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Summary Background Drug survival rates reflect efficacy and safety and may be influenced by the availability of alternative treatment options. Little is known about time‐dependent drug survival in psoriasis and the effect of increasing numbers of biologic treatment options. Objectives To determine whether drug survival is influenced by the availability of treatment options and by factors such as gender, psoriatic arthritis or previous biologic treatment. Methods This observational, retrospective, multicentre cohort study analysed data from patients registered in the Austrian Psoriasis Registry (PsoRA) who were treated with biologics between 1 January 2015 and 30 November 2019. Results A total of 1572 patients who received 1848 treatment cycles were included in this analysis. The highest long‐term Psoriasis Area and Severity Index improvement was observed after treatment with ixekizumab, followed by ustekinumab and secukinumab, adalimumab and etanercept. Overall, ustekinumab surpassed all other biologics in drug survival up to 48 months. However, when adjusted for biologic naïvety, its superiority vanished and drug survival rates were similar for ixekizumab (91·6%), secukinumab (90·2%) and ustekinumab (92·8%), all of them superior to adalimumab (76·5%) and etanercept (71·9%) at 12 months and beyond. Besides biologic non‐naïvety (2·10, P, What is already known about this topic? Female gender and previous biologic exposure have been discussed as predictors for decreased drug survival in patients with psoriasis, but it remains unknown whether a time‐dependent increased availability of treatment options alters biologic drug survival. What does this study add? The increased availability of alternative biologic treatments over time leads to an elevated risk for treatment discontinuation overall; therefore, drug survival analysis has to be time adjusted.Moreover, the study reveals that the impact of previous biologic treatment on drug survival is tremendous and confirms worse drug survival in female patients. Linked Comment: Gniadecki. Br J Dermatol 2021; 184:996–997.

ObjectivesConsumption of fruits and vegetables has been shown to contribute to mental and cognitive health in older adults from Western industrialized countries. However, it is unclear whether this effect replicates in older adults from non-Western developing countries. Thus, the present study examined the contribution of fruit and vegetable consumption to mental and cognitive health in older persons from China, India, Mexico, Russia, South Africa and Ghana.DesignRepresentative cross-sectional and cross-national study.Setting/SubjectsWe used data from the WHO Study on Global Ageing and Adult Health (SAGE), sampled in 2007 to 2010. Our final sample size included 28 078 participants.ResultsFruit and vegetable consumption predicted an increased cognitive performance in older adults including improved verbal recall, improved delayed verbal recall, improved digit span test performance and improved verbal fluency; the effect of fruit consumption was much stronger than the effect of vegetable consumption. Regarding mental health, fruit consumption was significantly associated with better subjective quality of life and less depressive symptoms; vegetable consumption, however, did not significantly relate to mental health.ConclusionsConsumption of fruits is associated with both improved cognitive and mental health in older adults from non-Western developing countries, and consumption of vegetables is associated with improved cognitive health only. Increasing fruit and vegetable consumption might be one easy and cost-effective way to improve the overall health and quality of life of older adults in non-Western developing countries.

The companies publishing predatory journals are an emerging problem in the area of scientific literature as they only seek to drain money from authors without providing any customer service for the authors or their readership. These predatory journals try to attract new submissions by aggressive email advertising and high acceptance rates. But in turn, they do not provide proper peer review, and therefore, the scientific quality of submitted articles is questionable. This is important because more and more people, including patients, are reading such journals and rely on the information they provide. Consequently, predatory journals are a serious threat to the integrity of medical science, and it is crucial for scientists, physicians and even patients to be aware of this problem. In this review, we briefly summarize the history of the open access movement, as well as the rise of and roles played by predatory journals. In conclusion, young and inexperienced authors publishing in a predatory journal must be aware of the damage of their reputation, of inadequate peer review processes and that unprofitable journals might get closed and all published articles in that journal might be lost.

Kompetenzorientierung, Backward Design, Constructive Alignment − Die didaktischen Modelle, die wir aus hochschuldidaktischen Schulungen kennen, klingen in der Theorie plausibel, die Anwendung auf ein oft gehaltenes Seminar verlangt jedoch grossen Zeitaufwand. Sollen zudem Erkenntnisse aus der Kognitionsforschung und Ergebnisse der Meta-Studie von Hattie eingebracht werden, ist der Wald vor lauter Bäumen bald nicht mehr zu sehen. Am Beispiel eines Einführungsseminars zu den Klassikern der Religionswissenschaft von Frazer bis Geertz wird ein textlastiges Seminar, das von den Referaten Studierender zu einzelnen Klassikern bestimmt wird, umgewandelt in eine facettenreiche Veranstaltung, in der ohne Referate dennoch die angestrebten Lernziele erreicht werden.

Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine tumor of the skin with an increasing incidence. The clinical course is variable and reliable prognostic factors are scarce. Tumor angiogenesis has been shown to have prognostic impact in different types of cancer. The aim of our study was to determine potential prognostic factors, including tumor vascularization, for clinical outcome of MCC.The medical records of 46 patients with MCC diagnosed between 1997 and 2010 were analyzed retrospectively. Tissue samples were immune-stained for the lymphatic endothelial vessel marker podoplanin/D2-40 and the panvascular marker CD31. These immunostained sections were analyzed using computer-assisted morphometric image analyses. Aside from the parameters of tumor vascularization, clinicopathologic features were investigated, and progression-free survival (PFS) and tumor-specific survival (TSS) were assessed. Univariate and multivariate analyses were performed to determine prognostic factors.Male sex of the MCC patients and a high cross-sectional whole vessel area (WVA) in relation to the entire tumor area as determined on CD31-stained tumor sections were found to be negative prognostic factors for PFS in a univariate and multivariate regression analysis. Ulceration of the primary tumor was significantly associated with both impaired PFS and TSS.Our results indicate a high prognostic impact of tumor vascularization on the clinical outcome of MCC patients. Male sex and ulceration of the primary MCC were identified as independent unfavorable prognostic markers for the clinical outcome. As an outlook, MCC patients with increased angiogenesis might be identified and subjected to a targeted anti-angiogenic treatment.

BACKGROUND AND OBJECTIVES Cutaneous squamous cell carcinoma (SCC) is known for its capacity to metastasize via lymphatic vessels. In recent studies, the level of lymphangiogenesis has been reported as a potential prognostic factor for several skin tumors. The aim of this study was to quantify lymphangiogenesis in SCC using either computer-assisted image analysis or the Chalkley count technique. Vascular parameters were evaluated and compared with respect to their predictive power for tumor metastasis. PATIENT AND METHODS In this case-control study, clinical and histological data of 15 metastatic and 15 nonmetastatic SCC patients were retrospectively analyzed. SCC samples were immunostained for the lymphatic endothelial marker D2-40 and the panvascular marker CD31, and analyzed using computer-assisted morphometric image analyses within hot spots as well as the digitalized Chalkley counting method. RESULTS Lymphatic vessel density, relative lymphatic vessel area, and lymphatic Chalkley count were significantly elevated in metastatic SCC. Tumor thickness was significantly higher in metastatic SCC, and had the highest predictive power for metastatic disease. Tumor thickness was a significant predictor of lymphangiogenic parameters. CONCLUSIONS Lymphangiogenesis is elevated in metastatic SCC but its extent is influenced by tumor thickness. Tumor thickness remains the most reliable predictive factor for metastatic disease.

Hintergrund und ziele Kutane Plattenepithelkarzinome (SCC) sind bekannt fur ihre Fahigkeit, uber Lymphgefase zu metastasieren. In neueren Studien wird das Ausmas der Lymphangiogenese als moglicher prognostischer Faktor bei einigen Hauttumoren genannt. Ziel dieser Studie war die Quantifizierung der Lymphangiogenese bei SCC entweder durch computergestutzte Bildanalyse oder mithilfe der Zahlmethode nach Chalkley. Gefasparameter wurden im Hinblick auf ihre Vorhersagekraft fur die Bildung von Tumormetastasen beurteilt und verglichen. Patienten und methoden In dieser Fallkontrollstudie wurden die klinischen und histologischen Daten von jeweils 15 SCC-Patienten mit bzw. ohne Metastasen retrospektiv analysiert. In den SCC-Proben wurde der fur das Lymphendothel spezifische Marker D2-40 und der pan-vaskulare Marker CD31 immunhistochemisch angefarbt und durch computergestutzte morphometrische Bildanalyse in Hotspots sowie mithilfe der digitalisierten Zahlmethode nach Chalkley analysiert. Ergebnisse Die Dichte von Lymphgefasen, die relative Lymphgefasflache und die mit der Chalkley-Methode ermittelte Zahl an Lymphgefasen (Chalkley-Count) waren bei metastasierten SCC signifikant erhoht. Die Tumordicke war bei metastasierten SCC signifikant hoher und besas die hochste Vorhersagekraft fur eine Metastasierung. Die Tumordicke war ein signifikanter Pradiktor fur Lymphangiogeneseparameter. Schlussfolgerungen Die Lymphangiogenese ist bei metastasierten SCC erhoht, doch ihr Ausmas wird von der Tumordicke beeinflusst. Die Tumordicke bildet weiterhin den zuverlassigsten pradiktiven Faktor fur die Metastasierung.

