in Germany was examined at three assessment points over 2 years (data collection 2003-2006). The SDQ-DP of children aged 9-13 years was evaluated using Latent Class Growth Analysis (LCGA). RESULTS: For both genders three trajectories with low (girls 67.0% and boys 59.5%), moderate (girls 28.0% and boys 31.7%) and high SDQ-DP (girls 5.0% and boys 8.8%) scores were detected. The courses of low and moderate subgroups were stable, while in the high SDQ-DP subgroup boys showed a decreasing and girls an increasing trend in symptom severity on a descriptive level. The results of the multinomial logistic regression analyses revealed a significant influence of mainly externalising but also internalising problems both increasing the risk of moderate and high SDQ-DP in both genders. Good quality of life was a protective factor for the SDQ-DP course in all subgroups. CONCLUSION: In addition to the known clinical and scientific value of the SDQ-DP, three distinguishable trajectories of SDQ-DP in boys and girls could be found. High externalising problems at the beginning of the trajectory were associated with an undesirable course of SDQ-DP. These findings might be helpful for better psychoeducation, counselling and monitoring in clinical cases and public health.

Traumatic lumbar disc herniation: A systemic case review and meta-analysis.

Introduction: Traumatic lumbar disc herniation (TLDH) without fracture in the in-situ motion segment is a rare occurrence compared with degenerative herniation. Research question: This study provides a systematic discussion of various aspects related to the diagnosis of TLDH. Material and methods: This review includes 12 cases of TLDH with MR-images since 2009 published in the PubMed and one adjunct illustration. The cases were categorized into two groups for a comprehensive analysis, TLDH with or without in-situ segment fracture. Additionally, we reported a case of a 43-year-old female patient with a recent stenosing TLDH at L5/S1, accompanied by a large sequestration (disc herniation stage-4, and Michigan State University Classification: MSU 3-AB) and an endplate compression fracture at L2 (AO A1). Results: Isolated traumatic lumbar disc herniation is possible, but it is required exclude cases with fractures in the in-situ motion segment. Discussion and conclusion: Trauma with related injury mechanisms is the highest priority for the diagnosis of TLDH. Low-grade disc degeneration without significant instability could be accepted for diagnosing TLDH. A TLDH on MR images might show a slightly lower T2-signal compared to the CSF and a homogeneous T1-signal like the spinal cord, as well as a similar STIR-signal of the sequestration and CSF. If necessary, a histological examination could be performed to evaluate the degenerative changes in the injured disc, especially to assist the evaluation due to legal reasons.

Clear-cell sarcoma of the soft tissue--a rare diagnosis with a fatal outcome.

Clear-cell sarcomas account for less than 1% of all soft tissue tumours. They most often occur in middle-aged adults as a deeply located lesion with predilection to the tendons and aponeuroses. The aim of the present study was to show possible influencing factors on the outcome after surgical treatment in a detailed case series. We reviewed the medical records of 11 patients with the diagnosis of a clear-cell sarcoma of the soft tissue. These cases were analysed with regard to age, gender, localisation, tumour size, recurrence free survival and overall survival. A minimum follow up of 12 months was achieved. The mean age at the point of diagnosis was 47.9 years. Metastases occurred after a mean of 19.2 months. In the cases with a tumour diameter >5 cm, metastases occurred earlier. When treated in a specialist centre, metastases occurred later. Patients died a mean of 18.4 months after developing metastatic disease. Patients with tumour size >5 cm at the point of primary diagnosis died earlier than patients with a tumour size <5 cm. It is important to detect clear-cell sarcomas as soon as possible and the final surgical treatment should be performed in a centre familiar with the treatment of soft tissue tumours not only to prolong overall survival, but also to treat the patient in a multiprofessional team.

[Problem cases of metatarsalgia]. / Problemfälle bei Metatarsalgie.

