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ImportanceThe cerebral serotonin 4 (5-HT4) receptor is a promising novel target for treatment of major depressive disorder (MDD), and pharmacological stimulation of the 5-HT4 receptor has been associated with improved learning and memory in healthy individuals.ObjectiveTo map the neurobiological signatures of patients with untreated MDD compared with healthy controls and to examine the association between cerebral 5-HT4 receptor binding and cognitive functions in the depressed state.Design, Setting, and ParticipantsThis case-control study used baseline data from the NeuroPharm clinical depression trial in Denmark. Adult participants included antidepressant-free outpatients with a current moderate to severe depressive episode and healthy controls. All participants completed positron emission tomography (PET) scanning with [11C]SB207145 for quantification of brain 5-HT4 receptor binding, but only the patients underwent cognitive testing. Data analyses were performed from January 21, 2020, to April 22, 2022.Main Outcomes and MeasuresThe main study outcome was the group difference in cerebral 5-HT4 receptor binding between patients with MDD and healthy controls. In addition, the association between 5-HT4 receptor binding and verbal memory performance in the patient group was tested. Other cognitive domains (working memory, reaction time, emotion recognition bias, and negative social emotions) were assessed as secondary outcomes.ResultsA total of 90 patients with untreated MDD (mean [SD] age, 27.1 [8.2] years; 64 women [71.1%]) and 91 healthy controls (mean [SD] age, 27.1 [8.0] years; 55 women [60.4%]) were included in the analysis. Patients with current MDD had significantly lower cerebral 5-HT4 receptor binding than healthy controls (−7.0%; 95% CI, −11.2 to −2.7; P = .002). In patients with MDD, there was a correlation between cerebral 5-HT4 receptor binding and verbal memory (r = 0.29; P = .02).Conclusions and RelevanceResults of this study show that cerebral 5-HT4 receptor binding was lower in patients with MDD than in healthy controls and that the memory dysfunction in patients with MDD was associated with lower cerebral 5-HT4 receptor binding. The cerebral 5-HT4 receptor is a promising treatment target for memory dysfunction in patients with MDD.

Concurrent anxiety is frequent in major depressive disorder and a shared pathophysiological mechanism between anxiety and other depressive symptoms is plausible. The serotonin 4 receptor (5-HT4R) has been implicated in both depression and anxiety. This is the first study to investigate the association between the cerebral 5-HT4R binding and anxiety in patients with depression before and after antidepressant treatment and the association to treatment response. Ninety-one drug-free patients with depression were positron emission tomography scanned with the 5-HT4R ligand [11C]-SB207145. Depression severity and concurrent anxiety was measured at baseline and throughout 8 weeks of antidepressant treatment. Anxiety measures included four domains: anxiety/somatization factor score; Generalized Anxiety Disorder 10-items (GAD-10) score; anxiety/somatization factor score ≥7 (anxious depression) and syndromal anxious depression. Forty patients were rescanned at week 8. At baseline, we found a negative association between global 5-HT4R binding and both GAD-10 score (p p = 0.06). Further, remitters had a higher baseline anxiety/somatization factor score compared with non-responders (p = 0.04). At rescan, patients with syndromal anxious depression had a greater change in binding relative to patients with non-syndromal depression (p = 0.04). Concurrent anxiety in patients with depression measured by GAD-10 score and anxiety/somatization factor score is negatively associated with cerebral 5-HT4R binding. A lower binding may represent a subtype with reduced natural resilience against anxiety in a depressed state, and concurrent anxiety may influence the effect on the 5-HT4R from serotonergic antidepressants. The 5-HT4R is a promising neuroreceptor for further understanding the underpinnings of concurrent anxiety in patients with depression.

