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A 71 year old female Caucasian farmer without any known immunosuppression presented with a painful ulcer of her right lower leg after a trauma caused by a wood billet. There was no response to empirical antibacterial treatment. An ulcer biopsy showed an invasive Candida infection of the soft tissue and leucocytoclastic vasculitis. Voriconazole treatment was followed by wound healing. Invasive Candida infection and localized Candida vasculitis represent a rare cause of persisting leg ulcers. The similar clinical picture of chronic venous leg ulcers might blur the true cause and refractory cases should therefore promptly be processed by histopathological diagnostics.

Meromictic lakes are permanently stratified lakes that display steep gradients in salinity, oxygen and sulphur compounds tightly linked to bacterial community structure and diversity. Lake Sælenvannet is a meromictic lake located south of Bergen, Norway. The 26 m deep lake is connected to the open sea and permanently stratified into two layers separated by a chemocline. The upper water layer is brackish with major input from water runoff from the surroundings. The bottom layer consists of old saline water with low or no oxygen concentrations. Bacteria from phylum Planctomycetes are reported to be ubiquitous in lake environments. They are involved in the degradation of complex carbon sources in aquatic environments and are also linked to anaerobic processes such as fermentation and sulphur reduction. To study Planctomycete distribution along a chemical gradient, we sampled the water column throughout Lake Sælenvannet in 2012 and profiled the microbial community using 16S rRNA amplicon sequencing (metabarcoding) with 454 pyrosequencing. Planctomycetes related 16S rRNA gene sequences were found to be present both in the oxic and anoxic parts of the lake and showed an uneven distribution throughout the water column, with the highest relative abundance of 10% found in the saline anoxic layer at 15 m depth. In a follow-up study in 2014, samples from eight different depths were collected for enrichment and isolation of novel Planctomycetes. This study resulted in successful isolation in pure culture of 10 isolates affiliated to four different genera from the family Planctomycetaceae. One strain closely related to Blastopirellula cremea was isolated from 9 m depth, and two novel strains affiliated to the genera Stieleria and Gimesia were isolated at 7 and 9 m depths, respectively. Furthermore, seven isolates with identical 16S rRNA gene sequences were retrieved from seven different depths which varied greatly in salinity and chemical composition. These isolates likely represent a new species affiliated to Rubinisphaera. The adaptation of this novel Planctomycete to water depths spanning the entire chemical gradient could indicate a high phenotypic plasticity and/or a very efficient survival strategy. Overall, our results show the presence of a diverse group of Planctomycetes in Lake Sælenvannet, with a strong potential for novel adaptations to chemical stress factors.

The creepage behavior of one thermosetting carbon fiber sheet molding compound (SMC) material was studied applying in-plane loading at 120 °C. Loads were applied in bending, tension and compression test setups at the same in-plane stress level of 47 MPa. Different creep strain rates were determined. The creep strain rate in flexural loading was significantly higher than in tensile loading. The test specimens in compression loading collapsed within minutes and no findings regarding the creep strain rates were possible. Overall, it was observed that the thermosetting press resin of this industrially used material had only little creep load bearing capacity at the mentioned temperature when loaded in mixed stress states. The test data has high usage for estimating design limits of structural loaded SMC components at elevated temperature.

