Association of HLA-DRB1 and TNF genotypes with dengue hemorrhagic fever

Genes coding for human leukocyte antigen (HLA) class II molecules and tumor necrosis factor (TNF)-α are polymorphic and have been shown to influence susceptibility to infectious diseases. In the present study, HLA-DRB1, -DQB1 and TNF gene polymorphisms were investigated in 114 dengue patients (DEN) [85 dengue fever (DF) cases and 29 dengue hemorrhagic fever (DHF) cases] and 110 healthy controls (HCs) using PCR based methods. The frequencies of HLA-DRB1^∗07 allele [DF vs. DHF, P = 0.0034, Pc = 0.044, OR 3.79] and HLA-DRB1^∗07/^∗15 genotype [DF vs. DHF, P = 0.00071, Pc = 0.038, OR 10.41] were significantly higher in DHF cases as compared to HCs and DF cases. Higher frequency of rs1800629 ‘G/A’ genotype was observed in DHF cases as compared to DF cases. The frequency of rs1799964 ‘C/C’ genotype of the TNF gene was found to be significantly higher in all patient groups compared to HCs [HCs vs. DEN, P = 0.0054, Pc = 0.0162, OR 3.57; HCs vs. DF, P = 0.036, OR 2.89; HCs vs. DHF, P = 0.0088, Pc = 0.0240, OR 5.11]. Presence of combination of HLA-DRB1^∗07/^∗15 with either rs1799964 ‘C/C’ genotype or rs1800629 ‘G/A’ genotype or both was present in 17.2% of DHF cases and 1.2% in HCs while this combination was not observed in DF cases. The results suggest that HLA-DRB1^∗07/^∗15 genotype in combination with TNF polymorphisms influence progression to DHF.     

Sleep deprivation lowers reactive aggression and testosterone in men

The role of sleep deprivation in aggressive behavior has not been systematically investigated, despite a great deal of evidence to suggest a relationship. We investigated the impact of 33 h of sleep loss on endocrine function and reactive aggression using the Point Subtraction Aggression Paradigm (PSAP) task. PSAP performance was assessed in 24 young men and 25 women who were randomly assigned to a sleep deprivation or control condition. Sleep deprivation lowered reactive aggression and testosterone (but not cortisol) in men, and disrupted the positive relationship between a pre-post PSAP increase in testosterone and aggression that was evident in rested control men. While women increased aggression following provocation as expected, no influence of sleep deprivation was found. This is the first experimental study to demonstrate that sleep deprivation lowers reactive aggression in men. Testosterone, but not cortisol, played a role in the relationship between sleep and reactive aggression in men.     

Development of a behaviour change communication tool for medical students: The ‘Tent Pegs’ booklet

Objective

To describe the development and validation of a behaviour change communication tool for medical students.

Methods

Behaviour change techniques (BCTs) were identified within the literature and used to inform a communication tool to support medical students in discussing health-related behaviour change with patients. BCTs were organized into an accessible format for medical students (the ‘Tent Pegs’ booklet) and validated using discriminant content validity methods with 11 expert judges.

Results

One-sample t-tests showed that judges reliably mapped BCTs onto six of the seven Tent Pegs domains (confidence rating means ranged from 4.0 to 5.1 out of 10, all p ≤ 0.002). Only BCTs within the ‘empowering people to change’ domain were not significantly different from the value zero (mean confidence rating = 1.2, p > 0.05); these BCTs were most frequently allocated to the ‘addressing thoughts and emotions’ domain instead.

Conclusion

BCTs within the Tent Pegs booklet are reliably allocated to corresponding behaviour change domains with the exception of those within the ‘empowering people to change’ domain.

Practice implications

The existing evidence-base on BCTs can be used to directly inform development of a communication tool to support medical students facilitate health behaviour change with patients.     

Older cancer patients’ information and communication needs: What they want is what they get?

Objective

To evaluate what information and communication aspects older cancer patients (≥65) consider important in preparing for chemotherapy treatment (CT), the extent to which this corresponds with what oncology nurses consider important, and the extent to which nurses attend to these aspects during real-life educational visits in oncology.

