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1.

Background

Unbalanced dietary intakes of saturated (SFAs) and polyunsaturated (PUFAs) fatty acids can profoundly influence the hypothalamic-pituitary-adrenal (HPA)-axis and glucocorticoid secretions in relation to behavioral performances. The beneficial effects of higher dietary PUFA intakes and PUFA:SFA ratios may also affect social interactions and social-living per se, where adequate physiological and behavioral responses are essential to cope with unstable social environmental conditions.

Methods

Effects of diets high in PUFAs or SFAs and a control diet were investigated in male and female guinea pigs after 60 days of supplementation. Plasma fatty acid patterns served as an indicator of the general fatty acid status. HPA-axis activities, determined by measuring saliva cortisol concentrations, social behaviors, and hierarchy ranks were analyzed during group housing of established single-sexed groups and during challenging social confrontations with unfamiliar individuals of the other groups.

Results

The plasma PUFA:SFA ratio was highest in PUFA supplemented animals, with female levels significantly exceeding males, and lowest in SFA animals. SFA males and females showed increased saliva cortisol levels and decreased aggressiveness during group housing, while sociopositive behaviors were lowest in PUFA males. Males generally showed higher cortisol increases in response to the challenging social confrontations with unfamiliar individuals than females. While increasing cortisol concentrations were detected in control and PUFA animals, no such effect was found in SFA animals. During social confrontations, PUFA males showed higher levels of agonistic and sociopositive behaviors and also gained higher dominance ranks among males, which was not detected for females.

Conclusions

While SFAs seemingly impaired cortisol responses and social behaviors, PUFAs enabled adequate behavioral responses in male individuals under stressful new social environmental conditions. This sex-specific effect was possibly related to a general sex difference in the n-3 PUFA bioavailability and cortisol responses, which may indicate that males are more susceptible to changing environmental conditions, and shows how dietary fatty acids can shape social systems.
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2.

Background

Options for male contraception are limited. The purpose of this study was to use a nonhuman primate model to evaluate Vasalgel?, a high molecular weight polymer being developed as a contraceptive device for men.

Methods

Sixteen adult male rhesus monkeys received intravas injections of Vasalgel, consisting of 25% styrene maleic acid in dimethyl sulfoxide. After a one-week recovery, males were returned to outdoor group housing, which included at least 3 and up to 9 intact, breeding females with a successful reproductive history.

Results

Treated males have had no conceptions since Vasalgel injections. All males were housed with intact females for at least one breeding season and seven have been almost continually housed with females for 2 years. Complications were minor and included one incident of incorrect placement of Vasalgel into the vas deferens and the development of a sperm granuloma in one animal. Three unilateral vasectomies were performed, one was necessary for incorrect placement of Vasalgel, the other two were elective.

Conclusions

Intravas injection of Vasalgel in sexually mature adult male rhesus monkeys was effective in preventing conception in a free-living, group environment. Complications were few and similar to those associated with traditional vasectomy.
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3.

Background

Early experiences influence the developing organism, with lifelong and potentially adaptive consequences. It has recently become clear that the effects of early experiences are not limited to the exposed generation, but can influence physiological and behavioral traits in the next generation. Mechanisms of transgenerational effects of parental early experiences on offspring development are often attributed to prenatal or postnatal parental influence, but recent data suggest that germ-line plasticity may also play a role in the transgenerational effects of early experiences. These non-genetic transgenerational effects are a potentially important developmental and evolutionary force, but the effects of parental experiences on behavior and physiology are not well understood in socially complex primates. In the non-human primate, the rhesus macaque, nursery rearing (NR) is an early life manipulation used for colony management purposes, and involves separating infants from parents early in life. We examined the effects of maternal and paternal early NR on infant rhesus macaque immunity, physiology, and behavior.

Results

We theorized that differences in behavior or physiology in the absence of parent-offspring social contact would point to biological and perhaps germ-line, rather than social, mechanisms of effect. Thus, all subjects were themselves NR. Male and female infant rhesus macaques (N= 206) were separated from parents and social groups in the first four days of life to undergo NR. These infants differed only in their degree of NR ancestry – whether their dams or sires were themselves NR. At 3-4 months of age, infants underwent a standardized biobehavioral assessment. Factors describing immunity, plasma cortisol, and emotion regulation were generated from these data using factor analysis. Paternal, but not maternal, NR was associated with greater emotionality and higher plasma cortisol, compared with infants born to CONTROL reared fathers.