Pain, particularly chronic pain, is still an unsolved medical condition. Central goals in pain control are to provide analgesia of adequate efficacy and to reduce complications associated with the currently available drugs. Opioids are the mainstay for the treatment of moderate to severe pain. However, opioid pain medications also cause detrimental side effects, thus highlighting the need of innovative and safer analgesics. Opioids mediate their actions via the activation of opioid receptors, with the mu-opioid receptor as the primary target for analgesia, but also for side effects. One long-standing focus of drug discovery is the pursuit for new opioids exhibiting a favorable dissociation between analgesia and adverse effects. In this study, we describe the in vitro and in vivo pharmacological profiles of the 14-O-phenylpropyl substituted analog of the mu-opioid agonist 14-O-methyloxymorphone (14-OMO). The consequence of the substitution of the 14-O-methyl in 14-OMO with a 14-O-phenylpropyl group on in vitro binding and functional activity, and in vivo behavioral properties (nociception and gastrointestinal motility) was investigated. In binding studies, 14-O-phenylpropyloxymorphone (POMO) displayed very high affinity at mu-, delta-, and kappa-opioid receptors (Ki values in nM, mu:delta:kappa = 0.073:0.13:0.30) in rodent brain membranes, with complete loss of mu-receptor selectivity compared to 14-OMO. In guinea-pig ileum and mouse vas deferens bioassays, POMO was a highly efficacious and full agonist, being more potent than 14-OMO. In the [35S]GTPγS binding assays with membranes from CHO cells expressing human opioid receptors, POMO was a potent mu/delta-receptor full agonist and a kappa-receptor partial agonist. In vivo, POMO was highly effective in acute thermal nociception (hot-plate test, AD50 = 0.7 nmol/kg) in mice after subcutaneous administration, with over 70- and 9000-fold increased potency than 14-OMO and morphine, respectively. POMO-induced antinociception is mediated through the activation of the mu-opioid receptor, and it does not involve delta- and kappa-opioid receptors. In the charcoal test, POMO produced fourfold less inhibition of the gastrointestinal transit than 14-OMO and morphine. In summary, POMO emerges as a new potent mixed mu/delta/kappa-opioid receptor agonist with reduced liability to cause constipation at antinociceptive doses.

Objective: Somatic symptoms are one of the most prevalent complaints in both psychiatric and general population, and validated scales are required to assess these problems. The present study was conducted to determine psychometric properties of the Persian version of Screening for Somatic Symptom Disorders-7(SOMS-7) in an Iranian population. Method: This was a multi centric comprehensive study conducted in Psychosomatic Research Center of Isfahan University of Medical Sciences in collaboration with Department of Clinical Psychology of Philipp University of Marburg, Germany. This part of the study includes 100 patients with anxiety/mood disorders and 291 healthy individuals. All participants completed the Patient Health Questionnaire (PHQ-15) and Screening for Somatic symptom disorders 7(SOMS-7). Data were analyzed by Pearson and Spearman correlation coefficient, factor analysis, independent t test, and discriminant analysis using SPSS-20 software. Results: Reliability coefficient based on Cronbach’s alpha was 0.92 and 0.94 (clinical vs. healthy sample). Validity index of the SOMS according to correlation between factor 1 and 2 with PHQ somatic subscale was. 51 and. 59, respectively. Score of 15.5 as cut-off point was accompanied with sensitivity of 77% and specificity of 66%. Factor analysis extracted 2 factors in patients and 4 factors in healthy population. Conclusion: Findings of this study indicated that the Persian version of SOMS-7 has appropriate reliability and validity for the assessment of somatic symptoms disorder and evaluation of treatment effects in these patients.

The application of chopped-fiber reinforced polymers in screwed connections at high temperatures raises the question of creep under long-term loading. While up to now thermoplastic materials have mainly been the focus of attention when it comes to creep, this paper shows that thermoset carbon-fiber SMCs (sheet mold compounds) can also be affected by this phenomenon. Screwed connections were investigated regarding their loss of preload force at 120 °C ambient temperature. Additionally, strain−time diagrams were recorded at different stress levels at 120 °C in a creep test setup of a universal testing machine by using optical strain tracking of SMC coupons. The transverse modulus under compression in thickness direction was determined in the same test setup. For data application within a FEA (finite element analysis) software power law curves according to Norton−Bailey creep law were fitted in the strain−time graphs. The applicability of the obtained creep law was crosschecked with a test carried out on the loss of preload force of a screwed connection. The developed simulative methodology offers the possibility to simulate various mounting situations of the bolted connection and to investigate measures against the loss of preload force easily. A promising possibility to limit the loss of preload force due to creep was simulatively evaluated.

