Lag Analysis of Fast fMRI Reveals Delayed Information Flow Between the Default Mode and Other Networks in Narcolepsy.

Narcolepsy is a chronic neurological disease characterized by dysfunction of the hypocretin system in brain causing disruption in the wake-promoting system. In addition to sleep attacks and cataplexy, patients with narcolepsy commonly report cognitive symptoms while objective deficits in sustained attention and executive function have been observed. Prior resting-state functional magnetic resonance imaging (fMRI) studies in narcolepsy have reported decreased inter/intranetwork connectivity regarding the default mode network (DMN). Recently developed fast fMRI data acquisition allows more precise detection of brain signal propagation with a novel dynamic lag analysis. In this study, we used fast fMRI data to analyze dynamics of inter resting-state network (RSN) information signaling between narcolepsy type 1 patients (NT1, n = 23) and age- and sex-matched healthy controls (HC, n = 23). We investigated dynamic connectivity properties between positive and negative peaks and, furthermore, their anticorrelative (pos-neg) counterparts. The lag distributions were significantly (P < 0.005, familywise error rate corrected) altered in 24 RSN pairs in NT1. The DMN was involved in 83% of the altered RSN pairs. We conclude that narcolepsy type 1 is characterized with delayed and monotonic inter-RSN information flow especially involving anticorrelations, which are known to be characteristic behavior of the DMN regarding neurocognition.

Prenatal exposure to maternal cigarette smoking and structural properties of the human corpus callosum.

Alterations induced by prenatal exposure to nicotine have been observed in experimental (rodent) studies. While numerous developmental outcomes have been associated with prenatal exposure to maternal cigarette smoking (PEMCS) in humans, the possible relation with brain structure is less clear. Here we sought to elucidate the relation between PEMCS and structural properties of human corpus callosum in adolescence and early adulthood in a total of 1,747 youth. We deployed three community-based cohorts of 446 (age 25-27 years, 46% exposed), 934 (age 12-18 years, 47% exposed) and 367 individuals (age 18-21 years, 9% exposed). A mega-analysis revealed lower mean diffusivity in the callosal segments of exposed males. We speculate that prenatal exposure to maternal cigarette smoking disrupts the early programming of callosal structure and increases the relative portion of small-diameter fibres.

Spectral entropy indicates electrophysiological and hemodynamic changes in drug-resistant epilepsy - A multimodal MREG study.

OBJECTIVE: Epilepsy causes measurable irregularity over a range of brain signal frequencies, as well as autonomic nervous system functions that modulate heart and respiratory rate variability. Imaging dynamic neuronal signals utilizing simultaneously acquired ultra-fast 10 Hz magnetic resonance encephalography (MREG), direct current electroencephalography (DC-EEG), and near-infrared spectroscopy (NIRS) can provide a more comprehensive picture of human brain function. Spectral entropy (SE) is a nonlinear method to summarize signal power irregularity over measured frequencies. SE was used as a joint measure to study whether spectral signal irregularity over a range of brain signal frequencies based on synchronous multimodal brain signals could provide new insights in the neural underpinnings of epileptiform activity. METHODS: Ten patients with focal drug-resistant epilepsy (DRE) and ten healthy controls (HC) were scanned with 10 Hz MREG sequence in combination with EEG, NIRS (measuring oxygenated, deoxygenated, and total hemoglobin: HbO, Hb, and HbT, respectively), and cardiorespiratory signals. After pre-processing, voxelwise SEMREG was estimated from MREG data. Different neurophysiological and physiological subfrequency band signals were further estimated from MREG, DC-EEG, and NIRS: fullband (0-5 Hz, FB), near FB (0.08-5 Hz, NFB), brain pulsations in very-low (0.009-0.08 Hz, VLFP), respiratory (0.12-0.4 Hz, RFP), and cardiac (0.7-1.6 Hz, CFP) frequency bands. Global dynamic fluctuations in MREG and NIRS were analyzed in windows of 2 min with 50% overlap. RESULTS: Right thalamus, cingulate gyrus, inferior frontal gyrus, and frontal pole showed significantly higher SEMREG in DRE patients compared to HC. In DRE patients, SE of cortical Hb was significantly reduced in FB (p = .045), NFB (p = .017), and CFP (p = .038), while both HbO and HbT were significantly reduced in RFP (p = .038, p = .045, respectively). Dynamic SE of HbT was reduced in DRE patients in RFP during minutes 2 to 6. Fitting to the frontal MREG and NIRS results, DRE patients showed a significant increase in SEEEG in FB in fronto-central and parieto-occipital regions, in VLFP in parieto-central region, accompanied with a significant decrease in RFP in frontal pole and parietal and occipital (O2, Oz) regions. CONCLUSION: This is the first study to show altered spectral entropy from synchronous MREG, EEG, and NIRS in DRE patients. Higher SEMREG in DRE patients in anterior cingulate gyrus together with SEEEG and SENIRS results in 0.12-0.4 Hz can be linked to altered parasympathetic function and respiratory pulsations in the brain. Higher SEMREG in thalamus in DRE patients is connected to disturbances in anatomical and functional connections in epilepsy. Findings suggest that spectral irregularity of both electrophysiological and hemodynamic signals are altered in specific way depending on the physiological frequency range.