Conclusions

These data suggest that macaque biobehavioral makeup is strongly influenced by paternal experiences, and via non-social mechanisms.
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4.
5.

Background

Despite being the most commonly used mammal in biomedical research, problems with perinatal mortality in mice have received little attention and the causes of pup death are still poorly known. Females are often housed alone with their litters and since the lost pups are generally eaten, it is commonly assumed that the mother has killed them. However, more detailed observations than have been reported previously in the literature are required to establish if the cause of death is infanticide. Litter loss can only be prevented efficiently after underlying causes have been carefully investigated and interpreted. The aim of this study was to investigate if females actively kill their pups by observing the behaviour of females and pups in litters that later were lost. We used video recordings of females that lost their entire litter to observe females in detail from parturition until the pups died. In total, 10 C57BL/6 females (wildtype and the knockouts Hfe?/? and β2m?/?) were studied, housed in Makrolon II cages with or without access to a small amount of nesting material.

Results

Three of the females had pups that were never seen moving, and another three females had one or two pups that never moved, indicating that some pups were most likely still-born. In five females with live-born pups, detailed observations from the time when a pup was last seen moving until it died were possible to carry out. We observed females eating dead offspring and interacting with both moving and dead pups. However, we never observed a pup stop moving when manipulated by the female, nor were any wounds seen in the pups. Hence, we found no evidence of infanticide when studying females that had lost their entire litter.

Conclusion

These results suggest that other causes than infanticide plays a major role in mouse pup death, and stress the need for more systematic and careful investigations of the causality of litter loss.
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6.

Background

Diabetes induces many complications including reduced fertility and low oocyte quality, but whether it causes increased mtDNA mutations is unknown.

Methods

We generated a T2D mouse model by using high-fat-diet (HFD) and Streptozotocin (STZ) injection. We examined mtDNA mutations in oocytes of diabetic mice by high-throughput sequencing techniques.

Results

T2D mice showed glucose intolerance, insulin resistance, low fecundity compared to the control group. T2D oocytes showed increased mtDNA mutation sites and mutation numbers compared to the control counterparts. mtDNA mutation examination in F1 mice showed that the mitochondrial bottleneck could eliminate mtDNA mutations.

Conclusions

T2D mice have increased mtDNA mutation sites and mtDNA mutation numbers in oocytes compared to the counterparts, while these adverse effects can be eliminated by the bottleneck effect in their offspring. This is the first study using a small number of oocytes to examine mtDNA mutations in diabetic mothers and offspring.
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7.

Background

In adults, hypothalamus–pituitary–adrenal (HPA) axis activity shows sexual dimorphism, and this is thought to be a mechanism underlying sex-specific disease incidence. Evidence is scarce on whether these sex differences are also present in childhood. In a meta-analysis, we recently found that basal (non-stimulated) cortisol in saliva and free cortisol in 24-h urine follow sex-specific patterns. We explored whether these findings could be extended with sex differences in HPA axis reactivity.

Methods

From inception to January 2016, PubMed and EMBASE.com were searched for studies that assessed HPA axis reactivity in healthy girls and boys aged ≤18 years. Articles were systematically assessed and reported in the categories: (1) diurnal rhythm, (2) cortisol awakening response (CAR), (3) protocolled social stress tests similar or equal to the Trier Social Stress Test for children (TSST-C), (4) pharmacological (ACTH and CRH) stress tests, and (5) miscellaneous stress tests.

Results

Two independent assessors selected 109 out of 6158 records for full-text screening, of which 81 studies (with a total of 14,591 subjects) were included. Studies showed that girls had a tendency towards a more variable diurnal rhythm (12 out of 29 studies), a higher CAR (8 out of 18 studies), and a stronger cortisol response to social stress tests (9 out of 21 studies). We found no evidence for sex differences in cortisol response after a pharmacological challenge or to miscellaneous stress tests.

