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Background: Risk factors for cutaneous squamous cell carcinoma (cSCC) metastasis have been investigated only in relatively small data sets. Objective: To analyze and replicate risk factors for metastatic cSCC. Methods: From English and Dutch nationwide cancer registry cohorts, metastatic cases were selected and 1:1 matched to controls. The variables were extracted from pathology reports from the National Disease Registration Service in England. In the Netherlands, histopathologic slides from the Dutch Pathology Registry were revised by a dermatopathologist. Model building was performed in the English data set using backward conditional logistic regression, whereas replication was performed using the Dutch data set. Results: In addition to diameter and thickness, the following variables were significant risk factors for metastatic cSCC in the English data set (n = 1774): poor differentiation (odds ratio [OR], 4.56; 95% CI, 2.99-6.94), invasion in (OR, 1.69; 95% CI, 1.05-2.71)/beyond (OR, 4.43; 95% CI, 1.98-9.90) subcutaneous fat, male sex (OR, 2.59; 95% CI, 1.70-3.96), perineural/lymphovascular invasion (OR, 2.12; 95% CI, 1.21-3.71), and facial localization (OR, 1.57; 95% CI, 1.02-2.41). Diameter and thickness showed significant nonlinear relationships with metastasis. Similar ORs were observed in the Dutch data set (n = 434 cSCCs). Limitations: Retrospective use of pathology reports in the English data set. Conclusion: cSCC staging systems can be improved by including differentiation, clinical characteristics such as sex and tumor location, and nonlinear relationships for diameter and thickness.

Current treatment of patients with saphenous trunk and tributary incompetence consists of truncal ablation with concomitant, delayed or no treatment of the tributary. However, reflux of the saphenous trunk may be reversible after treatment of the incompetent tributary. The aim of this study was to determine whether single ambulatory phlebectomy with or without delayed endovenous truncal ablation (SAP) is non-inferior to thermal endovenous ablation with concomitant phlebectomy (TAP), and whether SAP is a cost-effective alternative to TAP.A multicentre, non-inferiority RCT was conducted in patients with an incompetent great saphenous vein or anterior accessory saphenous vein with one or more incompetent tributaries. Participants were randomized to receive SAP or TAP. After 9 months, additional truncal treatment was considered for SAP patients with remaining symptoms. The primary outcome was VEnous INsufficiency Epidemiological and Economic Study Quality of Life/Symptoms (VEINES-QOL/Sym score) after 12 months. Secondary outcomes were, among others, cost-effectiveness, perceived improvement of symptoms, and anatomical success.Some 464 patients received the allocated treatment (SAP 227, TAP 237). VEINES-QOL scores were 52.7 (95 per cent c.i. 51.9 to 53.9) for SAP and 53.8 (53.3 to 55.1) for TAP; VEINES-Sym scores were 53.5 (52.6 to 54.4) and 54.2 (54.0 to 55.6) respectively. Fifty-eight patients (25.6 per cent) in the SAP group received additional truncal ablation. Treatment with SAP was less costly than treatment with TAP.One year after treatment, participants who underwent SAP had non-inferior health-related quality of life compared with those who had TAP. Treatment with SAP was a cost-effective alternative to TAP at 12 months.NTR 4821 (www.trialregister.nl).

Objective: To evaluate the efficacy of endovascular embolization of pelvic varicose veins in the treatment of pelvic venous disorders (PeVD). Methods: A single-center retrospective study was performed, including 156 women referred to the Erasmus University Medical Center between January 2011 and October 2020 for an evaluation of PeVD. Data on presenting symptoms, clinical workup, treatment, and clinical outcomes were collected. The primary end point was resolution of symptoms after treatment. Secondary outcomes were correlation between symptoms at presentation and relief of symptoms after treatment, minor or major procedural complications, recurrences, and additional treatments needed. Results: Ninety patients underwent a pelvic phlebography, of which 75 received embolization of pelvic varicose veins. Median follow-up after phlebography was 13.2 months (interquartile range, 6.0-40.1 months). Of the treated patients, 53 (70.7%) had partial or complete relief of symptoms. Forty-six women (61.3%) who received embolization of pelvic varicose veins required additional treatments for leg and/or vulvar varicose veins. Conclusions: This study found that endovascular embolization of pelvic varicose veins can be an effective treatment for PeVDs. However, additional treatments are often required for leg and/or vulvar varicose veins.

