Voigt Exceptional Points in an Anisotropic ZnO-Based Planar Microcavity: Square-Root Topology, Polarization Vortices, and Circularity.

Voigt points represent propagation directions in anisotropic crystals along which optical modes degenerate, leading to a single circularly polarized eigenmode. They are a particular class of exceptional points. Here, we report the fabrication and characterization of a dielectric, anisotropic optical microcavity based on nonpolar ZnO that implements a non-Hermitian system and mimics the behavior of Voigt points in natural crystals. We prove the exceptional-point nature by monitoring the complex-square-root topology of the mode eigenenergies (real and imaginary parts) around the Voigt points. Polarization state analysis shows that these artificially engineered Voigt points behave as vortex cores for the linear polarization and sustain chiral modes. Our findings apply to any planar microcavity with broken cylindrical symmetry and, thus, pave the way for exploiting exceptional points in widespread optoelectronic devices such as vertical cavity surface emitting lasers and resonant cavity light emitting diodes.

The effect of intermittent intraabdominal pressure elevations and low cardiac output on the femoral to carotid arterial blood pressure difference in piglets.

BACKGROUND: Our previous work in a laparoscopic setting in piglets revealed that the systolic femoral artery pressure was approximately 5 % higher than its carotid counterpart, whereas the mean and diastolic values showed no significant difference. This remained idem when the intraabdominal pressure (IAP) was gradually increased. In this study, we aimed to investigate the effect of (1) intermittent IAP elevations and (2) a low cardiac output (CO) on the blood pressure (BP) difference cranially (carotid artery) and caudally (femoral artery) of a capnoperitoneum (ΔP = P a fem-P a carot). METHODS: A total of twenty-two piglets (mean body weight 11.0 kg; range 8.9-13.3 kg) were studied. Of these, 14 underwent intermittent IAP elevations at 8 and 16 mmHg, and ΔP was measured. In another 8 piglets, a model of reduced CO was created by introducing an air embolism (2 ml/kg over 30 s) in the inferior caval vein (VCI) at 12 mmHg IAP to further assess the influence of this variable on ΔP. RESULTS: Systolic ΔP remained at a mean of 5.6 mmHg and was not significantly affected by insufflation or exsufflation up to an IAP of 16 mmHg. Diastolic and mean values showed no differences between P a carot and P a fem. P a fem, systol remained higher than its carotid counterpart as long as the cardiac index (CI) was above 1.5 l/min/m2, but fell significantly below P a carot, systol at a low CI. There was no CO-dependent effect on diastolic and mean ΔP. Repeated IAP elevations do not significantly influence ΔP. CONCLUSIONS: Intermittent IAP elevations do not significantly influence ΔP. Despite of a CO-dependent inversion of systolic ΔP, mean BP measurements at the leg during laparoscopy remain representative even at low CO values.

Heart Rate Variability during Inpatient Psychosomatic Treatment - A Naturalistic Observational Study.

OBJECTIVES: We tested the hypothesis that inpatient psychosomatic treatment would improve both psychological distress and autonomic dysfunction, indexed as heart rate variability (HRV). METHODS: 135 patients (mean age 47.2 years, 68.1% women) were enrolled. The most frequent diagnoses were somatoform disorders, adjustment disorders, major depression, eating disorders, and anxiety disorders.Mean duration of treatment was 21.8 ± 7.3 days. Complete HRV data were available on 105 patients. RESULTS: At the beginning of the treatment, psychological distress correlated with the low frequency/ high frequency ratio of HRV, indicating a shift of autonomic balance towards sympathetic predominance. Following treatment, psychological distress had improved, but parasympathetic activity was even lower. Tricyclic antidepressant use was associated with an increase in heart rate. No other associations between antidepressant use and autonomic function were observed. CONCLUSIONS: Reductions of psychological distress may not be reflected by improved autonomic function. Studies on interventions that may improve both psychological distress and autonomic dysfunction are desirable.

Tune it down to live it up? Rapid, nongenomic effects of cortisol on the human brain.

