Rehabilitation following rotator cuff repair: A nested qualitative study exploring the perceptions and experiences of participants in a randomised controlled trial.

OBJECTIVE: To investigate acceptability, barriers to adherence with the interventions, and which outcome measures best reflect the participants' rehabilitation goals in a pilot and feasibility randomised controlled trial evaluating early patient-directed rehabilitation and standard rehabilitation, including sling immobilisation for four weeks, following surgical repair of the rotator cuff of the shoulder. DESIGN: Nested qualitative study. SETTING: Five English National Health Service Hospitals. SUBJECTS: Nineteen patient participants who had undergone surgical repair of the rotator cuff and 10 healthcare practitioners involved in the trial. METHOD: Individual semi-structured interviews. Data were analysed thematically. RESULTS: Four themes: (1) Preconceptions of early mobilisation; many participants were motivated to enter the trial for the opportunity of removing their sling and getting moving early. (2) Sling use and movement restrictions; for some, sling use for four weeks was unacceptable and contributed to their pain, rather than relieving it. (3) Tensions associated with early mobilisation; clinical tensions regarding early mobilisation and the perceived risk to the surgical repair were apparent. (4) Processes of running the trial; participants found the trial processes to be largely appropriate and acceptable, but withholding the results of the post-operative research ultrasound scan was contentious. CONCLUSION: Trial processes were largely acceptable, except for withholding results of the ultrasound scan. For some participants, use of the shoulder sling for a prolonged period after surgery was a reported barrier to standard rehabilitation whereas the concept of early mobilisation contributed tension for some healthcare practitioners due to concern about the effect on the surgical repair.

Lymphocyte Index of Peripheral Blood in Rats at Different Stages of the Post-Stress Period under Conditions of Antigenic Exposure and Injection of Lipopolysaccharide.

Changes in the Shaganin lymphocyte index (ratio of the number of lymphocytes to segmented neutrophils) in the peripheral blood of rats after intraperitoneal administration of LPS (100 µg/kg) at the end of a single stress exposure in a model of 24-h restraint stress were studied. The lymphocyte index was analyzed 3 h later, on the 1st and 8th days after the stress load. Immobilization was accompanied by a decrease in this parameter 3 h after exposure. One day after the stress load, an increase in the lymphocyte index was noted, which remained on the 8th day of observation. LPS injection did not affect the changes in this parameter caused by 24-h immobilization on the 1st and 8th days of the study, but prevented a pronounced increase in the lymphocyte index on the 1st day after the stress load. The data obtained expand the existing scientific understanding of the specificity of the involvement of immunomodulatory substances in the implementation of adaptive-compensatory processes in mammals under conditions of emotional stress.

Effect of Exhaustive Training or Forced Immobilization on Physiological Condition and Main Metabolic and Stress Markers of Wistar Male Rats.

For correct and reliable experimental in vivo assessment of antistress effect of various bioactive substances, appropriate biomodels reproducing stress and organism response to stress in laboratory animals should be chosen. We chose treadmill test for simulating exhaustive physical load and forced immobilization accompanied by disorders of physiological and psychological condition. Verification of the models used indicates their wide applicability for testing certain biological manifestations under reproduced stress exposure.

Short-term upper-limb immobilization alters peripersonal space representation.

Peripersonal space is a multisensory interface between the environment and the body subserving motor interactions with the physical and social world. Although changing body properties has been shown to alter the functional processing of space, little is known about the effect of short-term limb immobilization specifically on the motor representation of peripersonal space. In the present study, we investigated the effect of a right upper-limb immobilization for a duration of 24 h on a reachability judgment task and a brightness judgment task. Analyses of perceptual thresholds revealed a reduction of peripersonal space representation after the immobilization period, which was not observed when there was no immobilization (control group). In contrast, no variation appeared in the brightness judgment task, suggesting no presence of specific visual perception or decisional deficits in the limb immobilization group. Considered together, the results confirm the crucial role of the motor system in the representation of peripersonal space. They also highlight the plasticity of the motor system resulting in a rapid change of its activity following limb immobilization, with a concomitant effect on motor-related perceptual and cognitive processes.