We study quantitatively the breakdown of the rotating-wave approximation (RWA) when calculating collective light emission by quantum emitters, in particular in the weak-excitation limit. Our starting point is a known multiple-scattering formalism where the full light–matter interaction leads to induced inter-emitter interactions described by the classical Green function of inhomogeneous dielectric media. When making the RWA in the light–matter interaction, however, these induced interactions differ from the classical Green function, and for free space we find a reduction of the interatomic interaction strength by up to a factor of two. By contrast, for the corresponding scalar model the relative RWA error for the inter-emitter interaction even diverges in the near field. For two identical emitters, the errors due to the RWA in collective light emission will show up in the emission spectrum, but not in the sub- and superradiant decay rates. In case of two non-identical emitters, also the collective emission rates will differ by making the RWA. For three or more identical emitters, the RWA errors in the interatomic interaction in general affect both the collective emission spectra and the collective decay rates. Ring configurations with discrete rotational symmetry are an interesting exception. Interestingly, the maximal errors in the collective decay rates due to making the RWA occur for finite emitter separations.

Introduction: The antipsychotic drug clozapine remains underutilized partly because of the risk of life-threatening adverse effects, such as neutropenia. Therefore, an extensive hematological monitoring program was set up to detect neutropenia. Methods: In this retrospective cohort study, we used registry-based data from the Capital Region of Denmark to investigate incidence rates of neutropenia among patients with a diagnosis of schizophrenia or other psychotic disorders and treated with clozapine for the first time. In a within-subject design, we compared rates of neutropenia in time periods where patients were exposed to clozapine versus time periods, where they were not exposed to clozapine. We also investigated whether the lengths of clozapine-associated neutropenia (CAN) were related to discontinuation of clozapine treatment. Results: Data from 520 clozapine users were included. The incidence rate of CAN was 3.2 cases per 100 person-years (95% confidence interval [CI]: 2.1–4.8) throughout the entire study. There was no significant difference in incidence rates of neutropenia during clozapine exposure and non-clozapine exposure, with an incidence rate ratio of 0.7 (95% CI: 0.4–1.3). One episode of severe neutropenia was detected. Episodes of CAN with only one sub-threshold neutrophil count were not associated with higher clozapine discontinuation (26%) than CAN episodes of more than one sub-threshold neutrophil count (28%). Conclusion: In the present study, we could not confirm that clozapine treatment was associated with neutropenia.

Background In cases with clinically suspected appendicitis, there is controversy regarding the decision to remove a macroscopically normal appearing appendix during laparoscopy when no other intra-abdominal pathology is found. The aim of this study was to examine the rate of appendicitis, along with readmission and reoperation rates following diagnostic laparoscopy of clinically suspected appendicitis in patients where the appendix was not removed. Methods We performed a retrospective cohort analysis of patients who underwent a diagnostic laparoscopy due to clinical suspicion of appendicitis where no other pathology was found and the appendix was not removed. The study period was from 2008 to 2013 and involved patients from two university hospitals in the Copenhagen area. Results Of the 271 patients included (81.6% women, median age 27), 56 (20.7%) were readmitted with right iliac fossa pain after a median time of 10 months (range 1–84). Twenty-two patients (8.1%) underwent a new laparoscopic procedure. Appendix was removed in 18 patients, of which only one showed histological signs of inflammation. The median follow-up time was 5.6 years (range 1–109 months). Conclusion There was a low rate of appendicitis after a previous negative diagnostic laparoscopy. Therefore, based on results from the current study, we do not consider that it is necessary to remove a macroscopic normal appendix during laparoscopy for clinically suspected appendicitis. The high readmission rate warrants the need for further investigation or follow-up.

Laughing gas inhalation is frequently used for intoxication purposes. This case report describes a 25-year-old man, who suffered from both pneumopericardium and pneumomediastinum after having inhalated laughing gas. After three days of observation, he was discharged from hospital without any complications. Pneumopericardium and pneumomediastinum are very rare but potentially life-threatening complications of laughing gas inhalation.

