[Increased report completeness and satisfaction with structured neurotological reporting in the interdisciplinary assessment of vertigo]. / Erhöhte Befundvollständigkeit und gesteigerte Zuweiserzufriedenheit bei strukturierter neurootologischer Befunderhebung in der interdisziplinären Schwindelabklärung.

BACKGROUND: Results of neurotological function diagnostics in the context of interdisciplinary vertigo assessment are usually formulated as free-text reports (FTR). These are often subject to high variability, which may lead to loss of information. The aim of the present study was to evaluate the completeness of structured reports (SR) and referrer satisfaction in the neurotological assessment of vertigo. MATERIALS AND METHODS: Neurotological function diagnostics performed as referrals (n = 88) were evaluated retrospectively. On the basis of the available raw data, SRs corresponding to FTRs from clinical routine were created by means of a specific SR template for neurotological function diagnostics. FTRs and SRs were evaluated for completeness and referring physician satisfaction (n = 8) using a visual analog scale (VAS) questionnaire. RESULTS: Compared to FTRs, SRs showed significantly increased overall completeness (73.7% vs. 51.7%, p < 0.001), especially in terms of patient history (92.5% vs. 66.7%, p < 0.001), description of previous findings (87.5% vs. 38%, p < 0.001), and neurotological (33.5% vs. 26.7%, p < 0.001) and audiometric function diagnostics (58% vs. 32.3%, p < 0.001). In addition, SR showed significantly increased referring physician satisfaction (VAS 8.8 vs. 4.9, p < 0.001). CONCLUSION: Neurotological SRs enable a significantly increased report completeness with higher referrer satisfaction in the context of interdisciplinary assessment of vertigo. Furthermore, SRs are particularly suitable for scientific data analysis, especially in the context of big data analyses.

Crystal structures of Scone: pseudosymmetric folding of a symmetric designer protein.

Recent years have seen an increase in the development of computational proteins, including symmetric ones. A ninefold-symmetric ß-propeller protein named Cake has recently been developed. Here, attempts were made to further engineer this protein into a threefold-symmetric nine-bladed propeller using computational design. Two nine-bladed propeller proteins were designed, named Scone-E and Scone-R. Crystallography, however, revealed the structure of both designs to adopt an eightfold conformation with distorted termini, leading to a pseudo-symmetric protein. One of the proteins could only be crystallized upon the addition of a polyoxometalate, highlighting the usefulness of these molecules as crystallization additives.

Subnanosecond phase transition dynamics in laser-shocked iron.

Iron is one of the most studied chemical elements due to its sociotechnological and planetary importance; hence, understanding its structural transition dynamics is of vital interest. By combining a short pulse optical laser and an ultrashort free electron laser pulse, we have observed the subnanosecond structural dynamics of iron from high-quality x-ray diffraction data measured at 50-ps intervals up to 2500 ps. We unequivocally identify a three-wave structure during the initial compression and a two-wave structure during the decaying shock, involving all of the known structural types of iron (α-, γ-, and ε-phase). In the final stage, negative lattice pressures are generated by the propagation of rarefaction waves, leading to the formation of expanded phases and the recovery of γ-phase. Our observations demonstrate the unique capability of measuring the atomistic evolution during the entire lattice compression and release processes at unprecedented time and strain rate.

[Current aspects of pain management during and after dermatologic surgery]. / Aktuelle Aspekte zum Schmerzmanagement während und nach dermatologischen Operationen.

The project "Pain-free Hospital" was the first attempt to improve the level of postoperative care by standardizing pain therapy standards (concepts) in the individual surgical disciplines. Dermatosurgery is no exception. In addition to drug therapy, it is also important to consider biopsychosocial aspects of the symptom pain, as this is the only way to prevent chronification of acute pain in the further course of a disease. Drug therapy should not only be adapted to the classic WHO system (only considering pain intensity), but should also address aspects of pain quality. In this article, we discuss these aspects in more detail and present our treatment concept for dermatosurgery.

[Lichen ruber planus : Better understanding, better treatment!] / Lichen ruber planus : Besser verstehen, besser behandeln!