Blood Cytokine Concentration in Rats during Antigenic Treatment after a Single Long-Term Stress Exposure.

We studied changes in the blood cytokine profile of rats 3 h, 1 day, and 8 days after acute stress on the model of 24-h immobilization followed by LPS administration (100 µg/kg intraperitoneally). The concentration of proinflammatory cytokines (particularly of IL-1ß and TNFα) significantly decreased at the early stage after stress exposure and physiological saline injection, but increased in the follow-up period and practically did not differ or even surpassed the control level by the end of observations. Under these conditions, the blood content of anti-inflammatory cytokine IL-10 increased most significantly on day 1 of the post-stress period. Restraint stress followed by LPS administration was accompanied by a decrease in the level of proinflammatory cytokines at the early (IFNγ and TNFα) and late stages (IL-1ß) of the experiment. Directed modulation of the immune status in animals after acute stress was followed by a significant increase in the content of IL-10 on days 1 and 8, as well as by a tendency toward elevation of IL-4 concentration by the end of the study. The directionality and degree of changes in the cytokine profile of mammalian tissues depend on the type of extreme exposure, duration of the post-stress period, and specific effects of exogenous pathogenic factors in the whole body.

Configuration-dependent variability of the effect of an electric field on the plasma glucocorticoid level in immobilized mice.

We recently reported that an immobilization stress-induced increase in glucocorticoid (GC) level was suppressed in mice exposed to an electric field (EF) of 50 Hz in a kV/m-dependent manner. In this study, we investigated the reproducibility of the suppressive effect induced by EF exposure by varying the voltage and distance between the electrodes (0.5 kV/50 mm, 1 kV/100 mm, 2 kV/200 mm) and comparing the effects on the plasma GC level. In addition, the effect of mice being in contact with the lower electrode or not was compared at 1 kV/100 mm. Immobilization-induced GC levels were significantly decreased in mice exposed to an EF at 1 kV/100 mm for 60 min (P < 0.01), but not in mice exposed to 0.5 kV/50 mm or 2 kV/200 mm. Furthermore, the suppressive effect of the 1 kV/100 mm EF was canceled when a polypropylene sheet (0.1 mm thick) was placed between the animal and lower electrode. Our findings corroborated that an EF of 10 kV/m inhibits stress-induced changes in the endocrine system in mice and demonstrated that this effect depends on the configuration of the EF exposure system, even when the EF strength remains the same. Bioelectromagnetics. 38:265-271, 2017. © 2017 Wiley Periodicals, Inc.

Absence of ALOX5 gene prevents stress-induced memory deficits, synaptic dysfunction and tauopathy in a mouse model of Alzheimer's disease.

Although the initial events of Alzheimer's disease (AD) are still not known, it is clear that the disease in its sporadic form results from the combination of genetic and environmental risk factors. Among the latter, behavioral stress has been increasingly recognized as an important factor in the propagation of AD. However, the mechanisms underlying this modulation remain to be fully investigated. Since stress up-regulates the ALOX5 gene product, 5-lipoxygenase (5LO), herein we investigated its role in modulating stress-dependent development of the AD phenotype. To reach this goal, triple transgenic (3xTg) mice and 3xTg genetically deficient for 5LO were investigated after undergoing a restraint/isolation paradigm. In the present paper, we found that 28 days of restraint/isolation stress worsened tau phosphorylation and solubility, increased glycogen synthase kinase 3ß activity, compromised long-term potentiation and impaired fear-conditioned memory recall in 3xTg animals, but not in 3xTg animals lacking 5LO (3xTg/5LO-/-). These results highlight the novel functional role that the ALOX5 gene plays in the development of the biochemical, electrophysiological and behavioral sequelae of stress in the AD context. They provide critical support that this gene and its expressed protein are viable therapeutic targets to prevent the onset or delay the progression of AD in individuals exposed to this risk factor.

