A gold speciation that adds a second layer to synergistic gold-copper toxicity in Cupriavidus metallidurans.

The metal-resistant bacterium Cupriavidus metallidurans occurs in metal-rich environments. In auriferous soils, the bacterium is challenged by a mixture of copper ions and gold complexes, which exert synergistic toxicity. The previously used, self-made Au(III) solution caused a synergistic toxicity of copper and gold that was based on the inhibition of the CupA-mediated efflux of cytoplasmic Cu(I) by Au(I) in this cellular compartment. In this publication, the response of the bacterium to gold and copper was investigated by using a commercially available Au(III) solution instead of the self-made solution. The new solution was five times more toxic than the previously used one. Increased toxicity was accompanied by greater accumulation of gold atoms by the cells. The contribution of copper resistance determinants to the commercially available Au(III) solution and synergistic gold-copper toxicity was studied using single- and multiple-deletion mutants. The commercially available Au(III) solution inhibited periplasmic Cu(I) homeostasis, which is required for the allocation of copper ions to copper-dependent proteins in this compartment. The presence of the gene for the periplasmic Cu(I) and Au(I) oxidase, CopA, decreased the cellular copper and gold content. Transcriptional reporter gene fusions showed that up-regulation of gig, encoding a minor contributor to copper resistance, was strictly glutathione dependent. Glutathione was also required to resist synergistic gold-copper toxicity. The new data indicated a second layer of synergistic copper-gold toxicity caused by the commercial Au(III) solution, inhibition of the periplasmic copper homeostasis in addition to the cytoplasmic one.IMPORTANCEWhen living in auriferous soils, Cupriavidus metallidurans is not only confronted with synergistic toxicity of copper ions and gold complexes but also by different gold species. A previously used gold solution made by using aqua regia resulted in the formation of periplasmic gold nanoparticles, and the cells were protected against gold toxicity by the periplasmic Cu(I) and Au(I) oxidase CopA. To understand the role of different gold species in the environment, another Au(III) solution was commercially acquired. This compound was more toxic due to a higher accumulation of gold atoms by the cells and inhibition of periplasmic Cu(I) homeostasis. Thus, the geo-biochemical conditions might influence Au(III) speciation. The resulting Au(III) species may subsequently interact in different ways with C. metallidurans and its copper homeostasis system in the cytoplasm and periplasm. This study reveals that the geochemical conditions may decide whether bacteria are able to form gold nanoparticles or not.

The specific expression patterns of sensory neuron membrane proteins are retained throughout the development of the desert locust Schistocerca gregaria.

The desert locust Schistocerca gregaria detects odorants through olfactory sensory neurons (OSNs) that are surrounded by non-neuronal support cells (SCs). OSNs and SCs are housed in cuticle structures, named sensilla found abundantly on the antenna in all developmental stages of the hemimetabolic insect. In insects, multiple proteins expressed by OSNs and SCs are indicated to play a pivotal role in the detection of odorants. This includes insect-specific members of the CD36 family of lipid receptors and transporters called sensory neuron membrane proteins (SNMPs). While the distribution pattern of the SNMP1 and SNMP2 subtypes in OSNs and SCs across different sensilla types has been elucidated for the adult S. gregaria antenna, their localization in cells and sensilla of different developmental stages is unclear. Here, we determined the SNMP1 and SNMP2 expression topography on the antenna of the first, third and fifth instar nymphs. Through FIHC experiments we found that in all developmental stages SNMP1 is expressed in OSNs and SCs of the trichoid and basiconic sensilla while SNMP2 is restricted to the SCs of the basiconic and coeloconic sensilla thus resembling the adult arrangement. Our results demonstrate that both SNMP types have defined cell- and sensilla-specific distribution patterns established already in the first instar nymphs and retained into the adult stage. This conserved expression topography underlines the importance of SNMP1 and SNMP2 in olfactory processes throughout the development of the desert locust.

Perimenopause and Postmenopause - Diagnosis and Interventions. Guideline of the DGGG and OEGGG (S3-Level, AWMF Registry Number 015-062, September 2020).