ObjectivesIn 2016, the SKINCATCH Trial, a clustered multi-centre randomised trial, was initiated to assess whether low-risk basal cell carcinomas (BCCs) can be treated by general practitioners (GPs) without loss of quality of care. The trial intervention consisted of a tailored 2-day educational course on skin cancer management. The aim of this process evaluation was to investigate GPs’ exposure to the intervention, implementation of the intervention and experiences with the intervention and trial.Research design and methodsData on exposure to the intervention, implementation and experiences were obtained at several points during the trial. Complementary quantitative components (ie, surveys, database analysis, medical record analysis) and qualitative components (ie, interviews and focus groups) were used. Quantitative data were analysed using descriptive statistics; qualitative data were summarised (barrier interviews) or audiorecorded, transcribed verbatim and thematically analysed using Atlas.Ti (focus groups).ResultsFollowing a 100% intervention exposure, results concerning the implementation of the trial showed that aside from the low inclusion rate of patients with low-risk BCCs (n=54), even less excisions of low-risk BCCs were performed (n=40). Although the intervention was experienced as highly positive, several barriers were mentioned regarding the trial including administrative challenges, lack of time and high workload of GPs, low volume of BCC patients and patients declining to participate or requesting a referral to a dermatologist.ConclusionsAlthough GPs’ participation in the highly valued training was optimal, several barriers may have contributed to the low inclusion and excision rate of low-risk BCCs. While some of the issues were trial-related, other barriers such as low patient-volume and patients requesting referrals are applicable outside the trial setting as well. This may question the feasibility of substitution of surgical excisions of low-risks BCCs from secondary to primary care in the current Dutch setting.Trial registration numberTrial NL5631 (NTR5746).

Lentigo maligna is an in situ melanoma which usually affects sun-damaged skin on the head and neck. In patients with lentigo maligna, the clinically visible demarcation often correlates poorly with the histopathologically confirmed demarcation. Micrograhic surgery of lentigo maligna offers certainty of the presence of clear histological margins and is at the same time tissue sparing. Because of the clear margins after micrographic surgery, this technique leads to fewer recurrences than standard excision.

Background Recurrent cutaneous squamous cell carcinoma (cSCC) has been associated with an increased risk of local functional and aesthetic comorbidity, metastasis and mortality. Objectives To compare the risk of recurrence between Mohs micrographic surgery (MMS) and standard excision for cSCC of the head and neck. Methods This was a retrospective cohort study of all patients with a cSCC treated with MMS or standard excision at the departments of dermatology of a secondary or tertiary care hospital in the Netherlands between 2003 and 2012. To detect all recurrences, patients were linked to the Dutch pathology registry. To compare the risk of recurrence between MMS and standard excision, hazard ratios (HRs) were used adjusted for clinical tumour size > 2 cm and deep tumour invasion. Results A total of 579 patients with 672 cSCCs were included: 380 cSCCs were treated with MMS and 292 with standard excision. The risk of recurrence was 8% (22 of 292) after standard excision during a median follow-up of 5 center dot 7 years [interquartile range (IQR) 3 center dot 5-7 center dot 8], which was higher than the 3% (12 of 380) after MMS during a median follow-up of 4 center dot 9 years (IQR 2 center dot 3-6 center dot 0). The cumulative incidence of recurrence was higher for standard excision than for MMS during the entire follow-up period of 8 center dot 6 years. Carcinomas treated with MMS were at a three times lower risk of recurrence than those treated with standard excision when adjusted for tumour size and deep tumour invasion (adjusted HR 0 center dot 31, 95% confidence interval 0 center dot 12-0 center dot 66). Conclusions MMS might be superior to standard excision for cSCCs of the head and neck because of a lower rate of recurrence.

Endovenous treatment has become the treatment of choice for patients with saphenous varicose veins (great saphenous vein and small saphenous vein). Current thermal treatment modalities are endovenous laser ablation, radiofrequency ablation and steam ablation. These treatments work by heating the vein, causing the vessel to become occluded. These thermal treatment methods require tumescent anaesthesia. The outstanding effectiveness of laser and radiofrequency ablation has now been demonstrated in countless randomised trials and meta-analyses. Steam ablation seems to be just as effective as the other thermal treatment methods, but there is less pain afterwards. Since the treatment is not reimbursed, steam ablation is currently not used in the Netherlands.

African sharptooth catfish Clarias gariepinus were housed under continuous dim light (1lx) or 12L:12D (350-0lx) cycles. The number of skin lesions, as indicator of aggressive acts, and plasma cortisol levels, as indicator of stress-axis activity, were measured at baseline as well as following a stressor (given in the light or dark phase). Results showed that (1) baseline plasma cortisol levels were not different between photoperiods, (2) the number of baseline skin lesions was highest for C. gariepinus housed under continuous dim light, (3) stressor-induced peak levels of plasma cortisol were highest in the light phase and (4) the number of skin lesions following a stressor was highest in the dark phase. The higher number of stressor-related skin lesions in the dark (active) phase suggests increased stressor-induced aggression while in the active phase. In addition, the data suggest that housing under continuous dim light does not result in higher stress-axis activity, as measured by baseline levels of cortisol, but does result in more stressor-induced aggression, as measured by the higher number of skin lesions. The latter may be related to the fact that the continuous dim light photoperiod has twice the number of dark-phase (active) hours in which stressor-induced aggression is stronger compared to the 12L:12D photoperiod, which has a light phase in which stressor-induced aggression is lower.