Discovering the mechanisms underlying serotonin (5-HT)2A and 5-HT2C receptor regulation following nicotine withdrawal in rats.

We have previously demonstrated that nicotine withdrawal produces depression-like behavior and that serotonin (5-HT)2A/2C receptor ligands modulate that mood-like state. In the present study we aimed to identify the mechanisms (changes in radioligand binding, transcription or RNA-editing) related to such a behavioral outcome. Rats received vehicle or nicotine (0.4 mg/kg, s.c.) for 5 days in home cages. Brain 5-HT2A/2C receptors were analyzed on day 3 of nicotine withdrawal. Nicotine withdrawal increased [(3)H]ketanserin binding to 5-HT2A receptors in the ventral tegmental area and ventral dentate gyrus, yet decreased binding in the nucleus accumbens shell. Reduction in [(3)H]mesulergine binding to 5-HT2C receptors was seen in the ventral dentate gyrus. Profound decrease in the 5-HT2A receptor transcript level was noted in the hippocampus and ventral tegmental area. Out of five 5-HT2C receptor mRNA editing sites, deep sequencing data showed a reduction in editing at the E site and a trend toward reduction at the C site in the hippocampus. In the ventral tegmental area, a reduction for the frequency of CD 5-HT2C receptor transcript was seen. These results show that the reduction in the 5-HT2A receptor transcript level may be an auto-regulatory response to the increased receptor density in the hippocampus and ventral tegmental area during nicotine withdrawal, while decreased 5-HT2C receptor mRNA editing may explain the reduction in receptor labeling in the hippocampus. Serotonin (5-HT)2A/2C receptor ligands alleviate depression-like state in nicotine-withdrawn rats. Here, we show that the reduction in 5-HT2A receptor transcript level may be an auto-regulatory response to the increased receptor number in the hippocampus and ventral tegmental area during nicotine withdrawal, while attenuated 5-HT2C receptor mRNA editing in the hippocampus might explain reduced inverse agonist binding to 5-HT2C receptor and suggest a shift toward a population of more active receptors. 5-HT, serotonin; 5-HT2A R, 5-HT2A receptor; 5-HT2C R, 5-HT2C receptor.

Chronic exercise prevents repeated restraint stress-provoked enhancement of immobility in forced swimming test in ovariectomized mice.

We assessed whether chronic treadmill exercise attenuated the depressive phenotype induced by restraint stress in ovariectomized mice (OVX). Immobility of OVX in the forced swimming test was comparable to that of sham mice (CON) regardless of the postoperative time. Immobility was also no difference between restrained mice (exposure to periodic restraint for 21 days; RST) and control mice (CON) on post-exposure 2nd and 9th day, but not 15th day. In contrast, the immobility of ovariectomized mice with repeated stress (OVX + RST) was profoundly enhanced compared to ovariectomized mice-alone (OVX), and this effect was reversed by chronic exercise (19 m/min, 60 min/day, 5 days/week for 8 weeks; OVX + RST + Ex) or fluoxetine administration (20 mg/kg, OVX + RST + Flu). In parallel with behavioral data, the immunoreactivity of Ki-67 and doublecortin (DCX) in OVX was significantly decreased by repeated stress. However, the reduced numbers of Ki-67- and DCX-positive cells in OVX + RST were restored in response to chronic exercise (OVX + RST + Ex) and fluoxetine (OVX + RST + Flu). In addition, the expression pattern of cAMP response element-binding protein (CREB) and calcium-calmodulin-dependent kinase IV (CaMKIV) was similar to that of the hippocampal proliferation and neurogenesis markers (Ki-67 and DCX, respectively). These results suggest that menopausal depression may be induced by an interaction between repeated stress and low hormone levels, rather than a deficit in ovarian secretion alone, which can be improved by chronic exercise.

Identification of multiple genetic loci in the mouse controlling immobility time in the tail suspension and forced swimming tests.