Methods

The QUOTE^chemo was used to have patients (n = 116) and nurses (n = 123) rate the importance of 66 aspects of patient education. Subsequently, the implementation of these 66 aspects during videotaped nursing visits (n = 155) with older cancer patients receiving CT for the first time was examined.

Results

Older cancer patients attached most importance to ‘treatment-related information’, ‘rehabilitation information’, ‘affective communication’ and discussing ‘realistic expectations’. Nurses placed great importance to almost all aspects except to discussing ‘realistic expectations’. Discrepancies were found between expressed importance and the actual performance during the videotaped consultations, particularly in discussing realistic expectations, coping information, interpersonal communication, and tailored communication.

Conclusion

Results pointed to aspects that need improvement to ensure high quality patient education tailored to the patients’ needs.

Practice implications

To make sure older cancer patients’ needs are met, more attention should be paid to the development of interventions supporting both needs assessment and fulfillment.     

The role of cerebrospinal fluid proteins as early diagnostic markers for sporadic Creutzfeldt–Jakob disease

The utility of cerebrospinal fluid (CSF) proteins such as 14-3-3, tau protein and S-100b as diagnostic markers in the early stages of sporadic Creutzfeldt–Jakob disease (sCJD) is unclear. We examined the diagnostic value of these CSF proteins in the early stages of sCJD (within 6 weeks of onset of symptoms). Four groups of patients were compared: patients with probable or neuropathologically confirmed sCJD with CSF taken within 6 weeks of onset (‘sCJD < 6-week group’, n = 47); patients with CSF taken within 6 weeks of disease onset but with a diagnosis other than CJD (‘non-sCJD < 6-week group’, n = 21); patients with neuropathologically proven sCJD where CSF was taken later than 6 weeks after onset (’sCJD > 6-week group’, n = 206); patients with CSF taken later than 6 weeks after onset of symptoms but with a diagnosis other than CJD (‘non-sCJD > 6-week group’, n = 166). The sensitivity and specificity of different combinations of neuronal proteins were ascertained. The sensitivities of all three markers were similar and ranged from 96% to 98%. The sensitivity of these markers was greater in the ‘sCJD < 6-week group’ than in the ‘sCJD > 6-week group’. This may be due to differences in the PRNP codon 129 and PrP isotype distribution between these groups. CSF tau protein had the greatest specificity (82%). We found all three CSF protein markers to be highly sensitive in the early stages of sCJD, with CSF tau protein having the greatest specificity and efficiency. Our findings indicate that CSF protein markers are effective tests in the early stages of sCJD.     

Hypocapnia-dependent facilitation of augmented breaths: observations in awake vs. anesthetized rats

We investigated whether commonly used injectable laboratory anesthetics alter the regulation of augmented breaths (ABs) in different respiratory backgrounds. Male rats were studied on three separate experimental days, receiving one of three injections in randomized order: ethyl carbamate (‘urethane’; 1.2 mg kg⁻¹), ketamine/xylazine (ket/xyl; 80/10 mg kg⁻¹), or normal saline. Following each of the three interventions, breathing was monitored during 15 min exposures to normoxia (room air), hypoxia (10% O₂) and hypoxia + CO₂ (10% O₂, 5% CO₂). Urethane anesthesia completely eliminated ABs from the breathing rhythm in room air conditions (p < 0.001), and decreased the hypocapnia-dependent component of this response (p < 0.001). ket/xyl left the normal incidence of ABs in room air breathing intact but significantly suppressed the hypoxia-induced facilitation of ABs (p = 0.0015). These results provide the first clear evidence that laboratory anesthesia can profoundly alter the regulation of ABs including the hypocapnia-dependent component of their facilitation.     