Successive exposure to aquaculture-related stressors may compromise the allostatic capacity of African catfish and lead to allostatic overload and poor welfare. Therefore, we tested the effect of (i) feeding during the light or dark phase, (ii) density (51 fish per 140 L versus 51 fish per 43 L) and (iii) altered available resting space/shelter on stress handling were studied in African catfish (Clarias gariepinus). Available resting space/shelter was manipulated by providing PVC-tubes in the tanks. Growth, baseline stress load (cortisol and osmolality), metabolism (glucose, lactate and non-esterified fatty acids) and aggression (measured by skin scar incidence) were assessed. Upon completion of the experimental period, we determined the adaptive capacity of the fish by the response to air exposure. We show that night-feeding enhances growth and lowers feed conversion ratio compared to day-feeding. No effects of density were found for baseline stress hormones, basal metabolism or aggression. Low density seems to stimulate aggressive behaviour after air exposure. Unexpectedly, providing PVC-tubes under high-density conditions increased aggression, raised baseline cortisol levels and decreased basal metabolism as well as growth; also the endocrine response to air exposure was stronger. We argue that these effects relate to a reduction in available space, i.e. a further increase in density, or to an increased competition for shelter. Overall, our data suggest that night-feeding optimizes growth and that care should be taken in using objects as shelter/enrichment for African catfish.

Recently, we established an inhibitory avoidance paradigm in Tupfel Long-Fin (TL) zebrafish. Here, we compared task performance of TL fish and fish from the AB strain; another widely used strain and shown to differ genetically and behaviourally from TL fish. Whole-body cortisol and telencephalic gene expression related to stress, anxiety and fear were measured before and 2 h post-task. Inhibitory avoidance was assessed in a 3-day paradigm: fish learn to avoid swimming from a white to a black compartment where a 3V-shock is given: day 1 (first shock), day 2 (second shock) and day 3 (no shock, sampling). Tupfel Long-Fin fish rapidly learned to avoid the black compartment and showed an increase in avoidance-related spatial behaviour in the white compartment across days. In contrast, AB fish showed no inhibitory avoidance learning. AB fish had higher basal cortisol levels and expression levels of stress-axis related genes than TL fish. Tupfel Long-Fin fish showed post-task learning-related changes in cortisol and gene expression levels, but these responses were not seen in AB fish. We conclude that AB fish show higher cortisol levels and no inhibitory avoidance than TL fish. The differential learning responses of these Danio strains may unmask genetically defined risks for stress-related disorders.

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Psycho-genetic studies have revealed a role for the brain serotonin system in gambling proneness and poor decision-making. We assessed whether manipulation of brain serotonin levels in rats affected performance in operant-based tasks for decision-making and gambling proneness. Male Wistar rats were exposed to an l -tryptophan (TRP) deficient diet (0.0 g/kg; T− group) or to a control, l -tryptophan containing diet (2.8 g/kg; T+ group). The same rats were tested for decision-making performance in the rodent Iowa Gambling Task (rIGT) using home-cage operant panels, and subsequently for gambling proneness in a Probabilistic Delivery Task (rPDT) using classic Skinnerboxes. At sacrifice, monoamines and metabolites were evaluated with HPLC analysis, confirming a drastically reduced serotonin synthesis, as well as altered dopamine turnover in the prefrontal cortex of T− rats. As expected, control rats (T+) progressively chose the option with the best long-term payoff in the rIGT, and also shifted from “Large & Luck-Linked” (LLL) to “Small & Sure” (SS) reinforcers in the rPDT. In contrast, depleted animals (T−) exhibited a weaker improvement of performance in the rIGT and maintained a sub-optimal attraction for LLL reinforcer in the rPDT. Comparing individual performances in both tests, we found a significant correlation between the two tasks in control (T+) but not in depleted (T−) rats. The present study revealed that (1) brain 5-HT depletion leads to poor decision-making and to gambling proneness; (2) the relationship between these two traits, shown in the control group, was disrupted in 5-HT depleted rats. The data are discussed in terms of changes within forebrain loops involved in cognitive and motivational/affective processes.

Testing rodents in their home cages has become increasingly popular. Since human intervention, handling, and transport are minimized, behavior can be recorded undisturbed and continuously. Currently existing home cage systems are too complex if only relatively simple operant-learning tests are to be carried out in rats. For that purpose, a new low-cost computer-controlled operant panel was designed, which can be placed inside the home cage. A pilot study was carried out, using an intolerance-to-delay protocol, classically developed for testing behavioral impulsivity. Male adult rats were tested in their home cages, containing the operant panel provided with nosepoking holes. Nose poking in one hole resulted in the immediate delivery of one food pellet (small-soon, SS), whereas nose poking in the other hole delivered five food pellets after a delay (large-late), which was increased progressively each day (0–150 sec). The two daily sessions, spaced 8 h apart, lasted 1 h each, and the time-out after food delivery was 90 sec. A clear-cut shift toward preference for SS, which is considered a classical index of cognitive impulsivity, was shown at the longest delay. It is noteworthy that rats shifted when the delay interval was longer than the mean intertrial interval—that is, when they experienced more than one delay-equivalent odds against discounting (see Adriani & Laviola, 2006). The shortened training (2 days) and testing (5 days) phases, as allowed by prolonged and multiple daily sessions, can be advantageous in testing rodents during selected short phases of development. Current research is focusing on further validation of this and similar protocols.

