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Objective To assess the natural history of saphenous and non-saphenous varicose veins using the results of the Bonn Vein Studies and data published in literature. Methods We used the data of the Bonn Vein Studies (BVS) 1 and 2 to assess if preexisting non-saphenous varicose veins (NSVV) in persons who had no saphenous varicose veins (SVV) at baseline have an impact on the incidence of SVV during the follow-up of 6.6 years and vice versa. SVV where defined as tortuous or not-tortuous refluxing saphenous veins. The statistical evaluation was performed using SAS version 9.4 (SAS Institute, Cary, North Carolina). In addition, we performed a review of publications concerning the natural history of varicose veins (VV) using PubMed. Results In the BVS the overall incidence of SVV within the follow-up time of 6.6 years was 8.0 % (n = 133 of 1661; 95 % CI: 6.8–9.4). 7.2 % (n = 107 of 1492) without VV in BVS 1 and 19.8 % (n = 26) of patients with preexisting NSVV developed SVV. The relative risk for the development of SVV in patients with preexisting NSVV was 2.44 (95% CI: 1.64–3.64) adjusted for age and sex. The overall incidence of NSVV was markedly higher with 13.3 % (n = 226 of 1661; 95 % CI: 11.8–15.1). During follow-up 148 patients (9.9 %) without VV in BVS 1 developed NSVV. 48.5 % (n = 78) of patients with preexisting SVV developed NSVV during follow-up. The relative risk for the development of NSVV in patients with preexisting SVV was 4.10 (95% CI: 3.26–5.16), adjusted for age and sex.In published studies the development of VV is preceded by venous reflux. Initial VV may develop at any segment and the results from literature suggest that the location of VV and reflux at the time of the investigation depends on age. In younger individuals more distal location are reported with an ascending progression in the majority but also descending progression is possible. Conclusions Based on the results of the Bonn Vein Studies 1 and 2 we could demonstrate, that preexisting SVV increase the risk of developing NSVV and preexisting NSVV increase the risk of developing SVV in a similar way. Venous reflux may initially occur in any segment of the venous system and may progress in antegrade and/or retrograde fashion. In younger adults initial VV seem to be localized more often in distal parts of the legs with an antegrade progression over time.

Negative attitudes towards medication in schizophrenia patients are one major factor contributing to non-adherence behavior. Besides, self-stigmatization represents another frequent and important obstacle in patients suffering from psychotic disorders. Here, we investigated possible associations between medication adherence attitude and the extent of self-stigmatization, while also exploring factors related to self-stigmatization. Sociodemographic characteristics, clinical variables, medication attitude and self-stigmatization were assessed among 81 subjects with schizophrenia or schizoaffective disorder. The cross-sectional data was then analyzed by multivariate analyses. A more positive attitude towards medication was predicted by better insight into illness, lower degree of self-stigmatization and good subjective knowledge about medication (adjusted R2 = 0.23). Furthermore, a higher level of self-stigmatization was associated with lower subjective wellbeing, more severe depressive symptoms and male gender (adjusted R2 = 0.58). Other clinical variables had no additional predictive value for medication adherence attitude or the extent of self-stigmatization. Our findings support the notion that self-stigmatization is an influential factor on medication attitude that should therefore be appreciated in clinical practice. Besides this, special emphasis should be taken on depressive symptoms and reduced wellbeing, especially in male patients, to lower the extent of self-stigmatization.

Objectives The aim was to study the association between venous disorders and leg symptoms in the population based cross sectional Bonn Vein Study 1 (BVS1). Methods A total of 1,350 men and 1,722 women aged 18–79 years were enrolled into BVS1. Chronic venous insufficiency (CVI), varicose veins (VVs), and clinical classes (C-classes/CEAP [Clinical, Etiological, Anatomical, and Pathophysiological]) were determined by clinical and duplex investigation. Leg symptoms (heaviness, tightness, swelling, pain after standing or sitting, pain while walking, muscle cramps, itching, and restless legs) were assessed in a standardized interview. For 2,624 subjects (48.7% male) with complete information on venous disorders, relevant characteristics and information on at least one leg symptom, multivariate logistic regression analysis was performed. Results More women (929/63.0%) reported at least one leg symptom within the last 4 weeks than men (560/48.7%). Prevalence of reported symptoms increased with age (45.4% of the 18–29 year olds, 73.9% of the 70–79 year olds). Leg symptoms were more frequent in obese and underweight subjects. As confirmed by clinical and duplex examination 22.6% had VV and 15.8% had CVI. VV (OR: 1.4; CI: 1.1–1.7) and CVI (OR: 1.8; CI: 1.3–2.3) were significantly associated with reporting at least one leg symptom. In particular, there was a positive association of VV and CVI with itching, feeling of heaviness, tightness, swelling, and pain after standing or sitting. C2–C6 showed a statistically significant association with feeling of heaviness, tightness, swelling, and itching, while for pain on walking and muscle cramps this was shifted towards C classes C3–C6 and C3–C4, respectively. Conclusions Venous disorders show significant associations with several leg symptoms. Itching, feeling of heaviness, or tightness seem to be more closely related than other symptoms. The associations between C classes and symptoms seem to be restricted to classes C2 or higher.

