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Shurin, D. Zhou, and S. Zwilling , Neuroimmunomodulation of Macrophage Function.

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Whitacre, S. Cummings, and A. Sheridan and C. Dobbs , Stress, Viral Pathogenesis, and Immunity. Laudenslager and M. Hall, J. Anderson, and M. Keller, S. Shiflett, S. Schleifer, and J. Bartlett , Stess, Immunity, and Health. Schneiderman, M. Antoni, G. Ironson, N. Klimas, A. LaPerriere, M. Kumar, B. Esterling, and M. Kiecolt-Glaser, W. Malarkey, J. Cacioppo, and R. Solomon and D. Benton , Psychoneuroimmunologic Aspects of Aging. Fawzy and N. Fawzy , Psychoeducational Interventions and Health Outcomes. Show More. Average Review.

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This well-illustrated Handbook pays particular attention to systematically organized details but also Upon completion of the cognitive tests, the subject was positioned in the dynamometer chair, stimulating electrodes were placed over the tibial nerve and electromyography electrodes were placed over the soleus SOL muscle of the right leg, and the reflexes were assessed. After a 5-min rest, during which the electrodes were moved from over the tibial nerve to over the posterior calf muscle, the force-generating capacity of the posterior calf muscle was assessed by applying 1-s trains of electrical stimuli at 1, 20, TT Hz and Hz.

About 3 s was needed to change the stimulation frequency. After a 1-min rest, two attempts of a 3 to 4 s maximal voluntary contraction MVC interspaced with a 1-min rest interval was performed with a TT Hz superimposed on the voluntary contraction. BS — blood samples, T re — rectal temperature, T mu — muscle temperature, T sk — skin temperature. Cognitive function CF testing involved the unpredictable task switching test executive function , the forward digit-span task test short term memory , and the forced-choice recognition memory test short term spatial recognition.

Neuromuscular NM testing involved evaluation of spinal H-reflexes, M-waves and supraspinal V-waves excitability, evaluation of muscle contractility characteristics induced by a 1-s electrical stimulation at 1 Hz, 20 Hz, Hz and TT Hz; evaluation of maximal voluntary contraction torque and central activation of exercising muscle was performed with a TT Hz superimposed stimulation on the maximal voluntary contraction.

After the muscle testing, the subject began the intermittent water immersion cooling protocol.

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It is suggested that intermittent cooling represents a more efficient way of removing body heat than compare to continue cooling [11]. During cooling, every 20 min, the subject was asked to step out of the bath and rest for 10 min in the room environment, and then to return to the water bath for the next 20 min of immersion. The procedure continued until the T re decreased to The exposure time until the T re achievement was recorded. During immersion and the rest intervals, the subject remained in a semi-recumbent posture with his arms folded across the chest and with the legs almost straight and together.

Ratings of subjective thermal and shivering sensation and T re were recorded every 5 min throughout the cooling procedure. Pulmonary gas exchange was recorded only during each min water immersion. After the end of the cooling protocol, cognitive and neuromuscular testing was performed in the same order as before the cold water immersion. The rectal thermistor sensor was placed by each subject. T mu and T sk were measured before and at the end of the water immersion.

The skin was prepared before each intramuscular temperature measurement by shaving and disinfecting before and after insertion with a cotton-wool tampon soaked with medicinal alcohol. After the first measurement, the insertion area was marked with a 0. This was done to ensure repeatability and to allow use of the same insertion point for each measurement i. The CSI was calculated as follows [43] :. T re and T sk were assigned a weighting using the constants 6.

The method to measure subjective ratings for the whole body has been described elsewhere [24] , [6]. Briefly, the rating of thermal sensation ranged from 1 very cold to 9 very hot , with 5 being neutral.

The shivering sensation ranged from 1 vigorously shivering to 4 not at all being neutral. The rating of perception was reported by the participants every 5 min during passive cooling. A mean rating score was calculated for each session. The isometric torque of ankle plantar flexion muscles was measured using an isokinetic dynamometer System 4; Biodex Medical Systems, Shirley, NY, USA calibrated according to the manufacturer's service manual with a correction for gravity performed using the Biodex Advantage program version 4. For MVC measurement, the subject was instructed to achieve and maintain maximal effort of ankle plantar flexion for 3 to 4 s.