Metatarsalgia is characterized by pain under the metatarsal heads and is a very common cause of foot pain among adults. Symptoms can be isolated or in combination with accompanying deformities occurring in the forefoot and/or hindfoot. In the foreground of the treatment is the exhaustion of conservative forms of therapy to minimize the symptoms of local pressure increase and callus under the metatarsal heads. In addition, various surgical methods are available, such as corrective osteotomy of the metatarsal bone, soft tissue interventions and the correction of associated deformities. The indications for surgical intervention should be made with caution in order to avoid failures and complaints persisting after surgery. The most common problems are an inadequate indication for surgery, technical problems and insufficient postoperative treatment.

The chondramides: cytostatic agents from myxobacteria acting on the actin cytoskeleton.

BACKGROUND: Chondramides are cyclodepsipeptides produced by strains of the myxobacterium, Chondromyces crocatus. These peptides, which have been reported to inhibit yeast and mammalian cell proliferation, are related to jasplakinolide, which has been isolated from marine sponges of the genus Jaspis and has been shown to interfere with the actin cytoskeleton (a structural component of cells that helps maintain their shape and is involved in processes, such as cell division and cell locomotion). We studied the effects of the chondramides (A, B, C, and D) on tumor cell growth, on cytoskeletal structure, and on actin polymerization in vitro and compared these effects with those of cytochalasin D and jasplakinolide. METHODS: Cell proliferation was measured by means of tetrazolium salt reduction assays. Effects on the cytoskeleton were studied by use of fluorescence techniques, and actin polymerization in vitro was measured by means of viscosimetry. RESULTS: Proliferation of tested tumor cell lines was inhibited by the chondramides. Concentrations that inhibited proliferation by 50% (IC50 values) ranged from 3 to 85 nM and were of the same order of magnitude as those found for cytochalasin D and jasplakinolide. Fluorescence staining of potoroo cells incubated with chondramides A and B showed that organization of the actin cytoskeleton was disrupted; however, the microtubule system was not affected. Viscosimetric measurement showed that, depending on the experimental conditions, chondramide A induced or accelerated actin polymerization in vitro. CONCLUSION: The chondramides--unlike jasplakinolide--can be produced in large amounts by fermentation, and, similar to jasplakinolide, they appear to have antiproliferative activity against carcinoma cell lines by targeting the actin cytoskeleton.

Metabolic diversity in myxobacteria: identification of the myxalamid and the stigmatellin biosynthetic gene cluster of Stigmatella aurantiaca Sg a15 and a combined polyketide-(poly)peptide gene cluster from the epothilone producing strain Sorangium cellulosum So ce90.

Myxobacterial strains producing polyketides (PKs) assumed to be biosynthesized by a type I polyketide synthase (PKS) were analysed. Myxobacteria also produce a variety of polypeptides (PP) and PKs with incorporated amino acids ('mixed PK-PP'). In order to be able to identify the biosynthetic gene clusters for these metabolites a PCR based approach has been developed to clone ketosynthase (KS) domains of PKS genes from these organisms. Conserved regions of peptide synthetases of the non-ribosomal type (NRPS) were also amplified via PCR. KS fragments from Stigmatella aurantiaca Sg a15 were used for chromosomal gene inactivation experiments resulting in a series of mutants including such that were unable to produce stigmatellins and myxalamids. A NRPS fragment and PKS fragments from Sorangium cellulosum So ce90 were used to identify cosmids hybridizing with both types of probes from a genomic library. Both a NRPS and a PKS fragment were cloned and sequenced from a relatively short restriction fragment of one of these cosmids. The method described here should be very useful to clone and identify PKS, NRPS and mixed PKS-NRPS from myxobacteria in general and thereby open opportunities to use the biochemical diversity of these bacteria for genetic engineering and combinatorial biosynthesis.

Novel features in a combined polyketide synthase/non-ribosomal peptide synthetase: the myxalamid biosynthetic gene cluster of the myxobacterium Stigmatella aurantiaca Sga15.

