Noninvasive cardiovascular markers of acoustically induced arousal from non-rapid-eye-movement sleep

STUDY OBJECTIVES: Changes in cardiovascular measures such as heart rate (HR) and pulse transit time (PTT) have been advocated as sensitive markers of autonomic arousal from sleep. In animal studies, alerting stimuli produce particularly marked skin vascular responses. We hypothesized that changes in skin vascular conductance would provide more sensitive markers of autonomic arousal during sleep compared to central cardiovascular response measures such as HR and PTT. DESIGN: Cardiovascular responses to auditory-induced arousals were recorded during overnight sleep studies. SETTING: Sleep disorders unit in a 270-bed teaching hospital. PARTICIPANTS: Eleven young healthy male subjects. INTERVENTIONS: Throughout ovemight sleep studies, auditory tones (5-second duration, 54-90 decibels, 22-56 per subject) were presented during non-rapid-eye-movement sleep. Beat-by-beat HR, PTT, laser-Doppler fingertip skin blood flow (SBF) and finger and ear photoplethysmogram pulse wave amplitudes (PWA) were measured in the 20 seconds preceding and 30 seconds following each tone and compared to control measurements obtained during 50-second periods of recording with no stimulus (no tone, 6-22 per subject). Electroencephalographic (EEG) arousals were scored according to standard criteria (American Sleep Disorders Association) into no discemible, 3- to 10-second duration, or 10- to 15-second duration arousals. Poststimulus cardiovascular measurements were expressed as a percentage of the prestimulus mean and response magnitudes quantified from peak responses and the area under the poststimulus response curve. The ability of each cardiovascular response measure to discriminate EEG arousals (EEG changes lasting more than 3 seconds) was assessed from the area under the receiver operating characteristic (ROC) curve. MEASUREMENTS AND RESULTS: There were no significant changes in any cardiovascular parameter during control recordings. In contrast to all other parameters, finger PWA and SBF decreased following tones that produced no discernible EEG arousal (P < 0.05). A significant HR rise and decreases in all cardiovascular measures occurred with greater than 3-second arousals, with longer duration arousals generally exhibiting larger responses. Conventional EEG arousals (greater than 3 seconds) were relatively poorly detected from HR responses (ROC area HR rise 0.80 +/- 0.04) compared to changes in SBF (0.85 +/- 0.02), PTT (0.85 +/- 0.03) and finger PWA (0.90 +/- 0.01). CONCLUSIONS: Decreases in skin vascular conductance (finger PWA and SBF) provide sensitive markers of autonomic arousal during sleep. They are at least as sensitive as PTT for detecting conventionally scored EEG arousals and may be more sensitive in detecting "subcortical" arousals.     

The relationship between interpersonal problems,negative cognitions,and outcomes from cognitive behavioral group therapy for depression

Background

Interpersonal functioning is a key determinant of psychological well-being, and interpersonal problems (IPs) are common among individuals with psychiatric disorders. However, IPs are rarely formally assessed in clinical practice or within cognitive behavior therapy research trials as predictors of treatment attrition and outcome. The main aim of this study was to investigate the relationship between IPs, depressogenic cognitions, and treatment outcome in a large clinical sample receiving cognitive behavioral group therapy (CBGT) for depression in a community clinic.

Methods

Patients (N=144) referred for treatment completed measures of IPs, negative cognitions, depression symptoms, and quality of life (QoL) before and at the completion of a 12-week manualized CBGT protocol.

Results

Two IPs at pre-treatment, ‘finding it hard to be supportive of others’ and ‘not being open about problems,’ were associated with higher attrition. Pre-treatment IPs also predicted higher post-treatment depression symptoms (but not QoL) after controlling for pre-treatment symptoms, negative cognitions, demographics, and comorbidity. In particular, ‘difficulty being assertive’ and a ‘tendency to subjugate one's needs' were associated with higher post-treatment depression symptoms. Changes in IPs did not predict post-treatment depression symptoms or QoL when controlling for changes in negative cognitions, pre-treatment symptoms, demographics, and comorbidity. In contrast, changes in negative cognitions predicted both post-treatment depression and QoL, even after controlling for changes in IPs and the other covariates.

Limitations

Correlational design, potential attrition bias, generalizability to other disorders and treatments needs to be evaluated.

Conclusions

Pre-treatment IPs may increase risk of dropout and predict poorer outcomes, but changes in negative cognitions during treatment were most strongly associated with improvement in symptoms and QoL during CBGT.     

The relationship between worry,rumination, and comorbidity: Evidence for repetitive negative thinking as a transdiagnostic construct

Background

Repetitive negative thinking (RNT) increases vulnerability to multiple anxiety and depressive disorders and, as a common risk factor, elevated RNT may account for the high levels of comorbidity observed between emotional disorders. The aims of this study were to (a) compare two common forms of RNT (worry and rumination) across individuals with non-comorbid anxiety or depressive disorders, and (b) to examine the relationship between RNT and comorbidity.

