Cognitive profiles in perimenopause: hormonal and menopausal symptom correlates.

OBJECTIVE: Perimenopause is associated with declines in attention, working memory and verbal memory; however, there are significant individual differences. Further, the contributions of hormones and menopausal symptoms to domain-specific cognitive functions remain unknown. This longitudinal study aimed to determine whether there were distinct cognitive profiles in perimenopause and to identify factors associated with each profile. DESIGN: In a sample of 85 women evaluated over 400 bi-annual visits, we administered a comprehensive neuropsychological battery, assessed menopausal symptoms and measured 17ß-estradiol and follicle stimulating hormone. Multilevel latent profile analysis was used to identify cognitive profiles. Regressions were conducted to determine differences in hormones and symptoms by profile after adjusting for Stages of Reproductive Aging Workshop + 10 (STRAW + 10) stage and demographic factors. RESULTS: Perimenopausal cognitive profiles consisted of cognitively normal (Profile 1; n = 162), weaknesses in verbal learning and memory (Profile 2; n = 94), strengths in verbal learning and memory (Profile 3; n = 98) and strengths in attention and executive function (Profile 4; n = 61). Profile 2 was differentiated by less hormonal variability and more sleep disturbance than Profile 1 (p < 0.05). CONCLUSIONS: There is significant heterogeneity in cognition during perimenopause. While most women do not develop impairments, a significant minority experience weaknesses in verbal learning and memory. Profile analysis may identify at-risk populations and inform interventions.

Charge exchange recombination spectroscopy at Wendelstein 7-X.

The Charge Exchange Recombination Spectroscopy (CXRS) diagnostic has become a routine diagnostic on almost all major high temperature fusion experimental devices. For the optimized stellarator Wendelstein 7-X (W7-X), a highly flexible and extensive CXRS diagnostic has been built to provide high-resolution local measurements of several important plasma parameters using the recently commissioned neutral beam heating. This paper outlines the design specifics of the W7-X CXRS system and gives examples of the initial results obtained, including typical ion temperature profiles for several common heating scenarios, toroidal flow and radial electric field derived from velocity measurements, beam attenuation via beam emission spectra, and normalized impurity density profiles under some typical plasma conditions.

Study of impaired cardiovascular and respiratory coupling during orthostatic stress based on joint symbolic dynamics.

The present study investigates the instantaneous coupling among the cardiac, vascular, and respiratory systems, using the heart rate, respiration, and systolic and diastolic blood pressure variability in 12 healthy and 16 vasovagal syncope female subjects during a head-up tilt (HUT) testing protocol at 70° This study contributes to the coupling analysis by using a nonlinear joint symbolic dynamics (JSD) in a high-temporal resolution scheme, based on 5 min segments of the time series that are shifted every minute. For each segment, a bivariate JSD matrix was constructed to obtain global and local coupling indices in accordance to Shannon's entropy and the probability of occurrence of various bivariate words, respectively. The novel approach revealed important findings in the coupling dynamics of the systems, thus allowing the detection of group differences during the early orthostatic phase, and during the HUT test, before the occurrence of any pre-syncopal symptoms. In patients, the global indices indicated a significant decrease of cardiovascular coupling, starting at 10 min after the tilt-up, manifested by reduced baroreflex sensitivity and cardiorespiratory coupling that was initiated 8 min after the onset of the orthostatic phase (OP). A decreased autonomic control on cardiovascular-respiratory couplings was further evidenced by increased alterations of the JSD indices during the OP compared to the supine position in patients compared to controls. Furthermore, findings based on local indices demonstrated that female patients showed reductions and disengagements in cardiovascular (p < 0.001) and cardiorespiratory (p < 0.01) couplings, as early as the first 5 min and during the complete OP.

Quadratus Lumborum Block as Sole, Homeostatic-Preserving Anesthetic for a Patient with Multiple System Atrophy Undergoing Open Inguinal Hernia Repair: A Case Report.

Quadratus Lumborum (QL) block has been successfully used for different abdominal procedures in the past. Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized mainly by autonomic instability, motor impairment, and cognitive dysfunction. We report a case of a patient with MSA with a history of multiple episodes of unplanned admissions following outpatient minor surgical procedures under general anesthesia scheduled to undergo open inguinal hernia repair. In our patient, QL block was successfully used for surgical anesthesia and it resulted in hemodynamic stability and an opioid-free perioperative course.

