Cortical abnormalities in bipolar disorder: an MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group.

Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen's d=-0.293; P=1.71 × 10-21), left fusiform gyrus (d=-0.288; P=8.25 × 10-21) and left rostral middle frontal cortex (d=-0.276; P=2.99 × 10-19). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD.

Grey matter structural differences in alcohol-dependent individuals with and without comorbid depression/anxiety-an MRI study.

Although depression and anxiety disorders are common comorbid conditions in alcohol dependence, few structural brain imaging studies have compared alcohol-dependent subjects with and without such comorbidity. In the current study, brain scans of 35 alcohol-dependent with and 40 individuals without diagnosis of a comorbid ICD-10 depressive or anxiety disorder receiving detoxification inpatient treatment were evaluated. Thickness and volumes of automatically segmented neuroanatomical structures were measured in FreeSurfer. Furthermore, associations of brain structure with biological markers and clinical severity markers of alcohol dependence were assessed. Despite comparable addiction severity, the non-comorbid group had evidence of higher cytotoxic effects of alcohol use on hepatic and haematological markers, and showed significantly smaller volumes of total cerebral, and cerebellar grey matter. Similarly, they showed unexpected smaller hippocampal and nucleus accumbens volumes, and thinner frontal, temporal and occipital cortices. Smaller brain volumes correlated with increased markers of hepatic and haematological dysfunction, and with longer duration of alcohol dependence in the non-comorbid group. Evidence of higher biomarkers of alcohol use may be indicative of more severe alcohol dependence or higher vulnerability to ethanol toxicity in this group. Furthermore, psychopathology-related drug treatment, which occurred in 53% of the comorbid group over the recent years, or tissue inflammation may have a moderate effect on the grade of cerebral atrophy in alcohol-dependent patients. Longitudinal studies are needed to investigate this issue more fully.

[Development of a Set of Rehabilitation Related Multiple-choice-questions in Medical Education]. / Entwicklung eines Prüfungsfragenpools für die rehabilitationsbezogene Lehre im Studiengang Humanmedizin.

In the rehabilitation related teaching as in other subjects of the medical training multiple choice (MC) examinations are the most frequent type of examinations. Compared to other subjects only a few MC questions are available for the interdisciplinary subject Rehabilitation. Therefore an internet-based online platform "Pool of rehabilitation related MC questions" was developed to assist teachers regarding the provision, design and organization of high-quality rehabilitation related MC questions. A total of 502 existing MC questions were collected from 12 German Medical Faculties. After removal of 59 questions not suitable for formal and content reasons a total of 443 questions were presented to 6 reviewers for triple reviews (a total of 1 329 expert reviews received). Of the 502 questions 335 (67%) were included in the final pool including short cases with 46 case studies. The questions refer to the following learning objectives: principles of rehabilitation (40%), rehabilitative interventions (20%), diagnosis and assessment (18%), initiation and control of the rehabilitation process (12%) and methods/quality of rehabilitative interventions (10%). The use of the online platform modules resp. the questions are for free for lecturers. This includes the compilation and output of complete examinations, the statistical evaluation, and other audit-related materials. This examination pool counteracts the current lack of quality-assured rehabilitation-related MC questions and contributes to set common standards for the Medical Faculties to rehabilitation related examinations.

[Analysis of therapeutic procedures in 5,838 rehab patients following total hip or total knee replacement]. / Ergebnisse einer Analyse der therapeutischen Leistungsdaten (KTL-Daten) von 5,838 Rehabilitandinnen und Rehabilitanden nach Hüft- bzw. Knieendoprothesenimplantation.

In the framework of the Practice Guidelines programme of the German Federal Pension Insurance (DRV Bund) evidence-based standards for rehabilitation following total hip or knee replacement are to be developed. The results of a quantitative analysis of present health-care on the basis of documented treatments (KTL) from 5 838 rehab patients are reported here. Based on a systematic review of international trials, treatment modules were specified and analyzed as to frequency and duration of current treatment. Furthermore, separate analyses were conducted for gender, age, and different clinics. No differences were found among rehab facilities as to exercise therapy, physiotherapy, or health education. However, psychological treatment and specific trainings differed considerably between centres.

Candidate gene networks and blood biomarkers of methamphetamine-associated psychosis: an integrative RNA-sequencing report.

