Neural correlates of subjective arousal and valence in health and panic disorder.

Aberrant emotion processing is a core characteristic of panic disorder (PD). Findings concerning the underlying neural pathways remain inconsistent. We applied functional magnetic resonance imaging (fMRI) in the context of a task based on the circumplex model of affect. This model links affective states to two underlying neurophysiological systems: arousal and valence. Twenty-two healthy participants and 20 participants with PD rated arousal and valence in response to affective faces during fMRI. In healthy controls, we found that arousal modulated the hemodynamic response in the parahippocampus, the ventromedial prefrontal cortex and the cuneus during face perception. Valence and extreme ratings of valence modulated the hemodynamic response in temporal, parietal, somatosensory, premotor and cerebellar regions. Comparing healthy controls to participants with PD, we found that healthy controls showed a stronger modulation of the hemodynamic response during face perception associated with extreme ratings of valence in the parahippocampus and the supplementary motor area. This suggests parahippocampal dysfunction in the processing of highly valenced affective faces in PD, which may underlie aberrant contextualization of strong affective stimuli. Our findings need to be interpreted with care as they were adjusted for multiple comparisons using a liberal correction procedure.

Extraction of Aortic Knuckle Contour in Chest Radiographs Using Deep Learning.

In this paper, we aim to extract the aortic knuckle (AK) contour in chest radiographs, an anatomical structure rarely being addressed in the literature. Since the AK structure is small and thin, simply adopting the deep network methods that are successful for large organ segmentation is inadequate for achieving good pixel-level accuracy and resolving local ambiguities. To address this challenge, we propose a new coarse-to-fine segmentation approach which focuses on global and local information contexts, respectively. Two convolutional networks are used. For the coarse segmentation, we use FasterRCNN; for the fine segmentation, we use U-Net. Our evaluation uses the publicly available JSRT dataset; the results are promising. Besides presenting these results, we analyze issues such as the imprecision of manual contour marking, and automatic generation of the coarse segmentation ground-truth mask used for deep network training. Our approach is general and can be applied to extract other curve-like objects-of-interest.

Diffusion of macromolecules in a polymer hydrogel: from microscopic to macroscopic scales.

To gain insight into the fundamental processes determining the motion of macromolecules in polymeric matrices, the dynamical hindrance of polymeric dextran molecules diffusing as probe through a polyacrylamide hydrogel is systematically explored. Three complementary experimental methods combined with Brownian dynamics simulations are used to study a broad range of dextran molecular weights and salt concentrations. While multi-parameter fluorescence image spectroscopy (MFIS) is applied to investigate the local diffusion of single molecules on a microscopic length scale inside the hydrogel, a macroscopic transmission imaging (MTI) fluorescence technique and nuclear magnetic resonance (NMR) are used to study the collective motion of dextrans on the macroscopic scale. These fundamentally different experimental methods, probing different length scales of the system, yield long-time diffusion coefficients for the dextran molecules which agree quantitatively. The measured diffusion coefficients decay markedly with increasing molecular weight of the dextran and fall onto a master curve. The observed trends of the hindrance factors are consistent with Brownian dynamics simulations. The simulations also allow us to estimate the mean pore size for the herein investigated experimental conditions. In addition to the diffusing molecules, MFIS detects temporarily trapped molecules inside the matrix with diffusion times above 10 ms, which is also confirmed by anisotropy analysis. The fraction of bound molecules depends on the ionic strength of the solution and the charge of the dye. Using fluorescence intensity analysis, also MTI confirms the observation of the interaction of dextrans with the hydrogel. Moreover, pixelwise analysis permits to show significant heterogeneity of the gel on the microscopic scale.

[Are members of fibromyalgia syndrome self-help groups "different"? Demographic and clinical characteristics of members and non-members of fibromyalgia syndrome self-help groups]. / Sind Mitglieder von Fibromyalgiesyndrom-Selbsthilfegruppen "anders"? Demografische und klinische Charakteristika von Mitgliedern und Nicht-Mitgliedern von Fibromyalgiesyndrom-Selbsthilfegruppen.