PURPOSE:Myocardial computed tomography perfusion (CTP) allows the assessment of the functional relevance of coronary artery stenosis. This study investigates to what extent the contour sharpness of sequences acquired by dynamic myocardial CTP is influenced by the following noise reduction methods: temporal averaging and adaptive iterative dose reduction 3D (AIDR 3D). MATERIALS AND METHODS:Dynamic myocardial CT perfusion was conducted in 29 patients at a dose level of 9.5±2.0 mSv and was reconstructed with both filtered back projection (FBP) and strong levels of AIDR 3D. Temporal averaging to reduce noise was performed as a post-processing step by combining two, three, four, six and eight original consecutive 3D datasets. We evaluated the contour sharpness at four distinct edges of the left-ventricular myocardium based on two different approaches: the distance between 25% and 75% of the maximal grey value (d) and the slope in the contour (m). RESULTS:Iterative reconstruction reduced contour sharpness: both measures of contour sharpness performed better for FBP than for AIDR 3D (d = 1.7±0.4 mm versus 2.0±0.5 mm, p>0.059 at all edges; m = 255.9±123.9 HU/mm versus 160.6±123.5 HU/mm; p0.052 at all edges and for m p

Depression has been associated with peripheral inflammatory processes and alterations in cellular immunity. Growing evidence suggests that immunological alterations may neither be necessary nor sufficient to induce depression in general, but seem to be associated with specific features. Using baseline data from the Outcome of Psychological Interventions in Depression trial, this exploratory study examines associations between depression subtypes and pathogenetic characteristics (i.e., melancholic vs non-melancholic depression, chronic vs non-chronic depression, age of onset, cognitive-affective and somatic symptom dimensions) with plasma levels of C-reactive protein (CRP), interleukin (IL)-6, IL-10, and numbers of leukocyte subpopulations in 98 patients with major depression (MD) and 30 age and sex-matched controls. Patients with MD exhibited higher CRP levels, higher neutrophil and monocyte counts, lower IL-10 levels, and an increased neutrophil to lymphocyte ratio (NLR) than controls. Patient with later age of onset had higher levels of two inflammatory markers (CRP, NLR) and lower cytotoxic T cell counts after adjusting for sociodemographics, lifestyle factors, and antidepressants. Furthermore, lower anti-inflammatory IL-10 levels were related to more severe somatic depressive symptoms. These results confirm and extend previous findings suggesting that increased levels of CRP are associated with a later onset of depression and demonstrate that also NLR as a subclinical inflammatory marker is related to a later onset of depression.

Karoline Pieritz, Winfried Rief, Frank EuteneuerDivision of Clinical Psychology and Psychotherapy, Philipps University Marburg, Marburg, GermanyAbstract: Childhood adversity has frequently been related to a wide range of psychosomatic complaints in adulthood. The present study examined the relationship between different forms of childhood adversity and laboratory measures of pain. Heat pain tolerance and perceived heat pain intensity were measured in a community-based sample of 62 women (aged 20–64 years). Participants completed the Childhood Trauma Questionnaire (CTQ), which assesses five forms of childhood adversity: physical abuse, sexual abuse, emotional abuse, physical neglect, and emotional neglect. Somatic symptoms, depressive symptoms, and pain catastrophizing were assessed as potential mediators. Bivariate analyses indicated that emotional abuse but no other forms of childhood adversity were significantly related to decreased heat pain tolerance (r=-0.27; P0.1). No significant associations were found between any forms of childhood adversity and heat pain intensity. Our findings indicate that the severity of emotional childhood abuse is associated with decreased pain tolerance, an affective component of pain, but not with heat pain intensity, which has been described as a sensory component of pain.Keywords: childhood adversity, emotional abuse, pain tolerance, pain intensity, somatic symptoms

"Phronesis," or practical wisdom developed through experience, is an Aristotelian concept that can shed light on the capacities of patients to make health-related decisions and engage in healthy behaviors. In this article, the authors develop a conceptual framework for understanding the role of "phronesis" in lifestyle change as well as its relationship to patient activation, which is considered to be a critical component of the Chronic Care Model and patient education in general. The authors develop the concept of "phronesis" by analyzing qualitatively the comments made by 35 participants working to manage chronic health issues in a weight-loss study. The authors iteratively coded transcribed passages of exit interviews for "phronesis" and patient activation. These passages provide experientially grounded content for evaluating the use of "phronesis" and its development among individuals engaging in lifestyle change. "Phronesis" is expressed in 31% of participant responses to questions regarding the relationship between the online lifestyle intervention, participant health, and participant readiness to engage in productive clinical encounters with health care practitioners. Of those responses, 73% express some level of patient activation. The authors conclude that "phronesis" may be an important new tool for understanding successful self-management support, with potential usefulness in the creation of tailored lifestyle interventions, the development of patient activation, and the ability of participants to enact health-related behaviors. (Contains 3 tables.)