Aim The aim of the interdisciplinary S3-guideline Perimenopause and Postmenopause - Diagnosis and Interventions is to provide help to physicians as they inform women about the physiological changes which occur at this stage of life and the treatment options. The guideline should serve as a basis for decisions taken during routine medical care. This short version lists the statements and recommendations given in the long version of the guideline together with the evidence levels, the level of recommendation, and the strength of consensus. Methods The statements and recommendations are largely based on methodologically high-quality publications. The literature was evaluated by experts and mandate holders using evidence-based medicine (EbM) criteria. The search for evidence was carried out by the Essen Research Institute for Medical Management (EsFoMed). To some extent, this guideline also draws on an evaluation of the evidence used in the NICE guideline on Menopause and the S3-guidelines of the AWMF and has adapted parts of these guidelines. Recommendations Recommendations are given for the following subjects: diagnosis and therapeutic interventions for perimenopausal and postmenopausal women, urogynecology, cardiovascular disease, osteoporosis, dementia, depression, mood swings, hormone therapy and cancer risk, as well as primary ovarian insufficiency.

Associação entre hábitos orais e má oclusão com problemas respiratórios em escolares de 5 anos / Association between oral habits and malocclusion with respiratory problems in 5-year-old schoolchildren

Introdução Toda má oclusão apresenta origem multifatorial, e dentre os fatores que a desencadeiam estão os hábitos. O surgimento de um hábito pode estar relacionado com o emocional, o fisiológico ou com o aprendizado condicionado do indivíduo. Objetivo Analisar as relações entre hábitos e más oclusões associado a problemas respiratórios em escolares de 5 anos. Material e método Foi realizado um estudo transversal com uma amostra de 753 crianças pertencentes à rede municipal de ensino da cidade de Araraquara, SP. Foram realizados exames clínicos para avaliação da má oclusão (Foster & Hamilton), além de aplicado questionários aos pais para avaliação de condição socioeconômica e demográfica, qualidade de vida relacionada à saúde bucal (ECOHIS) e hábitos. A análise dos dados foi feita pela análise bivariada por teste qui-quadrado seguida de modelo de regressão logística múltipla considerando nível de significância de 5%. Resultado A prevalência de crianças com problemas respiratórios e/ou alergias foi de 46,9%, com má oclusão foi de 58,7% e com algum tipo de hábito oral deletério foi de 12,0%. Apresentaram mais chance de ter problemas respiratórios e/ou alergias crianças do sexo masculino (1,40 vezes mais) e crianças com algum hábito oral deletério (1,95 vezes mais). Conclusão Observou-se que apresentaram maior chance de problemas respiratórios e/ou alergias as crianças do sexo masculino, crianças com algum hábito oral deletério e que apresentavam bruxismo.

Introduction All malocclusion has a multifactorial origin, and among the factors that trigger it are the habits. The appearance of a habit can be related to the emotional, physiological or conditioned learning of the individual. Objective Evaluate the relationship between habits and malocclusions associated with respiratory problems in 5-year-old students. Material and method A cross-sectional study were carried out with a sample of 753 children belonging to the municipal education network of the city of Araraquara-SP. Clinical exams were performed for malocclusion evaluation (Foster & Hamilton), applying questionnaires to the parents for evaluation of socioeconomic and demographic condition, oral health related quality of life (ECOHIS) and habits. Data analysis was performed by bivariate analysis using chi-square test followed by multiple logistic regression model considering 5% significance level. Result The prevalence of children with respiratory problems and/or allergies was 46.9%, with malocclusion was 58.7% and with some type of deleterious oral habit was 12.0%. Male children were 1.40 times more likely to present respiratory problems or allergies and children with some deleterious oral habits were 1.95 times more likely to present respiratory problems or allergies. Conclusion It was observed that male children, children that presented deleterious oral habits, and children with bruxism are more likely to have respiratory problems and/or allergies.

Odor-related brain hyper-reactivity in euthymic bipolar disorder: An fMRI and ERP study.