Each trace was inspected visually to ensure that there were no artefactual spikes at the start of the signal curve.

Psychoneuroimmunology and the "Faith Factor" in Human Health

The arms were crossed on the chest with the hands grasping the trunk-supporting belt during all tests on the dynamometer. To help ensure a maximal effort, standard vocal encouragement was provided during each voluntary ankle plantar flexion trial by the same experienced investigator. The subject was asked to perform two attempts with a rest interval of 1 min. The best attempt was recorded. The equipment and procedure for electrically stimulated torque have been described previously [7]. Peak torques induced by a 1-s electrical stimulation at 1 Hz P1; representing the properties of muscle excitation—contraction coupling , at 20 Hz P20; representing the steep section of the force—frequency relationship curve and at Hz P; which is close to maximal force were measured with a 3-s rest interval between electrical stimulations.

The half-relaxation time in ms was measured in resting TT Hz contractions. The half-relaxation time HRT was calculated as the time taken for torque to decline from the peak value to half of that value at the end of the TT Hz contraction. A rest interval of 1 min was set between the electrical stimulation trial and MVC measurements.

The subject positioning, testing environment and electrical stimulator assessment were essentially the same as those described above. After careful preparation of the skin shaving, abrading, and cleaning with alcohol wipes to obtain low impedance, bipolar Ag—AgCl surface bar electrode 10 mm diameter, 20 mm centre-to-centre distance DataLog type no.

The actual electrode position was marked, and the same recording site was used in the pre- and post-session measurements. The ground electrode was positioned on the tarsus of the same leg. The analogue signal was sampled and converted to digital form at a sampling frequency of 5 kHz. Before recording the EMG, we set the channel sensitivity at 3 V and excitation output at mV as recommended by the manufacturer. With increasing stimulation intensity, the H-reflex response initially increased progressively before decreasing and then disappearing, whereas the M-wave achieved its maximum and remained stable.

Thereafter, the subject was instructed to perform three brief MVCs of the plantar flexor muscles with at least a 1-min rest between contractions. A superimposed stimulus at M max intensity was evoked to obtain the V-wave V sup. The peak-to-peak amplitude of the V-wave reflects the magnitude of the central descending neural drive to spinal motor neurons, although spinal factors such as motor neuron excitability and pre- or post-synaptic inhibition may also be involved [1]. M-wave amplitude was also used to normalize the amplitude of the reflex waves recorded i. This was done to ensure that any changes in the evoked H max and V sup amplitudes reflected changes at the muscle fibre membrane or neuromuscular junction.

The latencies of the electrical evoked action potentials were calculated from the stimulation artefact at the peak of the wave. This system uses a tightly fitting face mask that covers the nose and mouth with a lightweight integrated flow meter Triple V volume sensor; 45 g with a dead space of 30 ml. The system monitors ventilatory parameters, oxygen uptake and VCO 2 production on a breath-by-breath basis. The processing, recording and battery system comprises two units attached to a belt, which was hung as close as possible to the subject's nose and mouth during immersion.

The data were stored on memory cards and PC hardware. This instrument was calibrated before recording as indicated in the manufacturer's manual by using the automatic volume- and gas-calibration functions. A flow-volume sensor calibration procedure assures that the Oxycon quantification system including the amplifier, Triple V sensors and pressure transducer is functioning correctly.

The gas analyser and delay time calibrations were also automatic, as provided by the manufacturer: a calibration gas at kPa Oxygen consumption was recorded in 5-s increments. As recommended, the data collected during each first 5 min of each min immersion were not used in any calculations because of reflex hyperventilation caused by cold water immersion. M shiv was calculated from the values measured at the end of immersion when T re and T sk were the lowest.

It has been well documented that sufferers from blood-injection-injury phobia often experience emotional fainting vasovagal syncope , display emotional disgust, excessive fear and avoidance behavior [3] , [26].