Summary Background: Despite the frequent use of medical compression stockings (MCS), reliable data are lacking on the frequency of MCS use and experience of patients with the treatment. Patients and methods: The Bonn Vein Study included 3,072 participants from the general population aged 18 to 79 years (1,350 men/1,722 women). Between 2007 and 2008 (Bonn Vein Study 2) 1,978 participants from the Bonn Vein Study 1 were reinvestigated. This paper combines the results of both investigations. Results: 14.6% (7.5% men, 20.3% women) reported having previously undergone treatment with compression stockings. A mean of 71.3% reported an improvement in their venous disease as a result of MCS treatment. During the 6.6 years of follow-up (Bonn Vein Study 2), significantly more prescriptions of MCS were given to patients in higher CEAP clinical stages. 12.2% of the population in C2 was treated with MCS as were 19.1% in C3 and 27.0% in C4–C6. Among participants with chronic venous insufficiency (CVI) (skin changes up to venous ulcers), about 60% were not treated by MCS or bandages in the past years. Conclusions: These results show that MCS is the most common treatment of venous disorders in the German population. At the same time, these figures also demonstrate severely lacking treatment with MCS in CVI.

Different aspects of self-stigmatization represent barriers for recovery in patients with psychosis disorders. It is unclear whether addressing patient's competence and control beliefs could attenuate the extent of self-stigmatization. The major aim of this study was to identify predictors of self-stigmatization derived from competence and control beliefs in patients (N = 80). Sociodemographic characteristics, clinical variables, competence and control beliefs and self-stigmatization were assessed among 80 patients with psychosis disorders. The cross-sectional data was analyzed by correlation and regression analyses. Results indicate deficits in self-concept of own competences, i.e. the capability of acting in new, difficult or ambiguous situations, resulting in also impaired self-efficacy and relatively increased externality in patients compared to a general population sample. Subjective well-being under neuroleptics, trait-anxiety and defining oneself as religious were the most influential predictors of competence and control beliefs. A weaker self-concept of own competences was also revealed as the strongest predictor of overall high self-stigmatization. Our results stress the importance of orienting treatment strategies towards strengthening the self-concept of own competences in patients in order to reduce self-stigmatization and enhance resilience.

Cellular apoptosis, the prototype of programmed cell death, can be induced by activation of so-called death receptors. Interestingly, soluble and membrane-bound members of death receptor ligands can differentially activate their receptors. Using the death receptor ligand tumor necrosis factor (TNF) presented on a surface in a nanoscaled pattern with spacings between 58 and 290 nm, we investigated its requirements for spatial arrangement and motility to efficiently activate TNF receptor (TNFR)1 and TNFR2 as well as its chimeras TNFR1-Fas and TNFR2-Fas. We show that the mere mechanical fixation of TNF is insufficient to efficiently activate TNFR2 that is responsive to only the membrane bound form of TNF but not its soluble form. Rather, an additional stabilization of TNFR2(-Fas) by cluster formation seems to be mandatory for efficient activation. In contrast, TNFR1(-Fas) is strongly activated by TNF spaced within up to 200 nm distances, whereas larger spacings of 290 nm fails completely. Furthermore, unlike for TNFR2(-Fas) no dose-response relationship to increasing distances of nanostructured ligands could be observed for TNFR1-(Fas), suggesting that compartmentalization of the cell membrane in confinement zones of approximately 200 nm regulates TNFR1 activation.

We herein present a novel platform of well-controlled ordered and disordered nanopatterns positioned with a cyclic peptide of arginine-glycine-aspartic acid (RGD) on a bioinert poly(ethylene glycol) background, to study whether the nanoscopic order of spatial patterning of the integrin-specific ligands influences osteoblast adhesion. This is the first time that the nanoscale order of RGD ligand patterns was varied quantitatively, and tested for its impact on the adhesion of tissue cells. Our findings reveal that integrin clustering and such adhesion induced by RGD ligands is dependent on the local order of ligand arrangement on a substrate when the global average ligand spacing is larger than 70 nm; i.e., cell adhesion is “turned off” by RGD nanopattern order and “turned on” by the RGD nanopattern disorder if operating at this range of inter-ligand spacing.

