Accuracy of approximate methods for the calculation of absorption-type linear spectra with a complex system-bath coupling.

The accuracy of approximate methods for calculating linear optical spectra depends on many variables. In this study, we fix most of these parameters to typical values found in photosynthetic light-harvesting complexes of plants and determine the accuracy of approximate spectra with respect to exact calculation as a function of the energy gap and interpigment coupling in a pigment dimer. We use a spectral density with the first eight intramolecular modes of chlorophyll a and include inhomogeneous disorder for the calculation of spectra. We compare the accuracy of absorption, linear dichroism, and circular dichroism spectra calculated using the Full Cumulant Expansion (FCE), coherent time-dependent Redfield (ctR), and time-independent Redfield and modified Redfield methods. As a reference, we use spectra calculated with the exact stochastic path integral evaluation method. We find the FCE method to be the most accurate for the calculation of all spectra. The ctR method performs well for the qualitative calculation of absorption and linear dichroism spectra when the pigments are moderately coupled (∼15cm-1), but ctR spectra may differ significantly from exact spectra when strong interpigment coupling (>100cm-1) is present. The dependence of the quality of Redfield and modified Redfield spectra on molecular parameters is similar, and these methods almost always perform worse than ctR, especially when the interpigment coupling is strong or the excitonic energy gap is small (for a given coupling). The accuracy of approximate spectra is not affected by resonance with intramolecular modes for typical system-bath coupling and disorder values found in plant light-harvesting complexes.

Altered functional connectivity in common resting-state networks in patients with major depressive disorder: A resting-state functional connectivity study.

The neural correlates of major depressive disorder (MDD) remain disputed. In the absence of reliable biological markers, the dysfunction and interaction of neural networks have been proposed as pathophysiological neural mechanisms in depression. Here, we examined the functional connectivity (FC) of brain networks. 51 healthy volunteers (mean age 33.57 ± 7.80) and 55 individuals diagnosed with MDD (mean age 33.89 ± 11.00) participated by performing a resting-state (rs) fMRI scan. Seed to voxel FC analyses were performed. Compared to healthy control (HC), MDD patients showed higher connectivity between the hippocampus and the anterior cingulate cortex (ACC) and lower connectivity between the insula and the ACC. The MDD group displayed lower connectivity between the inferior parietal lobule (IPL) and the superior frontal gyrus (SFG). The current data replicate previous findings regarding the cortico-limbic network (hippocampus - ACC connection) and the salience network (insula - ACC connection) and provide novel insight into altered rsFC in MDD, in particular involving the hippocampus - ACC and the insula - ACC connection. Furthermore, altered connectivity between the IPL and SFG indicates that the processing in higher cognitive processes such as attention and working memory is affected in MDD. These data further support dysfunctional neuronal networks as an interesting pathophysiological marker in depression.

Microsurgical testicular sperm extraction for testicular failure: the South African experience and first successful pregnancy.

BACKGROUND: In men with non-obstructive azoospermia (NOA), biological fatherhood is only possibly by specialised microsurgical sperm retrieval techniques (micro-TESE), only recently introduced to South Africa. This study aimed to analyse the spectrum of causes of NOA and the outcomes of micro-TESE, including live births, following the use of this technique in South Africa. METHODS: This was a retrospective review of all micro-TESE cases performed in South Africa by a single surgeon from 2014 to 2018. Data collected prospectively included: patient demographics, preoperative blood results, cause of azoospermia, intraoperative findings and postoperative complications. The primary outcome measured was surgical success of micro-TESE, which was defined as testicular sperm successfully retrieved and cryopreserved. Subsequent live births from assisted reproductive technology (ART) using the cryopreserved sperm were also documented. RESULTS: Twenty-six men with NOA underwent micro-TESE between May 2014 and April 2018. Mean preoperative total testosterone level was 12.0 nmol/l (IQR 5.2) and follicle-stimulating hormone level 23.5 IU/l (IQR 15.6). Genetic testing was performed as part of the preoperative work-up in only 10 of the 26 patients. A specific cause of NOA was identified in 9 of the 26 patients and included Klinefelter syndrome (1 patient), Y-chromosome AZFc microdeletion (1 patient), undescended testicles (5 patients) and chemotherapy (2 patients). The average testicular volume was 9.05 ml (IQR 5.6), and the mean duration of surgery 95.8 minutes (IQR 28.0). The overall sperm retrieval rate was 34.6%. A single pregnancy and subsequent live birth were recorded from a total of eight cycles of intracytoplasmic sperm injection (ICSI): four female partners had one ICSI cycle each and two females underwent two cycles each. Frozen and thawed sperm was used in seven of the ICSI cycles and fresh sperm in one cycle. CONCLUSION: In this South African series, sperm retrieval rates of micro-TESE for non-obstructive azoospermia were comparable to those reported internationally. Preoperative genetic testing should be increased to optimise the selection of surgical candidates.