Novel allelic variants in the human serotonin transporter gene linked polymorphism (5-HTTLPR) among depressed patients with suicide attempt

A polymorphism in the serotonin transporter gene (5-HTTLPR) is being extensively studied for association with suicidal behavior. A new allelic variant within the 5-HTTLPR polymorphism was described but it has not been thoroughly analyzed in the recent literature. The SNP functional analysis demonstrated that the A variant of the L allele (L_A) produces high levels of mRNA and that the G variant (L_G) is equivalent to the S allele. Our aims were to compare the frequency of 5-HTTLPR alleles in 94 depressed patients who attempted suicide compared to 94 controls free of psychiatric disorder, including the embedded SNP rs25531. Using the biallelic classification, our sample contained 62 (33%) LL, 76 (40.4%) LS, and 50 (26.6%) SS individuals. Using the functional classification system, our sample contained 43 (22.5%) L’L’, 84 (44.7%) L'S’, and 61 (32.4%) S'S’ individuals, with no significant differences between cases and controls in genotypic tests in either biallelic (χ² = 2.543; df = 2; p = 0.280) and functional models (χ² = 2.995; df = 2; p = 0.228). The minor allele frequency (MAF) – the S allele – did not show any distributional difference between cases and controls using biallelic classification system 0.51 vs. 0.43, (OR = 1.41; CI95% 0.94 to 2.12; p = 0.121). Also the S’ allele of the functional classification system did not show any distributional difference between the two groups 0.59. vs. 0.51 (OR = 1.35; CI95% 0.90 to 2.03; p = 0.178). This study provided the possibility of a re-analysis of novell 5-HTTLPR functional variants identified within L allele that alters its mRNA production and thus changes its functionality. We could not find any association between both biallelic and functional 5-HTTLPR in depressed patients with suicide attempt, being the small sample size an important limitation for these results. In conclusion, we can suggest that despite the several studies in this issue, the exact effect and role of 5-HTTLPR in genetics of suicide is still unclear and should be better investigated for future studies.     

Effects of extended-release quetiapine fumarate on long-term functioning and sleep quality in patients with Generalized Anxiety Disorder (GAD): Data from a randomized-withdrawal,placebo-controlled maintenance study

Background

This analysis evaluated effects of quetiapine XR maintenance treatment on functioning and sleep in patients with GAD.

Methods

Analysis of patient-reported data from a randomized-withdrawal, double-blind, placebo-controlled study of quetiapine XR monotherapy in GAD. Following open-label run-in (4–8 weeks) and a 12–18-week stabilization phase (quetiapine XR 50, 150, or 300 mg/day), eligible patients were randomized to continue on quetiapine XR or receive placebo for up to 52 weeks. Primary variable was time to an anxiety event. Secondary variables included the Sheehan Disability Scale (SDS) and Pittsburgh Sleep Quality Index (PSQI).

Results

In total, 432 patients were randomized (quetiapine XR, N=216; placebo, N=216). The risk of an anxiety event was significantly reduced for quetiapine XR vs. placebo (HR 0.19; 95% CI 0.12, 0.31; p<0.001). Quetiapine XR was more effective than placebo at maintaining SDS total scores (LSM change: −0.19 vs. 1.01; p=0.017) and non-work-related SDS domain score ‘family life/home responsibilities’ (−0.13 vs. 0.32; p=0.011), but not ‘social life’ (0.05 vs. 0.34; p=0.114). Quetiapine XR was more effective than placebo at maintaining the work-related SDS domain score ‘days lost’ (−0.05 vs. 0.11; p=0.027), but not ‘work/school’ (−0.10 vs. 0.29; p=0.051) or ‘days underproductive’ (0.06 vs. 0.13; p=0.619). PSQI global scores were reduced from randomization with quetiapine XR vs. placebo (0.39 vs. 1.60; p<0.001).

Limitations

Lack of active-comparator arm, exclusion of patients with comorbid depression.

Conclusions

In patients with GAD, long-term treatment with quetiapine XR (50–300 mg/day) monotherapy was effective at maintaining improvements in functioning and sleep quality.     