Quasi-hexagonal ordered arrays of noble-metal nanoparticles are synthesized by block copolymer micelle nanolithography (BCML) and electroless deposition. Two approaches are discussed to uniformly grow surface-deposited gold, platinum, and palladium nanoparticles independent of interparticle spacing (see figure). The geometrical order of the particles is preserved by either embedding them into a monolayer of alkylsiloxane molecules or using micelles as a stabilizing template.

The development of multilayered thin film assemblies containing (bio)molecules is driven by the need to miniaturize sensors, reactors, and biochips. Viral nanoparticles (VNPs) have become popular nanobuilding blocks for material fabrication, and our research has focused on the well-characterized plant virus Cowpea mosaic virus (CPMV). In a previous study, we have reported the construction of multilayer VNP assemblies. Here we extend these studies by providing further details on the formation and properties of arrays that are made by the alternating deposition of biotinylated CPMV particles and streptavidin molecules. Array formation was followed in real time by a quartz crystal microbalance with dissipation monitoring. Our data provide indications that multiple interactions between biotin and streptavidin not only promote the assembly of a multilayered structure but also generate cross-links within each layer of CPMV particles. The degree of intralayer and interlayer cross-linking and hence the mechanical properties and order of the array can be modulated by the grafting density and spacer length of the biotin moieties on the CPMV particles.

Background Trigeminal neuralgia is characterized by paroxysmal facial pain attacks. Adequate prophylactic drug therapy is often limited by the lack of efficacy and intolerance due to central nervous system side effects. Subcutaneous injections of botulinum toxin type A are a promising treatment option for patients with unsatisfactory response to drug therapy or neurosurgical intervention. Its effects are expected to last for at least 3 months, so it could be a potential long-term treatment. This is the study protocol of a prospective, placebo-controlled, double blind clinical trial investigating the add-on therapy of subcutaneous administration of botulinum toxin type A injections to standard treatment in therapy-refractory classical trigeminal neuralgia. Methods and design BoTN is a prospective, double blind, placebo-controlled trial with a randomized withdrawal design in which a single blind phase is followed by a double blind phase (see also Methods and design). Eligible patients with classical trigeminal neuralgia who are otherwise refractory to medical and neurosurgical treatment will receive subcutaneous injections of botulinum toxin type A into injection sites of the affected trigeminal branch. In the first phase all patients will receive botulinum toxin type A in a single blinded intervention. Twelve weeks later therapy responders will be allocated to the verum or placebo (saline) arm in a double blind, randomized manner. These injections will be performed at the same sites as the first injections. This trial will be conducted in a tertiary outpatient clinic specialized in the treatment of headache and facial pain. There will be three investigators performing the injections who are experienced in the treatment of headache and facial pain and trained in botulinum toxin type A injections. Discussion BoTN is designed to assess the efficacy and safety of subcutaneous botulinum toxin type A injections in addition to standard prophylactic treatment in therapy-refractory trigeminal neuralgia. Trial registration number EU Clinical Trials Register: EudraCT-No: 2014-001959-24 https://www.clinicaltrialsregister.eu/ctr-search/rest/download/trial/2014-001959-24/DE Date of trial registration 26 August 2014 Electronic supplementary material The online version of this article (doi:10.1186/s13063-015-1052-z) contains supplementary material, which is available to authorized users.

To investigate the long-term outcome of inter- disciplinary treatment in a tertiary care neuro-otology institution after 2 years as part of the Dizziness and Vertigo Registry study. Risk factors associated with unfavourable outcome were assessed. 3113 consecutive patients with disorders of vertigo and dizziness were recruited prospec- tively between March 2010 and February 2012. Patients were clinically assessed and treated according to their diagnosis. Standardized instruments were used at baseline and at 2-year follow-up (Dizziness Handicap Inventory (DHI), Quality of Life Questionnaire, General Depression Scale, Stait-Trait Anxiety Index), as well as a custom health-related questionnaire. The primary outcome variable of this observational study was the change in DHI after 2 years. Patients suffered from phobic postural vertigo (23 %), benign peripheral paroxysmal vertigo (14.4 %), unilateral vestibulopathy (10.5 %), central vestibular dis- orders (8 %), Meniere's disease (9.8 %), vestibular migraine (6.9 %), bilateral vestibulopathy (5.5 %), and vestibular paroxysmia (3.1 %). Mean disease duration was 4.6 ± 6.3 years. 1272 patients were available for follow- up, 1159 completed the DHI score. 72.1 % of patients improved in DHI score from baseline to 2 years follow-up. Mean reduction in DHI score was 14 points (p = 0.02). Long-term outcome following diagnosis and treatment in a specialized tertiary care centre is good and persistent after 2 years. Risk factors for an unfavourable outcome were advanced age, severe disability, constant vertigo or dizzi- ness, and concomitant back pain, while depression and anxiety did not contribute to this risk considerably.