Modeling ternary fluids in contact with elastic membranes.

We present a thermodynamically consistent model of a ternary fluid interacting with elastic membranes. Following a free-energy modeling approach for the fluid phases, we derive the governing equations for the dynamics of the ternary fluid flow and membranes. We also provide the numerical framework for simulating such fluid-structure interaction problems. It is based on the lattice Boltzmann method for the ternary fluid (Eulerian description) and a finite difference representation of the membrane (Lagrangian description). The ternary fluid and membrane solvers are coupled through the immersed boundary method. For validation purposes, we consider the relaxation dynamics of a two-dimensional elastic capsule placed at a fluid-fluid interface. The capsule shapes, resulting from the balance of surface tension and elastic forces, are compared with equilibrium numerical solutions obtained by surface evolver. Furthermore, the Galilean invariance of the proposed model is proven. The proposed approach is versatile, allowing for the simulation of a wide range of geometries. To demonstrate this, we address the problem of a capillary bridge formed between two deformable capsules.

Sexual cues alter working memory performance and brain processing in men with compulsive sexual behavior.

Pornography has been repeatedly at the centre of public attention and has been controversially discussed for a long time. However, little is known about the connection between pornographic stimuli and individual (neuronal) processing of attention and memory. Here, the impact and neural underpinnings of pornographic pictures on working memory processes in a sample of subjects with compulsive sexual behaviour was investigated. Therefore, whilst using functional magnetic resonance imaging (fMRI), a letter n-back task with neutral or pornographic pictures in the background was employed in 38 patients and 31 healthy controls. On the behavioural level, patients were slowed down by pornographic material depending on their pornography consumption in the last week, which was reflected by a higher activation in the lingual gyrus. In addition, the lingual gyrus showed a higher functional connectivity to the insula during processing of pornographic stimuli in the patient group. In contrast, healthy subjects showed faster responses when confronted with pornographic pictures only with high cognitive load. Also, patients showed a better memory for pornographic pictures in a surprise recognition task compared to controls, speaking for a higher relevance of pornographic material in the patient group. These findings are in line with the incentive salience theory of addiction, especially the higher functional connectivity to the salience network with the insula as a key hub and the higher lingual activity during processing of pornographic pictures depending on recent pornography consumption.

An Exploratory Study on the Central Nervous Correlates of Sexual Excitation and Sexual Inhibition.

The Sexual Inhibition/Sexual Excitation Scales (SIS/SES) measure sexual excitation and sexual inhibition proneness. We used SIS and SES scores of 62 heterosexual teleiophilic men (Mage 34.3, SD = 9.9) to predict brain activation levels during the presentation of male and female visual sexual stimuli in a magnetic resonance imaging (MRI) scanner. Statistical analyses revealed significant correlations. SES and SIS1 scores were positively associated with brain activation in various brain regions during the presentation of both male and female stimuli. SIS2 turned out to be a weaker predictor of brain activation, still revealing one significant correlation in the right lateral orbitofrontal cortex. Significant regions for SES and SIS1 were, among others, primary and supplementary motor areas, the caudate nucleus, the dorsal anterior cingulate cortex, anterior insula, and prefrontal areas. Our study can be seen as an exploratory investigation of SIS and SES with means of functional brain imaging. The results provide a promising contribution to the assertion of neurophysiological systems of sexual inhibition and excitation proneness.

The effect of a compression bandage on the distribution of radiodense contrast medium after palmar digital nerve blocks.