IL21 and IL21R polymorphisms and their interactive effects on serum IL-21 and IgE levels in patients with chronic hepatitis B virus infection

Interleukin (IL)-21 may affect both T-cell and B-cell responses and was suggested to be involved in response to HBV infection. This study explored IL21rs907715 and rs2221903 and IL21R T-83C and rs3093301 polymorphisms and serum IL-21 and IgE levels in 395 patients with chronic HBV infection, 75 HBV infection resolvers and 174 healthy controls. IL21R T-83C was not polymorphic in the study populations. IL21 rs2221903 AG was less frequent in HBV patients than in resolvers (p < 0.001, OR = 0.364, 95% CI = 0.211–0.629) or in controls (p = 0.017, OR = 0.589, 95% CI = 0.381–0.911). IL21R rs3093301 TT was more frequent in HBV patients than in controls [p value after Bonferroni correction (p_c) = 0.022, OR = 1.908, 95% CI = 1.158–3.142] and more frequent in resolvers than in controls (p_c = 0.010, OR = 2.965, 95% CI 1.375–6.392). The carriage of IL21 rs2221903 AG/IL21R rs3093301 CT + IL21 rs2221903 AG/IL21R rs3093301 TT was less frequent in patients than in resolvers (p_c = 0.007, OR = 0.236, 95% CI = 0.096–0.579) and more frequent in resolvers than in controls (p_c = 0.014, OR = 4.354, 95% CI = 1.660–11.420). IL21 rs2221903 was, by interaction with IL21R rs3093301, associated with serum IL-21 and IgE levels in HBV patients. It is suggested that IL21 rs2221903 and IL21R rs3093301 polymorphisms may, independently or interactively, affect the susceptibility to and/or persistence of HBV infection potentially through altering IL-21 and IgE production.     

The perception of shared medical decision making of expert and lay people: Effects of observing a movie clip depicting a medical consultation

Objective

To test for differences between experts and lay people in assessment of the degree to which a doctor engaged in a shared decision making (SDM) with a patient using the OPTION scale and a movie clip as stimulus material.

Methods

A segment of the movie ‘Wit’, depicting the communication of the diagnosis and the therapy proposed of a cancer, was shown to (a) university students with no knowledge about doctor–patient communication; (b) nurses working in medicine departments; (c) advanced medical students; (d) hospital physicians. The participants were asked to complete the OPTION scale which measures the extent to which physicians involve patients in medical decisions. An analysis of variance was used to compare OPTION scores across the four groups and to compare males and females.

Results

Being female [F_(1,190) = 11.9; p < .001] and being familiar with medical issues [F_(3,190) = 11.09; p < .001] were both significantly associated with a negative evaluations of the doctor's ability to involve the patient in the SDM.

Conclusion

Lay people and males (including male experts), are less demanding regarding SDM abilities.

Practice implications

A more systematic use of videos and the OPTION scale as validated outcome measure could be helpful educational strategy for the teaching of SDM.     

The effect of lung stretch during sleep on airway mechanics in overweight and obese asthma

Both obesity and sleep reduce lung volume and limit deep breaths, possibly contributing to asthma. We hypothesize that increasing lung volume dynamically during sleep would reduce airway resistance in asthma. Asthma (n = 10) and control (n = 10) subjects were studied during sleep at baseline and with increased lung volume via bi-level positive airway pressure (BPAP). Using forced oscillations, respiratory system resistance (R_rs) and reactance (X_rs) were measured during sleep and R_rs was partitioned to upper and lower airway resistance (R_up, R_low) using an epiglottic pressure catheter. R_rs and R_up increased with sleep (p < 0.01) and X_rs was decreased in REM (p = 0.02) as compared to wake. R_rs, R_up, and R_low, were larger (p < 0.01) and X_rs was decreased (p < 0.02) in asthma. On BPAP, R_rs and R_up were decreased (p < 0.001) and X_rs increased (p < 0.01), but R_low was unchanged. High R_up was observed in asthma, which reduced with BPAP. We conclude that the upper airway is a major component of R_rs and larger lung volume changes may be required to alter R_low.     