The clinical presentation, course and treatment of methamphetamine (METH)-associated psychosis (MAP) are similar to that observed in schizophrenia (SCZ) and subsequently MAP has been hypothesized as a pharmacological and environmental model of SCZ. However, several challenges currently exist in diagnosing MAP accurately at the molecular and neurocognitive level before the MAP model can contribute to the discovery of SCZ biomarkers. We directly assessed subcortical brain structural volumes and clinical parameters of MAP within the framework of an integrative genome-wide RNA-Seq blood transcriptome analysis of subjects diagnosed with MAP (N=10), METH dependency without psychosis (MA; N=10) and healthy controls (N=10). First, we identified discrete groups of co-expressed genes (that is, modules) and tested them for functional annotation and phenotypic relationships to brain structure volumes, life events and psychometric measurements. We discovered one MAP-associated module involved in ubiquitin-mediated proteolysis downregulation, enriched with 61 genes previously found implicated in psychosis and SCZ across independent blood and post-mortem brain studies using convergent functional genomic (CFG) evidence. This module demonstrated significant relationships with brain structure volumes including the anterior corpus callosum (CC) and the nucleus accumbens. Furthermore, a second MAP and psychoticism-associated module involved in circadian clock upregulation was also enriched with 39 CFG genes, further associated with the CC. Subsequently, a machine-learning analysis of differentially expressed genes identified single blood-based biomarkers able to differentiate controls from methamphetamine dependents with 87% accuracy and MAP from MA subjects with 95% accuracy. CFG evidence validated a significant proportion of these putative MAP biomarkers in independent studies including CLN3, FBP1, TBC1D2 and ZNF821 (RNA degradation), ELK3 and SINA3 (circadian clock) and PIGF and UHMK1 (ubiquitin-mediated proteolysis). Finally, focusing analysis on brain structure volumes revealed significantly lower bilateral hippocampal volumes in MAP subjects. Overall, these results suggest similar molecular and neurocognitive mechanisms underlying the pathophysiology of psychosis and SCZ regardless of substance abuse and provide preliminary evidence supporting the MAP paradigm as an exemplar for SCZ biomarker discovery.

Interaction of DNA with DNA binding proteins. III. Infectivity of protein-complexed phage fd DNA in Escherichia coli spheroplasts.

Complex formation of circular, single-stranded phage fd DNA with Escherichia coli DNA binding protein HD or phage fd gene 5 protein keeps infection of E. coli spheroplasts at the level of free phage DNA, whereas complexes of this DNA with E. coli DNA unwinding protein show a strongly reduced efficiency of transfection. Displacement of the unwinding protein by HD protein or gene 5 protein also maintains the poor adsorption of the complexes to spheroplasts. Free E. coli DNA unwinding protein and residual amounts of this protein bound to the DNA may interfere with the adsorption and the uptake of the phage genome.

Peritonitis by scedosporium apiospermum in a patient undergoing continuous ambulatory peritoneal dialysis.

A case of peritonitis due to Scedosporium apiospermum in a boy undergoing continuous ambulatory peritoneal dialysis is reported. The finding of suggestive tissual form of the fungus in the effluent hastened the diagnosis of the infection.

[Quality of water of dental units. A survey in the region of Berne, Switzerland]. / Wasserqualität in zahnärztlichen Behandlungseinheiten: Eine Standortbestimmung in der Region Bern.

The aim of this study was to assess the microbial contamination of the water from 175 dental units, which had not been in use for at least 12 hours, and to determine the usefulness of rinsing the water lines for 3 minutes. Only 10% of all units fulfilled all criteria for drinking water. Frequently the total bacterial counts markedly exceeded 100 CFU/ml. In all cases the rinsing decreased bacterial loads significantly. Bacterial contamination of water lines increased with the time the dental units remained unused. It is recommended to rinse dental unit water lines daily for at least 3 minutes before working on patients.

[Systematic literature analysis on therapies applied in rehabilitation of hip and knee arthroplasty: methods, results and challenges]. / Systematische Literaturanalyse zu Therapien in der Rehabilitation nach Hüft- und Kniegelenks-Total-Endoprothesen: Methoden, Ergebnisse und Herausforderungen.

Evidence-based medicine is a central issue in medical practice. This also applies to rehabilitation services. The German Statutory Pension Insurance meets this need in its guideline programme. Amongst others a guideline for rehabilitation following hip or knee arthroplasty is currently being developed. In this context a hierarchic, systematic literature analysis was conducted summarising the current state of evidence with reference to the effects and the treatment requirements (frequency and duration) of different rehabilitative therapies following total hip or knee replacement. In the first step, a search for evidence-based guidelines, systematic reviews and health technology assessments was conducted. Secondly, search strategies for primary literature in the following databases were designed: Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and PsychINFO (01/1997-09/2007). Additionally, a handsearch of several German journals not listed in the databases was conducted. Randomized trials were preferred, however, non-randomized trials were included if the intervention and control groups were comparable with regard to the baseline parameters. Results can be classified into three categories: (1) therapies for which evidence for (positive) effects was found, (2) therapies for which evidence was found, however, their transferability onto rehabilitation in Germany should be discussed (e. g., studies on immediate post-surgery interventions), and (3) therapies for which no methodologically appropriate trials could be found. The literature reviewed does not allow for final conclusions as to frequency and duration of different therapeutic interventions within the rehabilitation time frame in Germany (usually the first three weeks post discharge from hospital). Overall, there is a need for further research.