BACKGROUND: Studies have shown proximal diffusion of injected drugs in perineural blocks; such diffusion may affect specificity of the nerve block. OBJECTIVES: To investigate the effect of a compression bandage applied to the pastern region on proximal diffusion of contrast medium injected over the palmar digital nerves. STUDY DESIGN: Experimental study, randomised cross-over design. METHODS: Radiodense contrast medium was injected over the lateral and medial palmar digital nerves of the left front limb of nine mature horses. Each horse was injected on two separate occasions, once with a 5 cm wide compression bandage applied proximal to the injection site and once without. The order of the two treatments was randomised with a wash-out period between treatments of at least 7 days. Radiographs were obtained at 5, 10, 20 and 30 min and distribution of the contrast column assessed. RESULTS: Proximal distribution of the contrast medium was significantly reduced (P<0.01) with compression bandage. Furthermore, the compression bandage inhibited lymphatic drainage of the injected contrast medium. MAIN LIMITATIONS: Clinical effect of the differences in diffusion length was not assessed. CONCLUSIONS: The compression bandage reduced proximal diffusion and lymphatic drainage of contrast material causing it to stay localised around the injection site. Use of compression bandages could thus result in increased specificity of the nerve block and potentially prolong its effect.

Module-detection approaches for the integration of multilevel omics data highlight the comprehensive response of Aspergillus fumigatus to caspofungin.

BACKGROUND: Omics data provide deep insights into overall biological processes of organisms. However, integration of data from different molecular levels such as transcriptomics and proteomics, still remains challenging. Analyzing lists of differentially abundant molecules from diverse molecular levels often results in a small overlap mainly due to different regulatory mechanisms, temporal scales, and/or inherent properties of measurement methods. Module-detecting algorithms identifying sets of closely related proteins from protein-protein interaction networks (PPINs) are promising approaches for a better data integration. RESULTS: Here, we made use of transcriptome, proteome and secretome data from the human pathogenic fungus Aspergillus fumigatus challenged with the antifungal drug caspofungin. Caspofungin targets the fungal cell wall which leads to a compensatory stress response. We analyzed the omics data using two different approaches: First, we applied a simple, classical approach by comparing lists of differentially expressed genes (DEGs), differentially synthesized proteins (DSyPs) and differentially secreted proteins (DSePs); second, we used a recently published module-detecting approach, ModuleDiscoverer, to identify regulatory modules from PPINs in conjunction with the experimental data. Our results demonstrate that regulatory modules show a notably higher overlap between the different molecular levels and time points than the classical approach. The additional structural information provided by regulatory modules allows for topological analyses. As a result, we detected a significant association of omics data with distinct biological processes such as regulation of kinase activity, transport mechanisms or amino acid metabolism. We also found a previously unreported increased production of the secondary metabolite fumagillin by A. fumigatus upon exposure to caspofungin. Furthermore, a topology-based analysis of potential key factors contributing to drug-caused side effects identified the highly conserved protein polyubiquitin as a central regulator. Interestingly, polyubiquitin UbiD neither belonged to the groups of DEGs, DSyPs nor DSePs but most likely strongly influenced their levels. CONCLUSION: Module-detecting approaches support the effective integration of multilevel omics data and provide a deep insight into complex biological relationships connecting these levels. They facilitate the identification of potential key players in the organism's stress response which cannot be detected by commonly used approaches comparing lists of differentially abundant molecules.

Emergence of coexisting ordered states in active matter systems.

Active systems can produce a far greater variety of ordered patterns than conventional equilibrium systems. In particular, transitions between disorder and either polar- or nematically ordered phases have been predicted and observed in two-dimensional active systems. However, coexistence between phases of different types of order has not been reported. We demonstrate the emergence of dynamic coexistence of ordered states with fluctuating nematic and polar symmetry in an actomyosin motility assay. Combining experiments with agent-based simulations, we identify sufficiently weak interactions that lack a clear alignment symmetry as a prerequisite for coexistence. Thus, the symmetry of macroscopic order becomes an emergent and dynamic property of the active system. These results provide a pathway by which living systems can express different types of order by using identical building blocks.

Increased pericardial adipose tissue and cardiometabolic risk in patients with schizophrenia versus healthy controls.