In this study a simple modelling approach was applied to identify the need for spatial complexity in representing hydrological processes and their variability over different scales. A data set of 18 basins was used, ranging between 8 and 4011 km2 in area, located in the Nahe basin (Germany), with daily discharge values for over 30 years. Two different parsimoniously structured models were applied in lumped as well as in spatially distributed according to two distribution classifications: (1) a simple classification based on the lithology expressed in three permeability types and (2) a more complex classification based on seven dominating runoff production processes. The objective of the study was to compare the performances of the models on a local and on a regional scale as well as between the models with a view to identifying the accuracy in capturing the spatial variability of the rainfall-runoff relationships. It was shown that the presence of a specific basin characteristic or process of the distribution classification was not related with higher model performance; only a larger basin size promoted higher model performance. The results of this study also indicated that the permeability generally contained more useful information on the spatial heterogeneity of the hydrological behaviour of the natural system than did a more detailed classification on dominating runoff generation processes. Although model performance was slightly lower for the model that used permeability as a distribution classification, consistency in its parameter values was found, which was lacking with the more complex distribution classification. The latter distribution classification had a higher flexibility to optimize towards the variability of the runoff, which resulted in higher performance, however, process representation was applied inconsistently. Copyright © 2007 John Wiley & Sons, Ltd.

African sharptooth catfish Clarias gariepinus were housed under continuous dim light (1 lx) or 12L:12D (350-0 lx) cycles. The number of skin lesions, as indicator of aggressive acts, and plasma cortisol levels, as indicator of stress-axis activity, were measured at baseline as well as following a stressor (given in the light or dark phase). Results showed that (1) baseline plasma cortisol levels were not different between photoperiods, (2) the number of baseline skin lesions was highest for C. gariepinus housed under continuous dim light, (3) stressor-induced peak levels of plasma cortisol were highest in the light phase and (4) the number of skin lesions following a stressor was highest in the dark phase. The higher number of stressor-related skin lesions in the dark (active) phase suggests increased stressor-induced aggression while in the active phase. In addition, the data suggest that housing under continuous dim light does not result in higher stress-axis activity, as measured by baseline levels of cortisol, but does result in more stressor-induced aggression, as measured by the higher number of skin lesions. The latter may be related to the fact that the continuous dim light photoperiod has twice the number of dark-phase (active) hours in which stressor-induced aggression is stronger compared to the 12L:12D photoperiod, which has a light phase in which stressor-induced aggression is lower.

The objective of this study was to assess the effects of transportation of marketable eel (0.15 kg) in the Netherlands with respect to welfare. Eels (Anguilla anguilla) were obtained from a commercial farm and acclimatized for 7 weeks at the laboratory. Fish were transported according to regular commercial procedures. The animals were placed in water-filled transport tanks on the trailer. Fish density increased from 72 kg m-3 (husbandry) to 206 kg m-3 (fasting) and was further increased to 270–290 kg m-3 during transport. Fish transport lasted 3 h after which the eels were returned to laboratory recirculation systems to measure parameters indicative of stress load, i.e. mortality, plasma cortisol, lactate and non-esterified fatty acids (NEFA) as well as gill morphology. Samples were taken at 0, 6, 24, 48 and 72 h after transport in transported fish and non-transported counterparts (controls). Transportation affected water quality within known tolerable limits. No mortality during or after transport was observed. After 6 h, plasma cortisol levels had returned to baseline. However, energy metabolism had increased suggesting that transportation of eels resulted in an increased energy demand that lasted for at least 72 h in the fasted animals. Thus, it is conceivable that exposure to adverse conditions, prior to stunning/killing, in a slaughterhouse may result in allostatic overload in eel.

The inhibitory avoidance paradigm allows the study of mechanisms underlying learning and memory formation in zebrafish (Danio rerio Hamilton). For zebrafish, the physiology and behavior associated with this paradigm are as yet poorly understood. We therefore assessed the effects of environmental enrichment and fish age on inhibitory avoidance learning. Fish raised in an environmentally enriched tank showed decreased anxiety-like behavior and increased exploration. Enrichment greatly reduced inhibitory avoidance in 6-month (6M)- and 12-month (12 M)-old fish. Following inhibitory avoidance, telencephalic mRNA levels of proliferating cell nuclear antigen (pcna), neurogenic differentiation (neurod), cocaine- and amphetamine-regulated transcript 4 (cart4), and cannabinoid receptor 1 (cnr1) were lower in enriched-housed fish, while the ratios of mineralocorticoid receptor (nr3c2)/glucocorticoid receptor α [nr3c1(α)] and glucocorticoid receptor β [nr3c1(β)]/glucocorticoid receptor α [nr3c1(α)] were higher. This was observed for 6M-old fish only, not for 24-month (24 M) old fish. Instead, 24 M-old fish showed delayed inhibitory avoidance, no effects of enrichment, and reduced expression of neuroplasticity genes. Overall, our data show strong differences in inhibitory avoidance behavior between zebrafish of different ages and a clear reduction in avoidance behavior following housing under environmental enrichment.