BACKGROUND: No data were available on demographic and clinical characteristics of members of fibromyalgia syndrome (FMS) self-help groups in Germany. MATERIAL AND METHODS: The study was carried out from November 2010 to April 2011. A set of questionnaires was distributed by the German League Against Rheumatism and the German Fibromyalgia Association to members and to all consecutive FMS patients at nine clinical centres of different levels of care. The set included a self-developed questionnaire on demographic and medical data and on previously and currently used therapies, the patient health questionnaire (PHQ 4) and the fibromyalgia survey questionnaire. RESULTS: Members of FMS self-help groups (N = 1,014) were older and reported a longer duration of chronic widespread pain, less anxiety and depression and a more frequent current use of aerobic exercise, relaxation training and complementary alternative medication than participants not affiliated with FMS self-help groups (N = 630). CONCLUSIONS: Membership in FMS self-help groups was associated with less psychological distress and a more frequent use of active self-management strategies.

[Intersectoral pain treatment. The Algesiologikum group]. / Sektorübergreifende schmerzmedizinische Versorgung. Der Algesiologikum-Verbund.

Cross-sectoral clinical pathways for chronic pain patients in standard and routine care are a major challenge for the German healthcare system. The Algesiologikum group has developed such clinical pathways including an essential infrastructure. Cooperation partners of the Algesiologikum group are two outpatient medical care units, one neurosurgery practice and four hospitals. In the outpatient sector as well as in the inpatient sector the Algesiologikum group provides a multidisciplinary team caring for chronic pain patients. The range of treatment in the hospitals includes multimodal, invasive and surgical pain therapy. The present report illustrates possibilities and frontiers of the Algesiologikum concept based on all patients treated since 2009.

[German fibromyalgia consumer reports. Benefits and harms of fibromyalgia syndrome therapies]. / Der deutsche Fibromyalgieverbraucherbericht. Nutzen und Schaden von Behandlungen des Fibromyalgiesyndroms.

BACKGROUND: Consumer reports provide information on benefits and harms in routine clinical care. We report the first fibromyalgia syndrome (FMS) consumer reports in Europe. MATERIAL AND METHODS: The study was carried out from November 2010 to April 2011. The benefits and harms of pharmacological and non-pharmacological therapies experienced by the patient were assessed in an 11-point Likert scale (0=no, 10=very high benefit or harm) by a questionnaire. The questionnaire was distributed by the German League against Rheumatism and the German Fibromyalgia Association to their members and to all consecutive FMS patients of nine clinical centers of different levels of care. RESULTS: A total of 1,661 questionnaires (95% women, mean age 54 years) were analyzed. Self-management strategies (distraction, resting, aerobic exercise), physical therapies (warm and pool therapies), psychological therapies (education, psychotherapy), and inpatient multicomponent therapies were judged to be more efficacious and less harmful than all types of pharmacological therapies. CONCLUSION: The German fibromyalgia consumer reports highlight the importance of non-pharmcological therapies in the long-term management of FMS.

[German pain questionnaire and standardised documentation with the KEDOQ-Schmerz. A way for quality management in pain therapy]. / Deutscher Schmerzfragebogen (DSF) und standardisierte Dokumentation mit KEDOQ-Schmerz. Auf dem Weg zur gemeinsamen Qualitätsentwicklung der Schmerztherapie.

KEDOQ-Schmerz was developed by the German Pain Society (formerly DGSS) as a basic tool for documentation and quality management of pain therapy. It is planned to use KEDOQ-Schmerz as the data basis for nationwide, cross-sectional and independent scientific research in health services in Germany. With comparatively little effort, each participating institution (practices, pain clinics) will be able to provide quality control of their own diagnostic procedures and therapeutic effects by using benchmarking. In future KEDOQ-Schmerz will also be used as a method for external quality management in pain therapy in Germany.

Healthcare utilization of back pain patients: results of a claims data analysis.