Microgels for long-term storage of vitamins for extended spaceflight.

Biocompatible materials that can encapsulate large amounts of nutrients while protecting them from degrading environmental influences are highly desired for extended manned spaceflight. In this study, alkaline-degradable microgels based on poly(N-vinylcaprolactam) (PVCL) were prepared and analysed with their regard to stabilise retinol which acts as a model vitamin (vitamin A1). It was investigated whether the secondary crosslinking of the particles with a polyphenol can prevent the isomerisation of biologically active all-trans retinol to biologically inactive cis-trans retinol. Both loading with retinol and secondary crosslinking of the particles was performed at room temperature to prevent an early degradation of the vitamin. This study showed that PVCL microgels drastically improve the water solubility of hydrophobic retinol. Additionally, it is demonstrated that the highly crosslinked microgel particles in aqueous solution can be utilised to greatly retard the light- and temperature-induced isomerisation process of retinol by a factor of almost 100 compared to pure retinol stored in ethanol. The use of microgels offers various advantages over other drug delivery systems as they exhibit enhanced biocompatibility and superior aqueous solubility.

[Whether or not to perform an early endoscopy following ingestion of potentially caustic agents - a retrospective longterm analysis in a tertiary referral institution]. / Wann sollte eine frühe endoskopische Inspektion bei Verletzungen des oberen Gastrointestinaltrakts nach Ingestion von potenziell ätzenden Substanzen und anderen Noxen erfolgen? - Eine retrospektive 13-Jahres-Analyse in einem tertiären Haus der Maximalversorgung.

BACKGROUND: The optimal clinical management of patients following ingestion of potentially caustic lesions is still undetermined. In particular, the indication for early upper GI endoscopy in this context remains unclear. PURPOSE: To draft recommendations regarding the use of early upper GI endoscopy following hospital admissions of patients after ingestion of potentially caustic agents. METHODS: For this purpose, a retrospective cohort study of patients treated for ingestion of potentially caustic substances during a 13 year-period at the university hospital of Berne was performed. RESULTS: In total, 61 patients with acute ingestion of potentially caustic substances were identified. Overall mortality was 5 %. 11/61 patients had to be admitted to the intensive care unit. Most ingestions were performed in suicidal intention (62 %). In 53 % of these patients, a combined ingestion of several substances occurred. In 33 % of patients, an early upper GI endoscopy was performed within 24 hours after ingestion. The degree of burn depended upon the hazard potential of the respective substance. In patients with ingestion of low risk substances, upper GI endoscopy was only performed when additional risk factors were present. CONCLUSION: Based upon the results of the present study, ingestion of potentially caustic agents requires an individualized strategy whether or not to perform early endoscopy.

Joint Estimation of Treatment and Placebo Effects in Clinical Trials with Longitudinal Blinding Assessments.

In some therapeutic areas, treatment evaluation is frequently complicated by a possible placebo effect (i.e., the psychobiological effect of a patient's knowledge or belief of being treated). When a substantial placebo effect is likely to exist, it is important to distinguish the treatment and placebo effects in quantifying the clinical benefit of a new treatment. These causal effects can be formally defined in a joint causal model that includes treatment (e.g., new versus placebo) and treatmentality (i.e., a patient's belief or mentality about which treatment she or he has received) as separate exposures. Information about the treatmentality exposure can be obtained from blinding assessments, which are increasingly common in clinical trials where blinding success is in question. Assuming that treatmentality has a lagged effect and is measured at multiple time points, this article is concerned with joint evaluation of treatment and placebo effects in clinical trials with longitudinal follow-up, possibly with monotone missing data. We describe and discuss several methods adapted from the longitudinal causal inference literature, apply them to a weight loss study, and compare them in simulation experiments that mimic the weight loss study.

Men and women should be separately investigated in studies of orthostatic challenge due to different gender-related dynamics of autonomic response.