Depression is one of the most famous psychiatric disorders in humans in all over the countries and considered a complex neurobehavioral trait and difficult to identify causal genes. Tail suspension test (TST) and forced swimming test (FST) are widely used for assessing depression-like behavior and antidepressant activity in mice. A variety of antidepressant agents are known to reduce immobility time in both TST and FST. To identify genetic determinants of immobility duration in both tests, we analyzed 101 F2 mice from an intercross between C57BL/6 and DBA/2 strains. Quantitative trait locus (QTL) mapping using 106 microsatellite markers revealed three loci (two significant and one suggestive) and five suggestive loci controlling immobility time in the TST and FST, respectively. Results of QTL analysis suggest a broad description of the genetic architecture underlying depression, providing underpinnings for identifying novel molecular targets for antidepressants to clear the complex genetic mechanisms of depressive disorders.

Management of intolerance to casting the upper extremities in claustrophobic patients.

INTRODUCTION: Some patients showed unusual responses to the immobilization without any objective findings with casts in upper extremities. We hypothesized their that intolerance with excessive anxiety to casts is due to claustrophobia triggered by cast immobilization. The aim of this study is to analyze the relevance of cast immobilization to the feeling of claustrophobia and discover how to handle them. METHODS: There were nine patients who showed the caustrophobic symptoms with their casts. They were assesed whether they were aware of their claustrophobis themselves. Further we investigated the alternative immobilization to casts. RESULTS: Seven out of nine cases that were aware of their claustrophobic tendencies either were given removable splints initially or had the casts converted to removable splints when they exhibited symptoms. The two patients who were unaware of their latent claustrophobic tendencies were identified when they showed similar claustrophobic symptoms to the previous patients soon after short arm cast application. We replaced the casts with removable splints. This resolved the issue in all cases. CONCLUSIONS: We should be aware of the claustrophobia if patients showed unusual responses to the immobilization without any objective findings with casts in upper extremities, where removal splint is practical alternative to cast to continue the treatment successfully.

The opposite roles of glucocorticoid and α1-adrenergic receptors in stress triggered apoptosis of rat Leydig cells.

The stress-induced initiation of proapoptotic signaling in Leydig cells is relatively well defined, but the duration of this signaling and the mechanism(s) involved in opposing the stress responses have not been addressed. In this study, immobilization stress (IMO) was applied for 2 h daily, and animals were euthanized immediately after the first (IMO1), second (IMO2), and 10th (IMO10) sessions. In IMO1 and IMO2 rats, serum corticosterone and adrenaline were elevated, whereas serum androgens and mRNA transcription of insulin-like factor-3 in Leydig cells were inhibited. Reduced oxygen consumption and the mitochondrial membrane potential coupled with a leak of cytochrome c from mitochondria and increased caspase-9 expression, caspase-3 activity, and number of apoptotic Leydig cells was also observed. Corticosterone and adrenaline were also elevated in IMO10 rats but were accompanied with a partial recovery of androgen secretion and normalization of insulin-like factor-3 transcription coupled with increased cytochrome c expression, abolition of proapoptotic signaling, and normalization of the apoptotic events. Blockade of intratesticular glucocorticoid receptors diminished proapoptotic effects without affecting antiapoptotic effects, whereas blockade of intratesticular α(1)-adrenergic receptors diminished the antiapoptotic effects without affecting proapoptotic effects. These results confirmed a critical role of glucocorticoids in mitochondria-dependent apoptosis and showed for the first time the relevance of stress-induced upregulation of α(1)-adrenergic receptor expression in cell apoptotic resistance to repetitive IMOs. The opposite role of two hormones in control of the apoptotic rate in Leydig cells also provides a rationale for a partial recovery of androgen production in chronically stressed animals.

Differential effects of acute and repeated stress on hippocampus and amygdala inputs to the nucleus accumbens shell.