OBJECTIVES: The high life-time prevalence of chronic back pain (25-30% according to surveys in small samples) suggests that it may be a major source of healthcare cost and that prevention of chronic back pain may be both ethically and economically recommendable. To obtain valid economic data on the cost of back pain in Germany, a retrospective claims data analysis was performed. METHODS: Using data from 2006 of 5.2 million beneficiaries of a German statutory health insurance fund (DAK Unternehmen Leben) covering ~7% of the German population, mean value analyses report on key healthcare utilization figures from a sickness funds? perspective. In contrast to other studies, cost data are primary data and not extrapolated, but clinical characteristics include surrogate markers as no clinical case descriptions were available. RESULTS: Based on previously investigated diagnosis patterns three types of back pain could be identified: (other) specific back pain (n=211,216), pain due to spinal disk disease (n=195,712), and non-specific back pain (n=534,272). Of all back pain patients, 25.8% were identified as at risk to develop chronic pain, where only 2.6% were detected as patients with chronic back pain. Mean resource utilization and related healthcare costs were significantly higher for beneficiaries with indicators for chronic back pain than for beneficiaries with only risk factors for developing chronic back pain. This especially holds for outpatient analgesic prescriptions (p<0.05), for in-hospital multimodal pain therapy (p<0.05), for in-hospital care in general (p<0.05), as well as for direct cost of care (p<0.05). CONCLUSION: The results show the potential that could be made accessible by an early detection of back pain patients who bear a risk of pain becoming chronic, both in terms of quality-of-life as well as in financial terms.

[Epidural spinal cord stimulation for therapy of chronic pain. Summary of the S3 guidelines]. / Epidurale Rückenmarkstimulation zur Therapie chronischer Schmerzen. Zusammenfassung der S3-Leitlinie.

Epidural spinal cord stimulation (SCS) is a reversible but invasive procedure which should be used for neuropathic pain, e.g. complex regional pain syndrome I (CRPS) and for mostly chronic radiculopathy in connection with failed back surgery syndrome following unsuccessful conservative therapy. Epidural SCS can also successfully be used after exclusion of curative procedures and conservative therapy attempts for vascular-linked pain, such as in peripheral arterial occlusive disease stages II and III according to Fontaine and refractory angina pectoris. Clinical practice has shown which clinical symptoms cannot be successfully treated by epidural SCS, e.g. pain in complete paraplegia syndrome or atrophy/injury of the sensory pathways of the spinal cord or cancer pain. A decisive factor is a critical patient selection as well as the diagnosis. Epidural SCS should always be used within an interdisciplinary multimodal therapy concept. Implementation should only be carried out in experienced therapy centers which are in a position to deal with potential complications.

Waddlia, Parachlamydia and Chlamydiaceae in bovine abortion.

The etiology remains unknown in many cases of bovine abortion in Switzerland. Bacteria of the Chlamydiales order are known abortive agents, therefore cases of bovine abortion from three representative regions of Switzerland were investigated in this study. Particularly Chlamydiaceae as well as the Chlamydia-like organisms Waddlia and Parachlamydia were of interest, especially because of their possible zoonotic potential. Placenta samples (n=343) were tested for these bacteria by different PCR-methods, immunohistochemistry and serology for Chlamydia abortus. Additionally an attempt for the isolation of Waddlia and Parachlamydia was made by co-cultivation in amoebae. In 67.3% of the 343 cases a necrotizing and/or purulent placentitis was found histologically. By real-time PCR, 0.9% (3/343) of the cases were positive for Waddlia, 13.4% (46/343) positive for Parachlamydia and 14.6% (50/343) positive or questionable positive for Chlamydiaceae. Of these samples, confirmation by immunohistochemistry was possible in 2/3 cases for Waddlia, 25/46 for Parachlamydia and 4/50 for Chlamydiaceae. Of the 50 cases positive or questionable positive for Chlamydiaceae, species-identification by ArrayTube Microarray or 16S rRNA PCR resulted in 41 cases positive for C. abortus whereas the presence of Chlamydia suis was confirmed in four and Chlamydia pecorum in one case. This study brought evidence for the importance of different members of Chlamydiales in different regions of Switzerland although Waddlia is not occurring in a high prevalence. On the other hand mixed infections with different Chlamydiales as well as with other abortigenic agents could be found.