Negative neurocognitive bias is a core feature of major depressive disorder that is reversed by pharmacological and psychological treatments. This double-blind functional magnetic resonance imaging study investigated for the first time whether electroconvulsive therapy modulates negative neurocognitive bias in major depressive disorder. Patients with major depressive disorder were randomised to one active ( n=15) or sham electroconvulsive therapy ( n=12). The following day they underwent whole-brain functional magnetic resonance imaging at 3T while viewing emotional faces and performed facial expression recognition and dot-probe tasks. A single electroconvulsive therapy session had no effect on amygdala response to emotional faces. Whole-brain analysis revealed no effects of electroconvulsive therapy versus sham therapy after family-wise error correction at the cluster level, using a cluster-forming threshold of Z>3.1 ( p2.3; p

Cameras are already widely used for inspection and monitoring tasks in poultry slaughter houses. In this paper we evaluate the use of computer vision for broiler carcass weight estimation. We compare the use of 2D image features with 3D features extracted from a statistical shape model fitted to the image. The statistical shape model is built from 45 3D scans captured from broiler carcasses collected at a slaughter house. The use of this 3D prior gave a reduction in mean absolute error compared to 2D features alone and achieved an overall mean average percentage error of 3.47%. The algorithm can run real time and was tested on a dataset containing 136,472 images of broilers, captured at a real production site.

The manual postmortem inspection of broilers and their viscera is becoming a bottleneck as the slaughter rate increases. Computer vision can assist veterinarians during the inspection, but specular highlights can hide crucial details when inspecting for diseases on the viscera set. This study aims to restore details behind these specular highlights by capturing two images of the same viscera using shifting light positions. The dataset consists of images captured in-line at a poultry processing plant. The method achieves an average SSIM score of 0.96 over a test set of 100 image sets. The result is visually pleasing images with correct textural information instead of specular highlights.

The malacosporean Tetracapsuloides bryosalmonae was detected in kidneys from Atlantic salmon parr in 64 of 91 sampled Norwegian rivers. Using real-time PCR, this parasite was found to be present in Atlantic salmon parr in rivers along the whole coast, from the northernmost and southernmost areas of the country. In addition, T. bryosalmonae was found in kidneys from brown trout parr in 17 of 19 sampled rivers in south-east Norway, and in Arctic charr sampled in the River Risfjordelva, located at the northernmost edge of the European mainland. In conclusion, T. bryosalmonae has a widespread distribution in salmonids in Norwegian watercourses. Proliferative kidney disease (PKD) caused by T. bryosalmonae and PKD-induced mortality has been observed in salmonids in several Norwegian rivers and it can be speculated that more PKD outbreaks will occur as a result of climate change.

Automatic analysis of body movement to identify physical activity of patients who are at bed rest is crucial for treatment or rehabilitation purposes. Existing methods of physical activity analysis mostly focused on the detection of primitive motion/non-motion states in unimodal video data captured by either RGB or depth or thermal sensor. In this paper, we propose a multimodal vision-based approach to classify body motion of a person lying on a bed. We mimicked a real scenario of ‘patient on bed’ by recording multimodal video data from healthy volunteers in a hospital room in a neurorehabilitation center. We first defined a taxonomy of possible physical activities based on observations of patients with acquired brain injuries. We then investigated different motion analysis and machine learning approaches to classify physical activities automatically. A multimodal database including RGB, depth and thermal videos was collected and annotated with eight predefined physical activities. Experimental results show that we can achieve moderately high accuracy (77.68%) to classify physical activities by tracking the body motion using an optical flow-based approach. To the best of our knowledge this is the first multimodal RGBDT video analysis for such application.