Lichen ruber, also called lichen ruber planus or lichen planus (LP), is a noncontagious inflammatory skin disease. LP is the main representative and namesake of the group of lichenoid diseases, which are characterized by small papules often accompanied by severe itching. With 65% of cases, LP is primarily a disease of the mucous membranes. In 20% of the cases, the disease is found on the skin and mucous membranes; skin involvement alone is seen in only about 10% of cases. Cutaneous LP has a very favorable 1­year prognosis of almost 80% healing as opposed to the mucosa and the adnexal organs. Histologically, keratinocytes with vacuolar degeneration, leaving behind apoptotic Kamino bodies and the characteristic band-shaped lymphocytic infiltrate at the dermatoepithelial junction, are common to lichenoid diseases. The horny layer is firm and compact and the stratum granulosum is thickened as a correlate of the Wickham stripes. The molecular pathogenesis, still partially hypothetical, assumes trigger factors leading to the presentation of intrinsic or foreign antigens. The triggered inflammation becomes independent in the sense of a classical cell-mediated autoimmune disease. Other autoimmune diseases are often associated with LP. Classical anti-inflammatory-immunosuppressive therapeutic concepts dominate with systemic retinoids ranking first in the highest evidence class for cutaneous LP with limitations in treatment of both mucosal and adnexal LP. More recently, interesting and new complementary phototherapeutics have been identified.

[Postmenopausal lichen planopilaris also known as fibrosing frontotemporal alopecia Kossard : An evidence-oriented practical guide to treatment from the University of the Saarland, Hair Research Center of the Dr. Rolf M. Schwiete Foundation]. / Postmenopausaler Lichen planopilaris alias fibrosierende frontotemporale Alopezie Kossard : Ein evidenzorientierter "practical guide to treatment" des Haarforschungszentrums der Dr. Rolf M. Schwiete Stiftung an der Universität des Saarlandes.

Postmenopausal lichen planopilaris (PLPP), also known as fibrosing frontotemporal alopecia Kossard (FFAK), is a not uncommon inflammatory scalp disease affecting approximately 5% of patients at specialized hair centers. The overall incidence of sporadic occurrence is believed to be just under 1% in the older, predominantly female, general population. Since the disease is often undiagnosed, it is statistically likely to be underrepresented. It especially occurs in postmenopausal women who are in the 6th and 7th decade of life (90%), but also in about 10% of premenopausal women, and in men it is documented only in isolated cases. The result is a permanent scarring hair loss accentuated at the front hairline with backward movement towards the neck mostly accompanied by a typical loss of the eyebrows. The disease therefore often leads to significant mental distress and social anxiety in those affected. This is the basis for a compelling need to develop evidence-based therapeutic concepts. While numerous retrospective case series have characterized the phenomenology of FFAK very well, to date there are no randomized controlled trials on evidence-based therapy. Here, we present the Homburger Evidence-Oriented Therapy Algorithm, which is oriented along the available case series evidence: It may (1) serve as a therapy guide for practice and (2) can be used as a basis for working out reliable data based on study evidence. The article contains detailed practical information on photo documentation, biopsy and histological processing up to the practical implementation of, for example, intralesional steroid therapy as well as information on selection criteria for suitable systemic therapies.

[Practice-oriented pain therapy in dermatology : Concept with special emphasis on pain quality]. / Praxisorientierte Schmerztherapie in der Dermatologie : Konzept mit besonderer Berücksichtigung der Schmerzqualität.

In order to avoid chronification of pain, appropriate treatment has to be started as early as possible. Inpatient dermatology patients not only suffer from old age and associated multimorbidities but also from characteristic pain due to distinct dermatological diseases. In many cases clinicians have little experience with specific pain treatment but instead have many concerns about how to deal with analgesics. So far chronic pain has been treated according to the pain ladder of the World Health Organization (WHO), which prioritizes the intensity of pain. This article presents an easily implementable concept of pain therapy with special emphasis on the quality of pain. This provides information on whether it is neuropathic or nociceptive pain, which can ultimately be differentially treated. The primary aim is to provide treating dermatologists with a concept to assist in the initiation of an efficient and correct pain therapy. This brief introduction of an individualized pain treatment can reduce the risk of chronification of pain, which can severely impair the quality of life particularly in dermatology patients and also the frequent stigmatization due to the dermatosis.

A mild post-functionalization method for the vanadium substituted P2W15V3 Wells-Dawson polyoxometalate based on a copper catalyzed azide-alkyne cycloaddition.