Objective: Regular consumption of fruits and vegetables has been found to contribute to physical health and physical functioning. However, health is not limited to the absence of physical diseases ...

Antioxidants like carotenoids play a major role in the prevention of the destructive influence of free radicals in our skin. Carotenoids, as well as all other antioxidants, are substantial substances which must be supplied by nutrition. Resonance Raman spectroscopy (RRS) allows measurement of the carotenoid content of eggs, representing a rich carotenoid source in our nutrition. A previous study showed that eggs from organic production contain higher carotenoid levels in contrast to eggs from conventionally housed chicken. The uptake of these organically produced eggs led to an increased antioxidant concentration in the skin. In this study, the effects of different storage modalities, conservation techniques, and the effects of food processing on the carotenoid levels in eggs were investigated with RRS. Common storage modalities and preservation techniques showed only a limited influence on egg-derived carotenoid concentrations. However, a colder environment (at least for shell eggs) and high-pressure preservation had the best preservative influence on the carotenoid content. Surprisingly, food processing such as boiling increased the carotenoid concentration in eggs, whilst broiling destroyed the carotenoids almost completely. In conclusion, RRS is suitable for monitoring egg-derived carotenoid levels, and carotenoid levels in eggs are generally stable under common storage and preservation modalities. Boiling in contrast to broiling of eggs might be superior in terms of carotenoid preservation within food processing.

This retrospective multicentre analysis from the Psoriasis Registry Austria (PsoRA) was conducted to determine drug effectiveness and survival of anti-tumour necrosis factor alpha (anti-TNF-α) agents in patients with moderate-to-severe chronic plaque psoriasis over a 9-year period. Data on 1,019 treatment cycles with adalimumab (n = 460), etanercept (n = 501), and/or infliximab (n = 58) administered to 827 patients (272 women, 555 men) were available for analysis. Compared with etanercept, adalimumab and infliximab showed superior short-term effectiveness. Intention-to-treat-calculated median drug survivals for adalimumab (1,264 days) and etanercept (1,438 days) were similar to each other (p = 0.74), but significantly superior to that of infliximab (477 days) (p = 7.0e-07 vs. adalimumab and p=2.2e-07 vs. etanercept, respectively). Their drug survival rates at 36 months were 51.6%, 56.0%, and 22.6%, respectively. Survival rates correlated significantly with effectiveness for adalimumab and etanercept, but not for infliximab.

Summary Background Evidence of the efficacy of dithranol and patient perspectives on the treatment is scant. Patients and Methods Using a telephone interview survey, we collected retrospective data from 63 patients (41 men [65.1 %] and 22 women [34.9 %]) who had been treated with classic inpatient dithranol (CID). PsoRA (www.psoriasisregistry.at) was used to obtain clinical data and treatment responses, which were then correlated with the interview responses. Results Fifty-two (82.5 %) patients achieved a PASI75 and 51 (81 %) a PASI90 response within a median of 12.5 (range: 3 to 25) days. Ten out of twelve (83 %) patients showed a satisfactory response to CID (PASI75 or greater reduction) despite the fact that they had previously failed to adequately respond to methotrexate, oral retinoids, cyclosporine, or ustekinumab. Overall, patients recalled a median recurrence-free interval of four (95 % CI: 3–9) months after responding to CID, which was positively correlated with the patients’ recommendation of (p = 0.018) and their overall high satisfaction with the treatment (p = 0.012). Conclusions Despite the known limitations of CID, this survey indicates that dithranol remains a highly efficacious and valuable treatment option as induction therapy in psoriasis. CID can be effective in patients who have failed to respond to systemic therapy, including traditional agents and biologics.