Patients with schizophrenia are at increased risk of diabetes, cardiovascular disease (CVD) and associated mortality versus the general population. Increased intra-abdominal and pericardial adipose tissue are associated with elevated CVD and mortality in the general population, but little is known about these in patients with schizophrenia. This study examined pericardial and intra-abdominal adipose tissue in schizophrenia and compared this to healthy controls. Thirty-one patients with schizophrenia (mean age 41.2 years, 76% males) and 30 healthy volunteers (CTRL) were examined in this study. The primary outcomes were the volumes of pericardial adipose tissue and intra-abdominal adipose tissue, measured using magnetic resonance imaging. Secondary outcomes included diabetes and cardiac event risk assessed by established instruments. Volumes of pericardial adipose tissue were increased in male and female patients with schizophrenia compared to healthy controls after the adjustment of age, sex and body mass index (P < 0.005). The 10-year risk of a cardiac event was significantly higher in patients with schizophrenia. Furthermore, the risk for developing type-2 diabetes mellitus was slightly increased in schizophrenia. Volumes of intra-abdominal adipose tissue were slightly increased in male and female patients with schizophrenia, albeit not statistically significant. This study demonstrates that patients with schizophrenia have increased pericardial adipose tissue versus controls. This increased fat deposit around the heart is highly relevant for understanding the comorbidity between heart disease and schizophrenia. Interventions aiming to reduce pericardial and intra-abdominal adipose tissue, such as exercise, may be essential to reduce the burden of heart disease in schizophrenia.

Transcutaneous sacral nerve stimulation for intraoperative verification of internal anal sphincter innervation.

BACKGROUND: The current standard for pelvic intraoperative neuromonitoring (pIONM) is based on intermittent direct nerve stimulation. This study investigated the potential use of transcutaneous sacral nerve stimulation for non-invasive verification of pelvic autonomic nerves. METHODS: A consecutive series of six pigs underwent low anterior rectal resection. For transcutaneous sacral nerve stimulation, an array of ten electrodes (cathodes) was placed over the sacral foramina (S2 to S4). Anodes were applied on the back, right and left thigh, lower abdomen, and intra-anally. Stimulation using the novel method and current standard were performed at different phases of the experiments under electromyography of the autonomic innervated internal anal sphincter (IAS). KEY RESULTS: Transcutaneous stimulation induced increase of IAS activity could be observed in each animal under specific cathode-anode configurations. Out of 300 tested configurations, 18 exhibited a change in the IAS activity correlated with intentional autonomic nerve damage. The damage resulted in a significant decrease of the relative area under the curve of the IAS frequency spectrum (P<.001). Comparison of the IAS spectra under transcutaneous and direct stimulation revealed no significant difference (after rectal resection: median 5.99 µV•Hz vs 7.78 µV•Hz, P=.12; after intentional nerve damage: median -0.27 µV•Hz vs 3.35 µV•Hz, P=.29). CONCLUSIONS AND INFERENCES: Non-invasive selective transcutaneous sacral nerve stimulation could be used for verification of IAS innervation.

Aortic Elongation and Stanford B Dissection: The Tübingen Aortic Pathoanatomy (TAIPAN) Project.

OBJECTIVE/BACKGROUND: Aortic elongation has not yet been considered as a potential risk factor for Stanford type B dissection (TBD). The role of both aortic elongation and dilatation in patients with TBD was evaluated. METHODS: The aortic morphology of a healthy control group (n = 236) and patients with TBD (n = 96) was retrospectively examined using three dimensional computed tomography imaging. Curved multiplanar reformats were used to examine aortic diameters at defined landmarks and aortic segment lengths. RESULTS: Diameters at all landmarks were significantly larger in the TBD group. The greatest diameter difference (56%) was measured in dissected descending aortas (p < .001). The segment with the most considerable difference between the study groups with regard to elongation was the non-dissected aortic arch of patients with TBD (36%; p < .001). Elongation in the aortic arch was accompanied by a diameter increase of 21% (p < .001). In receiver-operating curve analysis, the area under the curve was .85 for the diameter and .86 for the length of the aortic arch. CONCLUSIONS: In addition to dilatation, aortic arch elongation is associated with the development of TBD. The diameter and length of the non-dissected aortic arch may be predictive for TBD and may possibly be used for risk assessment in the future. This study provides the basis for further prospective evaluation of these parameters.

Gray matter anomalies in pedophiles with and without a history of child sexual offending.