Previous studies on olfactory function in patients with bipolar disorder (BD) are limited and contradictory. The current study aimed to comprehensively analyze the olfactory function of patients with euthymic BD using psychophysical, electrophysiological and neuroimaging techniques. Twenty-one patients with BD in remission and 20 healthy controls were tested with the "Sniffin' Sticks" olfactory test. Block-design fMRI data to a pleasant and an unpleasant stimulus were acquired while recording intensity and hedonic ratings. Olfactory event-related potentials (OERP) to the same stimuli were additionally recorded. Results show no differences between patients and healthy controls in terms of self-rated olfactory function and tested olfactory domains (odor threshold, discrimination or identification) (p>0.05). Compared to healthy controls, patients showed an increased fMRI activation in multiple cortical and subcortical regions as a response to olfactory stimulation, as well as larger amplitudes of OERPs regardless of the hedonic valence of the odor. All in all, patients with euthymic BD showed a stronger central responsiveness to odorous stimuli in fMRI and OERPs despite of normal psychophysical results, indicating the probable existence of an odor-related over-reactive brain network in the remission phase of BD.

Sanctioning of Illegal and Dangerous Ruck Cleanouts During the 2018 Super Rugby Competition.

Rugby is a high contact sport that results in many injuries. The majority of injuries at senior elite levels result from contact phases during match-play. It is estimated that 10% of all match injuries are associated with the ruck in professional and community rugby. Surveillance of legal and illegal ruck cleanouts and the sanctions imposed by the on-field referees will help identify whether referees are actually enforcing the law according to the laws of the game, which will consequently contribute to the creation and implementation of further injury prevention strategies. Players should play the game in accordance with the laws of the game and be mindful of their own safety and that of others. Coaches and trainers of the game have the responsibility to ensure that players are prepared in a manner that comply with the World Rugby (WR) laws of the game and safe practices. Laws and law amendments are fundamental to the development of sport and introduced for a variety of reasons. The aim of this study was to investigate the rate of sanctioning of illegal and dangerous ruck cleanouts during the 2018 Super Rugby competition by using Nacsport Basic+ video software; 120 round robin matches from the 2018 Super Rugby competition were coded and analyzed. The analysis of the intra reliability showed an almost perfect (>0.95) agreement between all the performance indicators. In total, 22,281 ruck cleanouts were coded of which 9% (n = 2111) were illegal ruck cleanouts and 93% were not sanctioned by the referees; 57% (1087 out of 1953) of the illegal ruck cleanouts not sanctioned by the referees were deemed dangerous. The majority of dangerous illegal ruck cleanouts not sanctioned by the referees were "shoulder charge" (88%, n = 280), "neck roll" (86%, n = 100), and "contact above the shoulder" (81%, n = 201). To aid injury prevention efforts in rugby, future research studies should investigate why on-field referees are not sanctioning all illegal and dangerous ruck cleanouts according to WR Laws of the Game.

The effects of maternal dietary supplementation of cholecalciferol (vitamin D3) and 25(OH)D3 on sow and progeny performance.

A total of 69 sows (DNA Line 200 × 400) and their progeny were used to determine if feeding a combination of vitamin D3 and 25(OH)D3 influences neonatal and sow vitamin D status, muscle fiber morphometrics at birth and weaning, and subsequent growth performance. Within 3 d of breeding, sows were allotted to one of three dietary treatments fortified with 1,500 IU/kg vitamin D3 (CON), 500 IU/kg vitamin D3 + 25 µg/kg 25(OH)D3 (DL), or 1,500 IU/kg vitamin D3 + 50 µg/kg 25(OH)D3 (DH). When pigs were sacrificed at birth, there were no treatment effects for all fiber morphometric measures (P > 0.170), except primary fiber number and the ratio of secondary to primary muscle fibers (P < 0.016). Pigs from CON fed sows had fewer primary fibers than pigs from sows fed the DH treatment (P = 0.014), with pigs from sows fed DL treatment not differing from either (P > 0.104). Pigs from CON and DL fed sows had a greater secondary to primary muscle fiber ratio compared to pigs from DH sows (P < 0.022) but did not differ from each other (P = 0.994). There were treatment × time interactions for all sow and pig serum metabolites (P < 0.001). Therefore, treatment means were compared within the time period. At all time periods, sow serum 25(OH)D3 concentrations differed for all treatments with the magnitude of difference largest at weaning (P < 0.011), where serum 25(OH)D3 concentration was always the greatest when sows were fed the DH diet. At birth, piglets from DH fed sows had greater serum 25(OH)D3 concentrations than piglets from sows fed the DL treatment (P = 0.003), with piglets from sows fed CON treatment not differing from either (P > 0.061). At weaning, serum concentrations of 25(OH)D3 in piglets from all sow treatments were different (P < 0.001), with the greatest concentration in piglets from DH sows, followed by CON, and followed by DL. There were no treatment × time interactions for any of the metabolites measured in milk and no treatment or time main effects for 24,25(OH)2D3 concentration (P > 0.068). Colostrum collected within 12 h of parturition contained less (P = 0.001) 25(OH)D3 than milk collected on day 21 of lactation. Regardless of time, concentrations of 25(OH)D3 in milk were different (P < 0.030), with the largest 25(OH)D3 concentration from DH fed sows, followed by DL, and then CON. In conclusion, combining vitamin D3 and 25(OH)D3 in the maternal diet improves the vitamin D status of the dam and progeny and it increases primary muscle fiber number at birth.