Zusammenfassung Hintergrund: Die Wirksamkeit von Dithranol sowie die Sicht der Patienten bezuglich dieser Behandlung ist nur unzureichend dokumentiert. Patienten und Methoden: Mittels telefonischer Befragung wurden retrospektiv Daten von 63 Patienten (41 Manner [65,1 %] und 22 Frauen [34,9 %]) nach klassischer, stationarer Dithranol-Behandlung (KSD) erhoben. Aus PsoRA (www.psoriasisregistry.at) konnten klinische Daten und Behandlungsergebnisse herangezogen und mit den Ergebnissen der Telefoninterviews korreliert werden. Ergebnisse: Innerhalb von durchschnittlich 12,5 Tagen (Spanne 3–25 Tage) erreichten 52 Patienten (82,5 %) eine PASI 75- und 51 Patienten (81 %) eine PASI 90-Reduktion. 10 von 12 Patienten (83 %) sprachen zufriedenstellend auf KSD (PASI 75 oder grosere Reduktion) an, obwohl sie zuvor auf Methotrexat, orale Retinoide, Ciclosporin oder Ustekinumab nicht adaquat angesprochen hatten. Die Patienten berichteten von einem symptomfreien Intervall von durchschnittlich vier Monaten (95 %-KI: 3–9) nach Ansprechen auf KSD; dies korrelierte positiv mit der Empfehlung der Patienten fur (p = 0,018) und ihrer grosen Zufriedenheit mit der Behandlung (p = 0,012) insgesamt. Schlussfolgerungen: Trotz der bekannten Limitationen von KSD zeigt diese Umfrage, dass Dithranol als Induktionstherapie von Psoriasis eine sehr wirksame und wertvolle Behandlungsoption darstellt. Bei Patienten, die auf systemische Therapie, inklusive herkommlicher Wirkstoffe und Biologika, nicht ansprechen, kann KSD wirksam sein. Summary Background: Evidence of the efficacy of dithranol and patient perspectives on the treatment is scant. Patients and Methods: Using a telephone interview survey, we collected retrospective data from 63 patients (41 men [65.1 %] and 22 women [34.9 %]) who had been treated with classic inpatient dithranol (CID). PsoRA (www.psoriasisregistry.at) was used to obtain clinical data and treatment responses, which were then correlated with the interview responses. Results: Fifty-two (82.5 %) patients achieved a PASI75 and 51 (81 %) a PASI90 response within a median of 12.5 (range: 3 to 25) days. Ten out of twelve (83 %) patients showed a satisfactory response to CID (PASI75 or greater reduction) despite the fact that they had previously failed to adequately respond to methotrexate, oral retinoids, cyclosporine, or ustekinumab. Overall, patients recalled a median recurrence-free interval of four (95 % CI: 3–9) months after responding to CID, which was positively correlated with the patients’ recommendation of (p = 0.018) and their overall high satisfaction with the treatment (p = 0.012). Conclusions: Despite the known limitations of CID, this survey indicates that dithranol remains a highly efficacious and valuable treatment option as induction therapy in psoriasis. CID can be effective in patients who have failed to respond to systemic therapy, including traditional agents and biologics.

Introduction Immunotherapy is a well-established treatment option in patients with metastatic melanoma. However, biomarkers that can be used to predict a response in these patients have not yet been found, putting patients at risk of severe side effects. Methods In this retrospective analysis, we investigated the association between the body mass index and ipilimumab treatment response in patients with metastatic melanoma. Patients with metastatic melanoma who received a monotherapy of up to 4 doses of ipilimumab (3 mg/kg) every 3 weeks from 2011 to 2014 in three major hospitals in Austria were included. Patients were classified into two groups: normal group (BMI