Background Negative neurocognitive bias is a core feature of depression that is reversed by antidepressant drug treatment. However, it is unclear whether modulation of neurocognitive bias is a common mechanism of distinct biological treatments. This randomized controlled functional magnetic resonance imaging study explored the effects of a single electroconvulsive therapy session on self-referent emotional processing. Methods Twenty-nine patients with treatment-resistant major depressive disorder were randomized to one active or sham electroconvulsive therapy session at the beginning of their electroconvulsive therapy course in a double-blind, between-groups design. The following day, patients were given a self-referential emotional word categorization test and a free recall test. This was followed by an incidental word recognition task during whole-brain functional magnetic resonance imaging at 3T. Mood was assessed at baseline, on the functional magnetic resonance imaging day, and after 6 electroconvulsive therapy sessions. Data were complete and analyzed for 25 patients (electroconvulsive therapy: n = 14, sham: n = 11). The functional magnetic resonance imaging data were analyzed using the FMRIB Software Library randomize algorithm, and the Threshold-Free Cluster Enhancement method was used to identify significant clusters (corrected at P < .05). Results A single electroconvulsive therapy session had no effect on hippocampal activity during retrieval of emotional words. However, electroconvulsive therapy reduced the retrieval-specific neural response for positive words in the left frontopolar cortex. This effect occurred in the absence of differences between groups in behavioral performance or mood symptoms. Conclusions The observed effect of electroconvulsive therapy on prefrontal response may reflect early facilitation of memory for positive self-referent information, which could contribute to improvements in depressive symptoms including feelings of self-worth with repeated treatments.

Neuronal genotoxic insults from oxidative stress constitute a putative molecular link between stress and depression on the one hand, and cognitive dysfunction and dementia risk on the other. Oxidative modifications to DNA are repaired by specific enzymes; a process that plays a critical role for maintaining genomic integrity. The aim of the present study was to characterize the pattern of cerebral DNA repair enzyme regulation after stress through the quantification of a targeted range of gene products involved in different types of DNA repair. 72 male Sprague–Dawley rats were subjected to either restraint stress (6 h/day) or daily handling (controls), and sacrificed after 1, 7 or 21 stress sessions. The mRNA expression of seven genes ( Ogg1, Ape1, Ung1, Neil1, Xrcc1, Ercc1, Nudt1 ) involved in the repair of oxidatively damaged DNA was determined by quantitative real time polymerase chain reaction in the prefrontal cortex (PFC) and hippocampus (HC). DNA repair gene expression in PFC exhibited a general trend towards an induction after acute stress and a decrease after subchronic exposure compared to control animals. After chronic stress, a normalization towards control levels was observed. A similar pattern was seen in HC, but with overall smaller effects and without the induction after acute stress. Nuclear DNA damage from oxidation as measured by the comet assay was unaffected by stress in both regions. We conclude that psychological stress have a dynamic influence on brain DNA repair gene expression; however, since we were unable to identify concurrent changes in DNA damage from oxidation, the down-stream consequences of this regulation, if any, remains unclear.

Electroconvulsive therapy (ECT) is the most effective treatment for severe depression but its neurocognitive mechanisms are unclear. This randomized, sham-controlled functional magnetic resonance imaging (fMRI) study explored the effects of a single ECT on neural response to affective pictures. Twenty-seven patients with major depressive disorder were randomized to a single active ECT (N = 15) or sham (N = 12) session in a double-blind, parallel-group design. On the following day, patients underwent fMRI during which they viewed pleasant, unpleasant and neutral pictures and performed a free recall test after the scan. Mood symptoms were assessed before ECT/sham and at the time of fMRI. Subsequently, all patients continued active ECT as usual. Mood symptoms were reassessed after six active ECT sessions. A single ECT vs. sham session reduced neural response to unpleasant vs. pleasant pictures in the medial prefrontal cortex, a region showing greater response in the more depressed patients. This effect occurred in the absence of between-group differences in picture recall, mood symptoms or concomitant medication. In conclusion, modulation of medial prefrontal hyper-activity during encoding of negative affective information may be a common mechanism of distinct biological depression treatments.