Discussion

Sex differences in HPA axis reactivity appear to be present in childhood, although evidence is not unequivocal. For a better evaluation of sex differences in HPA axis reactivity, standardization of protocols and reports of stress tests is warranted.
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8.

Background

Residual alcohol effects on physiological and psychological symptoms are commonly experienced the morning after alcohol consumption. The purpose of this study was to assess the effects of L-ornithine on subjective feelings and salivary stress markers the morning after alcohol consumption and to investigate whether L-ornithine acutely accelerates ethanol metabolism.

Methods

This study had a randomized, placebo-controlled, double-masked crossover design. Subjects were all healthy Japanese adults with the ‘flusher’ phenotype for alcohol tolerance. In experiment 1, 11 subjects drank 0.4 g/kg body weight alcohol 1.5 h before their usual bedtime. Half an hour after drinking, they ingested either a placebo or 400 mg ornithine. The next morning on awakening, subjects completed a questionnaire containing a visual analog scale (VAS), the Oguri-Shirakawa-Azumi sleep inventory MA version (OSA-MA), and a profile of mood states (POMS) and collected a saliva sample for measurement of salivary stress markers (cortisol, secretory immunoglobulin A, and α-amylase). In experiment 2, placebo or 400 mg ornithine were administrated to 16 subjects both before and after drinking, and the feeling of drunkenness, breath ethanol concentration and one-leg standing time were repeatedly investigated until 180 min after alcohol consumption.

Results

There were significant decreases in “awareness”, “feeling of fatigue” and “lassitude” VAS scores and in “anger-hostility” and “confusion” POMS scores and a significant increase in “sleep length” in the OSA-MA test. Salivary cortisol concentrations on awakening were reduced after ornithine supplementation. There were no differences between ornithine and placebo in any of the subjective or physiological parameters of acute alcohol metabolism.

Conclusions

Taking 400 mg ornithine after alcohol consumption improved various negative feelings and decreased the salivary stress marker cortisol the next morning. These effects were not caused by an increase in acute alcohol metabolism.
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9.

Background

The relatively fast selection of symbiotic bacteria within hosts and the potential transmission of these bacteria across generations of hosts raise the question of whether interactions between host and bacteria support emergent adaptive capabilities beyond those of germ-free hosts.

Results

To investigate possibilities for emergent adaptations that may distinguish composite host-microbiome systems from germ-free hosts, we introduce a population genetics model of a host-microbiome system with vertical transmission of bacteria. The host and its bacteria are jointly exposed to a toxic agent, creating a toxic stress that can be alleviated by selection of resistant individuals and by secretion of a detoxification agent (“detox”). We show that toxic exposure in one generation of hosts leads to selection of resistant bacteria, which in turn, increases the toxic tolerance of the host’s offspring. Prolonged exposure to toxin over many host generations promotes anadditional form of emergent adaptation due to selection of hosts based on detox produced by their bacterial community as a whole (as opposed to properties of individual bacteria).

Conclusions

These findings show that interactions between pure Darwinian selections of host and its bacteria can give rise to emergent adaptive capabilities, including Lamarckian-like adaptation of the host-microbiome system.

Reviewers

This article was reviewed by Eugene Koonin, Yuri Wolf and Philippe Huneman.
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10.

Background

Enhanced processing of emotional stimuli after stress exposure is reported to be associated with stress-induced cortisol. Because enhanced emotional information processing could make cognitive emotion regulation more difficult, it was hypothesized that stress-induced cortisol would be associated with non-negative interpretation generation associated with the cognitive reappraisal processes.

Methods

A total of 36 participants (Mean age?=?21.3 years, SD?=?1.8) watched video clips of depression-related stressful situations before and after the administration of a stress induction task. They were then asked to generate as many non-negative interpretations as possible to reduce the depressive mood. Saliva samples were obtained before and after the stress induction task to measure change in the cortisol level.

Results

Participants were allocated post-hoc to either a responder (n?=?19) or non-responder group (n?=?17) based on the cortisol response to the stress induction task. The number of non-negative interpretations generated following the stress induction task was reduced only in the cortisol responders. The number of post-stress non-negative interpretations was fewer in the responder group when compared by sex, baseline cortisol level, and the number of pre-stress non-negative interpretations, statistically controlled.