In studies of autonomic regulation during orthostatic challenges only a few nonlinear methods have been considered without investigating the effect of gender in young controls. Especially, the temporal development of the autonomic regulation has not yet been explicitly analyzed using short-term segments in supine position, transition and orthostatic phase (OP). In this study, nonlinear analysis of cardiovascular and respiratory time series was performed to investigate how nonlinear indices are dynamically changing with respect to gender during orthostatic challenges. The analysis was carried out using shifted short-term segments throughout a head-up tilt test in 24 healthy subjects, 12 men (26 ± 4 years) and 12 age-matched women (26 ± 5 years), at supine position and during OP at 70°. The nonlinear methods demonstrated statistical differences in the autonomic regulation between males and females. Orthostatic stress caused significantly decreased heart rate variability due to increased sympathetic activity mainly in men, already at the beginning and during the complete OP, revealed by (a) increased occurrence of specific word types with constant fluctuations as pW111 from symbolic dynamics, (b) augmented fractal correlation properties by the short-term index alpha1 from detrended fluctuation analysis, (c) increased slope indices (21ati and 31ati) from auto-transinformation and (d) augmented time irreversibility indices demonstrating more temporal asymmetries and nonlinear dynamics in men than in women. After tilt-up, both men and women increased their sympathetic activity but in a different way. Time-dependent gender differences during orthostatic challenge were shown directly between men and women or indirectly comparing baseline and different temporal stages of OP. The proposed dynamical study of autonomic regulation has the advantage of screening the fluctuations of the sympathetic and vagal activities that can be quantified by the temporal behavior of nonlinear indices. The findings in this paper strongly suggest the need for gender separation in studies of the dynamics of autonomic regulation during orthostatic challenge.

Orthostatic stress causes immediately increased blood pressure variability in women with vasovagal syncope.

The cardiovascular and respiratory autonomic nervous regulation has been studied mainly by hemodynamic responses during different physical stressors. In this study, dynamics of autonomic response to an orthostatic challenge was investigated by hemodynamic variables and by diverse linear and nonlinear indices calculated from time series of beat-to-beat intervals (BBI), respiratory cycle duration (RESP), systolic (SYS) and diastolic (DIA) blood pressure. This study included 16 young female patients (SYN) with vasovagal syncope and 12 age-matched female controls (CON). The subjects were enrolled in a head-up tilt (HUT) test, breathing normally, including 5min of baseline (BL, supine position) and 18min of 70° orthostatic phase (OP). To increase the time resolution of the analysis the time series were segmented in five-minute overlapping windows with a shift of 1min. Hemodynamic parameters did not show any statistical differences between SYN and CON. Time domain linear analysis revealed increased respiratory frequency and increased blood pressure variability (BPV) in patients during OP meaning increased sympathetic activity and vagal withdrawal. Frequency domain analysis confirmed a predominance of sympathetic tone by steadily increased values of low over high frequency power in BBI and of low frequency power in SYS and DIA in patients during OP. The nonlinear analysis by symbolic dynamics seemed to be highly suitable for differentiation of SYN and CON in the early beginning of OP, i.e., 5min after tilt-up. In particular the index SYS_plvar3 showed less patterns of low variability in patients reflecting a steadily increase in both BPV and sympathetic activity. The proposed dynamical analysis could lead to a better understanding of the temporal underlying mechanisms in healthy subjects and patients under orthostatic stress.

Physical factors affecting chloroquine binding to melanin.

Chloroquine is an antimalarial drug but is also prescribed for conditions such as rheumatoid arthritis. Long-term users risk toxic side effects, including retinopathy, thought to be caused by chloroquine accumulation on ocular melanin. Although the binding potential of chloroquine to melanin has been investigated previously, our study is the first to demonstrate clear links between chloroquine adsorption by melanin and system factors including temperature, pH, melanin type, and particle size. In the current work, two Sepia melanins were compared with bovine eye as a representative mammalian melanin. Increasing the surface anionic character due to a pH change from 4.7 to 7.4 increased each melanin's affinity for chloroquine. Although the chloroquine isotherms exhibited an apparently strong interaction with each melanin, isosteric heat analysis indicated a competitive interaction. Buffer solution cations competed effectively at low surface coverage; chloroquine adsorption occurs via buffer cation displacement and is promoted by temperature-influenced secondary structure swelling.

Cardiomyopathy in Duchenne Muscular Dystrophy: Current Value of Clinical, Electrophysiological and Imaging Findings in Children and Teenagers.