Aim of the study Diseases of the venous system are among the most frequently occurring diseases in the German population. However, the last comprehensive population-based German data were obtained in 1979. Since then, diagnostic methods have improved substantially. Here, we examine the prevalence of venous diseases in women and their association with pregnancies and intake of hormones. Methods We conducted a population-based cross-sectional study in Bonn and rural environments (Recruitment period: 11/2000 - 11/2001; response: 59 %; 3072 study participants (1350 men, 1722 women), 18 to 79 years of age; investigation: standardised medical history, physical examination, duplex sonography, photography and CEAP-classification of veins of the legs). The following definitions were used: 1) Varicosis: clinical classification C2-C6 (primary varicosis only, excluding those showing spider-bursts exclusively); 2) Chronic venous insufficiency (CVI): C3-C6. For women, the risk factors examined were the number of pregnancies (P) and intake of hormones. Odds ratios (OR) and 95 % confidence intervals (95 %-CI) were calculated by multiple logistic regression (adjusted for age, region of residence and socioeconomic status). In addition, never pregnant women and men were compared regarding the two outcome variables. Results 713 participants (23 %) had varicosis and 522 (17 %) CVI. The OR for women (reference group: men) was OR = 1.4, 95 %-CI: 1.25 - 1.79 (varicosis) and OR = 1.2, 95 %-CI: 0.93 - 1.42 (CVI). There was a positive dose-response relationship between the number of pregnancies and varicosis: 1 P: OR = 1.3 (95 %-CI: 0.89 - 1.96), 2 P: OR = 1.4 (95 %-CI: 1.00 - 2.07), 3 P: OR = 1.6 (95 %-CI: 1.05 - 2.41), 4 P: OR = 1.9 (95 %-CI: 1.18 - 3.20), > or = 5 P: OR = 2.2 (95 %-CI: 1.28 - 3.74) and this trend was similar for CVI. Never-pregnant women (n = 518) and men had a similar prevalence. We did not see a consistent effect of intake of hormones in varicosis (OR = 0.9 [95 %-CI: 0.68 - 1.22]), but a negative association with CVI (OR = 0.6 [95 %-CI: 0.47 - 0.89]). Conclusions Our results confirm the known association between diseases of the venous system and pregnancies, which seem to explain a big share of the sex-specific differences in the prevalence of these diseases.

ZusammenfassungZiel: Die Bonner Venenstudie zur Frage der Häufigkeit und Ausprägung von chronischen Venenkrankheiten in der städtischen und ländlichen deutschen Wohnbevölkerung im Alter von 18-79 Jahren fand zwischen dem 13. 11. 2000 und 15. 3. 2002 statt. Es nahmen insgesamt 3072 Probanden teil, die Response-Proportion lag insgesamt bei 59%. Ergebnisse: Eine Beinschwellung in der Anamnese trat bei jedem 6. Mann (16,2%) und bei nahezu jeder 2. Frau (42,1%) auf. Eine kurz zurückliegende ein- oder beidseitige Beinschwellung in den letzten vier Wochen gab jeder 6. Teilnehmer an. Dies entspricht 14,8% (7,9% der Männer, 20,2% der Frauen). Für Gefäßerkrankungen typische Beinbeschwerden innerhalb der letzten vier Wochen gab insgesamt jeder 2. der Probanden (56,4%) an. Bei der Beurteilung der klinischen Ausprägung gemäß der CEAP-Klassifikation fällt auf, dass lediglich 9,6% der Probanden keinerlei Venenveränderungen aufweisen. Bei 59% bestehen isoliert Teleangiektasien oder retikuläre Venen, bei 14,3% Krampfadern (C2) ohne weitere Zeichen einer chronischen venösen Insuffizienz. Auffällig ist, dass bei 13,4% ein prätibiales Ödem im Rahmen von Venenveränderungen zum Untersuchungszeitpunkt vorlag. Demgegenüber liegt die Zahl der fortgeschrittenen Zeichen der chronischen venösen Insuffizienz bei 3,3%. Die Häufigkeit des floriden oder abgeheilten Ulcus cruris lag bei 0,7%. Schlussfolgerungen: Jeder 6. Mann und jede 5. Frau hat somit chronische Veneninsuffizienz (C3–C6). Die Zahlen zeigen, dass Venenkrankheiten insgesamt nach wie vor eine hohe Prävalenz aufweisen, dass aber die schweren Ausprägungen der chronischen venösen Insuffizienz in den vergangenen 20 Jahren zurückgegangen sind.