Summary Background Cutaneous squamous cell carcinoma (cSCC) is a common cancer capable of metastasis. Sentinel lymph node biopsy (SLNB) may be a valuable adjunct for patients with cSCC at high risk for metastasis. However, data on risk factors for metastasis and results of SLNB from patients with cSCC are limited. Objectives To evaluate risk factors for metastasis in patients with cSCC in a large cohort study with long-term follow-up and to determine the value of SLNB. Methods We retrospectively analysed all records of patients who underwent excision of cSCC between January 2005 and August 2009 at a tertiary referral centre. In total, 143 patients were included in the cohort, including 17 patients with SLNB and a follow-up time of ≥ 24 months. Results Tumour thickness > 4 mm and recurrent cSCC were strongly associated with metastatic disease. All metastases in this cohort occurred within 24 months of follow-up. SLNB showed a low sensitivity with regard to the development of metastasis. Six of 17 patients developed metastatic disease despite a negative SLNB. Conclusions Patients with risk factors (cSCC with a tumour thickness > 4 mm or recurrent disease) may develop metastases within the first 2 years despite a negative SLNB. Therefore these patients should be closely monitored during the follow-up. Based on our data SLNB does not provide diagnostic value for patients with cSCC.

Hintergrund Patienten mit Psoriasis sind mit einer krankheitsbedingten Einschrankung ihrer Lebensqualitat konfrontiert, weshalb einer hochqualitativen dermatologischen Versorgung ein besonderer Stellenwert zukommt. Patienten und methodik Wir fuhrten einen bundesweiten Querschnitt-Survey in Osterreich (BQSAustria Psoriasis 2014/2015) mit dem Schwerpunkt auf Lebensqualitat und Therapiezufriedenheit bei Patienten mit Psoriasis in dermatologischer Behandlung vorwiegend an Zentren mit uberwiegend tertiaren Versorgungsaufgaben durch. Ergebnisse 70,2 % der 1184 befragten Patienten berichtete uber eine eingeschrankte Lebensqualitat (DLQI 2-5: 29,4 %; 6-10: 19,3 %; 11-15: 11,5 %; 16-20: 5,2 % und > 20: 4,9 %) trotz Behandlung innerhalb der letzten vier Wochen (mit lokaler Therapie in 88,2 % und/oder systemischer Therapie in 38,7 % der Falle). Mit den verabreichten Therapien konnte im Durchschnitt kein einziges von 25 definierten subjektiven Behandlungszielen im gewunschten Ausmas erreicht werden. So litten 82,2 % der Patienten trotz Behandlung weiter unter Juckreiz, wobei statistisch hochsignifikante Assoziationen mit einem schlechten Gesundheitszustand in der letzten Woche (Spear-man-Rangkorrelation; p = 1.1e-45), dem Ausmas des psoriatischen Korperoberflachenbefalls (p = 3.2e-11) und Kopfhautbefalls (p = 3.2e-11) sowie Schmerzen (p = 2.3e-22) vorlagen. Die Behandlung mit einem Biologikum war mit einer signifikant hoheren Patientenzufriedenheit verbunden (Wilcoxon-Test, p = 2.0e-16). Schlussfolgerungen Die Lebensqualitat der meisten osterreichischen Patienten mit Psoriasis in dermatologischer Versorgung ist krankheitsbedingt beeintrachtigt, und es besteht ein Verbesserungspotenzial bei der Umsetzung von Behandlungszielen.

BACKGROUND Patients with psoriasis experience impairment in quality of life. Thus, high-quality dermatological care is of particular importance. PATIENTS AND METHODS We performed a nationwide cross-sectional survey in Austria (BQSAustria Psoriasis 2014/2015) with a special focus on quality of life and satisfaction with treatment among psoriasis patients predominantly treated at tertiary care centers. RESULTS Overall, 70.2 % of 1,184 patients reported impaired quality of life (DLQI 2-5: 29.4 %; 6-10: 19.3 %; 11-15: 11.5 %; 16-20: 5.2 % and > 20: 4.9 %) despite treatment over the preceding four weeks (topical treatment in 88.2 % of cases and/or systemic treatment in 38.7 %). On average, none of the 25 defined subjective treatment goals was achieved to a sufficient degree. In particular, 82.2 % of patients continued to have pruritus despite treatment, which was highly significantly associated with a poor general health status over the preceding week (Spearman's rank correlation; p = 1.1e-45), the extent of body surface area (p = 3.2e-11) and scalp area (p = 3.2e-11) affected, as well as pain (p = 2.3e-22). Treatment with a biologic was significantly correlated with higher patient satisfaction (Wilcoxon-Test, p = 2.0e-16). CONCLUSIONS Despite dermatological care, the majority of Austrian psoriasis patients continues to experience impaired quality of life; there is potential for improvement in the achievement of treatment goals.