Pedophilia is a psychiatric disorder that is inter-related with but distinct from child sexual offending (CSO). Neural alterations reportedly contribute to both pedophilia and CSO, but until now, no study has distinguished the brain structural anomalies associated with pedophilia from those specifically associated with CSO in pedophilic men. Using high-resolution T1-weighted brain images and voxel-based morphometry, we analyzed the gray matter (GM) volume of the following 219 men recruited at four acquisition sites in Germany: 58 pedophiles with a history of CSO, 60 pedophiles without any history of CSO and 101 non-pedophilic, non-offending controls to control for the effects of age, education level, verbal IQ, sexual orientation and the acquisition site. Although there were no differences in the relative GM volume of the brain specifically associated with pedophilia, statistical parametric maps revealed a highly significant and CSO-related pattern of above vs below the 'normal' GM volume in the right temporal pole, with non-offending pedophiles exhibiting larger volumes than offending pedophiles. Moreover, regression analysis revealed that the lower GM volume of the dorsomedial prefrontal or anterior cingulate cortex was associated with a higher risk of re-offending in pedophilic child molesters. We believe our data provide the first evidence that CSO in pedophilia rather than pedophilia alone is associated with GM anomalies and thus shed new light on the results of previous studies on this topic. These results indicate the need for new neurobehavioral theories on pedophilia and CSO and may be potentially useful for treatment or prevention approaches that aim to reduce the risk of (re)offending in pedophilia.

[Neurobiological foundations underlying normal and disturbed sexuality]. / Neurobiologische Grundlagen der Sexualität und ihrer Probleme.

BACKGROUND: Sexual functions are regulated by hormonal and neurochemical factors as well as neuronal networks. An understanding of these basic principles is necessary for the diagnostics, counselling and treatment of sexual problems. OBJECTIVE: Description of essential mechanisms of sexual function on a neurochemical and neuronal level. MATERIAL AND METHODS: Literature search, selection and discussion of relevant studies. RESULTS: Analogous to the dual control model there are primary inhibitory (e. g. serotonin) and excitatory neurotransmitter systems (e.g. sex steroids and dopamine). Moreover, neuronal structures have been identified that are responsible for processing sexual stimuli. These networks are altered in subjects with sexual disorders or by pharmacological treatment, e. g. antiandrogens and selective serotonin reuptake inhibitors (SSRI) CONCLUSION: Knowledge of the neurobiology of sexuality forms the foundations for the treatment of sexual dysfunctions in psychiatry and other disciplines.

German Registry for Acute Aortic Dissection Type A: Structure, Results, and Future Perspectives.

The German Registry for Acute Aortic Dissection Type A (GERAADA) as an international registry for acute aortic dissection type A (AADA) offers a unique opportunity to answer questions regarding acute dissections that cannot be answered by single institution's database alone. GERAADA was started in 2006 by the German Society for Thoracic and Cardiovascular Surgery (GSTCVS) and has collected more than 3,300 AADA patients' data from 56 centers in Germany, Austria, and Switzerland up to now. In the second generated validated dataset comprising the years from 2006 to 2010, 2,137 patients were surgically treated for AADA with an overall 30-day mortality of 16.9%, and a new postoperative neurologic dysfunction of 9.5%. Risk factors for neurologic dysfunction were malperfusion syndromes, dissections of the supra-aortic vessels, and longer operating time. Neuroprotective drugs had no influence on stroke rates. Hypothermic circulatory arrest and antegrade selective cerebral perfusion (ACP) led to similar results if arrest times were less than 30 minutes while ACP for longer arrest periods is advisable. Septuagenarians had an early mortality rate (15.8%) similar to the whole cohort's, but the mortality rate in octogenarians (34.9%) was much higher. GERAADA with its validated 2,137 patient files (2006-2010) is the largest database on AADA worldwide and continues to collect data. Structured follow-up of more than 5 years will be available in the future.

Pericardial adipose tissue and the metabolic syndrome is increased in patients with chronic major depressive disorder compared to acute depression and controls.