BACKGROUND: Myxobacteria have been well established as a potent source for natural products with biological activity. They produce a considerable variety of compounds which represent typical polyketide structures with incorporated amino acids (e.g. the epothilons, the myxothiazols and the myxalamids). Several of these secondary metabolites are effective inhibitors of the electron transport via the respiratory chain and have been widely used. Molecular cloning and characterization of the genes governing the biosynthesis of these structures is of considerable interest, because such information adds to the limited knowledge as to how polyketide synthases (PKSs) and non-ribosomal peptide synthetases (NRPSs) interact and how they might be manipulated in order to form novel antibiotics. RESULTS: A DNA region of approximately 50000 base pairs from Stigmatella aurantiaca Sga15 was sequenced and shown by gene disruption to be involved in myxalamid biosynthesis. Sequence analysis reveals that the myxalamids are formed by a combined PKS/NRPS system. The terminal NRPS MxaA extends the assembled polyketide chain of the myxalamids with alanine. MxaA contains an N-terminal domain with homology to NAD binding proteins, which is responsible during the biogenesis for a novel type of reductive chain release giving rise to the 2-amino-propanol moiety of the myxalamids. The last module of the PKS reveals an unprecedented genetic organization; it is encoded on two genes (mxaB1 and mxaB2), subdividing the domains of one module from each other. A sequence comparison of myxobacterial acyl-transferase domains with known systems from streptomycetes and bacilli reveals that consensus sequences proposed to be specific for methylmalonyl-CoA and malonyl-CoA are not always reliable. CONCLUSIONS: The complete biosynthetic gene cluster of the myxalamid-type electron transport inhibitor from S. aurantiaca Sga15 has been cloned and analyzed. It represents one of the few examples of combined PKS/NRPS systems, the analysis and manipulation of which has the potential to generate novel hybrid structures via combinatorial biosynthesis (e.g. via module-swapping techniques). Additionally, a new type of reductive release from PKS/NRPS systems is described.

Multiple hybrid polyketide synthase/non-ribosomal peptide synthetase gene clusters in the myxobacterium Stigmatella aurantiaca.

Many bacterial and fungal secondary metabolites are produced by polyketide synthases (PKS) and non-ribosomal peptide synthetases (NRPS). Recently, it has been discovered that these modular enzymatic systems can also closely cooperate to form natural products. The analysis of the corresponding biosynthetic machineries, in the form of hybrid systems, is of special interest for combinatorial biosynthesis, because the combination of PKS and NRPS can lead to an immense variety of structures that might be produced. During our screening for hybrid PKS/NRPS systems from myxobacteria, we scanned the genome of Stigmatella aurantiaca DW4/3-1 for the presence of gene loci that encode both the PKS and NRPS genes. In addition to the previously characterized myxothiazol system, we identified three further hybrid loci, three additional PKS and one further NRPS gene locus. These were analyzed by hybridization, physical mapping, PCR with degenerate oligonucleotides and sequencing of fragments of the gene clusters. The function of these genes was not known but it had already been speculated that one compound produced by the strain and detected via HPLC was a secondary metabolite. This was based on the observation that its production is dependent on an active copy of the phosphopantetheinyl transferase gene mtaA. We show here that one of the identified hybrid gene loci is responsible for the formation of this secondary metabolite. In agreement with the genetic data, the chemical structure resembles a cyclic polypeptide with a PKS sidechain. Our data show that S. aurantiaca has a broader genetic capacity to produce natural products than the number of compounds isolated from the strain so far suggests.

Transcription and proper splicing of a mammalian gene in yeast.

The house mouse strain C57BL/6 harbours 64 copies of the multicopy gene Sp100-rs. Three of these are contained in the yeast artificial chromosome (YAC) clone yMm75. Four Sp100-rs transcripts of 3.0, 2.6, 1.6 and 1.3kb were detected by Northern hybridization in the yMm75-harbouring line of Saccharomyces cerevisiae. Additional and less abundant transcripts were detected by RT-PCR. With one exception, the YAC-derived Sp100-rs transcripts were a subset of those found in the C57BL/6 mouse. This indicates transcription and proper splicing of murine pre-mRNAs in yeast. Analysis of the splice sites shows that the yeast splicing machinery accepts splice sites that deviate from the standard yeast consensus sequences. It may be feasible, therefore, at least in a fair proportion of cases, to exploit the mammalian mRNAs present in transgenic yeast for gene recognition of YAC-inserts.

Diagnostic value of ambulatory Holter monitoring for the detection of coronary artery disease in patients with variable threshold angina pectoris.