The effect of tissue-tolerable plasma (TTP) on inflammatory diseases such as psoriasis was investigated. Three plaques of six psoriatic patients were subjected to different treatments (A: TTP, brine baths (BB)+5% salicylic acid ointment (SAO); B: BB+SAO; C: BB, UV irradiation, SAO+dithranol). While redness and infiltration was reduced in groups A and C, scaling was reduced in group C. TTP temporarily reduced the bacterial colonization on the skin lesions. In summary, the treatment of psoriatic plaques with TTP showed no significant advantage over conventional therapies.

Potential antimicrobial effects of sequential applications of tissue-tolerable plasma (TTP) and the conventional liquid antiseptic octenidine dihydrochloride (ODC) were investigated. 34 patients with chronic leg ulcers were treated with TTP, ODC or a combination of both. The bacterial colonization was measured semi-quantitatively before and immediately after treatment and changes in the microbial strains' compositions before and after antiseptic treatments were analyzed. All antiseptic procedures reduced the bacterial counts significantly. The sequential application of TTP and ODC displayed the highest antimicrobial efficacy. Me combined use of TTP and conventional antiseptics might represent the most efficient strategy for antiseptic treatment of chronic wounds.

The results of the risk assessment of the tissue-tolerable plasma (TTP) jet kINPen med ® and first results of pilot clinical studies are presented. Producing an atmospheric pressure plasma, this plasma jet entails no risk for humans in terms of temperature increase, UV radiation or free radical formation by the plasma. The antiseptic efficacy in vitro on porcine skin and in vivo on human skin was compared to that of octenidine. TTP could significantly reduce the bacterial load in comparison to untreated skin. However, the slightly reduced antiseptic properties of TTP are attributed to the current parameter set-up and technical limitations.

Compared to the onshore, the offshore wind farms have higher capacity factors. These high-capacity factors of the offshore wind farms and different wind conditions on the sea require new innovations to ensure a secure electricity grid. Wind power forecasting is indispensable to improve both the penetration of the wind energy in the energy mix and the economical and technical integration of a large share of the wind energy.

Serum markers can be important tools for prognostic classification and treatment monitoring in cancer patients. The MAP-kinase pathway, which is upregulated in the majority of melanoma patients, can be activated by hepatocyte-growth factor (HGF) through the proto-oncogene c-MET. The aim of this study was to evaluate the predictive and prognostic value of circulating HGF in terms of treatment outcome and survival compared with a widely established serum marker, protein S-100B, in patients with advanced metastatic melanoma. HGF and S-100B were measured in serum samples of 101 patients with metastatic melanoma (American Joint Committee on Cancer stage IV) before and after treatment and 50 patients with stage I/II melanoma. HGF and S-100B correlated significantly with the stage of disease (P=0.032 and P

Earlier investigations regarding the distribution of the bacterial flora on the human skin demonstrate that the hair follicle acts as a bacterial reservoir, providing a quick source for secondary recontamination. These findings highlight the importance of the hair follicle as a target for modern antiseptics. In the present study, we have assessed the follicular penetration of a curcumin-labeled particle-associated antiseptic into porcine skin by laser scanning microscopy. Therefore, the follicular penetration depth of the curcumin-labeled particle-associated antiseptic was compared to the follicular penetration depth of curcumin-labeled particles without antiseptic. The investigation was performed in vitro using porcine skin biopsies. By superposition of the images acquired in the transmission and the fluorescent modus, it was possible to visualize the distribution of the fluorescent dye inside the hair follicles. Quantitative and qualitative results showed that both dispersions penetrated efficiently into the hair follicles. The average penetration depth of the particles with attached antiseptic polihexanide was significantly higher than that of particles without the attached antiseptic. Also, whilst very little sample preparation was needed, laser scanning microscopy was found to be an efficient tool to visualize the skin relief and in particular the hair follicle shaft and localize fluorescent markers within the skin tissue and hair follicles.

Colonization and infection of wounds represent a major reason for the impairment of tissue repair. Recently, it has been reported that tissue-tolerable plasma (TTP) is highly efficient in the reduction of the bacterial load of the skin. In the present study, the antiseptic efficacy of TTP was compared to that of octenidine hydrochloride with 2-phenoxyethanol. Both antiseptic methods proved to be highly efficient. Cutaneous treatment of the skin with octenidine hydrochloride and 2-phenoxyethanol leads to a 99% elimination of the bacteria, and 74% elimination is achieved by TTP treatment. Technical challenges with an early prototype TTP device could be held responsible for the slightly reduced antiseptic properties of TTP, compared to a standard antiseptic solution, since the manual treatment of the skin surface with a small beam of the TTP device might have led to an incomplete coverage of the treated area.