Conclusions

Although baseline cortisol and sex may have impacted the results, the results suggest that stress-induced cortisol is associated with difficulty in non-negative interpretation generation during the cognitive reappraisal process.
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11.

Objectives

To explore potential effects of recombinant human fibroblast growth factor 20 (rhFGF20) in the growth of cultured mouse vibrissal follicles.

Results

The growth of cultured mouse vibrissal follicles was significantly induced by rhFGF20 in a dose dependent pattern in the in vitro vibrissal follicle organ culture model. However, too high concentration of rhFGF20 could inhibit the growth of vibrissal follicles. We further demonstrated that rhFGF20 stimulated the proliferation of hair matrix cells and activated Wnt/β-catenin signaling pathway.

Conclusions

The rhFGF20 might be a potential therapeutic agent to treat hair loss disorders.
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12.

Introduction

Primitively eusocial halictid bees are excellent systems to study the origin of eusociality, because all individuals have retained the ancestral ability to breed independently. In the sweat bee Halictus scabiosae, foundresses overwinter, establish nests and rear a first brood by mass-provisioning each offspring with pollen and nectar. The mothers may thus manipulate the phenotype of their offspring by restricting their food provisions. The first brood females generally help their mother to rear a second brood of males and gynes that become foundresses. However, the first brood females may also reproduce in their maternal or in other nests, or possibly enter early diapause. Here, we examined if the behavioural specialization of the first and second brood females was associated with between-brood differences in body size, energetic reserves and pollen provisions.

Results

The patterns of variation in adult body size, weight, fat content and food provisioned to the first and second brood indicate that H. scabiosae has dimorphic females. The first-brood females were significantly smaller, lighter and had lower fat reserves than the second-brood females and foundresses. The first-brood females were also less variable in size and fat content, and developed on homogeneously smaller pollen provisions. Foundresses were larger than gynes of the previous year, suggesting that small females were less likely to survive the winter.

Conclusions

The marked size dimorphism between females produced in the first and second brood and the consistently smaller pollen provisions provided to the first brood suggest that the first brood females are channelled into a helper role during their pre-imaginal development. As a large body size is needed for successful hibernation, the mother may promote helping in her first brood offspring by restricting their food provisions. This pattern supports the hypothesis that parental manipulation may contribute to promote worker behaviour in primitively eusocial halictids.
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13.

Background

The objective of this study was to assess whether sex-specific differences in fetal and infant growth exist.

Methods

This study was embedded in the Generation R Study, a population-based prospective birth cohort. In total, 8556 live singleton births were included. Fetal growth was assessed by ultrasound. During the first trimester, crown-rump-length (CRL) was measured. In the second and third trimester of pregnancy head circumference (HC), abdominal circumference (AC) and femur length (FL) were assessed. Information on infant growth during the first 2 years of life was obtained from Community Health Centers and included HC, body weight and length.

Results

In the first trimester, male CRL was larger than female CRL (0.12 SD [95% CI 0.03,0.22]). From the second trimester onwards, HC and AC were larger in males than in females (0.30 SD [95% CI 0.26,0.34] and 0.09 SD [95% CI 0.05,0.014], respectively). However, FL in males was smaller compared to female fetuses (0.21 SD [95% CI 0.17,0.26]). Repeated measurement analyses showed a different prenatal as well as postnatal HC growth pattern between males and females. A different pattern in body weight was observed with a higher body weight in males until the age of 12 months where after females have a higher body weight.

Conclusions

Sex affects both fetal as well as infant growth. Besides body size, also body proportions differ between males and females with different growth patterns. This sexual dimorphism might arise from differences in fetal programming with sex specific health differences as a consequence in later life.
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14.

Background

Stress is a recognized risk factor for mood and anxiety disorders that occur more often in women than men. Prefrontal brain regions mediate stress coping, cognitive control, and emotion. Here, we investigate sex differences and stress effects on prefrontal cortical profiles of gene expression in squirrel monkey adults.

Methods

Dorsolateral, ventrolateral, and ventromedial prefrontal cortical regions from 18 females and 12 males were collected after stress or no-stress treatment conditions. Gene expression profiles were acquired using HumanHT-12v4.0 Expression BeadChip arrays adapted for squirrel monkeys.