The stress hormone cortisol acts on the brain, supporting adaptation and time-adjusted coping processes. Whereas previous research has focused on slow emerging, genomic effects of cortisol, we addressed the rapid, nongenomic cortisol effects on in vivo neuronal activity in humans. Three independent placebo-controlled studies in healthy men were conducted. We observed changes in CNS activity within 15 min after intravenous administration of a physiological dose of 4 mg of cortisol (hydrocortisone). Two of the studies demonstrated a rapid bilateral thalamic perfusion decrement using continuous arterial spin labeling. The third study revealed rapid, cortisol-induced changes in global signal strength and map dissimilarity of the electroencephalogram. Our data demonstrate that a physiological concentration of cortisol profoundly affects the functioning and perfusion of the human brain in vivo via a rapid, nongenomic mechanism. The changes in neuronal functioning suggest that cortisol acts on the thalamic relay of background as well as on task-specific sensory information, allowing focus and facilitation of adaptation to challenges.

Air in the insufflation tube may cause fatal embolizations in laparoscopic surgery: an animal study.

BACKGROUND: The aim of this study was to evaluate the risk of an air embolization with the volume of the insufflation tube during induction of laparoscopy. A further objective was to determine the LD50 of air in young piglets. METHODS: End-tidal carbon dioxide pressure ([Formula: see text]), pulmonary arterial pressure (P pa), heart rate (f c), and mean arterial pressure (P a carot) were measured in 17 piglets divided into three groups: group 1 (n = 6), bolus application (CO2 embolization, followed by air embolization, 2 mL/kg each), group 2 (n = 7), continuous air embolization (30 min, 0.2 mL/kg/min), and group 3 (n = 4), continuous CO2 embolization (30 min, 0.4 mL/kg/min). RESULTS: All animals survived CO2 embolism. Air embolization as a bolus (2 mL/kg) or with an accumulated volume of 3.1 mL/kg led to death. Decreases in [Formula: see text] indicated air or massive CO2 embolization only. There was a good correlation between [Formula: see text] and P pa in case of air embolization (r = -0.80, p < 0.0001). In contrast, no dependency was recognized during CO2 embolism (r = -0.17, p = 0.2). CONCLUSIONS: In order to minimize the lethal risk of gas embolization, the insufflation system has to be completely filled with CO2 before connecting to the patient.

Exogenous cortisol facilitates responses to social threat under high provocation.

Stress is one of the most important promoters of aggression. Human and animal studies have found associations between basal and acute levels of the stress hormone cortisol and (abnormal) aggression. Irrespective of the direction of these changes--i.e., increased or decreased aggressive behavior--the results of these studies suggest dramatic alterations in the processing of threat-related social information. Therefore, the effects of cortisol and provocation on social information processing were addressed by the present study. After a placebo-controlled pharmacological manipulation of acute cortisol levels, we exposed healthy individuals to high or low levels of provocation in a competitive aggression paradigm. Influences of cortisol and provocation on emotional face processing were then investigated with reaction times and event-related potentials (ERPs) in an emotional Stroop task. In line with previous results, enhanced early and later positive, posterior ERP components indicated a provocation-induced enhanced relevance for all kinds of social information. Cortisol, however, reduced an early frontocentral bias for angry faces and--despite the provocation-enhancing relevance--led to faster reactions for all facial expressions in highly provoked participants. The results thus support the moderating role of social information processing in the 'vicious circle of stress and aggression'.

Broadband femtosecond spectroscopic ellipsometry.

We present a setup for time-resolved spectroscopic ellipsometry in a pump-probe scheme using femtosecond laser pulses. As a probe, the system deploys supercontinuum white light pulses that are delayed with respect to single-wavelength pump pulses. A polarizer-sample-compensator-analyzer configuration allows ellipsometric measurements by scanning the compensator azimuthal angle. The transient ellipsometric parameters are obtained from a series of reflectance-difference spectra that are measured for various pump-probe delays and polarization (compensator) settings. The setup is capable of performing time-resolved spectroscopic ellipsometry from the near-infrared through the visible to the near-ultraviolet spectral range at 1.3 eV-3.6 eV. The temporal resolution is on the order of 100 fs within a delay range of more than 5 ns. We analyze and discuss critical aspects such as fluctuations of the probe pulses and imperfections of the polarization optics and present strategies deployed for circumventing related issues.

Accelerated trace eyeblink conditioning after cortisol IV-infusion.