A mild post-functionalization method, based on a copper(i) catalyzed azide-alkyne cycloaddition, was developed for the fragile [P2W15V3]9- (PWV). PWV was functionalized with an azide and used as a platform to attach various alkyne functionalized compounds.

[Melasma : An update on the clinical picture, treatment, and prevention]. / Melasma : Ein Update zu Klinik, Therapie und Prävention.

Melasma, also known as chloasma or mask of pregnancy, presents clinically as hyperpigmented skin areas, which develop mostly in the face as a consequence of increased synthesis of melanin. The established treatment options, including topically applied agents and the use of various laser systems, mostly result in improvement but not in complete remission of the lesions. Because of its significant impact on quality of life and the limited effectivity of available treatment options, the management of melasma is challenging for the treating physician. Although many risk factors, including pregnancy and UV exposure, have been identified, the pathogenesis is not yet fully understood. Avoiding solar or artificial UV exposure is of high importance both for the prevention of melasma and for the clinical outcome of existing lesions. In order to avoid vitamin D deficiency, oral vitamin D supplementation should be recommended. In this review, we give an update on clinical aspects, epidemiology, pathogenesis and therapy of melasma and give an outlook on future developments.

Polyoxometalates as artificial nucleases: hydrolytic cleavage of DNA promoted by a highly negatively charged ZrIV-substituted Keggin polyanion.

A highly negatively charged binuclear ZrIV-substituted Keggin polyoxometalate [{α-PW11O39Zr(µ-OH)(H2O)}2]8- (ZrK 2 : 2) has been shown to promote the hydrolytic cleavage of phosphoester bonds in the supercoiled plasmid pUC19 DNA under physiological pH and temperature, giving relaxed and linear forms of pUC19 as hydrolysis products. The interaction between ZrK 2 : 2 and DNA was experimentally proven by circular dichroism (CD) spectroscopy and 31P diffusion ordered NMR spectroscopy.

Following the stability of amphiphilic nanoaggregates by using intermolecular energy transfer.

An intermolecular energy transfer system is developed for studying the stability of nanoaggregate(s) (NAs) in complex solution and cell culture by one- and two-photon fluorescence microscopy and optical imaging. The system allows facile addition of one or more tumor targeting molecules, one of which is exemplified here. NAs functionalized with an MRI and optical probe, with and without folic acid, remain stable in fetal bovine serum for at least 4 hours. HeLa cell cultures showed a clear difference between NAs non-targeted and targeted to folate receptors, with both NAs appearing to be taken up by the cells through different mechanisms. An MRI relaxivity, r1, of 9 mM-1 s-1 at 310 K and 1.4 T was measured associated with the increased rotational correlation time of the NAs. These NAs may have application in the targeted drug delivery of hydrophobic drugs such as doxorubicin (DOX).

Adjuvant treatment with pegylated interferon α-2a versus low-dose interferon α-2a in patients with high-risk melanoma: a randomized phase III DeCOG trial.

BACKGROUND: Adjuvant treatment with interferon (IFN)-α-2a improved disease-free survival (DFS) and showed a trend for improving overall survival (OS) in melanoma. This trial was designed to examine whether PEG-IFN is superior to IFN with regard to distant metastasis-free survival (DMFS), DFS and OS. PATIENTS AND METHODS: In this multicenter, open-label, prospective randomized phase III trial, patients with resected cutaneous melanoma stage IIA(T3a)-IIIB (AJCC 2002) were randomized to receive PEG-IFN (180 µg subcutaneously 1×/week; 24 months) or IFN α-2a (3MIU subcutaneously 3×/week; 24 months). Randomization was stratified for stage, number of metastatic nodes, age and previous IFN treatment. The primary end point was DMFS; secondary end points were OS, DFS, quality of life (QoL) and tolerability. RESULTS: A total of 909 patients were enrolled (451 PEG-IFN versus 458 IFN). Neither 5-year DMFS [PEG-IFN 61.0% versus IFN 67.3%; hazard ratio (HR) 1.16, P = 0.21] nor 5-year OS (PEG-IFN 73.2% versus IFN 75.2%; HR 1.05, P = 0.70) nor 5-year DFS (PEG-IFN 57.3% versus IFN 60.9%; HR 1.09, P = 0.40) showed significant differences. Subgroup analyses in patients ± ulcerated primaries and of different tumor stages did not find differences in DMFS, OS or DFS between the treatment groups. One hundred and eighteen patients (26.2%) in the PEG-IFN and 61 patients (13.3%) in the IFN population did not receive the full dosage and length of treatment due to adverse events (P < 0.001). Leukopenia and elevation of liver enzymes were more common in the PEG-IFN arm (56% versus 23.5% LCP; 19.1% versus 9.4% AST; 33.0% versus 16.5% ALT). QoL was identical for nearly all domains. CONCLUSION: PEG-IFN did not improve the outcome over IFN. A higher percentage of patients under PEG-IFN discontinued treatment due to toxicity. CLINICAL TRIALSGOV IDENTIFIER: NCT00204529.