Increasing levels of wind energy are adding to the uncertainty and variability inherent in electricity grids and are consequently driving changes. Here, some of the possible evolutions in optimal short-term energy balancing to better deal with wind energy uncertainty are investigated. The focus is mainly on managing reserves through changes in scheduling, in particular market structure (more regular and higher resolution scheduling), reserve procurement (dynamic as opposed to static), and improved operational planning (stochastic as opposed to deterministic). Infrastructure changes including flexible plant, increased demand side participation, more interconnection, transmission, larger balancing areas, and critically improved forecasting can also be significant and are dealt with in the discussion. The evolutions are tightly coupled, their impact is system-dependent and so no “best” set is identifiable but experience of system operators will be critical to future developments. Science Foundation Ireland Deposited by bulk import

Background Actinic cheilitis (AC) represents the equivalent of actinic keratosis on the lip. Various treatment modalities are available and the efficacy of diclofenac in hyaluronic acid has recently been described. Reflectance confocal microscopy (RCM) is a non-invasive imaging technique which has recently been applied for the diagnosis of actinic keratoses. Herein, we describe the applicability of RCM for the diagnosis of AC and for monitoring of treatment response of AC to diclofenac in hyaluronic acid. Methods Ten Caucasian patients with clinical suspicion for AC were included in this study. To obtain a non-invasive diagnosis, RCM was performed at baseline, followed by biopsy and respective confocal-histopathological correlation. Six patients with a histological diagnosis of AC were treated with diclofenac in hyaluronic acid, whereby monitoring was performed by RCM. Results Reflectance confocal microscopy was able to correctly identify 6/7 cases of AC and 3/3 cases of benign lesions. The most important RCM criteria for diagnosis of AC were cellular atypia at the stratum spinosum and granulosum with atypical honeycomb pattern. One patient with AC was misclassified as inflammatory cheilitis by RCM as it showed marked inflammatory response and lacked clear signs of cellular atypia on RCM imaging. Following topical treatment with diclofenac gel, 5/6 patients (83%) showed a good treatment response with regression of dysplasia on consecutive RCM examination. Conclusions Reflectance confocal microscopy is a promising tool for the non-invasive diagnosis and monitoring of actinic cheilitis. However, marked inflammation represents a potential diagnostic pitfall. In this regard, biopsy should be performed in doubtful cases.

Human papillomaviruses infect the squamous epithelia of the skin and cause warts, and are occasionally found in squamous cell carcinomas. Since cell-mediated immunity plays a crucial role in the control of HPV-infections, organ transplant recipients, unable to mount an adequate T-helper 1 cell-mediated immune surveillance, frequently develop widespread and resistant induced warts. Skin tumors, especially squamous cell carcinomas, are the most common post-transplantation neoplasm. Warts, actinic keratoses and invasive squamous cell carcinomas are known to develop at the same time in the areas. The role of HPV in the development of invasive squamous cell carcinoma under immunosuppression, remains to be elucidated in respect to common risk factors and increased numbers of warts potentially indentifing patients at increased risk for carcinoma. We prospectively studied 1690 organ transplant recipients in the dermatology clinic at the Charite University Hospital in Berlin, to evaluate risk factors being involved in the development of HPV-induced warts and to assess a potential association of with the development of non-melanoma skin cancers in this population. The cumulative incidence of warts steadily increased throughout the post-transplant years. The presence of more than 10 verrucae was associated with the development of actinic keratoses, invasive squamous cell carcinoma and basal cell carcinoma. This study shows clear evidence that certain risk factors of skin carcinogenesis in organ transplant recipient such as increased age at transplantation, a high dose of immunosuppression related to a specific type of graft and use of azathioprine or cyclosporine are strongly associated with an increased incidence of warts. Furthermore, HPV-induced verrucae vulgares could be used as a potential predictor for the development of coincidental non melanoma skin cancer in organ transplant recipients and therefore could serve as an early identification marker of skin cancer high-risk patients. The challenging management of warts in organ transplantation patients is reviewed.