BACKGROUND: Progressive cardiomyopathy (CMP) is one main cause of death in DMD. This cross-sectional assessment of different cardiac diagnostic procedures focusses on preterm diagnosis of cardiac dysfunction. PATIENTS: 39 male DMD patients aged 6-20 years were included. 6 patients were still ambulatory, 21 patients received corticosteroid therapy. METHODS: All patients were investigated by ECG, Holter ECG and heart rate variability (HRV), B-type natriuretic peptide (BNP), echocardiography (TTE), tissue Doppler Imaging (TD) and magnetic resonance imaging (MRI) with Late Gadolinium enhancement (LE) and segmental wall motion analysis (WMA). RESULTS: 56% of the patients showed repolarization abnormalities and 76% altered HRV. Subnormal ventricular function was found in 25% by TTE and in 34% by MRI. TD differed from normal controls only in the apical septum. In MRI 89% of the patients showed different distribution and intensity of LE and WM restriction. The extent of LE was less in patients after steroid treatment (p<0.05). DISCUSSION: MRI with segmental LE- and WM-analysis seems to be superior to TTE and TD in exploring regional distribution and severity of damage of the myocardium. ECG and HRV abnormalities are common in DMD-patients but not tightly predictive for segmental and global left ventricular dysfunction. Targeted treatment of CMP in DMD needs prospective evaluation. CONCLUSION: A timely cardiac MRI is the most sensitive investigation for the identification of early myocardial changes in DMD which is a prerequisite for early interventions and therapeutic strategies.

Training potential in minimally invasive surgery in a tertiary care, paediatric urology centre.

BACKGROUND: Minimally invasive surgery (MIS) is being utilized more frequently as a surgical technique in general surgery and in paediatric urology. It is associated with a steep learning curve. Currently, the centre does not offer a MIS training programme. It is hypothesized that the number of MIS procedures performed in the low-volume specialty of paediatric urology will offer insufficient training potential for surgeons. OBJECTIVE: To assess the MIS training potential of a highly specialized, tertiary care, paediatric urology training centre that has been accredited by the Joint Committee of Paediatric Urology (JCPU). STUDY DESIGN: The clinical activity of the department was retrospectively reviewed by extracting the annual number of admissions, outpatient consultations and operative procedures. The operations were divided into open procedures and MIS. Major ablative procedures (nephrectomy) and reconstructive procedures (pyeloplasty) were analysed with reference to the patients' ages. The centre policy is not to perform major MIS in children who are under 2 years old or who weigh less than 12 kg. RESULTS: Every year, this institution provides approximately 4300 out-patient consultations, 600 admissions, and 1300 procedures under general anaesthesia for children with urological problems. In 2012, 35 patients underwent major intricate MIS: 16 pyeloplasties, eight nephrectomies and 11 operations for incontinence (seven Burch, and four bladder neck procedures). In children ≥2 years of age, 16/21 of the pyeloplasties and 8/12 of the nephrectomies were performed laparoscopically. The remaining MIS procedures included 25 orchidopexies and one intravesical ureteral reimplantation. DISCUSSION: There is no consensus on how to assess laparoscopic training. It would be valuable to reach a consensus on a standardized laparoscopic training programme in paediatric urology. Often training potential is based on operation numbers only. In paediatric urology no minimum requirement has been specified. The number of procedures quoted for proficiency in MIS remains controversial. The MIS numbers for this centre correspond to, or exceed, numbers mentioned in other literature. To provide high-quality MIS training, exposure to laparoscopic procedures should be expanded. This may be achieved by centralizing patients into a common centre, collaborating with other specialities, modular training and training outside the operating theatre. CONCLUSION: Even in a high-volume, paediatric urology educational centre, the number of major MIS procedures performed remains relatively low, leading to limited training potential.

QT variability improves risk stratification in patients with dilated cardiomyopathy.