Structural properties of the human corpus callosum: Multimodal assessment and sex differences.

A number of structural properties of white matter can be assessed in vivo using multimodal magnetic resonance imaging (MRI). We measured profiles of R1 and R2 relaxation rates, myelin water fraction (MWF) and diffusion tensor measures (fractional anisotropy [FA], mean diffusivity [MD]) across the mid-sagittal section of the corpus callosum in two samples of young individuals. In Part 1, we compared histology-derived axon diameter (Aboitiz et al., 1992) to MRI measures obtained in 402 young men (19.55 ± 0.84 years) recruited from the Avon Longitudinal Study on Parents and Children. In Part 2, we examined sex differences in FA, MD and magnetization transfer ratio (MTR) across the corpus callosum in 433 young (26.50 ± 0.51 years) men and women recruited from the Northern Finland Birth Cohort 1986. We found that R1, R2, and MWF follow the anterior-to-posterior profile of small-axon density. Sex differences in mean MTR were similar across the corpus callosum (males > females) while these in FA differed by the callosal segment (Body: M>F; Splenium: F>M). We suggest that the values of R1, R2 and MWF are driven by high surface area of myelin in regions with high density of "small axons".

Brain structural changes in women and men during midlife.

Brain development during childhood and adolescence differs between boys and girls. Structural changes continue during adulthood and old age, particularly in terms of brain volume reductions that accelerate beyond age 35 years. We investigated whether brain structural change in mid-life differs between men and women. 43 men and 28 women from the Northern Finland 1966 Birth Cohort underwent MRI brain scans at age 33-35 (SD=0.67) and then again at age 42-44 (SD=0.41). We examined sex differences in total percentage brain volume change (PBVC) and regional brain change with FSL SIENA software. Women showed significant PBVC reduction compared with men between the ages of 33-35 and 42-44 years (Mean=-3.21% in men, Mean=-4.03% in women, F (1, 68)=6.37, p<0.05). In regional analyses, women exhibited greater brain reduction than men in widespread areas. After controlling for total percent brain volume change, men show greater relative regional brain reduction than women in bilateral precentral gyri, bilateral paracingulate gyri, and bilateral supplementary motor cortices. The results indicate sex differences in brain changes in mid-life. Women have more total brain reduction, and more reduction on the outer brain surface than men, whereas men exhibit more brain reduction on the mid-line surface than women after co-varying for total brain volume loss. These changes could contribute to sex differences in midlife behaviour and health.

Intravenous metoprolol versus biatrial pacing in the prevention of atrial fibrillation after coronary artery bypass surgery: a prospective randomized open trial.