Influence of lower body negative pressure release on soleus H reflex,respiratory sensations and reflexes in human subjects

Using a physiological model of acutely increasing venous return into the lungs, i.e. by applying and then releasing lower body negative pressure (LBNP) to mimic the natural stimulus of juxtapulmonary capillary (J) or pulmonary C fibre receptors, produced an immediate and significant reduction in the amplitude of the Hoffman (H) reflex by 81 ± 4% (P = 0.001) in a majority of subjects 70% (n = 5). Accompanying this was a notable change in the respiratory pattern with tidal volume (V_T) increasing in all subjects from (mean) 0.462 ± .038 to 0.777 ± .061 l/min (P = 0.001) and the respiratory rate (F_R) in 40% from 14 ± 1 to 24 ± 0.8 breaths/min. A feeling of pressure in throat, upper chest was reported by all and a shortness of breath-by 70% of the subjects. These were similar in nature to the respiratory sensations felt with threshold doses of intravenous lobeline, a well-established chemical stimulant of J receptors. All effects lasted for 15–20 s and within a minute the parameters resumed their earlier control values.     

Type D personality is associated with low cardiovascular reactivity to acute mental stress in heart failure patients

Background

The distressed (Type D) personality is associated with adverse coronary heart disease outcomes, but the mechanisms accounting for this association remain to be elucidated. We examined whether myocardial and hemodynamic responses to mental stress are disrupted in Type D patients with chronic heart failure (HF).

Methods

Ninety-nine HF patients (mean age 65 ± 12 years; 75% men) underwent a public speech task, during which heart rate (HR) and blood pressure (BP) were recorded. Type D personality and its components negative affectivity (NA) and social inhibition (SI) were assessed with the DS14. General linear models with repeated measures and logistic regression were used to assess differences in stress response and recovery.

Results

Type D personality was associated with a reduced HR response (F_1,93 = 4.31, p < .05) independent of the use of beta adrenergic blocking agents and the presence of atrial fibrillation. There were no differences between HF patients with and without a Type D personality with respect to the BP response. Examining continuous NA and SI scores and their interaction (NA ∗ SI), revealed a significant association of NA ∗ SI with the SBP response (F_1,93 = 4.11, p < .05), independent of BP covariates. Results with respect to HR and DBP responses were comparable to the findings using the dichotomous Type D measure. No significant associations between Type D and recovery patterns were found.

Conclusion

HF patients with Type D personality may show an inadequate response to acute social stress, characterized by a blunted HR response.     

Dehydroepiandrosterone in nails of infants: a potential biomarker of intrauterine responses to maternal stress

Easily accessible biomarkers for fetal stress biology are lacking. We here explore whether quantification of major fetal steroids, dehydroepiandrosterone (DHEA) or DHEA sulfate (DHEAS), with liquid chromatography/tandem mass spectrometry in infant nails is a tool to assess fetal stress biology in response to maternal stressful life events during pregnancy. Sufficient nail (≥1 mg) was available from 80 infants (93% of those providing samples). The concentration of DHEA, but not DHEAS, was increased in infants of mothers with stressful life events during pregnancy (DHEA: F_1,41 = 6.105, P = 0.018; DHEAS: F_1,77 = 0.767, P = 0.384). DHEA concentrations were not related to maternal stress before pregnancy (F_1,41 = 0.010, P = 0.922). Infant nail DHEA may be a fetal biological correlate of intrauterine exposure to maternal stress. The method promises the first non-invasive retrospective biomarker for intrauterine stress biology, opening new ways for research and clinical applications in fetal medicine, endocrinology, obstetrics, gynecology, and for understanding the developmental origins of health and disease.     