Fingerprinting and characterization of anthocyanins in 94 colored wheat varieties and blue aleurone and purple pericarp wheat crosses.

Colored wheat varieties and crosses were analyzed to figure out their anthocyanin profiles, and thus, their potential as health-related food. After method development, the obtained 94 anthocyanin fingerprints allowed the clear differentiation of the blue aleurone and purple pericarp genotypes as well as their breeding lines. The method was trimmed so that the complete analysis of the whole grain flour including sample preparation of up to 20 samples on one plate took less than 3 h (<9 min per sample) and total costs including sample preparation were <1.0 Euro/sample. Sample preparation of the complex wheat matrix was reduced to a minimum (only acidified methanol extraction of the ground whole wheat grain). Separation was well achieved on amino phases with a mixture of ethyl acetate, 2-butanone, water and formic acid. It was superior to the separation on either normal or reversed phases and more robust with regard to intrinsic pH variances of the sample extracts. Pattern recognition of anthocyanins was simply performed by visual detection (the image), a key feature of high-performance thin-layer chromatography. Wheat varieties and crosses with higher anthocyanin contents were easily selectable, and thus, successfully made out. Prominent anthocyanin zones were characterized by electrospray ionization mass spectrometry. Their sugar moiety was characterized via methanolysis and compared with the sugars available freely in the whole wheat grain. The developed profiling is a fast and efficient screening tool with option for quantification or identification on the same HPTLC plate.

Planar chromatographic screening and quantification of coumarin in food, confirmed by mass spectrometry.

A sensitive quantitative screening of coumarin in 43 commercially available cinnamons and cinnamon-containing foods was developed via HPTLC. Complex samples like cinnamon, tea, breakfast cereals, milk rice, jam, cinnamon stars and buns were extracted with methanol only. Separation was performed on silica gel with a mixture of n-hexane, ethyl acetate and ammonia. The specific detection via derivatization with an ethanolic potassium hydroxide solution resulted in fluorescent coumarin zones, measured at 365/>400nm after stabilization. Limits of detection and quantification were 200 and 400pg/band, respectively. Over all different sample types, the contents ranged from 0.3 to 5129mg/kg with a mean repeatability and mean intermediate precision of 4% each. HPTLC-MS of selected zones, eluted via the TLC-MS Interface into MS, confirmed the identity of coumarin. Effect-directed detection as bioanalytical tool for risk assessment showed coumarin to be active against Aliivibrio fischeri bacteria down to 100ng/band.

Male reproductive system and spermatogenesis of Limodromus assimilis (Paykull 1790).

Based on advanced light and electron microscopy, we describe the male reproductive system and sperm development of Limodromus assimilis. The genital tract consists of pairs of uni-follicular testes, spermatic ducts with diverticula regions, seminal vesicles, accessory glands, an unpaired ejaculatory duct and an aedeagus containing an internal sac equipped with sclerotic scales. Based on their morphology, we draw conclusions about their functions. After spermatogenesis within the follicle, the spermatozoa become released from the sperm cysts. The single spermatozoa move into the diverticula of the vasa deferentia I. Here, they become attached to central rods (spermatostyles), forming secondary conjugates (spermiozeugmata). The coordinated flagella movement of the conjugates possibly improves sperm velocity. Using super-resolution microscopy, we identified highly condensed reticulate chromatin in the lancet-shaped spermatozoa heads and the mitochondrial derivates of the flagella, likely formed by genomic and mitochondrial DNA, respectively. The results show, for the first time, sperm bundle formation in a Platynini species mainly corresponding to that found in Pterostichini species.