[Contact allergic gastritis : Rare manifestation of a metal allergy]. / Kontaktallergische Gastritis : Seltene Manifestation einer Metallallergie.

Only a few cases of contact allergic gastritis in patients with nickel allergy have been reported in the literature. We report a case of probable contact-allergic gastritis in a 46-year-old woman. Clinical examination revealed lichenoid mucosal lesions of the gums adjacent to a bridge and crowns that had been implanted several weeks previously. Since implantation, the patient suffered from gastrointestinal complaints including stomach pain. Gastroscopy and histological investigation of stomach biopsies showed eosinophilic gastritis. Patch testing done under the diagnosis of contact allergic stomatitis showed positive reactions to gold sodium thiosulphate, manganese (II) chloride, nickel (II) sulphate, palladium chloride, vanadium (III) chloride, zirconium (IV) chloride, and fragrances. The crowns and the bridge contained gold, palladium, and zirconium, hence they were replaced by titan-based dentition. Shortly after replacing the artificial dentition, all gastrointestinal symptoms resolved spontaneously without further treatment. Delayed-type allergy to components in the artificial dentition seem to have caused the gastritis.

Nanocarriers for optimizing the balance between interfollicular permeation and follicular uptake of topically applied clobetasol to minimize adverse effects.

The treatment of various hair disorders has become a central focus of good dermatologic patient care as it affects men and women all over the world. For many inflammatory-based scalp diseases, glucocorticoids are an essential part of treatment, even though they are known to cause systemic as well as local adverse effects when applied topically. Therefore, efficient targeting and avoidance of these side effects are of utmost importance. Optimizing the balance between drug release, interfollicular permeation, and follicular uptake may allow minimizing these adverse events and simultaneously improve drug delivery, given that one succeeds in targeting a sustained release formulation to the hair follicle. To test this hypothesis, three types of polymeric nanocarriers (nanospheres, nanocapsules, lipid-core nanocapsules) for the potent glucocorticoid clobetasol propionate (CP) were prepared. They all exhibited a sustained release of drug, as was desired. The particles were formulated as a dispersion and hydrogel and (partially) labeled with Rhodamin B for quantification purposes. Follicular uptake was investigated using the Differential Stripping method and was found highest for nanocapsules in dispersion after application of massage. Moreover, the active ingredient (CP) as well as the nanocarrier (Rhodamin B labeled polymer) recovered in the hair follicle were measured simultaneously, revealing an equivalent uptake of both. In contrast, only negligible amounts of CP could be detected in the hair follicle when applied as free drug in solution or hydrogel, regardless of any massage. Skin permeation experiments using heat-separated human epidermis mounted in Franz Diffusion cells revealed equivalent reduced transdermal permeability for all nanocarriers in comparison to application of the free drug. Combining these results, nanocapsules formulated as an aqueous dispersion and applied by massage appeare to be a good candidate to maximize follicular targeting and minimize drug penetration into the interfollicular epidermis. We conclude that such nanotechnology-based formulations provide a viable strategy for more efficient drug delivery to the hair follicle. Moreover, they present a way to minimize adverse effects of potent glucocorticoids by releasing the drug in a controlled manner and simultaneously decreasing interfollicular permeation, offering an advantage over conventional formulations for inflammatory-based skin/scalp diseases.

The impact of long-term confinement and exercise on central and peripheral stress markers.