Impairing effects of cortisol on learning performance have been shown in human trace eyeblink conditioning. As the effect is observed from 30 min to hours after administration, a genomic action of cortisol is assumed. Here we report rapid cortisol effects that were observed during the first 10 min after cortisol administration in humans. Young healthy males (n=24) received the cortisol synthesis inhibitor metyrapone (1.5 g per os) to avoid interference of the endogenous pulsatile secretion of cortisol. Next, 2mg cortisol or placebo was infused intravenously, immediately before the trace conditioning task. The probability of the conditioned eyeblink responses was assessed electromyographically during the trace eyeblink conditioning task (unconditioned stimulus: corneal air puff, 10 psi, 50 ms; conditioned stimulus: binaural pure tone, 7 dB, 1000 Hz, 400 ms; empty interval between CS and US: 550 ms). Cortisol resulted in a faster increase of conditioning (p=.02), reaching a comparable level to placebo later on. This result extends the well-known effects of stress on the quality and amount of learning by showing that cortisol also affects the speed of learning. We propose that cortisol accelerates trace eyeblink conditioning via a fast, non-genomic mechanism. This fast action of cortisol is part of the adaptive strategy during the early stress response.

Cortisol rapidly increases baroreflex sensitivity of heart rate control, but does not affect cardiac modulation of startle.

Cortisol, the final product of human HPA axis activation, rapidly modulates the cortical processing of afferent signals originating from the cardiovascular system. While peripheral effects have been excluded, it remains unclear whether this effect is mediated by cortical or subcortical (e.g. brainstem) CNS mechanisms. Cardiac modulation of startle (CMS) has been proposed as a method to reflect cardio-afferent signals at subcortical (potentially brainstem-) level. Using a single blind, randomized controlled design, the cortisol group (n = 16 volunteers) received 1 mg cortisol intravenously, while the control group (n = 16) received a placebo substance. The CMS procedure involved the assessment of eye blink responses to acoustic startle stimuli elicited at six different latencies to ECG-recorded R-waves (R + 0, 100, 200, 300, 400 and 500 ms). CMS was assessed at four measurement points: baseline, -16 min, +0 min, and +16 min relative to substance application. Baroreflex sensitivity (BRS) of heart rate (HR) control was measured non-invasively based on spontaneous beat-to-beat HR and systolic blood pressure changes. In the cortisol group, salivary cortisol concentration increased after IV cortisol administration, indicating effective distribution of the substance throughout the body. Furthermore, BRS increased in the cortisol group after cortisol infusion. There was no effect of cortisol on the CMS effect, however. These results suggest that low doses of cortisol do not affect baro-afferent signals, but central or efferent components of the arterial baroreflex circuit presumably via rapid, non-genomic mechanisms.

Modulation of spatial and stimulus-response learning strategies by exogenous cortisol in healthy young women.

Glucocorticoids (GCs) are known to influence learning and memory processes. While most studies focus on the effects of GCs on the performance within a single memory system, we asked whether GCs modulate also the transition between hippocampus-dependent spatial and caudate nucleus-dependent stimulus-response memory systems. Eighty-four young healthy women received a placebo, 5 or 30 mg hydrocortisone orally. One hour later, participants were asked to locate a win-card in a 3D model of a room. The card could be located via two strategies: spatial (multiple distal cues) and stimulus-response (a single proximal cue). Relocation of the proximal cue after 12 trials revealed the strategy, number of trials to learning criterion the performance. As expected, more trials were needed to acquire the task with hydrocortisone. Remarkably, hydrocortisone switched the use of learning strategies towards more spatial learning (dose-dependently: placebo 4% < 5 mg 21%< 30 mg 32%), independent of autonomic and subjective arousal. The learning curves of spatial and stimulus-response learners were comparable. Our results demonstrate that exogenous GCs prior to learning affect the performance within a memory system and also coordinate the use of multiple memory systems. Taking into account this dual action of GCs will contribute to a better understanding of stress (hormone) effects on learning and memory.

Stress effects on declarative memory retrieval are blocked by a beta-adrenoceptor antagonist in humans.

