Emotions are an integral part of the human experience and their interpretation can provide valuable but also misleading clues about oneself and other people’s state of mind. Negative emotional states can be perceived as uncomfortable and – when experienced chronically – can develop into anxiety and mood disorders. The more pervasive these disorders the more severely they affect and disable a person’s everyday functioning and often their sleep as well. According to Lang and colleagues (1998), emotions may be expressed verbally, behaviorally, and physiologically, i.e., emotions can be reported, observed, and objectively measured. Each measurement approach provides important, unique, and often conflicting information that can be used in the assessment and treatment evaluation of psychological disorders affecting the emotions. Autonomic measures have been used to indicate the physiological components of emotions, such as those along the worry-anxiety-fear-panic spectrum. Worry has been shown to suppress cardiac responses to imaginal feared material (see Borkovec, Alcaine, & Behar, 2004) and reduce autonomic variability (Hoehn-Saric, McLeod, Funderburk, & Kowalski, 2004; Hoehn-Saric, McLeod, & Zimmerli, 1989). Results for panic and anticipatory anxiety are less conclusive but theoretically these states should go along with increased autonomic arousal. Abnormal autonomic arousal might also be present during sleep as both panic disorder and worrying have been associated with sleeping difficulties. However, most empirical research has been confined to the laboratory where high internal validity is achieved at the cost of poor ecological validity. Thus, the purpose of this doctoral dissertation is to extend and validate laboratory findings on worry, anticipatory anxiety, and panic using ambulatory monitoring. Twenty-four hour monitoring not only can give valuable insights into a person’s daytime emotional experience but also allows observing how these emotions might affect their sleep in their natural environment. In the following chapter, the reader will be introduced to a conceptual framework that ties together worry, anxiety, fear, and panic, and related anxiety disorders (section 2.1), to autonomic arousal and electrodermal and cardiac arousal in particular (section 2.2), to sleep and its relation to autonomic arousal and anxiety disorders (section 2.3), and to ambulatory monitoring (section 2.4). After illustrating the aims of this thesis (chapter 3), chapters 4 to 6 present the results of three empirical studies conducted as part of this doctoral research. The first study deals solely with electrodermal monitoring and how it is affected by confounding variables in an ambulatory context (chapter 4). The next study then seeks to investigate the relationship between electrodermal arousal and anticipatory anxiety and panic in a sample of panic disorder patients and healthy controls. The last study focuses primarily on the effect of trait and state worry on subjective and objective sleep and electrodermal and cardiac arousal in a group of high and low worriers. Chapters 7 to 9 summarize and integrate the findings from these three empirical studies, discuss methodological limitations, and provide an outlook into future research.

Zymosan-induced peritonitis is a model commonly used to study systemic inflammatory response syndrome and multiple organ dysfunction syndrome. However, effects of zymosan on cardiac function have not been reported. We evaluated cardiac responses to zymosan in mice and the role of β-Glucan and dectin-1 in mediating these responses. Temperature and cardiac function were evaluated before and after intraperitoneal (i.p.) injection of zymosan (100 or 500 mg/kg) or saline. Chronotropic and dromotropic functions were measured using electrocardiograms (ECGs) collected from conscious mice. Cardiac inotropic function was determined by echocardiography. High-dose zymosan caused a rapid and maintained hypothermia along with visual signs of illness. Baseline heart rate (HR) was unaffected but HR variability (HRV) increased, and there was a modest slowing of ventricular conduction. High-dose zymosan also caused prominent decreases in cardiac contractility at 4 and 24 h. Because zymosan is known to cause gastrointestinal tract pathology, peritoneal wash and blood samples were evaluated for bacteria at 24 h after zymosan or saline injection. Translocation of bacterial occurred in all zymosan-treated mice (n=3), and two had bacteremia. Purified β-Glucan (50 and 125 mg/kg, i.p.) had no effect on temperature or ECG parameters. However, deletion of dectin-1 modified the ECG responses to high-dose zymosan; slowing of ventricular conduction and the increase in HRV were eliminated but a marked bradycardia appeared at 24 h after zymosan treatment. Zymosan-treated dectin-1 knockout mice also showed hypothermia and visual signs of illness. Fecal samples from dectin-1 knockout mice contained more bacteria than wild types, but zymosan caused less translocation of bacteria. Collectively, these findings demonstrate that zymosan-induced systemic inflammation causes cardiac dysfunction in mice. The data suggest that dectin-1-dependent and -independent mechanisms are involved. Although zymosan treatment causes translocation of bacteria, this effect does not have a major role in the overall systemic response to zymosan.