BACKGROUND AND AIMS: Atrial fibrillation (AF) is the most common arrhythmia after coronary artery bypass surgery (CABG). Intravenous metoprolol and biatrial pacing have been reported to be effective in AF prophylaxis after cardiac surgery. The purpose of this trial was to compare the efficacy of intravenous metoprolol versus biatrial pacing combined with oral metoprolol in the prevention of AF after CABG. METHODS: A single-centre prospective randomized open trial of 165 consecutive patients undergoing their first CABG. Patients were randomized to receive either intravenous metoprolol infusion 1-3 mg per hour or biatrial overdrive pacing and oral metoprolol (50-150 mg) daily for 72 hours after CABG starting immediately after the surgery. AAI pacing with a pacing rate of 10 beats/minute above the baseline heart rate was used. Patients had continuous ECG-monitoring. The primary end point was the first episode of AF. RESULTS: The incidence of postoperative AF in the intravenous metoprolol and biatrial pacing groups did not differ from each other (14% vs. 18% respectively, p=0.66). There was no difference in the time of AF onset between the groups (28.2 ± 16.2 h vs. 30.1 ± 21.2 h respectively, p = 0.8). Intravenous metoprolol infusion had to be temporarily interrupted for one hour in eleven patients because of hypotension or bradycardia. One case of bleeding from the left atria related to the pacemaker electrode wire was found. CONCLUSION: We found no difference in the incidence of AF between patients treated with intravenous metoprolol or the combination of biatrial pacing and oral metoprolol.

The current standard measure of cardiorespiratory fitness introduces confounding by body mass: the DR's EXTRA study.

OBJECTIVE: Cardiorespiratory fitness is currently estimated by dividing maximal oxygen consumption (VO(2max)) by body weight (per-weight standard). However, the statistically correct way to neutralize the effect of weight on VO(2max) in a given population is adjustment for body weight by regression techniques (adjusted standard). Our objective is to quantify the bias introduced by the per-weight standard in a population distributed across different categories of body mass. DESIGN: This is a cross-sectional study. SUBJECTS AND METHODS: Baseline measures from participants of the Dose-Responses to Exercise Training Study (DR's EXTRA), 635 men (body mass index (BMI): 19-47 kg m⁻²) and 638 women (BMI: 16-49 kg m⁻²) aged 57-78 years who performed oral glucose tolerance tests and maximal exercise stress tests with direct measurement of VO(2max). We compare the increase in VO(2max) implied by the per-weight standard with the real increase of VO(2max) per kg body weight. A linear logistic regression model estimates odds for abnormal glucose metabolism (either impaired fasting glycemia or impaired glucose tolerance or Type 2 diabetes) of the least-fit versus most-fit quartile according to both per-weight standard and adjusted standard. RESULTS: The per-weight standard implies an increase of VO(2max) with 20.9 ml min⁻¹ in women and 26.4 ml min⁻¹ in men per additional kg body weight. The true increase per kg is only 7.0 ml min⁻¹ (95% confidence interval: 5.3-8.8) and 8.0 ml min⁻¹ (95% confidence interval: 5.3-10.7), respectively. Risk for abnormal glucose metabolism in the least-fit quartile of the population is overestimated by 52% if the per-weight standard is used. CONCLUSIONS: In comparisons across different categories of body mass, the per-weight standard systematically underestimates cardiorespiratory fitness in obese subjects. Use of the per-weight standard markedly inflates associations between poor fitness and co-morbidities of obesity.

Two-minute heart rate recovery after cycle ergometer exercise and all-cause mortality in middle-aged men.

BACKGROUND: A slow heart rate recovery (HRR) after an exercise test is associated with an increased risk of all-cause mortality in asymptomatic individuals, but the data regarding additional prognostic information provided by HRR beyond other exercise test variables are inconsistent. We investigated the prognostic significance of HRR for premature death, particularly in relation to other exercise test variables. METHODS: The study subjects were a representative population-based sample of 1102 men (42-61 years of age) without cardiovascular disease, cancer or diabetes. HRR was defined as the difference between maximal HR and HR 2 min after a maximal symptom-limited exercise test using a cycle ergometer. The association between HRR and premature mortality was examined with Cox regression models. RESULTS: During an average follow-up of 18 years, 238 deaths occurred. HRR was an independent predictor of death [for a decrease of 12 beats min(-1) , relative risk (RR) 1.16, 95% CI 1.02-1.33, P = 0.02] after adjustment for age and established risk factors. When added in a Cox model with chronotropic response (decrease of 12 beats min(-1) , RR 1.09, 95% CI 0.93-1.27, P = 0.26) or cardiorespiratory fitness (decrease of 12 beats min(-1) , RR 1.12, 95% CI 0.98-1.30, P = 0.08), the association between a slow HRR and an increased risk of death was clearly weaker. CONCLUSION: A slow 2-min HRR after a cycle ergometer exercise test was an independent predictor of death in healthy middle-aged men after accounting for demographic and clinical characteristics. However, it was no longer predictive after accounting for chronotropic response and exercise capacity.