Long-term isolation has been reported to have impact on psycho-physiological performance in humans. As part of the 520 days isolation study (MARS500, n=6) from June 3rd 2010 to November 4th 2011, this study aimed to show that stress caused by isolation and confinement is mirrored in cortical activity and cortisol levels and that exercise is a valid countermeasure. Cortical activity was measured by electroencephalography (EEG) pre- and post-moderate exercise every two weeks, salivary cortisol was taken every 60 days. Data show a decrease of global cortical activity, in both alpha- and beta-activity (p<.05-p<.001), and an increase of salivary cortisol (p<.05-p<.001), during the isolation, indicating that isolation acts as a chronic stressor with impact on cortical activity and cortisol levels. Moderate exercise leads to an increase (p<.01) in cortical activity. Therefore, during long-term space missions the factor isolation must be kept in mind as the reduction of cortical activity and the heightened stress level could impair performance. However moderate exercise might be able to counteract this impairment.

Same Site Recurrence is More Frequent After Endovenous Laser Ablation Compared with High Ligation and Stripping of the Great Saphenous Vein: 5 year Results of a Randomized Clinical Trial (RELACS Study).

OBJECTIVE: To compare the long-term clinical efficacy of endovenous laser ablation (EVLA) with high ligation and stripping (HLS) as standard treatment for great saphenous vein (GSV) incompetence. DESIGN: Investigator initiated two centre randomized controlled trial with 5 year follow up. MATERIALS AND METHODS: Interventions were performed on ambulatory and hospitalized patients at two vein centres, a university dermatology department (EVLA) and a specialized vein clinic (HLS). Four hundred patients suffering from GSV incompetence were assigned to EVLA or HLS of the GSV. One hundred and eighty five and 161 patients (=limbs), respectively, were treated per protocol. Main outcome measures were clinically recurrent varicose veins after surgery (REVAS classification, primary study objective), Duplex detected saphenofemoral recurrence, clinical venous severity scoring (Homburg Varicose Vein Severity Score), quality of life (Chronic Venous Insufficiency Questionnaire 2), side effects, and patient satisfaction 5 years after treatment. RESULTS: Two hundred and eighty one legs (81% of the study population) were evaluated with a median follow up of 60.4 (EVLA) and 60.7 months (HLS). Overall, REVAS was similarly observed in both groups: 45% (EVLA) and 54% (HLS), p = .152. Patients of the EVLA group showed significantly more clinical recurrences in the operated region (REVAS: same site): 18% vs. 5%, p = .002. In contrast, more different site recurrences were observed in the HLS group: 50% vs. 31%, p = .002. Duplex detected saphenofemoral refluxes occurred more frequently after EVLA: 28% vs. 5%, p < .001. Both treatments improved disease severity and quality of life without any difference. CONCLUSIONS: EVLA and HLS are comparably effective concerning overall REVAS, improvement of disease severity, and quality of life. In terms of same site clinical recurrence and saphenofemoral refluxes, HLS is superior to EVLA 5 years after treatment. CLINICAL TRIAL REGISTRATION: ISRCTN18322872.

Intrathecal Baclofen therapy in Germany: Proceedings of the IAB-Interdisciplinary Working Group for Movement Disorders Consensus Meeting.

Continuous intrathecal Baclofen application (ITB) through an intracorporeal pump system is widely used in adults and children with spasticity of spinal and supraspinal origin. Currently, about 1200 new ITB pump systems are implanted in Germany each year. ITB is based on an interdisciplinary approach with neurologists, rehabilitation specialists, paediatricians and neurosurgeons. We are presenting the proceedings of a consensus meeting organised by IAB-Interdisciplinary Working Group for Movement Disorders. The ITB pump system consists of the implantable pump with its drug reservoir, the refill port, an additional side port and a flexible catheter. Non-programmable pumps drive the Baclofen flow by the reservoir pressure. Programmable pumps additionally contain a radiofrequency control unit, an electrical pump and a battery. They have major advantages during the dose-finding phase. ITB doses vary widely between 10 and 2000 µg/day. For spinal spasticity, they are typically in the order of 100-300 µg/day. Hereditary spastic paraplegia seems to require particularly low doses, while dystonia and brain injury require particularly high ones. Best effects are documented for tonic paraspasticity of spinal origin and the least effects for phasic muscle hyperactivity disorders of supraspinal origin. Oral antispastics are mainly effective in mild spasticity. Botulinum toxin is most effective in focal spasticity. Myotomies and denervation operations are restricted to selected cases of focal spasticity. Due to its wide-spread distribution within the cerebrospinal fluid, ITB can tackle wide-spread and severe spasticity.