There is increasing evidence that vascular remodeling and endothelial cell activation promote acute and chronic inflammation. Thrombospondin 1 (TSP-1) is a potent endogenous angiogenesis inhibitor thought to play an important role in maintaining cutaneous vascular quiescence. We first investigated TSP-1 expression in human and contact hypersensitivity (CHS) reactions and found that TSP-1 was upregulated in the inflamed skin of patients and in mice. To elucidate the function of TSP-1 in cutaneous inflammation, we induced CHS reactions in the skin of mice with targeted epidermal TSP-1 overexpression in TSP-1-deficient mice and in wild-type mice. We found decreased edema formation, angiogenesis, and inflammatory infiltrate in the inflamed skin of TSP-1 transgenic mice. Conversely, TSP-1-deficient mice exhibited an enhanced and prolonged inflammation, characterized by increased edema formation, enhanced vascular remodeling, and increased neutrophilic infiltrate, when compared with wild-type mice. Moreover, we found strong upregulation of the proinflammatory cytokines IL-1beta, macrophage inflammatory protein 2, and tumor necrosis factor-alpha in the inflamed skin of TSP-1-deficient mice. Our results indicate that TSP-1 downregulates cutaneous delayed-type hypersensitivity reactions by acting on several distinct pathways mediating skin inflammation.

Cutaneous adverse drug reactions (CADRs) in psychiatric pharmacotherapy are common, potentially harmful, and among the most frequent types of adverse events. To date, most of the data regarding CADRs to psychotropic medications are anecdotal, and systematic studies are lacking, particularly with respect to modern "second-generation" drugs.Data were drawn from a database of 208,401 psychiatric inpatients monitored by the multicenter drug safety surveillance project Drug Safety in Psychiatry (Arzneimittelsicherheit in der Psychiatrie [AMSP]) during the years 1993-2005. The project surveys clinically relevant adverse reactions to all marketed psychotropic drugs.Two hundred fourteen cases of clinically relevant CADRs with a "probable" or "definite" attribution to a single psychotropic compound were identified (0.1%), of which 7 were life threatening (3.3% of CADR cases). Eruptions occurred irrespective of age and mainly in women. The gender effect was significant only for mood-stabilizing antiepileptic drugs (AEDs; P = .001). Substances with the highest and statistically significant CADR risk were AEDs (P.0001), particularly lamotrigine and carbamazepine. For the most part, the incidence in antidepressants did not differ from the mean CADR rate of the monitored drugs in this survey (0.103%). However, CADRs were seen significantly less often with modern antidepressants (such as selective serotonin reuptake inhibitors and dual-mechanism or other second-generation antidepressants) than with classical tricyclic and tetracyclic antidepressants (P = .048). Conventional and atypical antipsychotics alike had the lowest rates of dermatologic side effects.Although serious complications are rare, clinicians should be aware of CADRs, particularly with AED mood stabilizers. Modern second-generation drugs appear to be associated with a rather low CADR risk.

Endothelial cells are critically involved in the pathogenesis of inflammation, which is characterized by vasopermeability, plasma leakage, leukocyte recruitment, and neovascularization. Therefore, inhibitors of endothelial cell function could reduce inflammation. In this study, we evaluated the effects of the angiogenesis inhibitor vasostatin on inflammations induced by contact hypersensitivity reactions in mouse ears. Vasostatin-treated mice revealed significantly reduced edema formation, resulting from lower plasma leakage and inhibition of inflammation-associated vascular remodeling. Intravital microscopy studies of inflamed ears showed a decrease in the fraction of rolling leukocytes in vasostatin-treated mice, and Lycopersicon esculentum lectin-perfused ears revealed fewer leukocytes adherent to the vessel wall. The inflammatory infiltrate from vasostatin-treated mice was characterized by fewer CD8+ T cells, neutrophils, and macrophages compared to the saline-treated animals. In a modified Miles assay, vasostatin inhibited vascular endothelial growth factor-A-induced permeability, and inflamed ear tissues from vasostatin-treated mice expressed significantly reduced levels of the vascular destabilizer angiopoietin-2. These results reveal a previously unrecognized anti-inflammatory property of the angiogenesis inhibitor vasostatin, and suggest that vasostatin is a potential candidate drug for the treatment of inflammation.