Comparison and characterization of soybean and sunflower lecithins used for chocolate production by high-performance thin-layer chromatography with fluorescence detection and electrospray mass spectrometry.

The scarce availability of nongenetically modified soybeans on the world market represents a growing problem for food manufacturers. Hence, in this study the effects of substituting soybean with sunflower lecithin were investigated with regard to chocolate production. The glycerophospholipid pattern of the different lecithin samples was investigated by high-performance thin-layer chromatography fluorescence detection (HPTLC-FLD) and by HPTLC-positive ion electrospray ionization mass spectrometry (ESI(+)-MS) via the TLC-MS Interface and by scanning HPTLC-matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOFMS). Especially, the contents of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were of interest due to the influencing effects of these two glycerophospholipids on the rheological parameters of chocolate production. The lecithin substitution led to only slight differences in the rheological parameters of milk and dark chocolate. Limits of detection (LODs) and limits of quantification (LOQs) of seven glycerophospholipids were studied for three detection modes. Mean LODs ranged from 8 to 40 mg/kg for HPTLC-FLD and, using a single-quadrupole MS, from 10 to 280 mg/kg for HPTLC-ESI(+)-MS as well as from 15 to 310 mg/kg for HPTLC-FLD-ESI(+)-MS recorded after derivatization with the primuline reagent.

Homeopathy for depression: a randomized, partially double-blind, placebo-controlled, four-armed study (DEP-HOM).

BACKGROUND: The specific clinical benefit of the homeopathic consultation and of homeopathic remedies in patients with depression has not yet been investigated. AIMS: To investigate the 1) specific effect of individualized homeopathic Q-potencies compared to placebo and 2) the effect of an extensive homeopathic case taking (case history I) compared to a shorter, rather conventional one (case history II) in the treatment of acute major depression (moderate episode) after six weeks. METHODS: A randomized, partially double-blind, placebo-controlled, four-armed trial using a 2×2 factorial design with a six-week study duration per patient was performed. RESULTS: A total of 44 from 228 planned patients were randomized (2∶1∶2∶1 randomization: 16 homeopathic Q-potencies/case history I, 7 placebo/case history I, 14 homeopathic Q-potencies/case history II, 7 placebo/case history II). Because of recruitment problems, the study was terminated prior to full recruitment, and was underpowered for the preplanned confirmatory hypothesis testing. Exploratory data analyses showed heterogeneous and inconclusive results with large variance in the sample. The mean difference for the Hamilton-D after 6 weeks was 2.0 (95%CI -1.2;5.2) for Q-potencies vs. placebo and -3.1 (-5.9;-0.2) for case history I vs. case history II. Overall, no consistent or clinically relevant results across all outcomes between homeopathic Q-potencies versus placebo and homeopathic versus conventional case taking were observed. The frequency of adverse events was comparable for all groups. CONCLUSIONS: Although our results are inconclusive, given that recruitment into this trial was very difficult and we had to terminate early, we cannot recommend undertaking a further trial addressing this question in a similar setting. Prof. Dr. Claudia Witt had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. TRIAL REGISTRATION: clinicaltrials.gov identifier NCT01178255. Protocol publication: http://www.trialsjournal.com/content/12/1/43.

Development of a planar chromatographic method for quantitation of anthocyanes in pomace, feed, juice and wine.