A programmed cognitive test battery was used to assess executive function, short-term memory, and visual recognition memory. All tasks were computer controlled, and the information was presented on the screen of a laptop HP Compaq b. This test reflects cognitive flexibility executive function , which is defined as the ability to adjust to changing demands [16]. Forty randomized single-digit stimuli from 0 to 9 of s duration were displayed with varying inter-stimulus intervals in the middle of the screen.

As fast as possible, the subject had to press the button for the even right button or odd left button digit corresponding to the digit presented. In a highly cited article, the psychologist Miller [42] suggested that normal adult short-term memory has a forward memory span of about seven items plus or minus two. The forward digit-span task [42] , [16] tests the ability to remember a sequence of digits in a short time.

This test assesses short-term memory [16] , which can hold a limited amount of information in a very accessible state temporarily. The subject was instructed to remember a seven-digit sequence displayed for 3 s in the middle of the screen. The subject then immediately entered the digits using a numeric keyboard in the same consecutive sequence as presented. If the digits were identified correctly, for the next attempt, the sequence was one digit longer; if an error was made, the next sequence was one digit shorter.

There were 16 sequences. The mean number of digits identified successfully was recorded. The forced-choice recognition memory test [52] assesses visual recognition memory. After looking at nine visual figures displayed for 15 s in the middle of the screen, the subject was required to recognize the nine items from 28 figures presented in the study list in any order. The number of correctly identified images was recorded.

Blood samples were collected by venepuncture into vacuum tubes EDTA-K3, 3 ml before and after cold water immersion, mixed gently by inverting 8—10 times, and kept at room temperature until analysed for differential blood cell counting of neutrophils, leucocytes, lymphocytes and monocytes. Blood samples were analysed 1 to 2 h after blood collection using an automated haematology analyser XE, Sysmex Corp. Blood samples were taken in the morning time 8 a. The data were tested for normal distribution using the Kolmogorov—Smirnov test, and all scale data were normally distributed.

Statistical analysis involved general linear model analysis of variance ANOVA for repeated measures with FC and SC as a between-group factor and time as within-group factor of two levels before and after cooling on dependent variables body temperatures, pulmonary gas exchange, MHP, reflexes, blood variables, and motor and cognitive performance. For all ordinal data the nonparametric Wilcoxon signed-rank test was used to compare changes in subjective ratings of perceptions thermal and shivering sensations. Pearson correlation coefficients were used to identify relationships between variables.

Descriptive data are presented as mean and standard deviation SD. Observed power OP was calculated for all mechanical indicators based on an alpha level of 0. In the FC group, the time to cool the body from a T re of In the SC group, the time to cool the body from a T re of In the FC group, T mu decreased during cooling by 6. In the SC group, T mu decreased during cooling by 6.

In the FC group, T sk decreased during cooling by In the SC group, T sk decreased during cooling by During cooling, the changes in subjective sensations did not differ significantly between the FC and SC groups Table 4. The CSI after cooling was 7. However, contrary to our expectation, motor and cognitive performance did not differ between the FC and SC groups. In the SC group, whose CSI was lower, the cold stress seemed to stimulate some markers of innate natural; for instance changes in neutrophils immunity but suppressed markers of specific adaptive; for instance changes in lymphocytes and monocytes immunity.

By contrast, the increases in the concentrations of cortisol, epinephrine and norepinephrine, as stress markers, did not differ between the FC and SC groups. T mu and T sk did not differ between the FC and SC groups before and after cold exposure, whereas T re decreased more and faster during cooling in the FC group.

On acute exposure to cold, all subjects had an insulative response a reduction in T sk relative to T re , hypothermic response a reduction in T re and a metabolic response an increase in heat production. The mean T sk decreased significantly in both groups. These mechanisms can also induce hormonal and metabolic changes. According to the definitions of Makinen [38] , the response of the FC group to cooling vs the SC group response was more likely an insulative—hypothermic response, because the T re decreased more in relation to changes in the T sk and MHP compared with the SC group T sk decreased and MHP increased significantly in both groups, but there was no significant difference between the groups.

There are large individual differences in the relative contribution of the insulative response and the metabolic response to mild cold exposure. It is interesting to note that metabolic shivering was significantly greater in the FC than in the SC group, but subjective shivering did not differ between groups. We do not know whether the subjects displayed non-shivering thermogenesis during cold exposure, and we can only speculate that non-shivering thermogenesis may have been greater in the SC group, because this group displayed a smaller decrease in T re and less metabolic shivering, but similar changes in T sk compared with the FC group.