Despite controversy regarding the classification and diagnostic status of hoarding disorder, there remains a paucity of research on the nosology of hoarding that is likely to inform the classification debate. The present investigation examined the latent structure of hoarding in three, large independent samples. Data for three well-validated measures of hoarding were subjected to taxometric procedures, including MAXimum EIGenvalue, Mean Above Minus Below A Cut, and Latent-Mode factor. Two symptom measures, one of which closely mirrors the proposed diagnostic criteria for hoarding disorder, and a measure of hoarding beliefs were analyzed. Sample 1 (n = 2,501) was representative of the general German population, while Samples 2 (n = 1,149) and 3 (n = 500) consisted of unselected undergraduate students. Findings across all three samples and taxometric procedures provided converging evidence that hoarding is best conceptualized as a dimensional construct, present in varying degrees in all individuals. Results have implications across research and treatment domains, particularly with respect to assessment approaches, treatment response determination, and policy decisions. These findings underscore the need for further investigations on the nosology of hoarding, to help validate this construct as we move forward with respect to our research and treatment efforts, as well as the potential inclusion of hoarding disorder in the "Diagnostic and Statistical Manual of Mental Disorders" (5th ed.; "DSM-5"; American Psychiatric Association, 2012). (Contains 2 tables and 3 figures.)

Modifying patients’ expectations by exposing them to expectation violation situations (thus maximizing the difference between the expected and the actual situational outcome) is proposed to be a crucial mechanism for therapeutic success for a variety of different mental disorders. However, clinical observations suggest that patients often maintain their expectations regardless of experiences contradicting their expectations. It remains unclear which information processing mechanisms lead to modification or persistence of patients’ expectations. Insight in the processing could be provided by Neuroimaging studies investigating prediction error (PE, i.e., neuronal reactions to non-expected stimuli). Two methods are often used to investigate the PE: (1) paradigms, in which participants passively observe PEs (”passive” paradigms) and (2) paradigms, which encourage a behavioral adaptation following a PE (“active” paradigms). These paradigms are similar to the methods used to induce expectation violations in clinical settings: (1) the confrontation with an expectation violation situation and (2) an enhanced confrontation in which the patient actively challenges his expectation. We used this similarity to gain insight in the different neuronal processing of the two PE paradigms. We performed a meta-analysis contrasting neuronal activity of PE paradigms encouraging a behavioral adaptation following a PE and paradigms enforcing passiveness following a PE. We found more neuronal activity in the striatum, the insula and the fusiform gyrus in studies encouraging behavioral adaptation following a PE. Due to the involvement of reward assessment and avoidance learning associated with the striatum and the insula we propose that the deliberate execution of action alternatives following a PE is associated with the integration of new information into previously existing expectations, therefore leading to an expectation change. While further research is needed to directly assess expectations of participants, this study provides new insights into the information processing mechanisms following an expectation violation.

[This corrects the article DOI: 10.1371/journal.pone.0162866.].