Coaches are constantly seeking more ecologically valid and reliable data to improve professional sporting performance. Using unobtrusive, valid and reliable mobile physiological monitoring devices may assist in achieving this aim. For example, there is limited information regarding professional fast bowlers in cricket and understanding this role during competitive in-match scenarios rather than in simulated bowling events could enhance coaching and physical conditioning practices. The BioharnessTM is a mobile monitoring device and assesses 5 variables (Heart rate [HR], Breathing frequency [BF], Accelerometry [ACC], Skin temperature [ST] and Posture [P]) simultaneously. Therefore, the aims of this research were to assess the effectiveness of the BioharnessTM mobile monitoring device during professional sporting performance using fast bowlers in cricket and this was to be achieved in five research studies. Study 1 presented the physiological profile of professional cricketers reporting fitness data with other comparable professional athletes, with a specific interest in fast bowlers who were to be the focus of this work. The 2nd and 3rd study assessed the reliability and validity of the BioharnessTM through controlled laboratory based assessment. For validity, strong relationships (r = .89 to .99, P < .01) were reported for HR, BF, ACC and P. Limits of Agreement reported HR (-3 ± 32 beat.min-1), BF (-3.5 ± 43.7 br.min-1) and P (0.2 ± 2.6o). ST established moderate relationships (-0.61 ± 1.98 oC; r =.76, P <.01). Reliability between subject data reported low Coefficient of Variation (CV) and strong correlations for ACC and P (CV < 7.6%; r = .99, P <.01). HR and BF (CV ~ 19.4%; r ~.70, P <.01) and ST (CV 3.7%; r = .61, P < .01), present more variable data. Intra and inter device data presented strong relationships (r > .89, P < .01, CV < 10.1%) for HR, ACC, P and ST. BF produced weaker data (r < .72, CV < 17.4%). Study 4 assessed reliability and validity of the BioharnessTM in a field based environment using an intermittent protocol. Precision of measurement reported good relationships (r = .61 to .67, P < .01) and large Limits of Agreement for HR (> 79.2 beat.min-1) and BF (> 54.7 br.min-1). ACC presented excellent precision (r = .94, P < .01). Results for HR (r = ~ .91, P < .01: CV <7.6%) and ACC (r > .97, P < .01; CV < 14.7%) suggested these variables are reliable in the field environment. BF presented more variable data (r = .46 - .61, P < .01; CV < 23.7%). In all studies, as velocity of movement increased (> 10 km.h-1) variables became more erroneous. HR and ACC were deemed as valid and reliable to be assessed during in-match sporting performance in study 5. This final study sought to utilise and assess the BioharnessTM device within professional cricket, assessing physiological responses of fast-medium bowlers within a competitive sporting environment, collected over three summer seasons. The BioharnessTM presented different physiological profiles for One Day (OD) and Multi Day (MD) cricket with higher mean HR (142 vs 137 beats.min-1, P < .05) and ACC (Peak acceleration (PkA) 227.6 vs 214.9 ct.episode-1, P < .01) values in the shorter match format. Differences in data for the varying match states of bowling (HR, 142 vs 137 beats.min-1, PkA 234.1 vs 226.6 ct.episode-1), between over (HR, 129 vs 120beats.min-1, PkA 136.4 vs 126.5 ct.episode-1) and fielding (115 vs 106 beats.min-1, PkA 1349.9 vs 356.1 ct.episode-1) were reported across OD and MD cricket. Therefore, this information suggests to the coach that the training regimes for fast bowlers should be specific for the different demands specific to the format of the game employed. Relationships between in-match BioharnessTM data and bowling performance were not clearly established due to the complexities of uncontrollable variables within competitive cricket. In conclusion, the BioharnessTM has demonstrated acceptable validity and reliability in the laboratory and the field setting for all variables (Heart rate, Breathing frequency, Accelerometry, Skin temperature and Posture) but with limitations for heart rate and breathing frequency at the more extreme levels of performance. Furthermore, taking these limitations into account it has successfully been utilised to assess performance and provide further insight into the physiological demands in the professional sport setting. Therefore, this work suggests that coaches and exercise scientists working together should seek to utilise new mobile monitoring technology to access unique insights in to sporting performance which may be unobtainable in the laboratory or a simulated field based event.