Here we present a newly developed tool for continuous recordings and analysis of novelty-induced and baseline behaviour of mice in a home cage-like environment. Aim of this study was to demonstrate the strength of this method by characterizing four inbred strains of mice, C57BL/6, DBA/2, C3H and 129S2/Sv, on locomotor activity. Strains differed in circadian rhythmicity, novelty-induced activity and the time-course of specific behavioural elements. For instance, C57BL/6 and DBA/2 mice showed a much faster decrease in activity over time than C3H and 129S2/Sv mice. Principal component analysis revealed two major factors within locomotor activity, which were defined as 'level of activity' and 'velocity/stops'. These factors were able to distinguish strains. Interestingly, mice that displayed high levels of activity in the initial phase of the home cage test were also highly active during an open-field test. Velocity and the number of stops during movement correlated positively with anxiety-related behaviour in the elevated plus maze. The use of an automated home cage observation system yields temporal changes in elements of locomotor activity with an advanced level of spatial resolution. Moreover, it avoids the confounding influence of human intervention and saves time-consuming human observations.

Captive animals are often provided with cage enrichments in order to improve their welfare. Swimming water is an often-discussed requirement for farmed mink. The present study aimed to give insight into the value of swimming water for farmed mink by measuring anticipatory and stereotypical behaviour in subjects raised and housed in the presence and absence of swimming water and in subjects that were deprived of swimming water. The major findings of the present experiments are that: (1) there was no significant difference in anticipatory behaviour between subjects reared and housed in the presence or absence of swimming water; nor was there a significant difference in anticipatory behaviour after removing the water for 2.5 weeks, (2) there was no significant difference in stereotypical behaviour in winter in the presence, absence and after 2.5 months deprivation of swimming water, and finally, (3) there was no significant correlation between anticipatory activity and stereotypical behaviour. The results suggest that mink might not experience consequences, in the sense of increased reward-sensitivity or stereotypy levels, due to the absence of swimming water if they never experienced this incentive before, and that swimming water and an empty bath, such as used in this experiment, might be equally valued incentives for mink.

Rationale. Previous observations revealed that defeated and subsequently individually housed rats do not display behavioral anticipatory responses to the conditioned presentation of a bell/light stimulus associated with free access to a 5% sucrose solution reward. The absence of the appetitive responses suggests a decreased sensitivity to reward. This might be homologous to anhedonia, a symptom of human depression. Objectives. To further validate the inability to anticipate as indicative for a depressionlike state we investigated whether antidepressant treatment restores the impaired anticipatory responses in defeated and subsequently individually housed animals. Methods. Male rats were defeated and subsequently individually housed or subjected to a control treatment. In the 19–20th weeks after the exposure to defeat rats were either injected daily with imipramine (20 mg/kg per os, dissolved in water) or water. Anticipatory behavior was measured both before and after 3–5 weeks of chronic treatment with imipramine. Results. The long-term impairment of anticipatory behavior in defeated and subsequently individually housed rats was restored by chronic imipramine treatment. Impaired appetitive behavior in socially stressed rats was not accompanied by a decreased consumption of the 5% sucrose solution in the anticipatory tests. The recovery of the appetitive responses was independent of open field activity, body weight, and 5% sucrose preference in the home cage. Conclusions. Chronic imipramine administration restores the anhedonialike absence of anticipatory behavior in socially stressed rats. Predictive validity of the social stress model of human depression is suggested by the similar action of imipramine on the modeled behavior and on the anhedonia symptoms in depressive human patients.

Force plate analysis was used to measure ground reaction forces (GRF) and contact times, and calculate the centre of gravity at a walk of 10 dogs which had had a limb amputated, and the results were compared with the results from 22 normal dogs of the same weight. The loss of a limb caused significant changes in the GRF, impulses and contact times of the remaining limbs and in the location of the dogs' centre of gravity. The changes were greater in dogs which had lost a forelimb than in dogs which had lost a hindlimb.

Forty-four Dutch dog owners were interviewed by telephone about their experiences with their dog after it had had a limb amputated. Most of the dogs adapted to walking on three legs within a month, sooner than most of the owners had expected. There were few complications after the amputation, although changes in behaviour were observed in approximately one-third of the dogs.

In many western countries endovenous thermal ablation techniques have largely replaced classical surgery for the treatment of saphenous varicose veins as they are more effective and patient friendly. Because these treatments can be performed under local tumescent anaesthesia, patients can mobilize immediately after the procedure. A new method of thermal ablation is endovenous steam ablation, which is a fast and easy procedure. Steam ablation may cause less pain than laser ablation and it is also cheaper and more flexible than segmental radiofrequency ablation.