There is recent evidence that non-shivering thermogenesis metabolic response strategy by sympathetic, norepinephrine-induced mitochondrial heat production in brown adipose tissue is a component of this metabolic response in healthy men and that body fat content correlates negatively with brown adipose tissue content [65]. Our finding of a significant negative correlation between body fat mean thickness and MHP in both groups is consistent with this inverse relationship between body fat level and brown adipose tissue content. Body fat thickness did not differ significantly between the FC and SC groups in our study.

As suggested by van Marken Lichtenbelt et al. In our study, metabolic shivering was significantly greater in the FC than in the SC group, and we speculate that the SC group might have had more active brown adipose tissue. This study was designed to examine the acute effects of intermittent cold exposure. Our cold exposure protocol does not represent the typical conditions that humans encounter during daily activities that might provoke a natural stress response.

According to Kozyreva et al. However, contrary to our expectation, the stress markers in the blood cortisol, epinephrine, norepinephrine and corticosterone concentrations did not differ between the SC and FC groups. We had expected that the FC group with a higher CSI should have had greater activation of the sympathetic—adrenomedullary and hypothalamic—pituitary—adrenocortical systems, as generally occurs in response to stress [23]. These results should be interpreted with some limitation because the duration of cooling differed between the groups; i.

We speculate that the stress markers in the SC group would have increased less if they had experienced the same duration of cold water exposure. We did not find significant differences in the perception of cold between the FC and SC groups. We expected that the immune system response to cold stress would be greater in the FC group because the CSI was greater.

However, contrary to our expectation, markers of immunity changed significantly only in the SC group, which had a lower CSI. This concurs with other research data showing that stress-induced changes in plasma corticosterone are accompanied by significant decreases in the numbers and percentages of lymphocytes and increases in the numbers and percentages of neutrophils. Our data suggest that cold exposure stimulated innate natural immunity and suppressed specific adaptive immunity only in the SC group.

These data are consistent with the view that acute stressors are associated with potentially adaptive upregulation of some parameters of natural innate immunity and downregulation of some aspects of specific immunity. Specific immunity is characterized by greater specificity and a slower response than natural immunity [56]. However, the results of our study should be interpreted with some limitation because the immune response to cold stress depends on the cooling protocol [27] , [33] and because not all markers of natural and specific immunity respond similarly Table 8.

Consistent with the results of human studies, in our study, acute cold stress increased circulating leucocyte and neutrophil counts. In contrast to Brenner et al. However, our results agree with those of Jansky et al. Brenner et al. They concluded that natural immunity is better suited than specific immunity to managing the potential complications of life-threatening situations, which can unfold more rapidly, because innate immunity is subject to fewer inhibitory constraints and requires less energy to be diverted from other bodily systems that support the fight-or-flight response [17].

Acute stress stimulates whereas chronic stress suppresses immune function [15]. The stress responses involve a variety of immune system hormones referred to as cytokines [30].

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  • Charmandari et al. Elevation of IL-6 concentration may increase symptoms of depression. Pro-inflammatory cytokines are signalling molecules of the inflammatory immune system that initiate and coordinate the cascade of immune events [20]. There is no current consensus about the response of the immune system to cold stress. Even brief exposure to cold increased the levels of norepinephrine, cortisol and lymphocytes [33].

    Data obtained mainly on small mammals suggest that acute exposure to severe chilling suppresses several cellular and humoral components of the immune response [58]. Experiments on cell lines and in animals along with human experiments indicate that short-term 2—4-h hypothermia increases the levels of anti-inflammatory cytokines and decreases the levels of pro-inflammatory cytokines [50].

    We believe that further studies are needed to explain fully whether and to what extent cold exposure stimulates or suppresses the immune response. We observed no significant difference in the changes in the electrically induced and voluntary properties of skeletal muscles and spinal and supraspinal reflexes after cooling between the FC and SC groups Table 6. This was contrary to our expectations because we had expected that the larger CSI in the FC group would induce more changes in motor response.