[Identification and grouping of pain patients according to claims data]. / Identifikation und Gruppierung von Schmerzpatienten anhand von Routinedaten einer Krankenkasse.

The ICD classification does not provide the opportunity to adequately identify pain patients. Therefore we developed an alternative method for the identification and classification of pain patients which is based on prescription and diagnoses data from the year 2006 of one nationwide sickness fund (DAK) and which is led by two main assumptions: 1. Beneficiaries without prescription of an analgetic drug but with a diagnosis pattern that is characteristic of patients who are treated with opioids are also likely to be pain patients. 2. Each combination of diagnosis groups can be traced back to one primary diagnosis out of a diagnosis group according to the patient classification system CCS (Clinical Classifications Software). The selection of this diagnosis group (CCS) allows for the allocation of the beneficiary to only one pain type. As a result we identified 65 combinations of CCS diagnosis groups--aggregated to nine "CCS pain types"--to which 77.1% of all patients with at least two opioid prescriptions can be allocated: 26.3% to pain due to arthrosis, 18.0% to pain due to intervertebral disc illnesses, 13.1% to other specific back pain, 6.7% to neuropathic pain, 4.5% to unspecific back pain, 4.2% to headache, 2.4% to pain after traumatic fractures, 1.3% to pain of multimorbid, high-maintenance patients, and 0.6% to cancer pain. Based on our method beneficiaries who have a high probability of suffering from moderate to strong pain can be identified and included in further claims data analyses of health care delivery and utilization pattern of pain-related disorders in Germany.

The ABRF Edman Sequencing Research Group 2008 Study: investigation into homopolymeric amino acid N-terminal sequence tags and their effects on automated Edman degradation.

The Edman Sequence Research Group (ESRG) of the Association of Biomolecular Resource designs and executes interlaboratory studies investigating the use of automated Edman degradation for protein and peptide analysis. In 2008, the ESRG enlisted the help of core sequencing facilities to investigate the effects of a repeating amino acid tag at the N-terminus of a protein. Commonly, to facilitate protein purification, an affinity tag containing a polyhistidine sequence is conjugated to the N-terminus of the protein. After expression, polyhistidine-tagged protein is readily purified via chelation with an immobilized metal affinity resin. The addition of the polyhistidine tag presents unique challenges for the determination of protein identity using Edman degradation chemistry. Participating laboratories were asked to sequence one protein engineered in three configurations: with an N-terminal polyhistidine tag; with an N-terminal polyalanine tag; or with no tag. Study participants were asked to return a data file containing the uncorrected amino acid picomole yields for the first 17 cycles. Initial and repetitive yield (R.Y.) information and the amount of lag were evaluated. Information about instrumentation and sample treatment was also collected as part of the study. For this study, the majority of participating laboratories successfully called the amino acid sequence for 17 cycles for all three test proteins. In general, laboratories found it more difficult to call the sequence containing the polyhistidine tag. Lag was observed earlier and more consistently with the polyhistidine-tagged protein than the polyalanine-tagged protein. Histidine yields were significantly less than the alanine yields in the tag portion of each analysis. The polyhistidine and polyalanine protein-R.Y. calculations were found to be equivalent. These calculations showed that the nontagged portion from each protein was equivalent. The terminal histidines from the tagged portion of the protein were demonstrated to be responsible for the high lag during N-terminal sequence analysis.

Nasal osteoma in a dairy cow: a combined clinical, imaging and histopathological approach to diagnosis.

An 8-year-old Brown Swiss dairy cow was presented with unilateral epistaxis and mild inspiratory stridor. At that time endoscopic examination revealed a smooth-surfaced mass within the left nasal cavity. Biopsy samples were collected and a diagnosis of fibrosarcoma was made. Eighteen months later the animal developed severe respiratory distress that led to difficulties in feeding and consequently to emaciation and a dramatic drop in milk production. The cow was humanely destroyed and submitted for post-mortem examination. The head was subject to further investigation by radiography, computed tomography and magnetic resonance imaging. These techniques revealed a non-infiltrative, well-circumscribed mass of both radiodense and heterogeneously intense structures. Histopathological examination revealed a mass consisting of well-differentiated and interlacing bone trabeculae lined by osteoblasts and multinucleated osteoclasts. In contrast to the initial diagnosis, the later diagnostic approaches supported the diagnosis of osteoma.