Differences in eye-movement patterns between anorexic and control observers when judging body size and attractiveness.

Attentional biases may influence the eye-movements made when judging bodies and so alter the visual information sampled when making a judgment. This may lead to an overestimation of body size. We measured the eye-movements made by 16 anorexic observers and 16 age-matched controls when judging body size and attractiveness. We combined behavioural data with a novel eye-movement analysis technique that allowed us to apply spatial statistical techniques to make fine spatial discriminations in the pattern of eye-movements between our observer groups. Our behavioural results show that anorexic observers overestimate body size relative to controls and find bodies with lower body mass indexes more attractive. For both judgments, the controls' fixations centre on the stomach, but the anorexic observers show a much wider fixation pattern extending to encompass additional features such as the prominence of the hip and collar bones. This additional visual information may serve to alter their behavioural judgments towards an overestimation of body size and shift their ideal body size towards a significantly lower value.

Surgical wound infections after vascular surgery: prospective multicenter observational study.

BACKGROUND AND AIMS: this multicenter prospective observational study defined the incidence and risk factors of surgical wound infections (SWI) after infrarenal aortic and lower limb vascular surgery procedures and evaluated the severity and costs of these infections. METHODS: the study cohort comprised of 184 consecutive patients. Postoperative complications were recorded. The additional costs attributable to SWI were calculated. RESULTS: Eighty-four (46%) patients had critical ischaemia, 81 (45%) patients underwent infrainguinal bypass surgery and 64 (35%) received vascular prosthesis or prosthetic patch. Forty-nine (27%) patients developed SWI. Staphylococcus aureus was the leading pathogen cultured from the wound. Forty-seven of the 49 infected wounds responded to and healed with the treatment. SWI was the cause of one major amputation. Independent predictors for SWI were infrainguinal surgery (OR 7.2, 95% Cl 2.92-17.65, p < 0.001), obesity (OR 6.1, 95% Cl 2.44-15.16, p < 0.001) and arteriography injection site within the operative area (OR 2.5, 95% Cl 1.13-5.48, p = 0.02). The average cost attributable to SWI was 3320 Ä. CONCLUSION: the incidence of SWI after vascular surgery is high. The risk factors for SWI are infrainguinal surgery, obesity and arteriography injection site within the operative area. SWI increases morbidity and costs of operative treatment.

Long-term follow-up of a randomized clinical trial of open versus laparoscopic appendicectomy.

BACKGROUND: The aim of this study was to assess long-term outcome following open versus laparoscopic appendicectomy. METHODS: A total of 105 patients with suspected acute appendicitis were randomized to LA (51) or OA (54) between 1997 and 1999 at one hospital. Perioperative factors and follow-up data from the outpatient clinic were recorded. Information about symptoms and overall satisfaction was obtained by telephone interview. In addition, appendicectomy data for 2008 were analysed retrospectively for comparison in a contemporary setting. RESULTS: Data from 52 patients who had OA and 47 who had LA were analysed. OA was performed mostly by trainees, but LA was more likely to be undertaken by a consultant. The open procedure was quicker than the laparoscopic operation in the trial period (median 38 versus 65 min respectively; P < 0.001), but the difference was only 10 min in 2008. The OA group returned to work later than the LA group (median 13 versus 8 days; P = 0.013) and had more complications (22 versus 6; P = 0.014). Only one patient (OA) had a reoperation, owing to abdominal adhesions. Among 76 patients available for telephone interview, satisfaction scores were marginally higher for LA than OA. CONCLUSION: LA has some advantages compared with an open approach. REGISTRATION NUMBER: NCT00908804 (http://www.clinicaltrials.gov).

Quality of cardiopulmonary resuscitation on manikins: on the floor and in the bed.