PURPOSEExoseal is a vascular clo­sure device consisting of a plug applier and a bio-absorbent polyglycolic acid plug available in sizes 5 F, 6 F, and 7 F. In this study, we aimed to evaluate the effectiveness and safety of the Exoseal vascular closure device (Cordis Corporation, Bridgewater, New Jersey, USA) for puncture site closure after antegrade endovascular procedures in peripheral arterial occlusive disease (PAOD) patients. MATERIALS AND METHODSIn this retrospective study, a total of 168 consecutive patients who underwent an interventional procedure due to PAOD, were included. In each case, an antegrade peripheral endovascular procedure was performed via the common femoral artery using the Seldinger technique, and Exoseal 5 F, 6 F, or 7 F was used for access site closure. The primary endpoint was a technically successful application of Exoseal. All complications at the access site within 24 hours were registered as a secondary endpoint.RESULTSIn a group of 168 patients (64.9% men, average age 71.9±11.9 years), the technical application of Exoseal was successful in 166 patients (98.8%). Within the first 24 hours after the procedure, 12 complications (7.2%) were recorded including, three pseudoaneurysms (1.8%) and nine hematomas (5.4%). None of the complications required surgical intervention.CONCLUSIONExoseal is a safe and effective device with high technical success and acceptable complication rates for access site closure after antegrade peripheral endovascular procedures.

Katharina Dannehl,1 Winfried Rief,1 Markus J Schwarz,2 Annika Hennings,1 Sabine Riemer,1 Verena Selberdinger,3 Theresa Stapf,3 Frank Euteneuer11Division of Clinical Psychology and Psychotherapy, Philipps Universität Marburg, Marburg, Germany; 2Institute for Laboratory Medicine, Ludwig-Maximilian Universität, Munich, Germany; 3Department of Psychiatry, Ludwig-Maximilian Universität, Munich, GermanyContext: Elevated concentrations of proinflammatory cytokines have been hypothesized as an important factor in the pathophysiology of depression. Depression itself is considered to be a heterogeneous disorder. Current findings suggest that “cognitive” and “somatic” symptom dimensions are related to immune function in different ways. So far, little research has been done on the longitudinal aspects of inflammation in patients with major depression, especially with respect to different symptom dimensions of depression. Therefore, we investigated which aspects of depression may predict changes in tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 over 4 weeks. Methods: Forty-one patients with major depression diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), and 45 healthy controls were enrolled. Serum measurements of TNF-alpha and IL-6 were conducted at baseline and 4 weeks later. Psychometric measures included the assessment of cognitive-affective depressive symptoms and somatic symptoms during the last 7 days as well as somatic symptoms during the last 2 years. Results: Patients with depression showed increased levels of TNF-alpha (P

Placebo responses contribute substantially to the effect and clinical outcome of medical treatments. Patients’ expectations have been identified as one of the major mechanisms contributing to placebo effects. However, to date a general theoretical framework to better understand how patient expectations interact with features of medical treatment has not been developed. In this paper we outline an expectation model that can be used as framework for experimental studies on both placebo and nocebo mechanisms. This model is based on psychological concepts of expectation development, expectation maintenance, and expectation change within the typical paradigms used in placebo research. This theoretical framework reflects the dynamic aspects of the interaction between expectations and medical treatment, and offers a platform to combine psychological and neurophysiological research activities.. Moreover, this model can be used to identify important future research questions. For example, we argue that the dynamic processes of expectation maintenance versus expectation changes are not sufficiently addressed in current research on placebo mechanisms. Therefore, the question about how to change and optimize patients’ expectations prior to treatment should be a special focus of future clinical research.

In highly aggressive malignancies like pancreatic cancer (PC), patient-derived tumor models can serve as disease-relevant models to understand disease-related biology as well as to guide clinical decision-making. In this study, we describe a two-step protocol allowing systematic establishment of patient-derived primary cultures from PC patient tumors. Initial xenotransplantation of surgically resected patient tumors (n = 134) into immunodeficient mice allows for efficient in vivo expansion of vital tumor cells and successful tumor expansion in 38% of patient tumors (51/134). Expansion xenografts closely recapitulate the histoarchitecture of their matching patients’ primary tumors. Digestion of xenograft tumors and subsequent in vitro cultivation resulted in the successful generation of semi-adherent PC cultures of pure epithelial cell origin in 43.1% of the cases. The established primary cultures include diverse pathological types of PC: Pancreatic ductal adenocarcinoma (86.3%, 19/22), adenosquamous carcinoma (9.1%, 2/22) and ductal adenocarcinoma with oncocytic IPMN (4.5%, 1/22). We here provide a protocol to establish quality-controlled PC patient-derived primary cell cultures from heterogeneous PC patient tumors. In vitro preclinical models provide the basis for the identification and preclinical assessment of novel therapeutic opportunities targeting pancreatic cancer.