In humans, high levels of anxiety are associated with poor performance in the Iowa Gambling Task (IGT). The IGT measures decision-making under conditions of uncertainty. In this study, we investigated the association between anxiety and decision-making in rats. Rats were screened for anxiety on the elevated plus maze (EPM) and subsequently tested in a rat analogue of the IGT (r-IGT). We explored the role of frontostriatal areas related to r-IGT performance using c-fos immunohistochemistry following the last training-session. High levels of anxiety were associated with poor r-IGT performance: high anxious rats made fewer choices for the advantageous option and collected fewer sucrose pellets in the r-IGT than low anxious rats. Analysis of win-stay/lose-shift behaviour of choices for the advantageous option revealed that good performing-low anxious subjects showed an increase in win-stays and a decrease in lose-shifts across trial blocks while poor performing-high anxious subjects did not. Furthermore, decision-making performance and, indirectly, anxiety levels were related to neural activity in parts of the medial prefrontal cortex, that is prelimbic and infralimbic cortex, and in parts of the striatum, that is nucleus accumbens shell and core. These data suggest a similar frontostriatal circuitry underlying affective decision-making in humans and rats. Highlights ▶Anxiety affects decision-making performance in a rat version of the Iowa Gambling Task (r-IGT). ▶Effects of anxiety are most pronounced during the exploitation phase part of the r-IGT. ▶c-Fos activation in mPFC and ventral striatum is related to decision-making and anxiety.

Excessive levels of trait anxiety are a risk factor for psychiatric conditions, including anxiety disorders and substance abuse. High trait anxiety has been associated with altered cognitive functioning, in particular with an attentional bias towards aversive stimuli. Decision-making is a crucial aspect of cognitive functioning that relies on the correct processing and control of emotional stimuli. Interestingly, anxiety and decision-making share underlying neural substrates, involving cortico-limbic pathways, including the amygdala, striatum and medial and dorsolateral prefrontal cortices. In the present study, we investigated the relationship between trait anxiety, measured by the State-Trait Anxiety Inventory, and complex decision-making, measured by the Iowa Gambling Task, in healthy male and female volunteers. The main focus of this study was the inclusion of gender as a discriminative factor. Indeed, we found distinct gender-specific effects of trait anxiety: in men, both low and high anxiety groups showed impaired decision-making compared to medium anxiety individuals, whereas in women only high anxiety individuals performed poorly. Furthermore, anxiety affected decision-making in men early in the task, i.e. the exploration phase, as opposed to an effect on performance in women during the second part of the test, i.e. the exploitation phase. These findings were related to different profiles of trait anxiety in men and women, and were independent of performance in the Wisconsin Card Sorting Test and cortisol levels. Our data show gender-specific effects of trait anxiety on emotional decision-making. We suggest gender-specific endophenotypes of anxiety to exist, that differentially affect cognitive functioning.

Changes in spatio-temporal rainfall patterns have an effect on the hydrological behavior of river basins, the magnitude of the effects depending among others on the physiographic basin characteristics. To assess climate and discharge fluctuations, a visualization tool was developed as a contribution to exploratory data analysis. The tool combined statistical tests of hydro-climatological variables with physiographic basin characteristics. Test results agree with previous studies and suggested a relationship between rainfall, discharge and mean date of the annual maximum discharge on the one the hand and lithology, altitude and west to east positioning of the basins on the other hand. The visualization tool capable of combining the statistical test results with the geologic and topographic configuration of the study area and allowed a reflection on the hydro-climatological as well as spatio-temporal behavior of meso-scale basins by means of exploratory data analysis.

Prolymphocytic leukemia (PLL) is a rare clonal lymphoproliferative disorder of mature lymphocytes. The disease originates from B lymphocytes in approximately 80% of cases and from T lymphocytes in 20% of cases.[1][1] B-PLL and T-PLL are both characterized by an aggressive clinical course with

Decision-making plays a pivotal role in daily life as impairments in processes underlying decision-making often result in an inability to make profitable long-term decisions that incorporate expectations of future outcomes. In case of pathological gambling such impairments appear to be present as subjects continue to gamble despite the fact that this activity disrupts their personal, professional or financial life. Both from a research and treatment point of view, an important issue is whether differences between men and women exist in the tendency to engage in gambling as a leisure activity and to develop pathological gambling. I will discuss that differences between male and female subjects may exist regarding the trajectory towards pathological gambling: when considered in aggregate, there appears to be a (slightly) elevated risk for gambling problems or severity of gambling in men compared to women. These differences seem to be due to a complex interaction of genetic make-up, effects of the (social) environment on risk-taking behaviour, stress-related changes in risk-taking, and personality/information-processing characteristics related to decision-making. These different factors will be discussed. Future studies should address the interaction between these factors using among others ecologically valid research methods.

Drug-induced changes in somatosensory-evoked potentials (SEPs) are considered to reflect an altered nociceptive state. Therefore, the SEP is proposed to be a parameter of analgesic efficacy. However, at present, SEPs have not been studied in relation to animal pain. The present study aims to develop a rat model in which this relationship can be studied based on Pavlovian fear conditioning. Therefore, rats, implanted with epidural electro-encephalogram recording electrodes, were randomly assigned to either a paired or random-control group and subjected to an aversive-to-appetitive transfer paradigm. During the aversive phase, the SEP-stimulation paradigm (5 mA square wave pulses, n = 72, of 2 ms duration each, with a stimulus frequency of 0.5 Hz; total duration 144 s) was used as the unconditioned stimulus (US), while a tone (40 s, 1500 Hz, 85 dB sound pressure level) was used as the conditioned stimulus (CS). During the appetitive phase, the CS was presented paired to the presentation of a sugar pellet. When compared to the random-control group, the paired group showed significantly more freezing behavior and significantly less reward-directed behavior in response to the CS in the appetitive phase. In addition, SEPs were not significantly affected by fear conditioning. Based on these results, we conclude that the SEP-stimulation paradigm can be successfully employed as a US in fear conditioning. In future studies, fear conditioning can be carried out under different levels of an analgesic regimen to allow the changes in SEP parameters to be compared to changes in fear-induced behavior making this model potentially useful to validate SEP parameters as indicators of analgesia.