Previous evidence indicates that stress hormone effects on memory consolidation depend on concurrent emotional arousal-induced noradrenergic activity. Here, we asked whether this is also true for stress effects on memory retrieval and hypothesized that administration of the beta-adrenoceptor antagonist propranolol would block the effects of stress on declarative and procedural retrieval performance. In a double-blind, placebo-controlled, crossover study, 44 healthy young men learned a list of emotional and neutral words (declarative memory task) and completed a serial reaction time task (procedural memory task). On the following day, participants received either a placebo or 40 mg propranolol orally. One hour later, they were exposed to stress (socially evaluated cold pressor test (SECPT)) or a control condition 30 min prior to retention testing. Stress selectively enhanced the retrieval of emotionally arousing words. Pretreatment with propranolol had no effect on memory alone but blocked the stress-induced memory enhancement for emotional words, confirming the importance of noradrenergic activity in stress effects on memory retrieval. Memory for neutral words and the procedural task was neither affected by stress nor by propranolol. The present findings suggest that stress (hormone) effects on emotional memory retrieval require concurrent noradrenergic activation. Procedural memory retrieval and the retrieval of neutral verbal material appear to be less susceptible to stress.

Endogenous cortisol suppression with metyrapone enhances acoustic startle in healthy subjects.

Previous human studies have shown that excess cortisol sufficient to fully occupy central nervous system (CNS) corticosteroid receptors may reduce startle eye blink. The present study tested whether cortisol depletion and the resulting reduction in activity of CNS corticosteroid receptors has the opposite effect. In a single-blind, placebo-controlled, randomized study, eye blink EMG responses to 105 dB acoustic startle stimuli were assessed in 25 healthy subjects who received oral metyrapone (1500 mg) to suppress endogenous cortisol production, while 24 controls received oral placebo. As expected, metyrapone significantly reduced salivary cortisol, indicating effective endogenous cortisol suppression. Startle eye blink responses were significantly increased in the metyrapone group. Short-term habituation of the startle reflex was not different between groups. Our results suggest that startle is enhanced during depletion of cortisol. This effect may be mediated by CNS mechanisms controlling cortisol feedback.

Cardiac modulation of startle: effects on eye blink and higher cognitive processing.

Cardiac cycle time has been shown to affect pre-attentive brainstem startle processes, such as the magnitude of acoustically evoked reflexive startle eye blinks. These effects were attributed to baro-afferent feedback mechanisms. However, it remains unclear whether cardiac cycle time plays a role in higher startle-related cognitive processes, as well. Twenty-five volunteers responded first by 'fast as possible' button pushes (reaction time, RT), and second, rated perceived intensity of 60 acoustic startle stimuli (85, 95, or 105 dB; 50 ms duration; binaural; instantaneous rise time), which were presented either 230 or 530 ms after the R-wave, and eye blink responses were measured by EMG. RT was divided into evaluation and motor response time according to previous research. Increasing stimulus intensity enhanced startle eye blink, intensity ratings, and RT components. Eye blinks and intensity judgments were lower when startle was elicited at a latency of R+230 ms, but RT components were differentially affected: the evaluative component was attenuated, and the motor component was accelerated when stimuli were presented 230 ms after the R-wave. We conclude that the cardiac cycle affects the attentive processing of acoustic startle stimuli.

Evaluation of severely displaced radial neck fractures in children treated with elastic stable intramedullary nailing.

BACKGROUND: We performed a retrospective case study of 28 consecutive severely displaced radial neck fractures (Judet types III and IV) in children treated with elastic stable intramedullary nailing using the Metaizeau technique. METHODS: We reviewed all preoperative radiographs and classified the injuries according to Judet. All patients were asked to return for later assessment. They underwent physical examination; radiographs were taken; and they were asked for subjective assessment. An evaluation of clinical results was performed using the Mayo Elbow Performance Score (MEPS). RESULTS: According to Judet classification there were 13 type III and 15 type IV fractures. Using the MEPS, excellent results were achieved in 23 cases (82%) and good results in 5 cases (18%). The average MEPS was 97 points. Five patients complained of mild pain. Three malunions were observed. CONCLUSIONS: Elastic stable intramedullary nailing is a minimally invasive technique, allowing stable fixation and providing excellent to good outcomes with a low complication rate. LEVEL OF EVIDENCE: We performed a retrospective level 4 study of case series.

Intranasal insulin attenuates the hypothalamic-pituitary-adrenal axis response to psychosocial stress.