Background: Depression has been associated with increased oxidative stress and hypothesized to accelerate aging. Nucleic acid damage from oxidation is a critical part of the aging process, and a suggested early event in age-related somatic morbidities that are also prevalent in depression, such as dementia and type 2 diabetes. We hypothesized that increased severity of depression is associated with increased systemic oxidatively generated DNA and RNA damage, and that this increase is attenuated by an effective antidepressant treatment. Methods: The urinary excretion of markers of systemic oxidatively generated DNA and RNA damage, 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo), respectively, were determined in healthy controls (N ¼ 28), moderately depressed, non-medicated patients (N ¼ 26) and severely depressed patients eligible for electroconvulsive therapy (ECT) (N¼ 29). In the severely depressed patient group, samples were also obtained 1 week after the completion of ECT. Results: Systemic RNA damage from oxidation, as measured by 8-oxoGuo excretion, was higher with increasing severity of depression (controlsomoderately depressedo severely depressed) (P for trend ¼ 0.004). The 8-oxoGuo excretion was further increased after clinically effective ECT compared with pre-ECT values (P¼0.006). There were no differences in 8-oxodG excretion between the groups or pre- vs. post-ECT. Limitations: Small sample size and the inclusion of both unipolar and bipolar patients in the severely depressed group. Conclusions: Severe depression is associated with increased systemic oxidatively generated RNA damage, which may be an additional factor underlying the somatic morbidity and neurodegenerative features associated with depression. Due to the lack of normalization by clinically effective ECT, the phenomenon does not appear to be causally linked to the depressive state per se.

The aim of the present study was to investigate whether exposure to high levels of persistent organic pollutants (POPs) affected a fish population in Lake Mjøsa. Lake Mjøsa is known to be contaminated by polybrominated diphenyl ethers (PBDEs), a subgroup of brominated flame retardants from local industrial activities. Fish from Lake Losna, a less contaminated lake located close to Lake Mjøsa, was used as reference (control). The sampling of burbot (Lota lota) was carried out between 2005 and 2008. Hepatic levels of POPs were analysed in burbot from the two lakes, and the fish were examined for bacterial- and parasite infection and histopathological changes. The levels of polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethanes (DDTs), and PBDEs were about 10, 15 and 300 times higher in fish from Lake Mjøsa compared to fish from Lake Losna. Mycobacterium salmoniphilum was present in 7% and 35% of the fish from Lake Losna and Lake Mjøsa respectively. Significantly higher number of external and visceral macroscopic lesions, histopathological diffuse changes and granulomas were seen in fish from Lake Mjøsa compared to Lake Losna. Furthermore the parasite infection was higher and the hepatic lipid content was significantly lower in burbot from Lake Mjøsa. The results of the present study suggest that the high level of contamination in Lake Mjøsa could have a negative impact on the health status of wild fish inhabiting the lake.

Increased oxidatively generated damage to nucleic acids (DNA/RNA) may be a common mechanism underlying accelerated aging in psychological stress states and mental disorders. In the present study, we measured the urinary excretion of corticosterone and markers of systemic oxidative stress on nucleic acids, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo), respectively, in rats subjected to chronic restraint stress. To reliably collect 24h urine samples, the full 3-week restraint stress paradigm was performed in metabolism cages. We further determined frontal cortex and hippocampal levels of oxidatively generated nuclear DNA damage, as measured by oxoguanine DNA glycosylase and formamidopyrimidine DNA glycosylase sensitive sites detected by the comet assay, as well as the expression of genes involved in DNA repair (Ogg1 and Nudt1) and inflammation (Ccl2 and Tnf). The metabolism cage housing in itself did not significantly influence a range of biological stress markers. In the restraint stress group, there was a sustained 2.5 fold increase in 24h corticosterone excretion from day 2 after stress initiation. However, neither whole-body nor cerebral measures of nucleic acid damage from oxidation were affected by stress. In contrast, cerebral DNA repair enzymes exhibited a general trend towards an induction, which was significant for hippocampal Nudt1. The results and their implications for stress sensitivity and resilience are discussed.