Many tinnitus sufferers believe that their tinnitus has an organic basis and thus seek medical rather than psychological treatments. Tinnitus has been found to be associated with negative appraisal, dysfunctional attention shift, and heightened psychophysiological arousal, so cognitive-behavioral interventions and biofeedback are commonly suggested as treatments. This study developed and investigated the efficacy of a biofeedback-based cognitive-behavioral treatment for tinnitus. In total, 130 tinnitus patients were randomly assigned to an intervention or a wait-list control group. Treatment consisted of 12 sessions of a biofeedback-based behavioral intervention over a 3-month period. Patients in the wait-list group participated in the treatment after the intervention group had completed the treatment. Results showed clear improvements regarding tinnitus annoyance, diary ratings of loudness, and feelings of controllability. Furthermore, changes in coping cognitions as well as changes in depressive symptoms were found. Improvements were maintained over a 6-month follow-up period in which medium-to-large effect sizes were observed. The treatment developed and investigated in this study is well accepted and leads to clear and stable improvements. Through demonstration of psychophysiological interrelationships, the treatment enables patients to change their somatic illness perceptions to a more psychosomatic point of view. (Contains 1 figure, 4 tables, and 1 footnote.)

Writing--and lots of it in all genres--is at the heart of the language arts curriculum and the skills of critical thinking that students need to develop to become prepared consumers and citizens. In this article, the author reflects on her growth as a writer and teacher, and offers an overview of what people know about writing, what they need to do it well, what the students need to learn to do it well, and what obstacles are challenging teachers' ability to make it happen. She also shares what she has learned from educators, philosophers, researchers, her students, and her own practice. (Contains 3 figures.)

Background: We examined whether the difficulties of patients with somatoform disorders (SFDs) in integrating medical reassurance can be altered by preventing patients from devaluing reassuring information through defensive cognitive strategies. Method: Patients with SFD (n = 60), patients with major depression (n = 32), and healthy volunteers (n = 37) watched a videotaped doctor's report, which provided medical reassurance for gastroenterological complaints. Subsequently, participants were asked about their perception of the report. In the SFD sample, patients' appraisal of the reassuring was experimentally modulated: In one condition, doubts about the validity of the doctor's diagnostic assessment were triggered; in another condition, the devaluation of medical reassurance was blocked through underscoring the validity of the doctor's diagnostic assessment; and a control condition received no manipulation. Results: As evident on all outcome variables, patients with SFD had more difficulty integrating medical reassurance than depressed and healthy people. Within the SFD sample, participants from the experimental condition blocking the devaluation of medical reassurance rated the likelihood of an undetected serious disease to be significantly lower than the other two conditions. They also reported less emotional concern and a lower desire to seek the opinion of another doctor. Conclusions: By comparing patients with SFD to both a healthy and a clinical control group, the current study suggests that the difficulty in processing reassuring medical information is a specific psychopathological feature of SFD. Furthermore, our results suggest that the integration of medical reassurance can be improved by preventing patients from devaluing reassuring information through dismissive cognitive strategies. [ABSTRACT FROM AUTHOR]

Finding voice is often the most intimidating stumbling block to authentic writing in the classroom. Linda Rief offers insight into tapping students' passion and promoting personal responsibility for learning with her "quickwrites," and includes a checklist of ways to elicit writing that matters.

The present experiment examined the causal influence of subjective social status (SSS) on variables related to cardiovascular health (i.e., blood pressure, heart rate variability [HRV]). Participants were randomly assigned to one of two conditions involving a social comparison that either induced a temporary shift toward high SSS or toward low SSS. Cardiovascular variables were measured before (baseline), throughout, and after the manipulation (recovery). Participants in the low SSS condition had a significantly lower HRV during experimental manipulation than at baseline. They also showed a significantly stronger HRV reactivity compared to participants in the high SSS condition. Our results suggest that already temporary shifts of one’s SSS have measureable effects on cardiovascular variables. They support the notion that social status plays a causal role in the development of cardiovascular disease.