Heart rate variability (HRV) reflects dynamic variation in sympathetic and parasympathetic nervous system (SNS and PNS) activity. The parasympathetic vagus nerve is responsible for HRV between 0.12 and 0.4 Hz, which is thought to index the capacity for effective coping, and is linked to physical and emotional well-being. Yogic breathing to increase vagal activity is often paced below 0.12 Hz (< 7.2 breaths per minute (BrPM)), where its impact HRV can be due to both sympathetic and parasympathetic mechanisms. Five healthy volunteers completed three pharmacological blockade sessions (placebo, sympathetic blockade with Esmolol, and parasympathetic blockade with Glycopyrrolate) about 48 hours apart, and during each session completed 11 Sudarshan Kriya Yogic breathing exercises at 4-9 BrPM. HRV was the lowest under Glycopyrrolate (p < 0.001), and there was no significant difference between placebo and sympathetic blockade with Esmolol. In addition, the spectral power of specific HRV frequencies was greatest at similar frequencies of breathing, a pattern prevented only by Glycopyrrolate. These findings suggest that heart rate is vagally influenced at all breathing rates, and that the SNS is not the mechanism by which slow breathing increases HRV.

In this dissertation, I have focused on the role of serotonin (5-HT) as a modulator in heart rate, feeding and locomotion behaviors as well as sensorimotor circuit activity in Drosophila melanogaster. A general overview in the actions of the serotonergic (5-HTergic) system on the larval heart and nervous system in larvae and adults is reviewed in Chapter One. I sought to further study the actions of serotonergic system to provide additional insights into cellular and molecular underpinnings in the actions of 5-HT.In Chapter two, I present studies on mechanisms of action by 5-HT in larvae cardiac system. For this purpose, genetic and pharmacological approaches were used. The transgenic flies used expressed hM4Di receptors (designer receptors exclusively activated by designer drugs (DREADDs)) which were employed to manipulate the activity of Gαi heterotrimeric protein through activation of engineered G-protein coupled receptors hM4Di DREADD. The activation of hM4Di DREADD receptors by clozapine-N-oxide (CNO) arrested the heart beat; however, pharmacological manipulation of adenylyl cyclase activity and cAMP levels had no significant effect on heart rate. In Chapter Three the role of various 5-HT receptor subtypes that mediate 5-HT action in larval cardiac tissue is addressed. In this study, various 5-HT agonists and antagonists were employed. The pharmacological results demonstrate that a 5-HT2 agonist significantly increases the heart rate. Furthermore, 5-HT2 antagonist, markedly reduces the effect of 5-HT. In addition, I employed genetic approaches to corroborate the pharmacological results. In addition, I investigated the role of the 5-HTergic system in locomotion and feeding behaviors as well as in modulation of sensorimotor circuits. This study is delineated in Chapter Four. The 5-HT biosynthesis was dysregulated by feeding Drosophila larvae various pharmacological agents. 5-HT receptor subtypes were manipulated using RNA interference mediated knockdown and 5-HT receptor insertional mutations. Moreover, synaptic transmission at 5-HT neurons was blocked or induced in both larvae and adult flies. The results demonstrate that disruption of components within the 5-HT system significantly impairs locomotor activity and feeding behavior in larvae. In addition, acute activation of 5-HT neurons disrupts normal locomotor activity in adult flies. In Chapter Five, I addressed direct actions of fluoxetine on synaptic transmission at neuromuscular junctions (NMJs), neural properties, and cardiac function unrelated to fluoxetine’s action as a selective 5-HT reuptake inhibitor using Drosophila, crayfish and primary neurons in mouse model system. Fluoxetine application blocked action potentials in crayfish axons, enhanced occurrences of spontaneous synaptic vesicle fusion events at NMJs of both Drosophila and crayfish. In rodent primary neurons, fluoxetine application resulted in increase of cytoplasmic Ca2+. I also developed teaching modules, which are presented in Chapter Seven, to guide students how to exploit a vast array of genetic tools, such as optogenetics in Drosophila to manipulate various neural circuits and to observe their effects on behavior and sensorimotor circuit activity. I also developed a module to teach college level students a hands-on experiment regarding proprioception and tension receptors in crab limb, which is detailed in Chapter Eight.