Patients with chronic stable angina pectoris may present with either fixed or variable threshold symptoms. To evaluate the diagnostic value of ambulatory Holter monitoring for the detection of coronary artery disease (CAD) in patients with variable threshold angina, 216 consecutive candidates for coronary angiography were investigated prospectively. For comparison, a group of 55 consecutive patients with fixed threshold angina was studied under the same conditions. Patients with prior myocardial infarction or angiographically documented CAD were excluded. Within 4 months of Holter monitoring, the advised coronary angiography was performed in 77% of the patients with variable threshold angina and in 89% of the patients with fixed threshold angina (p less than 0.05). The prevalence of CAD was markedly lower in patients with variable threshold angina compared to patients with fixed threshold angina (54 vs 90%, p less than 0.001). CAD patients of both subgroups, however, did not differ significantly with respect to the number of obstructed vessels, the Gensini coronary score, the number with impaired left ventricular function (ejection fraction less than 50%) or the duration of ischemic episodes during Holter monitoring. Diagnostic accuracy of Holter monitoring did not differ between variable and fixed threshold angina groups (67 vs 78%). In 91% of the patients results obtained by Holter monitoring could be compared to the results of a bicycle stress test. In patients with fixed threshold angina the diagnostic accuracy was similar for both tests (80 vs 80%). In patients with variable threshold angina, the diagnostic accuracy of Holter monitoring exceeded that of the exercise stress test (68 vs 55%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Silent myocardial ischemia as a potential link between lack of premonitoring symptoms and increased risk of cardiac arrest during physical stress.

The risk of cardiac arrest is increased during strenuous physical exercise in patients with stable coronary artery disease (CAD). Because premonitoring symptoms are rarely observed, silent myocardial ischemia may represent the pathophysiological basis for the induction of malignant ventricular arrhythmias. Holter monitoring was, therefore, performed in 40 consecutive patients entering a randomized intervention trial on progression of CAD. In 20 of 21 participants (95%) in the intervention program greater than or equal to 1 episode of silent myocardial ischemia was observed during the initial training session. The mean duration of silent myocardial ischemia per patient was 25 +/- 13 min/hr of training session. During normal daily activity only 5 patients (24%) experienced greater than or equal to 1 episode of silent myocardial ischemia (p less than 0.001) yielding a mean duration of 0.6 +/- 1.3 minutes of silent myocardial ischemia/hr of ordinary activity per patient (p less than 0.001 vs training session). During a control period of 24 hours without exercise training the incidence (33%) and mean duration of silent myocardial ischemia (0.8 +/- 2.1 min/hr/patient) were similar to those during normal daily activity on the day of the training session. During the training session the occurrence of frequent or repetitive ventricular arrhythmias was related to 10 silent myocardial ischemia episodes detected in 5 patients. During normal daily activity in 1 patient only was the onset of malignant ventricular arrhythmias associated with silent myocardial ischemia (p less than 0.05). Conditions and results of the Holter studies in the control group patients were comparable to those of the patients in the intervention group on the day without physical exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Gene concentration varies in the macronucleus of Tetrahymena.

The ratio of amounts of specific genes to total DNA (gene concentration) in different lines of Tetrahymena and at different conditions has been determined by hybridization with specific gene probes. The concentration of the DNA coding for rRNAs is specific for different strains. It also decreases with growth rate, the extent of reduction being different in various species. The rDNA concentration increases unproportionally when the size mutant D9 grows to double the volume upon transfer to the non permissive temperature. rDNA concentration, therefore, changes specifically with physiological status. Genes on other DNA fragments occur in other proportions than the rDNA. The concentration of the S25 ribosomal protein gene is reduced significantly upon entering the stationary phase, while the concentrations of the other genes tested appear unchanged. The results indicate that the amounts of specific DNA molecules in the macronucleus of Tetrahymena are controlled depending on the strains used and on the conditions.

The aurachins, new quinoline antibiotics from myxobacteria: production, physico-chemical and biological properties.