An efficient HPTLC method was developed, which required minimal sample preparation for quantitation of the main anthocyanes in pomace, animal feed as well as various foods. The best separation of 11 anthocyanes was achieved on HPTLC plates silica gel 60 F254 with a mixture of ethyl acetate-2-butanone-formic acid-water for anthocyanins and ethyl acetate-toluene-formic acid-water for anthocyanidins. Due to the high flexibility of the HPTLC method, both anthocyane groups could be developed in a combined 2-step method. The second development was only necessary if anthocyanidins were detected in the samples. This normal phase separation was found superior to the best separation achieved on RP-18 phases with a mixture of water-n-propanol-formic acid. Absorbance measurement was performed using the multi-wavelength scan at 505 (or 510), 520, 530 and 555 nm. The correlation coefficients of the calibrations ranged between 0.9993 and 0.9999 for the 11 anthocyanes. LOQs were all ≤90 ng/zone, most even ≤30 ng/zone and for pn-3-glc and pg-3-glc even ≤7 ng/zone. With regard to the analysis of mv-3-glc in grape seed/marc meal and supplemented animal feed samples, the mean repeatabilities were 1.4% (laboratory 1) and 1.8% (laboratory 2). The intermediate precisions within a laboratory over several months were ≤6.7%. The ruggedness of the method was ≤5.5%. The method was transferred to other sample types. Juice and wine samples, which were from the same plant source, showed a comparable anthocyanin pattern, whereas the pattern was characteristically different between plant sources. Unknown anthocyanin sample components were analyzed via HPTLC-ESI-MS by eluting the zones of interest with the TLC-MS Interface, which was helpful for further characterization of unknowns. An interesting tool was demonstrated by effect-directed analysis with regard to radical scavenging properties and general bioactivity based on detection with Vibrio fischeri bacteria.

Psychopharmacological treatment of mood and anxiety disorders during pregnancy.

Many women with psychiatric disorders want to become mothers and only a minority seek advise prior to becoming pregnant. In those women, in whom pregnancy can be planned, the decision, if a medication is required for stabilisation and which one to choose if this is the case, is easier to make than in women in whom pregnancy occurs unplanned. The physician has to weigh the risk that a relapse of the psychiatric disorder during pregnancy poses to the foetus against the reproductive risk of psychotropic drugs. This presentation is intended to assist in understanding the general principles of pharmacotherapy during pregnancy as well as the morphological, perinatal and neurobehavioural toxicity of antidepressants, antipsychotics, benzodiazepines and mood stabilisers.

Homeopathy for depression--DEP-HOM: study protocol for a randomized, partially double-blind, placebo controlled, four armed study.

BACKGROUND: Homeopathy is often sought by patients with depression. In classical homeopathy, the treatment consists of two main elements: the case history and the prescription of an individually selected homeopathic remedy. Previous data suggest that individualized homeopathic Q-potencies were not inferior to the antidepressant fluoxetine in a sample of patients with moderate to severe depression. However, the question remains whether individualized homeopathic Q-potencies and/or the type of the homeopathic case history have a specific therapeutical effect in acute depression as this has not yet been investigated. The study aims to assess the two components of individualized homeopathic treatment for acute depression, i.e., to investigate the specific effect of individualized Q-potencies versus placebo and to investigate the effect of different approaches to the homeopathic case history. METHODS/DESIGN: A randomized, partially double-blind, placebo-controlled, four-armed trial using a 2 x 2 factorial design with a six-week study duration per patient will be performed. 228 patients diagnosed with major depression (moderate episode) by a psychiatrist will be included. The primary endpoint is the total score on the 17-item Hamilton Depression Rating Scale after six weeks. Secondary end points are: Hamilton Depression Rating Scale total score after two and four weeks; response and remission rates, Beck Depression inventory total score, quality of life and safety at two, four and six weeks. Statistical analyses will be by intention-to-treat. The main endpoint will be analysed by a two-factorial analysis of covariance. Within this model generalized estimation equations will be used to estimate differences between verum and placebo, and between both types of case history. DISCUSSION: For the first time this study evaluates both the specific effect of homeopathic medicines and of a homeopathic case taking in patients with depression. It is an attempt to deal with the challenges of homeopathic research and the results might be useful information in the current discussion about the evidence on homeopathy TRIAL REGISTRATION: ClinicalTrials.gov: NCT01178255.

Binge eating disorder and menstrual cycle in unmedicated women with bipolar disorder.

OBJECTIVE: Weight increase is a problem in women with bipolar disorder (BD). Furthermore, there is evidence that both binge eating disorder (BED) and menstrual cycle abnormalities occur more frequently in women with affective disorders than in the general population. We investigated whether there is a clinical link between the two disorders and menstrual cycle. METHOD: Epidemiological and clinical variables associated with both BD and BED were assessed as well as menstrual cycle influence. RESULTS: The prevalence of BED in the sample was 28.8%. Menstrual cycle significantly influenced BED in all participants in that BED became worse prior to menses. 80% of the participants noticed regular weight gain prior to menses. DISCUSSION: BED is a common comorbidity in unmedicated subjects with BD, as is overweight. In women with BD menstrual cycle should be taken into consideration, as it can worsen the BD itself and associated comorbidities such as BED and overweight. Alteration in menstrual cycle-associated eating behavior should be routinely assessed in women with BD.