Background Trigeminal neuralgia (TN) is a chronic disorder characterized by paroxysmal facial pain. Adequate prophylactic drug therapy is often limited by the lack of efficacy and intolerance due to central nervous system side effects. Subcutaneous injections of botuinum toxin type A (BT-A) are a promising treatment option for patients with insatisfactory response to drug therapy or neurosurgical intervention. This is the study protocoll of a prospective, placebocontrolled, double blind clinical trial investigating the add-on therapy of subcutaneous of BT-A injections to standard treatment.

Methods The German Headache Consortium studied a populationbased sample of 5,159 participants (21-71years) who were asked every three months between March 2010 and April 2012 about headache and stress. Log-linear regression in the framework of Generalized Estimating Equations was used to estimate regression coefficients presented as percent changes to describe the association between stress intensity (visual analogue scale [VAS] from 0-100) and headache frequency (days/month) stratified by headache subtypes and age groups. Percent changes were adjusted for sex, age, frequent intake of acute pain drugs, drinking, smoking, body mass index and education.

Introduction We studied the association between stress intensity and headache frequency for tension-type headache (TTH), migraine and migraine with coexisting TTH (MigTTH). Method We studied a population-based sample of 5159 participants (21–71 years) who were asked quarterly between March 2010 and April 2012 about headache and stress. Log-linear regression in the framework of generalized estimating equations was used to estimate regression coefficients presented as percent changes to describe the association between stress intensity (modified visual analog scale (VAS) from 0 to 100) and headache frequency (days/month) stratified by headache subtypes and age groups and adjusted for sex, age, frequent intake of acute pain drugs, drinking, smoking, BMI and education. Results TTH was reported in 31% participants (48.1 ± 12.5years, 51.5% women, 2.2 ± 3.9 mean headache days/month, 52.3 ± 26.7 mean stress), migraine in 14% (44.8 ± 11.3years, 73.3%, 4.5 ± 5.2 days/month, 62.4 ± 23.3), MigTTH in 10.6% (43.5 ± 11.5 years, 61.0%, 3.6 ± 4.8 days/month, 58.6 ± 24.1), 23.6% were unclassifiable, and 20.8% had no headache. In participants with TTH an increase of 10 points on VAS was associated with an increase of headaches days/month of 6.0% (adjusted). Higher effects were observed in younger age groups (21–30/31–40/41–50/51–60/61–71 years: 9.8/10.2/7.0/6.5/3.5%). Slightly lower effects were observed for migraine (4.3%, 8.1/5.1/3.4/6.3/0.3%) and MigTTH (4.2%, 5.5/6.8/6.9/5.8/–0.7%). Conclusion Our study provides evidence for an association between stress intensity and headache frequency.

Despite the frequent use of medical compression stockings (MCS), reliable data are lacking on the frequency of MCS use and experience of patients with the treatment.The Bonn Vein Study included 3,072 participants from the general population aged 18 to 79 years (1,350 men/1,722 women). Between 2007 and 2008 (Bonn Vein Study 2) 1,978 participants from the Bonn Vein Study 1 were reinvestigated. This paper combines the results of both investigations.14.6% (7.5% men, 20.3% women) reported having previously undergone treatment with compression stockings. A mean of 71.3% reported an improvement in their venous disease as a result of MCS treatment. During the 6.6 years of follow-up (Bonn Vein Study 2), significantly more prescriptions of MCS were given to patients in higher CEAP clinical stages. 12.2% of the population in C2 was treated with MCS as were 19.1% in C3 and 27.0% in C4-C6. Among participants with chronic venous insufficiency (CVI) (skin changes up to venous ulcers), about 60% were not treated by MCS or bandages in the past years.These results show that MCS is the most common treatment of venous disorders in the German population. At the same time, these figures also demonstrate severely lacking treatment with MCS in CVI.