Severity level and injury track determine outcome following a penetrating ballistic-like brain injury in the rat

Penetrating ballistic brain injury (PBBI) is a high-energy transfer wound causing direct damage to the cerebrum. Outcome is directly related to the ballistic's anatomical path and degree of energy transfer. In this study we evaluated differences in outcome induced by altering the ‘projectile’ paths and severity levels of a simulated bullet wound using a newly characterized rat model of PBBI. Severity levels (5, 10, and 15%) were compared across three distinct injury paths: (1) unilateral ‘frontal’, (2) ‘bilateral’ hemispheric, and (3) unilateral ‘caudal’ (including cerebellum/midbrain). Outcome was assessed by differences in mortality rate and motor dysfunction (e.g. neurological and balance beam deficits). Results indicated that outcome was dependent not only on the severity level of PBBI (P < 0.001, r = 0.535) but also brain regions injured (P < 0.001, r = 0.398). A unilateral caudal injury was associated with the highest degree of mortality (up to 100%) and motor dysfunction (64–100% disability). Bilateral hemispheric injuries were also potentially fatal, while the best outcomes were associated with a unilateral frontal injury (no mortality and 14–39% motor disability). These data closely resemble clinical reports of ballistic wounds to the head and further validate the rat PBBI model with the ultimate intent to investigate novel therapeutic approaches for diagnosis and treatment of the neuropathological damage associated with PBBI.     

Stress augments food 'wanting' and energy intake in visceral overweight subjects in the absence of hunger

Stress may induce eating in the absence of hunger, possibly involving changes in food reward, i.e. ‘liking’ and ‘wanting’. The objective of this study was to assess the effects of acute psychological stress on food reward, and on energy intake, in visceral overweight (VO) vs. normal weight (NW) subjects. Subjects (27 NW, age = 26 ± 9 yrs, BMI = 22 ± 2 kg/m²; 15 VO, age = 36 ± 12 yrs, BMI = 28 ± 1 kg/m²) came to the university twice, fasted, for either a rest or stress condition (randomized cross-over design). Per test-session ‘liking’ and ‘wanting’ for 72 items divided in six categories (bread, filling, drinks, dessert, snacks, and stationery (control)) were measured twice, each time followed by a wanted meal. Appetite profile (visual analogue scales, VAS), heart rate, mood state and level of anxiety (POMS/STAI questionnaires) were measured.High hunger and low satiety (64 ± 19, 22 ± 20 mmVAS) confirmed the fasted state. Elevated heart rate, anger and confusion scores (p ≤ 0.03) confirmed the stress vs. rest condition. Consumption of the first meal decreased hunger, increased satiety, and decreased ranking of ‘liking’ of bread vs. increased ranking of ‘liking’ of the control (p < 0.001). ‘Wanting’ for dessert and snacks, energy intake, carbohydrate and fat intake for the second meal stress vs. rest relatively increased in VO vs. decreased in NW (p < 0.02). During stress vs. rest VO showed a 6 ± 9% increase in percentage of daily energy requirements consumed over the two meals (p = 0.01).To conclude, visceral overweight subjects showed stress-induced food intake in the absence of hunger, resulting in an increased energy intake.     

An increase in salivary interleukin-6 level following acute psychosocial stress and its biological correlates in healthy young adults

Although interleukin-6 (IL-6) has been investigated frequently in stress research, knowledge regarding the biological processes of IL-6 in association with psychosocial stress remains incomplete. This study focused on salivary IL-6 and reports its temporal variation and biological correlates following acute psychosocial stress. Fifty healthy young adults (39 male and 11 female students) were subjected to the psychosocial stress test ‘Trier Social Stress Test’ (TSST), wherein the participants were asked to deliver a speech and perform a mental arithmetic task in front of 2 audiences. Collection of saliva samples, measurement of heart rate, and assessment of negative moods by visual analogue scales were conducted before, during, and after TSST. Salivary IL-6 levels increased by approximately 50% in response to the TSST and remained elevated for 20 min after the stress tasks were completed. Cluster analyses revealed that individuals with sustained elevation of IL-6 levels following the TSST exhibited a lower cortisol response compared to individuals with lower IL-6 levels. In the correlation analyses, a greater IL-6 response was associated with a higher heart rate during the mental arithmetic task (r = .351, p < .05) and with a lower cortisol response (r = −.302, p < .05). This study demonstrates that salivary IL-6 levels are elevated for a relatively long period following acute psychosocial stress, and suggests that sympathetic activity and cortisol secretion are involved in elevation of salivary IL-6 levels.     