The aurachins, new quinoline alkaloids, were extracted with acetone from the biomass of the myxobacterium, Stigmatella aurantiaca strain Sg a15 and purified by column chromatography. The four described aurachins A, B, C and D, were inhibitory for Gram-positive bacteria and a few yeasts and molds. They blocked NADH oxidation in beef heart submitochondrial particles.

Crocacin, a new electron transport inhibitor from Chondromyces crocatus (myxobacteria). Production, isolation, physico-chemical and biological properties.

Crocacin was isolated from the biomass of the myxobacterium Chondromyces crocatus, strain Cm c3. It inhibited the growth of a few Gram-positive bacteria and a wide spectrum of yeasts and molds. In beef heart submitochondrial particles, crocacin blocked the electron transport within the bc1-segment (complex III) and caused a red shift in the reduced spectrum of cytochrome b with a maximum at 569 nm.

Stigmatellin, a new antibiotic from Stigmatella aurantiaca (Myxobacterales). I. Production, physico-chemical and biological properties.

An antibiotic activity was extracted from the cell mass of the myxobacterium, Stigmatella aurantiaca strain Sg a15. The antibiotic was toxic for yeasts and filamentous fungi, but not for most bacteria. The compound had the molecular formula C30H42O7, appears to be a new antibiotic, and was named stigmatellin. In addition to stigmatellin, the strain produced relatively large quantities of a second, structurally unrelated antibiotic, a mixture of three myxalamid homologues.

Production, isolation, physico-chemical and biological properties of angiolam A, a new antibiotic from Angiococcus disciformis (Myxobacterales).

Angiolam A, a new lactone-lactam antibiotic, was isolated from the culture broth of the myxobacterium Angiococcus disciformis strain An d30. It was active against a few Gram-positive bacteria and mutant strains of Escherichia coli with increased permeability. It appears to interfere with protein synthesis.

Myxochelin A, a new iron-chelating compound from Angiococcus disciformis (Myxobacterales). Production, isolation, physico-chemical and biological properties.

Myxochelin A, a new catechole siderophore, was isolated from the culture broth of the myxobacterium, Angiococcus disciformis strain An d30. As is the case with other iron-chelating compounds the production of myxochelin A could be markedly increased up to 44 mg/liter by fermentation at low iron concentrations (10(-7) M FeCl3). The new substance showed weak activity against some bacteria.

Nannochelins A, B and C, new iron-chelating compounds from Nannocystis exedens (myxobacteria). Production, isolation, physico-chemical and biological properties.

Novel citrate-hydroxamate siderophores, named nannochelins A, B and C, were isolated from the culture broth of the myxobacterium Nannocystis exedens strain Na e485. The new substances showed weak growth-inhibitory activity against some bacteria and fungi.

Chondramides A approximately D, new antifungal and cytostatic depsipeptides from Chondromyces crocatus (myxobacteria). Production, physico-chemical and biological properties.

Novel depsipeptides, named chondramides were produced at levels up to 4.3 mg/liter by several myxobacteria of the genus Chondromyces. The compounds are structurally closely related to jaspamide/jasplakinolide from marine sponges of the genus Jaspis. Initially the chondramides were detected in acetone extracts of the biomass of Chondromyces crocatus, strain Cm c2. So far, four structural variants could be characterized, the chondramides A approximately D. They inhibited the growth of a few yeasts and showed high cytostatic activity against cultivated human and animal cells.

Apicularens A and B, new cytostatic macrolides from Chondromyces species (myxobacteria): production, physico-chemical and biological properties.

A novel macrolide, apicularen A, was produced by several species of the genus Chondromyces. Initially it was discovered by bioassay-guided RP-HPLC-fractionation of culture extracts of Chondromyces robustus, strain Cm a13. Apicularen A showed no antimicrobial activity, but was highly cytotoxic for cultivated human and animal cells, with IC50 values ranging between 0.1 and 3 ng/ml. A cometabolite of apicularen A, the N-acetylglucosamine glycoside apicularen B, was distinctly less cytotoxic with IC50 values between 0.2 and 1.2 microg/ml, and showed weak activity against a few Gram-positive bacteria. Apicularen A is chemically closely related to the salicylihalamides A and B from the marine sponge Haliclona sp.