The basolateral amygdala (BLA) and ventral subiculum (vSub) of the hippocampus convey emotion and context information, respectively, to the nucleus accumbens (NAc). Using in vivo extracellular recordings from NAc neurons, we examined how acute and repeated restraint stress alters the plasticity of the vSub and BLA afferent pathways. High-frequency (HFS) and low-frequency (LFS) stimulation was applied to the vSub to assess the impact on NAc responses to vSub and BLA inputs. In addition, iontophoretic application of the dopamine D2-antagonist sulpiride was used to explore the role of dopamine in the NAc in mediating the effects of stress on plasticity. Acute and repeated restraint caused disparate effects on BLA- and vSub-evoked responses in the NAc. Following repeated restraint, but not after acute restraint, HFS of the vSub failed to potentiate the vSub­NAc pathway while instead promoting a long-lasting reduction of the BLA­NAc pathway and these effects were independent of D2-receptor activity. In contrast, LFS to the vSub pathway after acute restraint resulted in potentiation in the vSub­NAc pathway while BLA-evoked responses were unchanged. When sulpiride was applied prior to LFS of the vSub after acute stress, there was a pronounced decrease in vSub-evoked responses similar to control animals. This work provides new insight into the impact of acute and repeated stress on the integration of context and emotion inputs in the NAc. These data support a model of stress whereby the hippocampus is inappropriately activated and dominates the information processing within this circuit via a dopaminergic mechanism after acute bouts of stress.

Increased resistance of immobilized-stressed mice to infection: correlation with behavioral alterations.

Immobilization is an easy and convenient method to induce both psychological and physical stress resulting in restricted motility and aggression and is believed to be the most severe type of stress in rodent models. Although it has been generally accepted that chronic stress often results in immunosuppression while acute stress has been shown to enhance immune responses, the effects of IS on the host resistance to Escherichia coli (E. coli) infection and associated behavioral changes are still not clear. In a series of experiments aimed at determining the level of hypothalamic COX-2, HSP-90, HSP-70, SOD-1 and plasma level of corticosterone, cytokine, antibody titer and their association with behavioral activities, mice were infected with viable E. coli during acute and chronic IS by taping their paws. In this study we show that acute and chronic IS enhances the resistance of mice to E. coli infection via inhibiting the production of pro-inflammatory cytokines, free radicals, and by improving the exploratory behavior. Altogether, our findings support the notion that cytokines released during immune activation and under the influence of corticosterone can modulate the open field behavior both in terms of locomotor activity as well as exploration. One of the features observed with chronic stressor was a lower ability to resist bacterial infection, although in case of acute stress, a better clearance of bacterial infection was observed in vivo with improvement of exploratory behavior and cognitive functions.

Treating Radiation Anxiety With Systematic Desensitization: Head and Neck Cancer Case Reports.

Introduction: Head and neck cancer patients have high rates of psychological distress, which may be exacerbated by the treatments they receive. Many patients who undergo radiation therapy report significant anxiety associated with the thermoplastic mask required for immobilization during treatment. Case Description: This report presents two examples of head and neck cancer patients reporting high mask anxiety, along with a history of claustrophobia, who expressed concern about their abilities to initiate and adhere to treatment. Both were referred to supportive care psychology before radiation treatment initiation. With counseling and the use of systematic desensitization, they were successfully able to complete their treatments. Discussion: Results of these case reports highlight the value of integrating early supportive care in the treatment of head and neck cancer and support the need for further study in future randomized controlled trials.

Upregulation of peroxiredeoxin III in the hippocampus of acute immobilization stress model rats and the Foxo3a-dependent expression in PC12 cells.

Stress induces structural plasticity in neurons of the adult central nervous system (CNS) and alters the levels of cellular production of reactive oxygen species (ROS), and these changes might involve modifications of the antioxidant defense system. This study investigated whether acute stress altered the expression pattern of peroxiredoxin (Prx) III, which is an antioxidant enzyme that controls cytokine-induced peroxide levels. Prx III immunoreactivity was upregulated in the pyramidal neurons of the hippocampus and in the motor neurons of the spinal cord in an acute immobilization stress (AIS) model. In addition, we tested whether the transcription factor Foxo3a was necessary for the expression of Prx III. The depletion of Foxo3a led to a marked reduction of Prx III and a compensatory enhancement of mitochondrial superoxide dismutase (Mn-SOD) in PC12 cells. The results of this study suggest that Foxo3a mediates the neuronal levels of expression of Prx III and the levels of expression of Mn-SOD in mitochondria. These mechanisms may play an important role in neuroprotection against oxidative stress. Furthermore, Prx III upregulation might be an useful approach for the management of stress.