The proportion and function of peripheral myeloid-derived suppressor cells do not correlate with systemic inflammation in chronic obstructive pulmonary disease

Myeloid-derived suppressor cells (MDSC) have been implicated in the regulation of chronic inflammation. Chronic obstructive pulmonary disease (COPD) involves persistent inflammation, but the role of MDSC has not been explored. Here, proportions of MDSC (CD14⁻HLA-DR⁻CD33⁺CD11b⁺ cells) were quantified in peripheral blood mononuclear cells (PBMC) isolated from patients with ‘stable’ COPD (n = 12), smokers with no evidence of COPD (n = 11) and healthy non-smokers (n = 11). The proportions of MDSC were similar in all groups. MDSC function was assessed by comparing T-cell and cytokine responses of whole and MDSC-depleted PBMC stimulated with Staphylococcus enterotoxin-B (SEB). Depletion of MDSC did not enhance CD4⁺ or CD8⁺ T-cell activation and proliferation, or alter IFNγ and IL-17 production in response to SEB. However production of TGFβ decreased after depletion of MDSC, so MDSC may be a source of this cytokine. In conclusion, COPD was not associated with perturbations in the proportion or function of MDSC in peripheral blood.     

Adrenal reactivity in lines of domestic fowl selected on feather pecking behavior

Domestic chicken lines of the White Leghorn layer type differing in their level of feather pecking have been developed by divergent selection specifically on feather pecking behavior. This paper describes an investigation of basal level, reactivity to manual restraint and maximal adrenal response to 1-24 ACTH in breeder birds of the sixth generation of selection (S6) and their control line. Birds from the three lines had comparable basal levels of corticosterone (1.6 ng/ml, anova F_2,101 = 0.62, ns), whereas males had higher basal levels than females, lsmean 1.9 vs. 1.5 ng/ml (anova F_1,103 = 6.03, P < 0.05). Reactivity to handling and restraint for 10 min differed with HFP birds showing higher reactivity than LFP birds, lsmean 11.0 vs. 7.9 ng/ml (t = − 2.00, P < 0.05), while control birds showed intermediate levels (10.2 ng/ml). Males had higher reactivity than females, lsmean 11.2 vs. 8.2 ng/ml (anova F_1,103 = 3.96, P < 0.05). Maximal response did not differ between lines (average 35.7 ng/ml, anova F_2,101 = 1.38, P > 0.05). Males had higher maximal response than females, lsmean 41.3 vs. 33.6 ng/ml (anova F_1,103 = 5.77, P < 0.05). The present study shows that selection against feather pecking behavior have resulted in lower levels of feather pecking as well as lower sensitivity to human handling and restraint in White Leghorn laying hen lines. From an animal welfare point of view this is a positive relationship.     

Augmented breaths (‘sighs’) are suppressed by morphine in a dose-dependent fashion via naloxone-sensitive pathways in adult rats

Morphine treatment can eliminate augmented breaths (ABs; ‘sighs’) during spontaneous breathing. In the present study, unanesthetized rats were studied to: (1) determine the involvement of naloxone-sensitive receptor pathways, and (2) establish the dose–response relationship of this side effect. At a dosage of 5 mg/kg (2–10 mg/kg is recommended range for analgesia) morphine eliminated ABs from the breathing rhythm across nearly 100 min post-administration (vs. 6.2 ± 1.6 ABs in 15 min, control condition, p < 0.001). This occurred despite no apparent effect on indices of ventilation. By contrast, when naloxone was co-administered with morphine, the occurrence of ABs was not different compared to control. The suppression of ABs by morphine followed a sigmoidal pattern across the low–mid dosage range (R² = 0.83), whereas tidal volume and breathing frequency were unaffected. We conclude that the opioid-induced suppression of ABs is mediated by naloxone-sensitive opioid receptor pathways, and that this side effect is potent across the low–mid dosage range, and cannot be simply avoided by restricting dosage.