Thesis (MMed)-- Stellenbosch University, 2013. / ENGLISH ABSTRACT: Misoprostol is often used for the purpose of induction of labour. However, its effect on fetal heart rate has not been systematically studied. Objective To assess the effect of misoprostol on fetal heart rate parameters during induction of labour from 38 completed weeks in women with previous intrauterine death or postterm pregnancy. Study design A retrospective descriptive study of 127 women for a period of 18 months. Method Women who underwent induction of labour with misoprostol for either previous intrauterine death or postterm pregnancy at Tygerberg hospital were eligible. The selected process of induction of labour happened according to the departmental protocol. The primary outcomes were changes in fetal heart rate (variability, accelerations and decelerations) pre-and post-administration of misoprostol. Secondary outcomes were neonatal highcare or intensive care unit (ICU) admissions. Results There was no statistical difference in the mean fetal heart rate and baseline variability in relation to time recordings after administration of misoprostol. There were no statistically significant differences in the distribution of accelerations and decelerations in different time intervals before and after administration. There were more reactive patterns at all time intervals after the administration of misoprostol, but these differences did not quite reach statistical significance. In both study groups no neonatal complications or intensive care admissions were reported. Conclusion In the absence of contra indications, 50mcg of oral misoprostol can be given to mothers for induction of labour as no harmful fetal heart tracing abnormalities were found for 45 minutes; however large prospective randomized controlled trials are still needed to confirm effectiveness and evaluate further maternal and neonatal safety issues. Optimal dose and frequency also still need robust interrogation. Based on this thesis it does appear that misoprostol is probably not harmful to the fetus under these circumstances. / AFRIKAANSE OPSOMMING: Misoprostol word dikwels gebruik vir induksie van kraam. Die effek daarvan op fetale hartspoed is egter nie sistematies ondersoek nie. Doel Om die effek van misoprostol op fetale hartspoedparameters gedurende die induksie van kraam van 38 voltooide weke in vroue met vorige intra-uteriene dood or oortyd swangerskap te evalueer. Studei-ontwerp „n Retrospektiewe beskrywende studie van 127 vroue oor „n periode van 18 maande. Metode Vroue wat induksie van kraam met misoprostol ondergaan het vir of vorige intra-uteriene dood of oortyd swangerskap by Tygerberg Hospitaal is ingesluit. Die proses van induksie van kraam is volgens departementele protokol uitgevoer. Die primêre uitkomste was veranderinge in fetale hartspoed (variasie, versnellings en verstadigings) pre- en post-toediening van misoprostol. Neonatale hoësorg of intensiewe sorg toelatings was sekondêre uitkomste. Resultate Ons het geen statistiese verskille in gemiddelde fetale hartspoed en basislynvariasie in verhouding tot die tyd na toediening van misoprostol gevind nie. Daar was geen statisties betekenisvolle verskille in die verspreiding van versnellings en verstadigings in verskillende tydsintervalle nie. Daar was meer reaktiewe patrone gedurende alle tydsintervalle na die toediening van misoprostol, maar hierdie verskille was nie statisties betekenisvol nie. In beide studiegroepe was daar geen neonatale komplikasies of intensiewe sorg toelatings nie. Gevolgtrekking In die afwesigheid van kontra-indikasies kan 50 mcg misoprostol aan moeders toegedien word vir induksie van kraam aangesien geen skadelike fetale hartsped abnormaliteite gevind is nie. Groot prospektiewe gerandomiseerde gekontroleerde studies word steeds benodig om effektiwiteit te bevestig en om moederlike en fetale veiligheidskwessies verder te evalueer. Optimale dosis en frekwensie benodig ook robuuste ondersoek. Gebaseer op hierdie tesis kom dit voor of misoprostol waarskynlik nie skadelik vir die fetus onder hierdie omstandighede nie.