Dogs with superficial or deep pyoderma (n = 228) presented to first opinion veterinarians (n = 20) were treated orally with either ibafloxacin, at a dosage of 15 mg/kg, or marbofloxacin, at a dosage of 2 mg/kg, once daily for 3-16 weeks. On initial presentation, 35% of the cases were classified as having recurrent pyoderma and 40% as having deep pyoderma. Staphylococci (mainly Staphylococcus intermedius) were isolated from over 90% of the cases. The average treatment periods were 41 +/- 26 and 38 +/- 21 days in the ibafloxacin and marbofloxacin groups, respectively. One week after the cessation of treatment, 74 and 81% of dogs (P > 0.05) in the ibafloxacin and marbofloxacin groups, respectively, were classified as having responded to treatment. One month after the cessation of treatment, 70% of the dogs in each group were still classified as cured or improved, and 3 and 11% (P < 0.05) in the ibafloxacin and marbofloxacin groups, respectively, were classified as having relapsed. Despite having different pharmacokinetic profiles, ibafloxacin and marbofloxacin produced similar results when used under field conditions at the recommended dosages.

Item does not contain fulltext In this study it was investigated whether ventral striatal dopamine-induced changes in switching to cue-directed behavioral patterns were funnelled via the rostral areas of the ventral pallidum/substantia innominata (VP/SI) complex and, if so, whether changes in switching to cue-directed behavioral patterns could be elicited in the VP/SI complex by manipulating GABAergic activity. To this end rats were bilaterally equipped with cannulae directed at the ventral striatum and/or rostral VP/SI complex and subjected to a swimming-test procedure for 6 min. Injections of the dopamine-releasing agent d-amphetamine (10 microg/0.5 microl per side) enhanced the number of different cue-directed behavioral patterns while they had no effect upon the number of different non-cue-directed behavioral patterns in line with previous studies (Life Sci - 1989 1697). This increase was attenuated by a low dose of the GABAa agonist muscimol (1 ng/0.5 microl) into the rostral VP/SI complex. This dose of muscimol when injected alone into the rostral VP/SI complex had no effect upon the number of different cue-directed behavioral patterns. Only the lowest dose of the GABAa antagonist bicuculline (10-25 ng/0.5 microl per side) into the rostral VP/SI complex slightly, and in a non-d-amphetamine-like manner, increased the number of different cue-directed behavioral patterns while none of the doses had an effect on the number of different non-cue-directed behavioral patterns. Both injections of d-amphetamine into the ventral striatum and injections of bicuculline into the rostral VP/SI complex strongly increased motor activity in the 10-min period preceding the swimming test. We conclude from the data that switching to cue-directed behavioral patterns is sensitive to manipulations with the dopaminergic activity in the ventral striatum but not with the GABAergic activity in the VP/SI complex although the VP/SI transmits it to other brain structures. In contrast motor activity is sensitive to manipulations with both ventral striatal dopamine and rostral VP/SI complex GABA.

In the present study, the consequences of individual rearing during the play period on adult responses to aggression were investigated in a complex social setting. In a group of either socially or individually reared rats, an aggressor was repeatedly introduced. Separate control groups of individually and socially reared rats were not exposed to an aggressor. To allow an interpretation of the altered reactivity to aggression in terms of (in)efficient or (in)adequate behavior, not only the responses in the presence of the aggressor but also the consequences of the altered reactivity on subsequent behavior in the absence of the aggressor were observed. We demonstrated that a higher number of injuries, more agitation of the aggressor, and more ultrasonic distress vocalizations accompanied the altered responses of individually reared rats in the presence of the aggressor. In the absence of the aggressor, individually reared rats displayed less social stress-reducing behaviors (play and social grooming) than socially reared rats. It was concluded that individually reared rats display a less adequate response to aggression in this social context.

In the present study, we investigated whether synaptic plasticity changes in the hippocampus of depressive-like socially stressed rats could be reversed by chronic antidepressant treatment. To that end, rats were either defeated and subsequently individually housed or subjected to control treatment followed by social housing. After a period of at least 3 months, rats were either treated chronically with imipramine (20 mg/kg per day, per os for at least 3 months) or the solvent solution (i.e. water). Then, long-term potentiation and depression were measured in the CA1 region of the hippocampus in vitro. Chronic imipramine treatment partially restored the attenuated induction of long-term potentiation and suppressed the facilitation of long-term depression-induction in socially stressed rats. The altered synaptic plasticity after social stress is discussed in relation to cognitive deficits and hippocampal changes that are observed in depressive patients.