Previous studies have shown that intranasally administered insulin exerts an inhibitory influence on the basal hypothalamic-pituitary-adrenal (HPA) axis activity. To date, however, it remains unclear as to whether intranasal insulin does furthermore affect HPA axis responsiveness in situations of stress. Here, we tested whether intranasally administered insulin attenuates the HPA axis response to psychosocial stress. Fifty minutes before being exposed to the Trier Social Stress Test (TSST), 26 healthy young male participants received a single intranasal dose of human insulin (40 I.U.) or placebo in a placebo controlled, double-blind between-subject design. Plasma cortisol, saliva cortisol, heart rate, and blood pressure were measured at resting baseline and in response to the TSST. Plasma cortisol (P<.001) and saliva cortisol (P<.001) increased in response to stress, as did heart rate (P<.001) and blood pressure (P<.001). Intranasal insulin did not influence plasma or saliva cortisol, heart rate, blood pressure, blood glucose, and plasma insulin levels at baseline. However, intranasal insulin diminished the saliva cortisol (two-way ANOVA; treatment by time interaction: P=.05) and plasma cortisol (two-way ANOVA; treatment by time interaction: P=.05) response to the TSST without affecting heart rate, and blood pressure stress reactivity. Our data show that a single intranasal insulin administration effectively lowers stress-induced HPA axis responsiveness. Intranasal insulin may offer a therapeutic potential to prevent hyperactivity of the HPA system.

Inhibition of cortisol production by metyrapone enhances trace, but not delay, eyeblink conditioning.

RATIONALE: Hypercortisolism [ corrected] impairs trace classical conditioning of the eyeblink response to an air puff but does not affect delay conditioning. OBJECTIVES: The opposite neurohormonal condition, hypocortisolism, may facilitate trace classical conditioning, which might be informative in understanding the role of classical conditioning in stress-sensitive syndromes such as fibromyalgia. MATERIALS AND METHODS: Volunteers (n = 82) were randomized to receive either an inhibitor of cortisol production (metyrapone, 1500 mg) or placebo and to complete a delay or a trace eyeblink conditioning protocol (unconditioned stimulus: corneal air puff, 10 psi, 50 ms; conditioned stimulus: binaural pure tone, 75 dB, 1000 Hz, 400 ms; empty interval in trace conditioning: 600 ms), where conditioned eyeblink response probability was assessed electromyographically. RESULTS: Metyrapone induced hypocortisolism, reflected by a 30% decrease of salivary cortisol levels (p < 0.01), and facilitated trace eyeblink conditioning (p < 0.001), while delay eyeblink conditioning remained unaffected. Moreover, extinction of delay-conditioned eyeblink responses was impaired (p = 0.023), but extinction of trace-conditioned responses remained unaffected. CONCLUSIONS: We conclude that acute mild metyrapone-induced hypocortisolism facilitates hippocampus-mediated classical trace eyeblink conditioning but suppresses the extinction of cerebellum-based delay-conditioned responses. Both results may be of theoretical and clinical significance for the generation and persistence of psychosomatic symptoms in patient groups characterized by relative hypocortisolism (e.g., fibromyalgia and chronic fatigue).

Melatonin reduces arousal and startle responsiveness without influencing startle habituation or affective startle modulation in young women.

Melatonin has been suggested to affect human emotion, but conflicting evidence exists. Therefore, we tested the effect of a single dose of a 4 mg prolonged release formulation of melatonin on a biologically based model of emotional processing. Affective modulation of acoustic white noise startle (103 dB) by emotional slides selected from the International Affective Picture System (IAPS) was assessed in 16 healthy young women twice, in a double-blind, placebo-controlled, balanced cross-over design. Melatonin significantly reduced startle responsiveness, but did not impact affective startle modulation, nor startle habituation. Melatonin significantly reduced arousal ratings and induced a parasympathetically dominated heart rate variability pattern indicative of a non-aroused state. We conclude that melatonin reduces arousal and startle responsiveness. However, no evidence for a direct emotion-modulating effect of melatonin was found in this healthy cohort.

Stress modulates the use of spatial versus stimulus-response learning strategies in humans.