The Observer-Rated Scale for Mania (ORSM): development, psychometric properties and utility.

BACKGROUND: The diagnosis of mania largely depends on the quality of information the physician is provided with. Often, the patient cannot give an accurate account of the symptom development and thus information from relatives and friends is required. No systematic rating instrument is available, however, to facilitate this. OBJECTIVE: In this study, the psychometric properties of the 49-item Observer-Rated Scale for Mania (ORSM) are reported. METHODS: The scale was used in 113 inpatients and the following psychometric aspects were assessed: reliability, test-retest reliability, construct validity (factor analysis, discriminant analysis, comparison of means), extreme-group validity, prognostic validity, sensitivity, specificity, positive and negative predictive values. RESULTS: The ORSM proved highly valid and reliable. Factor analysis revealed three factors which were labelled euphoric mania, instable mania and psychotic mania. CONCLUSION: The ORSM is a useful instrument to help non-professionals who are in regular contact with the patient diagnosed a manic/mixed episode. It thus complements existing rating scales for mania, which are either designed for professionals or are self-rating instruments.

Altered representation of expected value in the orbitofrontal cortex in mania.

OBJECTIVE: Increased responsiveness to appetitive and reduced responsiveness to aversive anticipatory cues may be associated with dysfunction of the brain reward system in mania. Here we studied neural correlates of gain and loss expectation in mania using functional magnetic resonance imaging (fMRI). METHOD: Fifteen manic patients and 26 matched healthy control individuals performed a monetary incentive delay task, during which subjects anticipated to win or lose a varying amount of money. Varying both magnitude and valence (win, loss) of anticipatory cues allowed us to isolate the effects of magnitude, valence and expected value (magnitude-by-valence interaction). RESULTS: Response times and total gain amount did not differ significantly between groups. FMRI data indicated that the ventral striatum responded according to cued incentive magnitude in both groups, and this effect did not significantly differ between groups. However, a significant group difference was observed for expected value representation in the left lateral orbitofrontal cortex (OFC; BA 11 and 47). In this region, patients showed increasing BOLD responses during expectation of increasing gain and decreasing responses during expectation of increasing loss, while healthy subjects tended to show the inverse effect. In seven patients retested after remission OFC responses adapted to the response pattern of healthy controls. CONCLUSIONS: The observed alterations are consistent with a state-related affective processing bias during the expectation of gains and losses which may contribute to clinical features of mania, such as the enhanced motivation for seeking rewards and the underestimation of risks and potential punishments.

Emotional vulnerability and cognitive control in patients with bipolar disorder and their healthy siblings: a pilot study.

UNLABELLED: Scheuch K, Bräunig P, Gauggel S, Kliesow K, Sarkar R, Krüger S. Emotional vulnerability and cognitive control in patients with bipolar disorder and their healthy siblings: a pilot study. OBJECTIVE: There is evidence that, even in remission, patients with bipolar disorder (BD) have deficits in cognitive function and emotional regulation. Siblings of patients with BD are also reported to exhibit minor dysfunction in neuropsychological domains. In this study, we examined the interference of acute mood state with reaction time (RT) and response inhibition in euthymic patients with BD, in their healthy siblings and in healthy controls. METHODS: A total of 34 patients with bipolar I disorder, 22 healthy siblings and 33 healthy controls performed a stop-signal paradigm after induction of a transient intense sadness and a relaxed mood state. The differences in RT and the response inhibition were compared between the groups. RESULTS: Euthymic patients with BD displayed a higher emotional reactivity compared with their siblings and with controls. Compared with controls, patients with BD showed longer RTs in a relaxed mood state and a delay in response inhibition during emotional activation. CONCLUSIONS: The present study provides evidence for the clinical observation that patients with BD have shorter RTs when in a state of emotional arousal rather than in a relaxed state. Inhibitory deficits in these patients may be because of a too strong emotional arousal. The results show that in patients with BD, relaxation and emotional arousal are inversely associated with performance in a neuropsychological task. This is in contrast to findings in healthy individuals suggesting a dysbalance in emotional regulation in these patients.