BACKGROUND: In general, in-hospital resuscitation is performed in a bed and out-of-hospital resuscitation on the floor. The surface under the patient may affect the cardiopulmonary resuscitation (CPR) quality; therefore, we evaluated CPR quality (the percentage of chest compressions of correct depth) and rescuer's fatigue (the mean compression depth minute by minute) when CPR is performed on a manikin on the floor or in the bed. METHODS: Forty-four simulated cardiac arrest scenarios of 10 min were treated by intensive care unit (ICU) nurses in pairs using a 30 : 2 chest compression-to-ventilation ratio. The rescuer who performed the compressions was changed every 2 min. CPR was randomly performed either on the floor or in the bed without a backboard; in both settings, participants kneeled beside the manikin. RESULTS: A total number of 1060 chest compressions, 44% with correct depth, were performed on the floor; 1068 chest compressions were performed in the bed, and 58% of these were the correct depth. These differences were not significant between groups. The mean compression depth during the scenario was 44.9+/-6.2 mm (mean+/-SD) on the floor and 43.0+/-5.9 mm in the bed (P=0.3). The mean chest compression depth decreased over time on both surfaces (P<0.001), indicating rescuer fatigue, but this change was not different between the groups (P=0.305). CONCLUSIONS: ICU nurses perform chest compression as effectively on the floor as in the bed. The mean chest compression depth decreases over time, but the surface had no significant effect.

Influence of chest compression rate guidance on the quality of cardiopulmonary resuscitation performed on manikins.

AIMS: The adequate chest compression rate during CPR is associated with improved haemodynamics and primary survival. To explore whether the use of a metronome would affect also chest compression depth beside the rate, we evaluated CPR quality using a metronome in a simulated CPR scenario. METHODS: Forty-four experienced intensive care unit nurses participated in two-rescuer basic life support given to manikins in 10min scenarios. The target chest compression to ventilation ratio was 30:2 performed with bag and mask ventilation. The rescuer performing the compressions was changed every 2min. CPR was performed first without and then with a metronome that beeped 100 times per minute. The quality of CPR was analysed with manikin software. The effect of rescuer fatigue on CPR quality was analysed separately. RESULTS: The mean compression rate between ventilation pauses was 137+/-18compressions per minute (cpm) without and 98+/-2cpm with metronome guidance (p<0.001). The mean number of chest compressions actually performed was 104+/-12cpm without and 79+/-3cpm with the metronome (p<0.001). The mean compression depth during the scenario was 46.9+/-7.7mm without and 43.2+/-6.3mm with metronome guidance (p=0.09). The total number of chest compressions performed was 1022 without metronome guidance, 42% at the correct depth; and 780 with metronome guidance, 61% at the correct depth (p=0.09 for difference for percentage of compression with correct depth). CONCLUSIONS: Metronome guidance corrected chest compression rates for each compression cycle to within guideline recommendations, but did not affect chest compression quality or rescuer fatigue.

The diet board: welfare impacts of a novel method of dietary restriction in laboratory rats.

Laboratory rats are commonly fed ad libitum (AL). Moderate dietary restriction (DR) decreases mortality and morbidity when compared with AL feeding, but there are several obstacles to the implementation of DR. Traditional methods of restricted feeding disrupt normal diurnal eating rhythms and are not compatible with group housing. We have designed a novel method, the diet board, to restrict the feeding of group-housed rats. Animals fed from the diet board had 15% lower body weight than the AL-fed animals at the age of 17 weeks. The welfare effects of diet board feeding were assessed by comparing the stress physiology of diet board fed animals with that of AL-fed animals. Diet board feeding was associated with higher serum corticosterone levels and lower faecal secretion of IgA, suggesting the diet board causes a stress reaction. However, the AL-fed group had larger adrenal glands with higher adrenaline and noradrenaline content than the diet board animals. No gastric ulcers were found in any of the animals at necropsy. The diet board thus appears to cause a stress reaction when compared with AL-fed rats, but no apparent pathology was associated with this reaction. The diet board could help to solve the health problems associated with AL feeding, while allowing the rats to be group-housed and to maintain their normal diurnal eating rhythms. The diet board can also be seen as a functional cage furniture item, dividing the cage into compartments and thus increasing the structural complexity of the environment. In conclusion, the diet board appears to possess refinement potential compared with traditional methods of DR.

Association between environmental stress and epidermal papillomatosis of roach Rutilus rutilus.