An unusual cause of traumatic reticulitis/reticuloperitonitis in a herd of Swiss dairy cows nearby an airport.

This report describes the findings in five cows from one dairy herd, in which all 31 cows were slaughtered or euthanised because of traumatic reticuloperitonitis. All the cows had numerous thin sharp pieces of metal attached to a magnet in the reticulum, giving the magnet a hedgehog-like appearance. Investigation revealed that the cattle had eaten forage harvested from a field immediately adjacent to an airport. The snow was cleared from the airport runways with a machine that had a wire-bristle brush attachment. Mechanical wear resulted in numerous wire bristles breaking and these were blown with the snow onto the field in question. The wire then became accidentally incorporated into the hay and grass silage at harvest the next summer and was ingested by the cattle in the fall and winter. To prevent further cases, approximately 200 tonnes of hay and grass silage contaminated with wire were discarded and 30 hectares of the 50-hectare field were cultivated and re-sown. The wire-bristles of the snow plow were replaced with plastic bristles. The cost of this and the livestock loss was several hundred thousand Swiss Francs.

The neural networks underlying auditory sensory gating.

One of the most consistent electrophysiological deficits reported in the schizophrenia literature is the failure to inhibit, or properly gate, the neuronal response to the second stimulus of an identical pair (i.e., sensory gating). Although animal and invasive human studies have consistently implicated the auditory cortex, prefrontal cortex and hippocampus in mediating the sensory gating response, localized activation in these structures has not always been reported during non-invasive imaging modalities. In the current experiment, event-related FMRI and a variant of the traditional gating paradigm were utilized to examine how the gating network differentially responded to the processing of pairs of identical and non-identical tones. Two single-tone conditions were also presented so that they could be used to estimate the HRF for paired stimuli, reconstructed based on actual hemodynamic responses, to serve as a control non-gating condition. Results supported an emerging theory that the gating response for both paired-tone conditions was primarily mediated by auditory and prefrontal cortex, with potential contributions from the thalamus. Results also indicated that the left auditory cortex may play a preferential role in determining the stimuli that should be inhibited (gated) or receive further processing due to novelty of information. In contrast, there was no evidence of hippocampal involvement, suggesting that future work is needed to determine what role it may play in the gating response.

Intravenous lipid infusion in the successful resuscitation of local anesthetic-induced cardiovascular collapse after supraclavicular brachial plexus block.

We describe a case of successful resuscitation with an i.v. lipid infusion of local anesthetic-induced cardiovascular toxicity after supraclavicular brachial plexus block with mepivacaine and bupivacaine. Lipid therapy was initiated after 10 min of unsuccessful resuscitation and resulted in restoration of cardiovascular activity and hemodynamic stability. This case illustrates the utility of i.v. lipid therapy in the treatment of local anesthetic toxicity.

[Structure of outpatient pain therapy in Germany. Results of a survey]. / Struktur der ambulanten Schmerztherapie in Deutschland. Ergebnisse einer Umfrage.

Every physician should be able to treat pain regardless of the specialty, but patients with a risk of chronification or chronic pain should receive care from specialized physicians and non-medical professionals. Specialized pain treatment is an additional qualification in Germany, which may be achieved in different specialties by defined structure criteria and experience. The German Society for the Study of Pain and the Professional Association of the German Society of Anesthetists conducted a survey on specialized outpatient pain treatment settings in Germany, encompassing personal and technical equipment, procedures and interdisciplinary multi-professional cooperation. The survey showed a clear increase in the number of pain treatment settings compared to previous surveys, but with a huge span from small single practice or outpatient services at hospitals to large specialized hospitals. However, the quality criteria suggested by the pain treatment societies were not always met. Treatment options for patients with a risk of chronification and chronic pain show regional variations and are insufficiently developed.