Recently it could be demonstrated that systolic and diastolic blood pressure variability (BPV) as well as segmented Poincare plot analysis (SPPA) contribute to risk stratification in patients suffering from dilated cardiomyopathy (DCM). The aim of this study was to improve the risk stratification applying a multivariate technique including QT variability (QTV). We enrolled and significantly separated 56 low risk and 13 high risk DCM patients by nearly all applied BPV and QTV methods, but not with traditional heart rate variability analysis. The optimum set of two indices calculating the multivariate discriminate analysis (DA) included one BPV index calculated by symbolic dynamics method (DBP(Shannon)) and one index calculated from QTV (QTV(log)) achieving an area under the receiver operating characteristics curve (AUC) of 92%, sensitivity of 92.3% and specificity of 89.3%. Performing only electrocardiogram analysis, the optimum multivariate approach including indices from segmented Poincaré plot analysis and QTV still achieved a remarkable AUC of 88.3%. Increasing the number of indices for multivariate DA up to three, we achieved an AUC of 95.7%, sensitivity of 100% and specificity of 85.7% including one clinical, one BPV and one QTV index. Summarizing, we identified DCM patients with an increased risk of sudden cardiac death applying QTV analysis in a multivariate approach.

Body morphology differs in wild juvenile Chinook salmon Oncorhynchus tshawytscha that express different migratory phenotypes in the Willamette River, Oregon, U.S.A.

Body morphology of juvenile Chinook salmon Oncorhynchus tshawytscha in the upper Willamette River, Oregon, U.S.A., was analysed to determine if variation in body shape is correlated with migratory life-history tactics followed by juveniles. Body shape was compared between migrating juveniles that expressed different life-history tactics, i.e. autumn migrants and yearling smolts, and among parr sampled at three sites along a longitudinal river gradient. In the upper Willamette River, the expression of life-history tactics is associated with where juveniles rear in the basin with fish rearing in downstream locations generally completing ocean ward migrations earlier in life than fish rearing in upstream locations. The morphological differences that were apparent between autumn migrants and yearling smolts were similar to differences between parr rearing in downstream and upstream reaches, indicating that body morphology is correlated with life-history tactics. Autumn migrants and parr from downstream sampling sites had deeper bodies, shorter heads and deeper caudal peduncles compared with yearling smolts and parr from the upstream sampling site. This study did not distinguish between genetic and environmental effects on morphology; however, the results suggest that downstream movement of juveniles soon after emergence is associated with differentiation in morphology and with the expression of life-history variation.

Coupling of heart rate and systolic blood pressure in hypertensive pregnancy.

INTRODUCTION: This article is part of the Focus Theme of Methods of Information in Medicine on "Biosignal Interpretation: Advanced Methods for Studying Cardiovascular and Respiratory Systems". BACKGROUND: Hypertensive pregnancy disorders affect 6 - 8 percent of all pregnancies and can result in severe complications for both the mother and the fetus. OBJECTIVES: The aim of this study was to improve risk stratification of pregnant women suffering from hypertension and pre-eclampsia (PE) by applying bivariate Segmented Poincaré plot analysis (BSPPA). METHODS: From 35 pregnant women suffering from chronic hypertension, gestational hypertension and PE, 30 minutes of noninvasive systolic blood pressure and beat- to-beat intervals were continuously recorded and analyzed by applying BSPPA to quantify their couplings. RESULTS: We revealed significant different couplings between chronic hypertension (CH), gestational hypertension and PE, indicating that cardiovascular regulation can be considerably altered depending on the type of hypertensive disorder. The optimal multivariate set of two BSPPA indices was determined which distinguish best between CH and PE. It achieved a sensitivity of 100%, a specificity of 77.8% and an area under the receiver operator characteristic curve of 90.8%. CONCLUSIONS: The BSPPA method a) provides improved risk stratification for pregnant women suffering from hypertension and PE, b) increases the ability to diagnose pathological changes, and c) could contribute substantially to the differential diagnosis of hypertensive pregnancy disorders.

Chloroquine and hydroxychloroquine binding to melanin: Some possible consequences for pathologies.

For many years chloroquine was used as a prophylactic agent against malaria, and more recently as a mild immunosuppressive. However, due to lengthy treatment periods, adverse effects have become apparent, which included retinopathy. The structurally related hydroxychloroquine is less toxic, thought to be owing to a lower tissue accumulation in melanin rich areas. This study primarily focused on quantifying melanin binding between chloroquine and hydroxychloroquine at physiological pH to investigate the potential link between binding and reported toxicity. In addition, for the first time this study quantified the actual extent of adsorption of chloroquine and hydroxychloroquine to melanin and examined the desorption profile of both drugs from melanin to demonstrate the affinity between the pigment and the solutes. The results suggest that there is a difference between the adsorption affinities of chloroquine and hydroxychloroquine, potentially explaining the differences in bioaccumulation in retinal tissue. In addition, both solutes displayed a strong physical attraction to the absorbent.