[Therapeutic results with the aromatic retinoid (Tigason) in Sharp syndrome and progressive scleroderma]. / Therapeutische Erfolge mit aromatischem Retinoid (Tigason) bei Sharp-Syndrom und progressiver Sklerodermie.

As experimental findings indicated inhibitory action of aromatic retinoid on microtubule polymerisation and collagen metabolism of mesenchymal cells, we decided to treat 5 patients suffering from progressive systemic sclerosis as well as 3 patients with Sharp's syndrome with aromatic retinoid (Tigason). All 8 patients of this preliminary study responded positively to this therapy, but there were individual differences. The dosage corresponded to that applied in psoriasis. There were no severe side effects observed. In our opinion, these results justify the application of aromatic retinoid in patients suffering from progressive systemic sclerosis or Sharp's syndrome.

Molecular cloning and expression of 4-coumarate:coenzyme A ligase, an enzyme involved in the resistance response of soybean (Glycine max L.) against pathogen attack.

We have isolated three classes of cDNAs that probably encode three 4-coumarate:coenzyme A ligase (4CL) isoenzymes in soybean (Glycine max L.). The deduced amino acid sequences reveal several regions of extended sequence identity among 4CLs of all plants analyzed to date. The sequences of two of these regions are consistent with a domain structure proposed for a group of enzymes catalyzing the ATP-dependent covalent binding of AMP to their substrates during the reaction sequence. By using two cDNA fragments that do not cross-hybridize under the conditions used, we demonstrate that 4CL in soybean is very likely encoded by a small gene family. Members of this family are differentially expressed in soybean cell cultures treated with beta-glucan elicitors of Phytophthora megasperma f. sp. glycinea or in soybean roots infected with either an incompatible or compatible race of the fungus. These results are in agreement with our previous observation that elicitor treatment of soybean cells caused a preferential enhancement in the activity level of one of the 4CL isoenzymes. In soybean, 4CL isoenzymes possessing different substrate affinities for substituted cinnamic acids, and showing differential regulation to environmental stress, may play a pivotal role in distributing substituted cinnamate intermediates at a branch point of general phenylpropanoid metabolism into subsequent specific pathways.

Inhibitory action of a conditioning procedure on visual responsive neurons of the nucleus reticularis thalami in rats.

In urethane anesthetized rats neuronal responses of the visual part of nucleus reticularis thalami (vTR) to light were compared with those during pairing light as a conditioned stimulus (CS) with the electrical stimulation of the rat's tail (US). The intensity of the US was adjusted to the minimum required to evoke a slight freezing behavior in the awake rat. The firing rate of most vTR neurons decreased in the period between light and US application (P less than 0.01). Significant response modulations to light were observed in 39% of the units, in most of them they persisted over an extinction period of 15 min. In addition, neurons which were predominantly inhibited by conditioning sometimes changed from regular spiking to a burst pattern. The results support the hypothesis that conditioning related facilitation of geniculate neurons observed in previous experiments can be explained at least partly by disinhibition of geniculate units from vTR.

A DNA fragment from the origin of single-strand to double-strand DNA replication of bacteriophage fd.

A specific complex is formed between fd DNA, Escherichia coli DNA unwinding protein, and RNA polymerase (EC 2.7.7.6; nucleosidetriphosphate:RNA nucleotidyltransferase) during the first steps in the conversion of the single-stranded viral DNA to the double-stranded replicative form. In this complex a unique DNA fragment of about 120 nucleotides is protected against nuclease digestion. Both the requirements for its isolation and its position on the map of the phage genome indicate that the fragment contains the origin of single-strand to double-strand DNA replication. The isolated DNA fragment possesses double-strand-like characteristics, which protect it from being covered by the DNA unwinding protein and thus indirectly positions the RNA polymerase to the origin of replication.

[Magnesium seeding in therapy of pediatric hemangioma of the temporal region, lower eyelid and orbit]. / Magnesium-Spickung zur Therapie eines kindlichen Hämangioms im Bereich von Schläfe, Unterlid und Orbita.

BACKGROUND: Magnesium seeding of haemangiomas is a form of treatment already successfully used in 1900. PATIENT: We report about a male infant with a haemangioma of the left temporal region, underlid and orbit. Maximum depth at the time of indication for magnesium seeding was 28 mm with an intraorbital extension of 7 mm. COURSE OF THERAPY: Magnesium seeding of the haemangioma first lead to a standstill and within 8 weeks to a significant remission. After this period, maximum depth was 6.7 mm without any intraorbital extension. CONCLUSION: Magnesium seeding is a hopeful and low-risked alternative in the therapy of infantile haemangiomas.