Methods

A structured diagnostic interview and measures of rumination, worry, anxiety, and depression were completed by a large clinical sample with an anxiety disorder or depression (N=513) presenting at a community mental health clinic.

Results

Patients without (n=212) and with (n=301) comorbid diagnoses did not generally differ across the principal diagnosis groups (depression, generalised anxiety disorder, social anxiety disorder, panic disorder) on worry or rumination. As predicted, comorbidity was associated with a higher level of RNT.

Limitations

Cross-sectional design precluded causal conclusions and findings may not generalize to excluded anxiety disorders.

Conclusions

Consistent with the transdiagnostic hypothesis, RNT was associated with a range of anxiety disorders and depression and with comorbidity for those with a principal depressive disorder, supporting recent evidence that RNT is a transdiagnostic process. The presence of RNT, specifically worry and rumination, should be assessed and treated regardless of diagnostic profile. Future research may show that both pure and comorbid depressed or anxious patients receive incremental benefit from transdiagnostic protocols developed to treat core pathological processes of RNT traditionally associated with separate disorders.     

How effective is patient-controlled analgesia? A randomized comparison of two protocols for pain relief during oocyte recovery

Although the conventional method of pain relief during outpatient oocyte recovery involves physician-administered drugs, patient- controlled analgesia (PCA) offers an alternative technique with the potential to give women more control over peroperative analgesia. We conducted a prospective randomized study to compare the effect of fentanyl administered either through a PCA delivery system or by a physician. Thirty-nine women were randomized to PCA during egg collection while 42 were allocated to receive intermittent doses administered by a physician. Pain was evaluated by means of a 100 mm linear analogue scale. The mean (SD) pain score in the PCA group was 38.5 (19.8) while in the other group it was 46.1 (21.3) (P = 0.1). In the PCA group, 64% of women felt very satisfied with their analgesia as compared with 57% in the non-PCA group (P = 0.6). Among the PCA users, 39% of demands were successful. Significantly more fentanyl (97.5 microg) was used in the PCA group than in the other group (84.6 microg) (P = 0.03). Though intraoperative PCA with fentanyl is an effective alternative to physician-administered techniques, many women still feel the need for more analgesia during the procedure.      

Emerging entities in NUTM1‐rearranged neoplasms

Structural alterations of NUTM1 were originally thought to be restricted to poorly differentiated carcinomas with variable squamous differentiation originating in the midline organs of children and adolescents. Termed NUT carcinomas (NCs), they were defined by a t(15;19) chromosomal rearrangement that was found to result in a BRD4‐NUTM1 gene fusion. However, the use of DNA and RNA‐based next‐generation sequencing has recently revealed a multitude of new NUTM1 fusion partners in a diverse array of neoplasms including sarcoma‐like tumors, poromas, and acute lymphoblastic leukemias (ALLs) that we propose to call NUTM1‐rearranged neoplasms (NRNs). Intriguingly, the nosology of NRNs often correlates with the functional classification of the fusion partner, suggesting different oncogenic mechanisms within each NRN division. Indeed, whereas NCs are characterized by their aggressiveness and intransigence to standard therapeutic measures, the more positive clinical outcomes seen in some sarcoma and ALL NRNs may reflect these mechanistic differences. Here we provide a broad overview of the molecular, nosological, and clinical features in these newly discovered neoplastic entities. We describe how aberrant expression of NUTM1 due to fusion with an N‐terminal DNA/chromatin‐binding protein can generate a potentially powerful chromatin modifier that can give rise to oncogenic transformation in numerous cellular contexts. We also conclude that classification, clinical behavior, and therapeutic options may be best defined by the NUTM1 fusion partner rather than by tumor morphology or immunohistochemical profile.     

Relationship between serum follicle stimulating hormone in the male and standard sperm parameters, and the results of intracytoplasmic sperm injection

Serum follicle stimulating hormone (FSH) is routinely measured when evaluating the infertile male for intracytoplasmic sperm injection (ICSI). However, among the sperm parameters, only its relationship with sperm concentration is well documented. Few investigations concern the relationship between FSH and sperm motility and morphology, and the results of ICSI. A retrospective study of 316 couples who underwent ICSI was carried out to determine the relationships between serum FSH concentrations in the male and (i) standard sperm parameters_(concentration, motility and morphology) and (ii) fertilization, cleavage, pregnancy and implantation rates after ICSI. There was an inverse correlation with sperm concentration and total motility but no relationship was found with progressive motility and sperm morphology. Neither was any relationship found between serum FSH and fertilization, cleavage, pregnancy and implantation rates, and the results of ICSI. These findings suggest the need to review the routine measurement of serum FSH in the infertile male when ICSI is the planned treatment procedure.      