The purpose of this study was to review the current evidence for an association between Fusobacterium necrophorum (FN) and acute tonsillitis (AT), to assess the prevalence of FN in AT, to identify the better FN detection method, and to characterize the clinical characteristics of FN-positive patients with uncomplicated AT. A systematic literature search was conducted in the PubMed, EMBASE, and SweMed+ databases for studies reporting on the recovery rates of FN in patients with AT. A total of 498 unique records were identified. Eleven studies were included in a qualitative synthesis and six studies were included in a meta-analysis. Considerable heterogeneity (I(2) = 60 %) and risk of bias and confounders was found among the studies, though a subset of studies (prospective) had lower heterogeneity and higher study quality. FN was recovered significantly more frequently from patients (21.2 %) compared to healthy controls (7.6 %) (p < 0.001). FN recovery rates were similar between culture-based studies (20.3 %) and studies using polymerase chain reaction (PCR) methodology (22.2 %) (p = 0.462). The typical FN-positive AT patient was a smoking young (15-25 years) male presenting with tonsillar exudates and a Centor score of 2 or higher. A clear association between FN and AT was found. FN is likely to be a significant and prevalent pathogen in AT, especially in teenagers and young adults. However, no evidence for causality between FN and AT has been established and it is unexplored if timely antibiotic therapy directed against FN accelerates the resolution of symptoms and decreases the risk of complications.

Ny forskning fra Aalborg Universitet viser lovende potentialer for brugen af termiske kameraer i undersøgelse knyttet til trafik og bevægelse. De varmesensitive kameraer har flere fordele. For det første er man ude over problemstillingen med personidentifikation og dermed overvågning i offentlige rum. For det andet er metoden interessant, da ny forskning inden for Computer Vision-området giver mulighed for at registrere det, kameraet ”ser” som kvantitative data, der efterfølgende kan repræsenteres som bevægelseslinjer på kort eller såkaldte ”heat maps”, der viser intensiteter. Metoderne med termiske kameraer i trafikplanlægning giver dermed nye muligheder for valide datasæt, der omfatter fodgængere såvel som biler. I denne artikel diskuteres dette med udgangspunkt i et forskningsprojekt med termisk kameraovervågning i universitetets bygning på havnefronten i Aalborg.

This paper presents an approach for automatic visual inspection of chicken entrails in RGB-D data. The point cloud is first over-segmented into supervoxels based on color, spatial and geometric information. Color, position and texture features are extracted from each of the resulting supervoxels and passed to a Random Forest classifier, which classifies the supervoxels as either belonging to heart, lung, liver or misc. The dataset consists of 150 individual entrails, with 30 of these being reserved for evaluation. Segmentation performance is evaluated on a voxel-by-voxel basis, achieving an average Jaccard index of 61.5 % across the four classes of organs. This is a 5.9 % increase over the 58.1 % achieved with features derived purely from 2D.

Although Giardia duodenalis is considered a parasite of mammals, different genotypes have been identified as infecting several species of freshwater and marine fish in Australia. Establishment of G. duodenalis infection in common laboratory zebrafish (Danio rerio), could provide an excellent tool for a range of studies on Giardia. We conducted preliminary experiments to investigate this possibility. Zebrafish were inoculated with viable G. duodenalis cysts from two different Assemblages (A and D) using a modified oro-gastric tube. Direct microscopy and immunofluorescent antibody test were used to check for Giardia cysts/trophozoites in the intestine, and histology was performed on intestinal mucosa to evaluate possible pathological changes. Giardia cysts were successfully deposited in the zebrafish alimentary tract using a modified oro-gastric tube, and were maintained in the fish gut for at least 8 days. Although a single trophozoite was observed in one fish three days post-exposure, we were unable to demonstrate established, propagative infection under the conditions tested.

Spironucleus salmonicida is a diplomonad flagellate known to cause systemic infections in farmed salmonids. In northern Norway, outbreaks of spironucleosis in farmed Atlantic salmon Salmo salar have been a recurring problem. Common to all these outbreaks was the origin of smolts: all came from the same farm. In the present study, wild Arctic char Salvelinus alpinus and brown trout Salmo trutta were sampled from the lakes used as a water source for the smolt supplier. In addition, smolt and three-spined sticklebacks Gasterosteus aculeatus were sampled from the smolt farm. Bile and intestinal contents from the sampled fish were examined by light microscopy and PCR. Spironucleus salmonicida was identified in both wild Arctic char and brown trout from the lakes used as water sources by the smolt farm, suggesting that the farmed fish were exposed to this pathogen before transfer to the sea. Spironucleus barkhanus and Spironucleus salmonis were also identified in the sampled fish. The present study also demonstrated that infections with multiple Spironucleus species are present in wild salmonids. No indications of disease related to diplomonad infections were observed in the wild fish, suggesting that wild salmonids are reservoir hosts of Spironucleus salmonicida.