OBJECTIVE: Major depressive disorder (MDD) is associated with an estimated fourfold risk for premature death, largely attributed to cardiovascular disorders. Pericardial adipose tissue (PAT), a fat compartment surrounding the heart, has been implicated in the development of coronary artery disease. An unanswered question is whether people with chronic MDD are more likely to have elevated PAT volumes versus acute MDD and controls (CTRL). METHODS: The study group consists of sixteen patients with chronic MDD, thirty-four patients with acute MDD, and twenty-five CTRL. PAT and adrenal gland volume were measured by magnetic resonance tomography. Additional measures comprised factors of the metabolic syndrome, cortisol, relative insulin resistance, and pro-inflammatory cytokines (interleukin-6; IL-6 and tumor necrosis factor-α, TNF-α). RESULTS: PAT volumes were significantly increased in patients with chronic MDD>patients with acute MDD>CTRL. Adrenal gland volume was slightly enlarged in patients with chronic MDD>acute MDD>CTRL, although this difference failed to reach significance. The PAT volume was correlated with adrenal gland volume, and cortisol concentrations were correlated with depression severity, measured by BDI-2 and MADRS. Group differences were found concerning the rate of the metabolic syndrome, being most frequent in chronic MDD>acute MDD>CTRL. Further findings comprised increased fasting cortisol, increased TNF-α concentration, and decreased physical activity level in MDD compared to CTRL. CONCLUSION: Our results extend the existing literature in demonstrating that patients with chronic MDD have the highest risk for developing cardiovascular disorders, indicated by the highest PAT volume and prevalence of metabolic syndrome. The correlation of PAT with adrenal gland volume underscores the role of the hypothalamus-pituitary-adrenal system as mediator for body-composition changes. Metabolic monitoring, health advices and motivation for the improvement of physical fitness may be recommended in depressed patients, in particular in chronic depression.

A trial model for medical subspecialty training in South Africa.

This article outlines the trial model in reproductive medicine that was created as a first step in the development of a business model for medical subspecialty training to complement the current academic subspecialty training in South Africa. A two-tiered training model was developed over time. The hurdles that had to be overcome were the development of a curriculum and academic capacity, acquisition of appropriate funding, acceptance and accreditation of the decentralised training facility, and lastly, registration of the fellowship with the Health Professions Council of South Africa. The end result of the trial programme was a two-year full-time training with supportive funding, or a four-year programme, where the subspecialists would spend three weeks of the month in their home practice environment, attached to an accredited unit, and the last week in an academic institution. Due to the trial program's success for the South African context and the potential of such model for the developing world, it was evident that the trial programme had to be tested to determine whether and how it can be implemented on a wider basis.

Proteomic biomarkers for psoriasis and psoriasis arthritis.

UNLABELLED: Although several new biomarkers have been recently proposed for psoriasis (Ps) and psoriasis arthritis (PsA), nothing is known about their diagnostic sensitivity and specificity, and their routine use. We therefore searched in-depth for new biomarker candidates using a biobank with EDTA-plasma from 158 individuals, patients and healthy controls. Samples from 6 selected pairs (patients against healthy controls) were searched proteomically using a workflow of extensive and precise design that is highly comprehensive. Subsequent verification was performed using ELISA and the entire biobank. By proteomic methods, 208 altered proteins were identified. Of these, 15 biomarker candidates were selected for verification. Of these 15, 4 individual parameters and 11 combinations significantly discriminated between patient and control groups. These individual parameters were Zn-α2-glycoprotein, complement C3, polymeric immunoglobulin receptor, and plasma kallikrein. Significant discrimination was obtained by combinations of 2 or 3 parameters. One combination seemed suitable for diagnosing PsA. Moreover, several candidates desmoplakin, complement C3, polymeric immunoglobulin receptor, and cytokeratin 17, correlated with PASI in all patients. This first comprehensive proteomic study on non-depleted plasma identified several biomarker candidates that have not been described before as well as some known from previous studies. BIOLOGICAL SIGNIFICANCE: Our non-gel proteomic analysis is based on the highly comprehensive and significantly optimized chromatographic protein pre-fractionation. The method allows a biomarker search in non-depleted plasma. The subsequent verification by ELISA identifies several biomarker-candidates for the unbiased diagnosis of psoriasis and psoriasis arthritis. Four of the identified candidate markers might be used individually. Combinations of several parameters improve the diagnostic sensitivity and specificity. The still not validated candidates form a reserve for further evaluation. Moreover, mass spectrometric data uncover several biomarker-candidates which show diverse protein species of the same protein with opposing changes in the same sample.