Interleukin-18 expression in pig salivary glands and salivary content changes during acute immobilization stress.

Interleukin-18 (IL-18) has recently been considered a promising marker of stress responses. In this study, to evaluate IL-18 as a noninvasive stress marker in pigs, we investigated the expression of IL-18 in porcine salivary glands and its presence in saliva, and its dynamics during acute immobilization stress in pigs. IL-18 mRNA was detected robustly in the pig salivary glands by RT-PCR. Immunohistochemical staining of IL-18 protein expression revealed that the expression patterns differed among the three types of salivary glands (parotid, submandibular, and sublingual gland). IL-18 was also detected in pig saliva by ELISA, and a diurnal rhythm with a peak in the afternoon was observed. The IL-18 concentration in saliva was significantly increased during a 60-min acute immobilization stress in thirteen 5-month-old pigs. These results are the first evidence of a stress-related change of IL-18 in pig saliva. Salivary IL-18 may thus become a useful noninvasive marker for the evaluation of acute stress in pigs.

Disruption to radiation therapy sessions due to anxiety among patients receiving radiation therapy to the head and neck area can be predicted using patient self-report measures.

OBJECTIVE: This analysis sought to determine whether patient self-report measures were associated with disruption to radiation therapy sessions due to anxiety among cancer patients undergoing radiation therapy to the head and neck region. METHOD: A cohort of patients undergoing radiation therapy to the head and neck region at a major regional radiation oncology treatment centre (ROTC) in Australia completed self-report measures of anxiety, history of panic and fears relevant to use of an immobilising mask. The treating Radiation Therapist (RT) rated the level of session disruption due to patient anxiety during the Computerised Tomography/Simulation (CT/Sim) (baseline) session and first treatment session. RESULTS: Complete data were obtained for 90 patients. RTs rated 11 and 24% of patients as having some level of session disruption session due to anxiety at baseline and Treatment 1, respectively. Five factors were significantly associated with session disruption at baseline in bivariate analyses: currently taking psycho-active medication (p=0.008); fear of enclosed spaces (p=0.006); fear of face being covered up (p=0.006); fear of movement restriction (p=0.041) and ever had an anxiety attack (p=0.034). Sensitivity ranged from 0.57 to 0.75 and specificity ranged from 0.68 to 0.90. Only session disruption at baseline predicted disruption at Treatment 1 (p<0.01). CONCLUSIONS: This study offers some preliminary insights into the prevalence of patient anxiety severe enough to cause session disruption and patient self-report measures which might be used to flag patients for prophylactic treatment. Further development and replication in a larger sample is warranted before introduction of these measures into routine practice.

Short-term upper limb immobilization and the embodied view of memory: A pilot study.

The present study aimed to explore the contribution of the manual sensorimotor system to the memory of graspable objects. Participants in the experimental group underwent a short-term upper limb immobilization design to decrease arousal to their dominant hand. Such designs are known to elicit updating of sensorimotor representations and to hardened use of implicit motor simulation, a process that occurs when observing graspable objects. Subsequently, a free recall and a recognition task of graspable and non-graspable objects took place. We found slower recognition for graspable than for non-graspable objects in the control group, while no differences appeared for the immobilized group. Moreover, the recognition latency for graspable objects tended to be slower for the control than for the immobilized group. These results suggest that a time demanding reactivation of motor simulation is elicited when a graspable object is correctly recognized by control participants. The effect of immobilization could prevent this reactivation, leading to faster recognition. Hence, immobilization selectively affects graspable object memory, showing a close relationship with the manual sphere of the sensorimotor system. We suggest that recognition accuracy would probably be affected in cases of stronger disruption of sensorimotor arousal.