Diplomonad flagellates infect a wide range of fish hosts in aquaculture and in the wild in North America, Asia and Europe. Intestinal diplomonad infection in juvenile farmed trout can be associated with morbidity and mortality, and in Germany, diplomonads in trout are commonly reported, and yet are poorly characterised. We therefore undertook a comprehensive study of diplomonads from German rainbow trout Oncorhynchus mykiss, using scanning and transmission electron microscopy, and sequencing of the small subunit (ssu) rRNA gene. The diplomonad was identified as Spironucleus salmonis, formerly reported from Germany as Hexamita salmonis. Our new surface morphology studies showed that the cell surface was unadorned and a caudal projection was present. Transmission electron microscopy facilitated new observations of functional morphology, including vacuoles discharging from the body surface, and multi-lobed apices of the nuclei. We suggest the lobes form, via hydrostatic pressure on the nucleoplasm, in response to the beat of the anterior-medial flagella. The lobes serve to intertwine the nuclei, providing stability in the region of the cell exposed to internal mechanical stress. The ssu rRNA gene sequence clearly distinguished S. salmonis from S. barkhanus, S. salmonicida, and S. vortens from fish, and can be used for identification purposes. A 1405 bp sequence of the ssu rRNA gene from S. salmonis was obtained and included in a phylogenetic analysis of a selection of closely related diplomonads, showing that S. salmonis was recovered as sister taxon to S. vortens.

OBJECTIVES: The aims of the present study were to (i) cross-culturally adapt a Danish consensus version of the 10-item Perceived Stress Scale (PSS-10) and (ii) evaluate its psychometric properties in terms of agreement, reliability, validity, responsiveness, and interpretability among patients with work-related stress complaints.METHODS: A consensus-building process was performed involving the authors of the three previous Danish translations and the consensus version was back-translated into English and pilot-tested. Psychometric properties of the final version were examined in a sample of 64 patients with work-related stress complaints.RESULTS: The face validity, reliability, and internal consistency of the Danish consensus version of the PSS-10 were satisfactory, and convergent construct validity was confirmed. Receiver operating characteristic (ROC) curves of the change scores showed that the ability of the PSS-10 to correctly classify patients as improved or unchanged according to the patients' own judgment was acceptable. The estimates of minimal clinically important change were 11 points and 28% for absolute and relative change scores, respectively.CONCLUSION: The Danish consensus version of the PSS-10 appears to be feasible for use in clinical research settings and has good psychometric properties in terms of agreement, reliability, validity, responsiveness, and interpretability.

BackgroundHealthy first-degree relatives of patients with major depression (rMD+) show brain structure and functional response anomalies and have elevated risk for developing depression, a disorder linked to abnormal serotonergic neurotransmission and reward processing.MethodIn a two-step functional magnetic resonance imaging (fMRI) investigation, we first evaluated whether positive and negative monetary outcomes were differentially processed by rMD+ individuals compared to healthy first-degree relatives of control probands (rMD−). Second, in a double-blinded placebo-controlled randomized trial we investigated whether a 4-week intervention with the selective serotonergic reuptake inhibitor (SSRI) escitalopram had a normalizing effect on behavior and brain responses of the rMD+ individuals.ResultsNegative outcomes increased the probability of risk-averse choices in the subsequent trial in rMD+ but not in rMD− individuals. The orbitofrontal cortex (OFC) displayed a stronger neural response when subjects missed a large reward after a low-risk choice in the rMD+ group compared to the rMD− group. The enhanced orbitofrontal response to negative outcomes was reversed following escitalopram intervention compared to placebo. Conversely, for positive outcomes, the left hippocampus showed attenuated response to high wins in the rMD+ compared to the rMD− group. The SSRI intervention reinforced the hippocampal response to large wins. A subsequent structural analysis revealed that the abnormal neural responses were not accounted for by changes in gray matter density in rMD+ individuals.ConclusionsOur study in first-degree relatives of depressive patients showed abnormal brain responses to aversive and rewarding outcomes in regions known to be dysfunctional in depression. We further confirmed the reversal of these aberrant activations with SSRI intervention.