We studied the association between environmental stress and epidermal papillomatosis of roach Rutilus rutilus L. in Finnish waters using a 'matched pairs' design. Populations impacted by industrial and/or sewage effluents were compared to reference populations from pristine sites. We examined both the prevalence (proportion of diseased fish) and intensity (number of scales covered by tumors) of the disease. Results of Generalized Linear Mixed Models (GLMM) indicated that the risk of papillomatosis was 7.5 times higher in males than females, and increased 1.3 times for every 10 mm increment in fish length. We controlled for the possible effects of fish size, sex and temporal variation through sampling procedures and statistical analyses. Mean prevalence of epidermal papillomatosis was 16.6 and 5.8% in impact and reference populations, respectively (10 population pairs; nfish = 1714). Results of GLMM suggested that the risk of being diseased was 2.7 times higher in the impact than reference populations. Thus, the prevalence of epidermal papillomatosis in roach can be used as an indicator of environmental stress. Results of Linear Mixed Models indicated no difference in the intensity of the disease between impact and reference populations (5 population pairs; nfish = 73; mean+/-SE 10.7+/-1.8 and 11.7+/- 2.9 scales, respectively), although prevalence was higher in impact populations in those 5 population pairs. The possible relationship between environmental stress and intensity of epidermal papillomatosis in natural roach populations remains to be demonstrated.

Postprandial behavior of plasma squalene and non-cholesterol sterols in men with varying cholesterol absorption.

BACKGROUND: The purpose of this study was to investigate, whether low vs. high absorption of cholesterol affects the postprandial lipid clearance (squalene as the surrogate marker) and postprandial cholesterol metabolism evaluated with plasma levels of cholesterol absorption (cholestanol and plant sterols) and synthesis markers (desmosterol and lathosterol). METHODS: Fifteen normo- or mildly hypercholesterolemic men were divided into low or high cholesterol absorbers on the basis of plasma cholestanol to cholesterol ratio and they volunteered to an oral fat load test containing fat 35 g/m(2) body surface. RESULTS: Plasma squalene to cholesterol ratio did not differ between the groups throughout the postprandial follow-up of 8 h. The level differences in the plasma absorption and synthesis markers seen at baseline remained between the groups, so that in high absorbers the absorption markers remained high and synthesis markers low throughout the postprandial follow-up. The postprandial response curves of desmosterol (p<0.05) and lathosterol (p=0.052) to cholestanol decreased linearly in the low, but not in the high absorbers. CONCLUSIONS: Low vs. high absorption of cholesterol does not affect the first 8-h postprandial lipid clearance. The metabolic profile of cholesterol is maintained postprandially. The postprandial decrease in cholesterol synthesis differs in low vs. high absorbers especially through the desmosterol pathway.

Slow vasomotor fluctuation in fMRI of anesthetized child brain.

Signal intensity changes in fMRI during rest caused by vasomotor fluctuations were investigated in this work. Resting-state baseline fluctuations were evaluated in 12 children anesthetized with thiopental. Five subjects had fluctuations related to subvoxel motion. In seven subjects without significant motion, slow signal fluctuation at 0.025-0.041 Hz near one or more primary sensory cortices was observed. In each subject the amplitude and frequency of the fluctuations were stable. It is hypothesized that thiopental, which reduces blood pressure and flow in the cortex, alters the feedback in neurovascular coupling leading to an increase in the magnitude and a reduction in the frequency of these fluctuations. The use of anesthesia in fMRI may provide new insight into neural connectivity and the coupling of blood flow and neural metabolism.

Study of straight metatarsal osteotomy for the treatment of plantar callosities.

BACKGROUND AND AIMS: [corrected] To evaluate the outcome of transverse distal metatarsal osteotomies for intractable plantar callosity without hammer toe deformity and associated toe corns. MATERIAL AND METHODS: Twenty-five plantar callosities were treated in 19 feet of 13 patients (mean age 48 years, 5 male, 8 female) with transverse distal metatarsal osteotomy. RESULTS: Twenty-four of the osteotomies united primarily, one after revision. After a 7-year follow-up, 23 of the callosities had healed, two of them after an oblique reosteotomy. Eight hammer toe deformities had developed in the involved rays of four feet. Eight plantar callosities had developed outside the operated rays in five feet. Hallux valgus was a frequent finding in both operated and non-operated feet. CONCLUSION: It seems that transverse distal metatarsal osteotomy is an effective treatment of intractable plantar callosities. Harmful hammer toe deformities and transfer lesions below adjacent metatarsal heads tend to develop over time.