This study compared psychological and physiological differences between children diagnosed with migraine and their healthy peers. Physiological measures were obtained at baseline, after discussing an emotionally relevant stressor, and after recovery in 21 children with pediatric migraine and 32 healthy peers. Comparisons were also made on psychological measures investigating sleep problems, anxiety, and family stress. It was hypothesized that children with migraine compared to their peers 1) would report more sleep disturbances, anxiety, and family stress 2) would exhibit greater sympathetic activation at rest, in response to an emotional stressor, and after a recovery period and 3) that autonomic functioning would mediate the relation between the presence of pediatric migraine and sleep disturbances. Results indicated that the migraine group reported significantly greater anxiety compared to peers but there were no significant differences in sleep disturbances or family stress. Within the migraine group, migraine severity was significantly associated with total sleep disturbance and greater incidence of parasomnias, while migraine duration was significantly associated with greater night time awakenings. Migraine children also exhibited a significantly higher pulse rate compared to their peers at rest and a significantly higher diastolic blood pressure and marginally significant higher LF/HF ratio at recovery from an emotional stressor. These findings suggest that sleep disturbance and pediatric migraine are significantly related but the relation is unclear and warrants additional research. Results also indicate that children with migraine may experience more anxiety than peers. Of most interest, results suggest that children with migraine may experience a disinhibition of the autonomic nervous system characterized by a dominance of the sympathetic nervous system resulting in a longer recovery period following an emotional stressor.

A criterion method to evaluate cardiorespiratory health is measuring peak oxygen consumption (VO2 peak) from a maximal graded exercise test (GXT). While VO2 peak is a valuable measure, heart rate recovery (HRRec) and endothelial function (EF) also describe cardiorespiratory health and fitness. The purpose of this study was to investigate whether differences exist in VO2 peak, HRRec, and EF between healthy-weight (HW) and obese (OB) women and children and to determine if there were significant correlations among these variables. A total of 60 women and children participated in this study. Anthropometric, body composition, resting heart rate and blood pressure (BP) were measured. EF was evaluated to determine the reactive hyperemia index (RHI). Finally, each subject performed a graded exercise test (GXT) to determine VO2 peak. Following the GXT, the subjects’ recovery responses were monitored for 5 minutes. A factorial MANOVA was used to evaluate differences between obesity status and age in relative VO2 peak and relative HRRec. The MANOVA resulted in a significant (p < 0.001) main effect for obesity status and age, but there was no interaction effect. HW individuals had a greater relative VO2 peak compared to OB individuals. Children had a greater relative VO2 peak and HRRec compared to adults. Absolute VO2 peak and absolute HRRec were examined using univariate ANOVAs. Women had greater absolute VO2 peak values compared to children (p2 peak and absolute HRRec, relative HRRec, and RHI. Relative VO2 peak was significantly correlated to RHI. Absolute HRRec was correlated with relative HRRec and RHI. Relative HRRec was correlated with RHI. Lack of significant differences in HRRec and EF across adiposity levels were likely due to the obese, but otherwise healthy population recruited for this study. Age affected the response to all variables included in this study.