Both non-pathological psychological stress states and mental disorders are associated with molecular, cellular and epidemiological signs of accelerated aging. Oxidative stress on nucleic acids is a critical component of cellular and organismal aging, and a suggested pathogenic mechanism in several age-related somatic disorders. The overall aim of the PhD project was to investigate the relation between psychopathology, psychological stress, stress hormone secretion and oxidatively generated DNA and RNA damage, as measured by the urinary excretion of markers of whole-body DNA/RNA oxidation (8-oxodG and 8-oxoGuo, respectively). The main hypothesis was that psychological stress states are associated with increased DNA/RNA damage from oxidation. In a study of 40 schizophrenia patients and 40 healthy controls matched for age and gender, we found that 8-oxodG/8-oxoGuo excretion was increased in schizophrenia patients, providing a possible molecular link between schizophrenia and its associated signs of accelerated aging. We found no association between psychopathology, perceived stress or cortisol secretion and 8-oxodG/8-oxoGuo excretion in the patients. In the controls, there were positive correlations between 8-oxodG/8-ocoGuo excretion and 9AM plasma cortisol, but no associations to perceived stress. In an animal study of experimentally induced chronic stress performed in metabolism cages, we found no increase in urinary 8-oxodG/8-oxoGuo or cerebral (hippocampal and frontal cortex) levels of oxidatively generated nucleic acid damage. However, there was a trend towards an increased expression of genes involved in DNA repair, possibly reflecting a compensatory mechanism. In a study of 220 elderly, mostly healthy individuals from the Italian InChianti cohort, we found a significant association between the 24 h urinary cortisol excretion and the excretion of 8-oxodG/8-oxoGuo, determined in the same samples. Collectively, the studies could not confirm an association between psychological stress and oxidative stress on nucleic acids. Systemic oxidatively generated DNA/RNA damage was increased in schizophrenia, and linked to cortisol levels in healthy humans. Finally, the cerebral repair of DNA may be an aspect of the adaptation that, to our knowledge, has not previously been addressed.

Diplomonads are aerotolerant anaerobic, binucleate flagellates, which are commonly found in the intestinal tract of wild and farmed fish. Of the diplomonad genera, Spironucleus, composed of opportunistic pathogens, poses the greatest threat to aquaculture. Immunocompromised hosts or fish without acquired immunity are thought to be more susceptible to parasitism by these otherwise commensal agents. Accumulation of flagellates along the intestinal tract often leads to systemic Spironucleosis causing high mortality of both ornamental and food fish in aquaculture. The life cycle of these piscine diplomonads is direct, consisting of a motile, parasitic trophozoite and a resilient encysted stage, which facilitates water-borne transmission. Confusion in the nomenclature, as well as numerous reassignments of taxa, hampers our understanding of host range and geographical distribution of fish diplomonads. Accurate identification requires transmission electron microscopy to characterise intricate ultrastructural features. Additionally, sequencing of the small subunit ribosomal RNA gene allows identification of cryptic Spironucleus spp. In vitro culture provides a convenient source of flagellates for biochemical and physiological research, allowing the identification of novel parasite-specific molecular pathways such as H2 production within Spironucleus sp. This provides insight into the pathogenicity of these organisms and offers potential new targets for chemotherapy. Restrictions on the administration of the current drug of choice, metronidazole, in aquacultural settings, as well as reported cases of drug resistance, means that control of Spironucleosis is especially difficult. Allium sativum (garlic)-derived compounds have proven highly effective at inhibiting parasite growth in vitro, showing great potential as a novel alternative therapy in the treatment of Spironucleosis. Further characterisation of the biochemistry, pathogenicity and taxonomy of fish diplomonads is required in order to fully appreciate the true impact and economic consequences of Spironucleus spp. in aquaculture.