Animal studies provided evidence that stress modulates multiple memory systems, favoring caudate nucleus-based "habit" memory over hippocampus-based "cognitive" memory. However, effects of stress on learning strategy and memory consolidation were not differentiated. We specifically address the effects of psychosocial stress on the applied learning strategy in humans. We designed a spatial learning task that allowed differentiating spatial from stimulus-response learning strategies during acquisition. In 13 subsequent trials, participants (88 male and female students) had to locate a "win" card out of four placed at a fixed location in a 3D model of a room. Relocating one cue in the last trial allowed inferring the applied learning strategy. Half of them participated first in the "Trier Social Stress Test." Salivary cortisol and heart rate measurements were taken. Stressed participants used a stimulus-response strategy significantly more often than controls. Subsequent verbal report revealed that spatial learners had a more complete awareness of response options than stimulus-response learners. Importantly, learning performance was not affected by stress. Taken together, stress prior to learning facilitated simple stimulus-response learning strategies in humans-at the expense of a more cognitive learning strategy. Depending on the context, we consider this as an adaptive response.

Patient Variables Associated with the Assignment of a Formal Dementia Diagnosis to Positively Screened Primary Care Patients.

BACKGROUND: Main objective was to analyze the associations of patient variables (depression, quality of life, anti-dementia drug treatment, knowledge about dementia) with the assignment of a formal diagnosis of dementia to community-dwelling primary care patients who have screened positive for dementia. METHODS: DelpHi-MV (Dementia: life- and person-centered help in Mecklenburg-Western Pomerania) is a general practitioner based randomized controlled intervention trial. Present analyses are based on cross-sectional data of 319 positively screened patients (age 70+, living at home) who had not been formally diagnosed with dementia before the screening. The medical diagnoses (ICD-10) were retrieved from the patient's medical records. Depression (Geriatric Depression Scale; GDS), quality of life in Alzheimer's disease (Qol-AD), knowledge about dementia, and anti-dementia drug treatment were assessed after the screening test at the baseline examination. RESULTS: At the baseline examination, 171 out of 319 patients (54%) had been formally diagnosed with dementia after they have screened positive. Univariate comparisons showed no statistically significant differences between diagnosed and undiagnosed patients regarding depression (GDS≥6: 11% vs. 15%; p=0.396), quality of life (mean (SD): 2.8 (0.3) vs. 2.8 (0.4); p=0.833), and the knowledge about dementia (75% vs. 75%; p>0.999). Patients who had received a formal diagnosis were more often treated with anti-dementia drugs (20% vs. 11%; p=0.040). Multivariate analyses controlled for confounding variables confirmed these findings. CONCLUSION: Present findings do not support concerns that the assignment of a formal dementia diagnosis after screening is associated with potential harms. If confirmed in a prospective study, our data would suggest that patients may benefit from being formally diagnosed regarding anti-dementia drug treatment.

Cardiovascular reactivity to mental stress is not affected by alpha2-adrenoreceptor activation or inhibition.

RATIONALE: It has been postulated that cardiovascular reactivity to mental stress varies with tonic central sympathetic nervous system activity, but pharmacological evidence is missing. OBJECTIVE: To test whether modulation of central sympathetic nervous system activity by alpha2-adrenergic agonism and antagonism affects cardiovascular reactivity to mental stress. MATERIALS AND METHODS: On three five-stepped dose/concentration-response study days, 12 healthy male volunteers received intravenous infusions of dexmedetomidine (alpha2-agonist, target plasma concentrations: 0.04-0.32 ng/ml), yohimbine (alpha2-antagonist, doses: 0.016-0.125 mg/kg), and placebo, respectively. During each dose step, subjects performed a 5-Choice Reaction Time Task (CRTT) and a Paced Auditory Serial Addition Task (PASAT) to induce moderate mental stress. Prestress baseline, as well as stress-induced responses of heart rate, and noninvasive finger arterial blood pressure (Finapres) were assessed. RESULTS: Prestress baseline heart rate and blood pressure decreased with increasing doses of dexmedetomidine and increased with increasing doses of yohimbine. However, dexmedetomidine and yohimbine did not affect stress-induced heart-rate and blood-pressure changes. CONCLUSIONS: Cardiovascular reactivity to mental stress is not related to pharmacologically manipulated tonic central sympathetic nervous system activity by alpha2-adrenergic agonists and antagonists. These results do not support the assumption that cardiovascular reactivity is an index of tonic central sympathetic nervous system activity.