The impact of poverty on educational outcomes for children

Over the past decade, the unfortunate reality is that the income gap has widened between Canadian families. Educational outcomes are one of the key areas influenced by family incomes. Children from low-income families often start school already behind their peers who come from more affluent families, as shown in measures of school readiness. The incidence, depth, duration and timing of poverty all influence a child’s educational attainment, along with community characteristics and social networks. However, both Canadian and international interventions have shown that the effects of poverty can be reduced using sustainable interventions. Paediatricians and family doctors have many opportunities to influence readiness for school and educational success in primary care settings.     

Simultaneous Intracranial EEG-fMRI Shows Inter-Modality Correlation in Time-Resolved Connectivity Within Normal Areas but Not Within Epileptic Regions

For the first time in research in humans, we used simultaneous icEEG-fMRI to examine the link between connectivity in haemodynamic signals during the resting-state (rs) and connectivity derived from electrophysiological activity in terms of the inter-modal connectivity correlation (IMCC). We quantified IMCC in nine patients with drug-resistant epilepsy (i) within brain networks in ‘healthy’ non-involved cortical zones (NIZ) and (ii) within brain networks involved in generating seizures and interictal spikes (IZ1) or solely spikes (IZ2). Functional connectivity (h ² ) estimates for 10 min of resting-state data were obtained between each pair of electrodes within each clinical zone for both icEEG and fMRI. A sliding window approach allowed us to quantify the variability over time of h ² (vh ²) as an indicator of connectivity dynamics. We observe significant positive IMCC for h ² and vh ², for multiple bands in the NIZ only, with the strongest effect in the lower icEEG frequencies. Similarly, intra-modal h ² and vh ² were found to be differently modified as a function of different epileptic processes: compared to NIZ, \(h_{\text{BOLD}}^{2}\) was higher in IZ1, but lower in IZ2, while \(h_{\text{icEEG}}^{2}\) showed the inverse pattern. This corroborates previous observations of inter-modal connectivity discrepancies in pathological cortices, while providing the first direct invasive and simultaneous comparison in humans. We also studied time-resolved FC variability multimodally for the first time, finding that IZ1 shows both elevated internal \(h_{\text{BOLD}}^{2}\) and less rich dynamical variability, suggesting that its chronic role in epileptogenesis may be linked to greater homogeneity in self-sustaining pathological oscillatory states.     

Alcohol alters sensory processing to respiratory stimuli in healthy men and women during wakefulness

Study Objectives:

Alcohol can cause sleep-disordered breathing in healthy men, increase O₂ desaturation in men who snore, and worsen obstructive sleep apnea (OSA) severity in men with OSA. These findings are less consistent among women, and the underlying mechanisms are incompletely understood. Respiratory-load sensory processing, which underpins upper-airway and respiratory responses to increased breathing load, is potentially impaired by alcohol. Using respiratory-related evoked potentials (RREPs) during wakefulness, this study aimed to test the hypothesis that alcohol impairs respiratory-load sensory processing and to explore potential sex differences.

Design:

Within-subjects cross-over design in men versus women.

Setting:

Sleep physiology laboratory.

Participants:

Twenty healthy individuals (9 women) aged 18 to 38 years.

Interventions:

Within each subject, RREP waveform components were generated by ∼60 brief early-inspiratory negative-pressure pulses (−13 cm H₂O mask pressure, 200 ms) before and after acute alcohol administration (1.5 mL/kg body weight). Choanal and epiglottic pressures were recorded to monitor stimulus magnitude and upper-airway resistance.

Measurements and Results:

The latency of several RREP waveform components increased after the administration of alcohol (ΔN1 = 11 ± 5 ms, ΔN2 = 6 ± 3 ms, ΔP3 = 26 ± 10 ms), and P2 amplitude decreased (3.4 ± 1.5 μV vs 1.2 ± 0.8 μV). There were no changes in P1 latency or amplitude. During relaxed breathing, nasal resistance increased after alcohol ingestion (1.38 ± 0.16 vs 1.86 ± 0.18 cm H₂O·l^-1·s^-1), but pharyngeal and supraglottic resistances remained unchanged. RREP waveform components and upper-airway resistance measures were not different in men versus women before or after alcohol ingestion.

Conclusions:

These data demonstrate that alcohol alters sensory processing of respiratory neural information, but not early neural transmission (P1), to a similar extent in healthy men and women. Altered sensory processing to respiratory stimuli, as well as nasal congestion, may be important mechanisms contributing to alcohol-related sleep disordered breathing.

Citation:

Eckert DJ; Elgar NJ; McEvoy RD; Catcheside PG. Alcohol alters sensory processing to respiratory stimuli in healthy men and women during wakefulness. SLEEP 2010;33(10):1389-1395.