In contrast to the well-documented acute effects on behavioural sensitivity, chronic effects that persist for weeks or even months after the cessation of the stressor received relatively little attention. This study aimed at the long-term effects of a severe stressor, i.e. social defeat followed by individual housing. Defeated and subsequently individually housed animals displayed impaired social memory, decreased social interaction and diminished anticipation for a sucrose solution for up until a period of 3 months after defeat. Remarkably, social housing counteracted the defeat-induced effects. The impaired capability to anticipate for a reward was discussed in relation to anhedonia, an important symptom of human depression. Moreover, the disturbed memory, the chronic nature of the effects, and the therapeutic effects of social housing, suggest that the defeat model may serve as a potential model for human psychopathology.

Recently I discussed a framework to study consciousness in animals (Van den Bos 2000).This framework comprised: i) a hierarchical negative feedback model of the central nervous system in which behaviour is the control of input (perception) expressed as transitions of behavioural patterns (= motion) and as transitions of mental states (= consciousness; Van den Bos 1997). Consciousness is hypothesized to be a property of neuronal networks of self-organizing systems dedicated to dealing with rapidly-changing environments affording flexibility of behavioural patterning;ii) mental states - mental representations - as intentional states as described in folk psychology (feelings, desires; beliefs, insights, etc);iii) the separation of mental states into two components, an invariant part (‘the presence as such’; that) and a variant part (‘the way it looks’; how), which are separately related to the organization of the central nervous system, ie a ‘neuronal network’ and ‘momentary active connections within the neuronal network determined by input and output of this neuronal network’ respectively;iv) the idea that every mental state (psychological trait) - whether feelings, desires or beliefs - can be viewed conceptually as the product of a specialized neuronal network and information encoded in the network (neuronal input-output relations) which is expressed as a specific series of spontaneous behavioural patterns or in specific tests; andv) a phylogeny based on the invariant part, ie mental states, and the presence of a neuronal network.

Data show that tachykinin NKA injected into the nucleus accumbens potentiated the locomotor effects of intra-accumbens d-amphetamine in habituated rats, while the spontaneous locomotor activity of habituated rats was not altered. The present results extend previous data suggesting an interaction between tachykinins and dopamine. The results point to a differential regulation of horizontal (locomotion) and vertical (rearing) movements in the nucleus accumbens of the rat consistent with previous results

The ability of intra-accumbens phenylephrine (PE) and oxymetazoline to potentiate the ‘explosive motor behaviour’ (EMB) elicited from the deeper layers of the superior colliculus by picrotoxin injections was examined in Wistar rats. Using a dose of intracollicular picrotoxin that was 10 ng lower than the threshold dose for generating EMB, evidence was obtained for the selective potentiation of EMB by α-noradrenergic agonists. The PE-induced potentiation was prevented by phentolamine given 48 h prior to PE. Damage caused by multiple injections of intra-accumbens PE prevented the PE-induced effect. It is concluded that the PE-induced effect is accumbens- and noradrenaline-specific. When rats were injected with intervals of 48 h or more, two types of rats could be discerned: responders, i.e. rats that consistently displayed EMB during all trials, and non-responders, i.e. rats that never displayed EMB. When the intertrial interval was 24 h, responders became temporary non-responders, and vice versa. This temporary change in sensitivity was found to be a drug-induced after-effect. The dose-dependency of the PE-induced after-effect in responders differed significantly from that in non-responders. It is concluded that rats belonging to the same strain are nevertheless marked by an individual-specific, neurochemical state within the nucleus accumbens. It is tentatively suggested that responders are marked by noradrenergic neurones with a low firing rate in contrast to non-responders which are marked by noradrenergic neurones with a high firing rate. Finally, evidence was obtained that ergometrine and (3,4-dihydroxyphenylamino)-2-imidazoline (DPI) act simultaneously at dopaminergic sites which are involved in the control of locomotor activity in a familiar environment and at α-noradrenergic sites which are involved in the control of EMB elicited from the superior colliculus.

A Ca2+-dependent transglutaminase (EC 2.3.2.13) has been demonstrated in the eye lenses of several mammalian species [Lorand, L., Hsu, L. K. M., Siefring, G. E., Jr., & Rafferty, N. S. (1981) Proc. Natl. Acad. Sci. USA 78, 1356-1360]. Using [3H]methylamine as a convenient probe for transglutaminase activity, we have explored the action of this enzyme in the bovine eye lens. We could characterize the glutamine residues acting as acyl-donor sites in three beta-crystallin chains, which are the only substrates for lens transglutaminase among the various lens-specific structural proteins, the crystallins. A single glutamine was found to bind [3H]methylamine in each of these three chains: glutamine -9 in beta Bp (beta B2), glutamine -21 in beta B3, and glutamine -23 or -24 in beta A3. The four glutamines are all located in the NH2-terminal regions, which presumably extend from the compact two-domain structure of the beta-crystallin chains. It was, moreover, established that several components of the lens cytoskeleton are substrates for transglutaminase.