Array tomography.

In array tomography ordered, ribbon-like assemblies of ultrathin serial sections are deposited on a solid substrate and imaged afterwards. The resulting images are then aligned and reconstructed into a three-dimensional representation of the object. Depending on the preparation and labelling regime, different imaging modalities can be applied. When using light microscopy, the labelling with fluorescent markers would be the obvious choice, whereas the imaging in a scanning electron microscope would require impregnation with heavy metals. Depending on preparative constraints, the combination of diverse imaging modalities or truly correlative imaging is possible.

Composition and diversity patterns of megafauna discards in the deep-water shrimp trawl fishery off Brazil.

Composition and spatial diversity patterns of retained and discarded catches in the deep-water shrimp (family Aristeidae) trawling fishery off Brazil were assessed by observers on-board commercial operations in 2005 and 2006. These trawls caught 19,440 kg and 180,076 individuals of which 76·0 and 65·2%, respectively, were discarded at sea. Finfishes represented 54% of the numerical catch but were almost fully discarded (98%). Crustaceans represented 40% of the numerical catch and were mostly retained (80%). The scarlet shrimp Aristaeopsis edwardsiana comprised approximately half of the retained catch. The remainder of the retained proportion comprised mainly the red giant shrimp Aristaeomorpha foliacea, the alistado shrimp Aristeus antillensis and small quantities of Argentine hake Merluccius hubbsi and gulf hake Urophycis mystacea. Discards comprised 108 species including 72 fish species, 19 crustaceans and 10 cephalopods. The large-scaled lanternfish Neoscopelus macrolepidotus was dominant in the discards, followed by the benthopelagic fishes Monomitopus agassizii, Synagrops bellus, Dibranchus atlanticus and Gadella imberbis and various macrurid species. This fishery was restricted to a limited bathymetric range (700-800 m), where discrete megafauna assemblages exist and may have been significantly affected.

Influence of age and gender on complexity measures for short term heart rate variability analysis in healthy subjects.

Short-term heart rate variability (HRV) analyses (less than 30 min) are suitable for ambulatory care and patient monitoring and can provide an almost immediate test result. Short-term 5 min HRV indices from nonlinear dynamics were determined from 782 females and 1124 males from the KORA S4 database. We applied various fractal and complexity measures with focus on entropies and investigated the influence of age in terms of five age decades (25-34, 35-44, 45-54, 55-64 and 65-74 years) and gender on these HRV indices. The analyses revealed significant modifications of the indices especially by age but partly also by gender especially in the younger groups. These results should be considered in future studies applying nonlinear dynamics, especially if major age and gender differences between the investigated groups are expected.

Differences in MMPI-2 FBS and RBS scores in brain injury, probable malingering, and conversion disorder groups: a preliminary study.

This study examined differences in raw scores on the Symptom Validity Scale and Response Bias Scale (RBS) from the Minnesota Multiphasic Personality Inventory-2 in three criterion groups: (i) valid traumatic brain injured, (ii) invalid traumatic brain injured, and (iii) psychogenic non-epileptic seizure disorders. Results indicate that a >30 raw score cutoff for the Symptom Validity Scale accurately identified 50% of the invalid traumatic brain injured group, while misclassifying none of the valid traumatic brain injured group and 6% of the psychogenic non-epileptic seizure disorder group. Using a >15 RBS raw cutoff score accurately classified 50% of the invalid traumatic brain injured group and misclassified fewer than 10% of the valid traumatic brain injured and psychogenic non-epileptic seizure disorder groups. These cutoff scores used conjunctively did not misclassify any members of the psychogenic non-epileptic seizure disorder or valid traumatic brain injured groups, while accurately classifying 44% of the invalid traumatic brain injured individuals. Findings from this preliminary study suggest that the conjunctive use of the Symptom Validity Scale and the RBS from the Minnesota Multiphasic Personality Inventory-2 may be useful in differentiating probable malingering from individuals with brain injuries and conversion disorders.