In order to have a complete understanding of the relationship between physical activity (PA) and health, it is essential to be able to accurately assess PA in free-living situations. The purpose of this study was to use three accelerometers located on the dominant ankle, hip, and wrist and a heart rate (HR) monitor to estimate energy expenditure (EE) compared to measured EE while completing activities of daily living (ADL). The regression equation developed showed a significant relationship (P < 0.05) with EE. Together, HR and the hip-worn accelerometer explained 73.4% of the variance in EE with HR accounting for 59.3% (P < 0.05). Type of activity, the wrist-, and ankle-worn accelerometer each explained an additional 5%, 3% and 3% of the variance in EE, respectively (P < 0.05). The regression equation developed is a good predictor of EE during selected ADL, and allows researchers to more accurately quantify free-living PA. / School of Physical Education, Sport, and Exercise Science

Superior swimming stamina in adult fish is presumably passed on to their offspring, but the ontogeny of the appearance of superior stamina and the requisite enhanced cardio-respiratory support for locomotion in larval fishes has not been determined. Is the expression of the suite of parental traits enabling superior swimming stamina in their offspring dependent upon their achieving juvenile/adult morphology, or does it appear earlier in their larvae? To answer this, adults were classified into three groups based on swimming stamina, followed by measurement of length, mass, and width. Larval offspring from the two parental groups -high stamina larvae (HSL) and low stamina larvae (LSL)- were reared at 27°C in aerated water (21% O2). Routine and active heart rate, routine and active mass specific oxygen consumption were recorded through 21dpf, and cost of transport (COT) and factorial aerobic scope were derived from oxygen consumption measurements. Routine heart rate at 2dpf of LSL was 164 ± 1 b·min-1, compared to only 125 ± 2 b·min-1 for HSL. Routine heart rate subsequently peaked at 203 ± 1 b·min-1 at 5dpf in the HSL group, compared to 207 ± 1 b·min-1, at 4dpf in the LSP larvae. Active heart rate at 5 dpf of LSL was 218 ± 2 b·min-1 compared to 216 ± 2 b·min-1 for HSL. Active heart rate increased slightly to 227 ± 2 b·min-1 for LSL before decreasing again, while active heart rate remained relatively constant for HSL. Routine O2 consumption at 2dpf of HSL was 0.09 μmol·mg-1·hr-1, compared to 0.03 μmol·mg-1·hr-1 in LSL. Routine O2 consumption subsequently peaked at 0.70 μmol·mg-1·hr-1 at 9dpf in the HSL, compared to 0.71 μmol·mg-1·hr-1, at 9dpf in the LSL. These values dramatically decreased before leveling off at around 0.20 μmol·mg-1·hr-1 and 0.15 μmol·mg-1·h-1, respectively. Active O2 consumption at 5dpf for HSL was 0.38 μmol·mg-1·hr-1, compared to 0.57 μmol·mg-1·hr-1 for LSL. Active O2 consumption subsequently peaked at 0.97 μmol·mg-1·hr-1 at 10dpf in HSL, compared to 1.19 μmol·mg-1·hr-1 at 7dpf in LSL. These values also dramatically decreased and leveled off. Significant differences (p < 0.05) in heart rate and oxygen consumption persisted through 21dpf. The onset of differences observed in routine and active heart rate in early larvae, correlated with parent stamina, show that juvenile or adult features are not required as a precondition for the emergence of phenotypic physiological differences.