Results

Extensive variation between prefrontal cortical regions was discerned in the expression of numerous autosomal and sex chromosome genes. Robust sex differences were also identified across prefrontal cortical regions in the expression of mostly autosomal genes. Genes with increased expression in females compared to males were overrepresented in mitogen-activated protein kinase and neurotrophin signaling pathways. Many fewer genes with increased expression in males compared to females were discerned, and no molecular pathways were identified. Effect sizes for sex differences were greater in stress compared to no-stress conditions for ventromedial and ventrolateral prefrontal cortical regions but not dorsolateral prefrontal cortex.

Conclusions

Stress amplifies sex differences in gene expression profiles for prefrontal cortical regions involved in stress coping and emotion regulation. Results suggest molecular targets for new treatments of stress disorders in human mental health.
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15.

Aims

Plant growth forms can influence carbon cycling, particularly in carbon-rich ecosystems like northern peatlands; however, mechanistic evidence of this relationship is limited. Our aim was to determine if northern peatland plant growth forms alter belowground dissolved carbon chemistry and enhance carbon release through stimulated microbial metabolism.

Methods

We used replicated, peat monoliths populated exclusively by Sphagnum mosses, graminoids, or bare peat and quantified changes in belowground dissolved organic carbon chemistry, microbial metabolism, as well as respired CO2.

Results

The graminoid growth form was significantly distinct in belowground dissolved organic carbon chemistry with carbon compound lability 20 % and 11 % greater than bare peat and Sphagnum moss respectively. The labile dissolved organic carbon stimulated the microbial community, as indicated by greater microbial metabolic activity and richness values in conjunction with 50 % higher respired CO2 fluxes under the graminoid treatment.

Conclusions

Our results provide mechanistic evidence that peatland plant growth forms can drive carbon cycling processes by altering dissolved organic carbon chemistry to prompt cascading effects on the microbial community and carbon release — trends suggestive of microbial priming effects. Should climate change increase graminoid prevalence at the expense of Sphagnum moss northern peatland carbon store stability may be threatened by this mechanism.
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16.

Background

The efficacy of physical exercise as an augmentation to pharmacotherapy with antidepressants for depressive patients has been documented. However, to clarify the effectiveness of exercise in the treatment of depression, it is necessary to distinguish the effect of the exercise itself from the effect of group dynamics. Furthermore, an objective measurement for estimation of the effect is needed. Previous reports adopted a series of group exercises as the exercise intervention and mainly psychometric instruments for the measurement of effectiveness. Therefore, this clinical study was done to examine the effectiveness of a single session of individual exercise on depressive symptoms by assessing the change in saliva free cortisol level, which reflects hypothalamic-pituitary-adrenocortical axis function that is disturbed in depressive patients.

Method

Eighteen medicated patients, who met the DSM-IV-TR criteria for major depressive disorder, were examined for the change in saliva free cortisol levels and the change in subjective depressive symptoms before and after pedaling a bicycle ergometer for fifteen minutes. Within a month after the exercise session, participants conducted a non-exercise control session, which was sitting quietly at the same time of day as the exercise session.

Results

Depressed patients who participated in this study were in remission or in mild depressive state. However, they suffered chronic depression and had disturbed quality of life. The saliva free cortisol level and subjective depressive symptoms significantly decreased after the exercise session. Moreover, the changes in these variables were significantly, positively correlated. On the other hand, although the subjective depressive symptoms improved in the control session, the saliva free cortisol level did not change.

Conclusion

For the first time in depressive patients, we were able to show a decrease in the saliva free cortisol level due to physical exercise, accompanied by the improvement of subjective depressive symptoms. This identified a possible influence of exercise on the hypothalamic-pituitary-adrenal axis in depression.These results suggest the utility of assessing the effect of physical exercise by saliva free cortisol level in depressive patients who suffer from bio-psycho-social disability.
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17.

Introduction

In some fish species, it is difficult to distinguish mature females from immature females or females that have already spawned via appearance or other convenient methods. Few studies have investigated plasma metabolite profiling for the prediction of fish maturation.