    It has been suggested recently that stress also can modulate movement through activation of the hypothalamic—pituitary—adrenal axis HPA-axis and stress-associated emotional changes [41]. We also found that cold stress significantly increased the excitability of spinal H-wave and supraspinal V-wave reflexes in both groups but that there was no significant difference between the groups.

    These data agree with those of Dewhurst et al. It was concluded that norepinephrine increases the response of motor neurons to their synaptic inputs and the excitability of interneurons that mediate group I input to motor neurons [25]. An excess of norepinephrine in the blood could contribute to the change in reflex excitability following body cooling. We have not found any data in the literature about how cold stress influences the V-wave.

    The V-wave indicates the level of descending voluntary drive conveyed by the motor neurons, and an increase in the V-wave size indicates increased motor neuron discharge rates or recruitment [1]. However, according to Aagaard et al. There is a clear effect of temperature on motor [22] and cognitive performance [46] , which appears to follow an inverted U relationship.

    Stressful events can lead to immediate and marked impairments in working memory, which is an executive function [57]. There is evidence showing that the mechanisms and neural circuits that drive emotion and cognition are inextricably linked. There are two major components of the stress response: rapidly acting autonomic sympathetic system and the slower acting HPA-axis, which can affect cognitive functioning [28] , [36] , [37] , [55]. Epinephrine can indirectly affect the brain through its action on vagus outside the brain-barrier with information transmitted in to the brain via nucleus of the solitary tract and locus coeruleus leading to the release of norepinephrine in the brain [28].

    Activation of the HPA-axis as a result of stress or other causes of arousal initiates a flood of hormone and neurotransmitter release throughout the brain affecting the way we think, decide, and behave. Activation of the HPA-axis leads through intermediate steps to the release of glucocorticoid cortisol from the adrenal cortex [28] , [36] , [37] , [64] , [55] , which travels through the bloodstream and accesses the brain where it binds to glucocorticoid receptors [28] , [36] , [37] , [64] , [55].

    Stress-Related Changes in Proinflammatory Cytokine Production in Wounds

    The prefrontal cortex, a brain region that governs higher-level cognitive processes and executive function, becomes markedly impaired by stress, producing measurable deficits in working memory [57]. Most of all cold stress had to affect unpredictable task switching of executive function because this task requires maintenance and additional processing i. Moreover, there is evidence of a dose—response relationship between decreased cognitive performance and core body temperature [46] , suggesting greater deterioration of cognitive function with more marked core cooling.

    We failed, however, to find any other study showing the effect of cooling of different duration and different level of core body cooling on changes in the release of blood stress markers and cognitive functioning. In this study of the cognitive performance tests, cooling significantly affected only choice reaction time, however, contrary to our expectations, there was no difference between groups.

    Similar activation of autonomic sympathetic system and activation of HPA-axis might be expected here in both FC and SC groups because of similar release of stress markers in the blood found after the cooling and it might in part explain why there was no difference in cognition between groups. Specifically, the forward digit-span task and the forced-choice recognition memory test mainly involve the passive maintenance of information and require less cognitive resources [20] , [21] , [45] , therefore, results of these tests did not change significantly in both groups during cold stress.

    Our study had some limitations. This indicates that the SC group originally had a physiological advantage in prolonged exposure to an acute cold environment compared with the FC group. In this study, we found that immune variables changed from before to after cold exposure only in the SC group, which seems to be a more time-dependent variable than a T re -dependent variable. In line with the majority of thermal studies, we have used a protocol involving only two sampling time points to assess the responses of the HPA-axis, autonomic nervous system, and immune system to cold exposure.

    It is known, however, that in vitro mild hypothermia can suppress inflammatory reactions, and that moderate hypothermia can delay the induction of proinflammatory cytokines [29]. Therefore, in future studies, it will be important to examine the kinetics of the postcooling effect in FC and SC groups, as it seems that the analysis of a single time point at the end of cold stress does not cover the whole response curve. This study reports several new findings. Despite the larger CSI in the FC group the changes in stress markers increases in cortisol, epinephrine and norepinephrine concentrations did not differ between groups.