Objectives

We investigated the comprehensive metabolic profiles of plasma among immature females and mature females ready to spawn, as well as already spawned breeders of blunt snout bream (Megalobrama amblycephala). The purpose of this study was to screen out potential biomarkers for sexually mature female M. amblycephala compared to immature female individuals and already spawned breeders.

Methods

Three groups were set up in this study, which included 1-year-old immature females, 2-year-old sexually mature females ready to spawn and successfully spawned females of M. amblycephala. Plasma samples were collected to investigate comprehensive metabolic profiles through UPLC-MS/MS based on a metabolomics analysis method.

Results

According to multivariate and univariate statistical analysis, plasma metabolite profiles of the three groups were clearly separated. The differential plasma metabolites from three hormone related pathways including the GnRH signaling pathway, steroid hormone biosynthesis and steroid biosynthesis, were analyzed. A total of 29 metabolites were identified as differential biomarkers associated with the female maturation status.

Conclusion

The identified potential biomarkers could be useful in separating mature M. amblycephala from immature individuals or ovulation-induced female individuals, which would allow for more effective artificial breeding. The results may contribute to a better understanding of the maturation mechanisms of fish in the aspect of metabolomics.
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18.

Background and aims

Peatland moss communities play an important role in ecosystem function. Drivers such as fire and atmospheric pollution have the capacity to influence mosses via multiple pathways. Here, we investigate physical and chemical processes which may influence establishment and growth of three key moss species in peatlands.

Methods

A controlled factorial experiment investigated the effects of different peat bulk density, ash deposition and rainwater chemistry treatments on the growth of Sphagnum capillifolium, S. fallax and Campylopus introflexus.

Results

Higher peat bulk density limited growth of both Sphagnum species. S. capillifolium and C. introflexus responded positively to ash deposition. Less polluted rain limited growth of C. introflexus. Biomass was well correlated with percentage cover in all three species.

Conclusions

Peat bulk density increases caused by fire or drainage can limit Sphagnum establishment and growth, potentially threatening peatland function. Ash inputs may have direct benefits for some Sphagnum species, but are also likely to increase competition from other bryophytes and vascular plants which may offset positive effects. Rainwater pollution may similarly increase competition to Sphagnum, and could enhance positive effects of ash addition on C. introflexus growth. Finally, cover can provide a useful approximation of biomass where destructive sampling is undesirable.
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19.

Background

The ideal method for monitoring trilostane therapy in dogs with hypercortisolism is still open to debate. Recently, determination of the pre-trilostane (prepill) cortisol concentration has been proposed to be more repeatable than either post-trilostane or post-ACTH cortisol. The aim of this study was to compare two prepill cortisol concentrations in dogs with hypercortisolism during trilostane therapy. Sixteen client-owned dogs with naturally occurring hypercortisolism were prospectively included and cortisol concentrations were measured twice, 1?h apart, before the morning trilostane dose (prepill 1 and 2 cortisol).

Results

A total of 47 prepill cortisol measurement pairs were included. Compared to prepill 1, prepill 2 cortisol was higher in 15, equal in 8 and lower in 24 pairs. Group agreement between prepill 1 and 2 cortisol was 70% (moderate agreement - weighted kappa 0.55). In 30% of the pairs, group assignment was discrepant, implying a different therapeutic decision. In some dogs certain circumstances (e.g. excessive barking, difficulties during blood collection, excitement at arrival) were identified as potential factors explaining the discrepancy between prepill 1 and 2 cortisol measurements.

Conclusions

In a substantial number of dogs treated with trilostane, the two prepill cortisol concentrations differed. Part of this difference might be ascribable to stressful events during test performance. When using prepill cortisol measurements to monitor trilostane therapy, recording of any incident during handling that might affect cortisol release might be helpful to make a reliable decision about a trilostane dose adaptation.
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20.

Background

In recent years the visualization of biomagnetic measurement data by so-called pseudo current density maps or Hosaka-Cohen (HC) transformations became popular.

Methods

The physical basis of these intuitive maps is clarified by means of analytically solvable problems.

Results

Examples in magnetocardiography, magnetoencephalography and magnetoneurography demonstrate the usefulness of this method.

Conclusion

Hardware realizations of the HC-transformation and some similar transformations are discussed which could advantageously support cross-platform comparability of biomagnetic measurements.
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