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While the incidence of infections with the human immunodeficiency virus largely remained unchanged in Germany, an increase of other sexually transmitted infections (STIs) was observed. The aim was to analyse the effectiveness of our sexual education lecture for students in improving the awareness, knowledge and prevention of STIs. We conducted a cross-sectional survey after students had attended our extra-curricular lecture at the Department of Dermatology of the Ludwig-Maximilians-University of Munich, Germany (LMU). We compared the data with a previously performed study in which the same survey was carried out before the lecture had started. A total of 5866 questionnaires were included in the analysis. After attending the lecture significantly more students were aware of STIs (syphilis: 36.8% (before) vs. 63.5% (after); chlamydia: 30.5% vs. 49.3%; gonorrhoea: 22.4% vs. 38.2%; human papillomaviruses (HPV): 17.7% vs. 30.2%), the transmission pathways of STIs (oral: 36.6% vs. 82.6%; vaginal: 81.8% vs. 97.3%; anal: 42.8% vs. 94.0%; penile: 68.7% vs. 92.1%), knew that the HPV vaccination is directed against a virus (36.8% vs. 56.9%) and were interested in receiving a vaccination (57.7% vs. 78.8%). This study demonstrates the positive educative effects of our lecture for awareness and improved knowledge of STIs. To satisfy the need for a comprehensive sexual education, a combination of school and health facility-based programmes should be implemented as one single lecture cannot convey the entire information about STIs. [ABSTRACT FROM AUTHOR]

Background: Demodex spp. mites are the most complex resident of the human skin microbiome. Although they are considered commensals, they can be pathophysiologically relevant in inflammatory skin diseases like rosacea. Until now, there is no culture system available for these mites except for using live vertebrate hosts. Objectives: Our aim was to establish an ex vivo culture of human Demodex mites and to characterize the sebogenesis‐dependent mite density. Methods: Demodex mites were cultivated in pilosebaceous units of human skin explants, called human organotypic skin explant culture (hOSEC). Furthermore, different sebogenesis‐modifying additives were evaluated. Mites and mite survival were evaluated using light and fluorescence microscopy. Results: After 90 days of incubation, living Demodex mites – including eggs, larvae and nymphs – were detected in the dissected skin samples. Incubation for 30 days with anabolic steroids (testosterone and trenbolone) as well as retinol and retinoic acid (isotretinoin) yielded a reduced mite density. Conclusions: With this technique, mites can be cultivated ex vivo for the first time, thereby establishing new ways to investigate Demodex spp. The sebostatic effect of isotretinoin might explain the mechanism of action in the off‐label treatment of rosacea. We anticipate our findings to be the basis of an accelerated research on our most complex commensal, its life, biology and physiology. [ABSTRACT FROM AUTHOR]

While the incidence of infections with the human immunodeficiency virus largely remained unchanged in Germany, an increase of other sexually transmitted infections (STIs) was observed. The aim was to analyse the effectiveness of our sexual education lecture for students in improving the awareness, knowledge and prevention of STIs. We conducted a cross-sectional survey after students had attended our extra-curricular lecture at the Department of Dermatology of the Ludwig-Maximilians-University of Munich, Germany (LMU). We compared the data with a previously performed study in which the same survey was carried out before the lecture had started. A total of 5866 questionnaires were included in the analysis. After attending the lecture significantly more students were aware of STIs (syphilis: 36.8% (before) vs. 63.5% (after); chlamydia: 30.5% vs. 49.3%; gonorrhoea: 22.4% vs. 38.2%; human papillomaviruses (HPV): 17.7% vs. 30.2%), the transmission pathways of STIs (oral: 36.6% vs. 82.6%; vaginal: 81.8% vs. 97.3%; anal: 42.8% vs. 94.0%; penile: 68.7% vs. 92.1%), knew that the HPV vaccination is directed against a virus (36.8% vs. 56.9%) and were interested in receiving a vaccination (57.7% vs. 78.8%). This study demonstrates the positive educative effects of our lecture for awareness and improved knowledge of STIs. To satisfy the need for a comprehensive sexual education, a combination of school and health facility-based programmes should be implemented as one single lecture cannot convey the entire information about STIs. [ABSTRACT FROM AUTHOR]

Dermal replacement materials bioactivated with cyanobacteria have shown promising potential for wound regeneration. To date, extraction of cyanobacteria RNA from seeded scaffolds has not been described. The aim of this study was to develop a method to isolate total RNA from bioactivated scaffolds and to propose a new approach in determining living bacteria based on real‐time PCR. Transgenic Synechococcus sp. PCC 7002 (tSyn7002) were seeded in liquid cultures or scaffolds for dermal regeneration in vitro and in vivo for 7 days. RNA was extracted with a 260/280 ratio of ≥2. The small subunit of the 30S ribosome in prokaryotes (16S) and RNAse P protein (rnpA) were validated as reference transcripts for PCR analysis. Gene expression patterns differed in vitro and in vivo. Expression of 16S was significantly upregulated in scaffolds in vitro, as compared to liquid cultures, whilst rnpA expression was comparable. In vivo, both 16S and rnpA showed reduced expression compared to in vitro (16S: in vivo Ct value 13.21 ± 0.32, in vitro 12.44 ± 0.42; rnpA in vivo Ct value 19.87 ± 0.41, in vitro 17.75 ± 1.41). Overall, the results demonstrate rnpA and 16S expression after 7 days of implantation in vitro and in vivo, proving the presence of living bacteria embedded in scaffolds using qPCR. [ABSTRACT FROM AUTHOR]

Background: Intralesional 5‐fluorouracil (5‐FU) in combination with triamcinolone acetonide (TAC) has been recommended as a promising alternative for keloids not responding to silicone‐based products, cryotherapy or intralesional corticosteroids alone. Although numerous studies support the efficacy of this regime, there is a lack of objective data. Objectives: In this study, we evaluate the therapeutic effect of four courses of intralesional 5‐FU in combination with TAC (3 : 1) utilizing 3D analysis (PRIMOS®pico), ultrasound and scar scales such as the Patient and Observer Scar Assessment Scales (POSAS) and the Dermatology Life Quality Index (DLQI). Methods: Twenty‐five patients with keloids were treated using 5‐FU and TAC every 4 weeks. Objective assessments were performed and the scar scales administered at baseline, as well as during consecutive visits at 1‐ and 12‐month follow‐up (FU). Routine laboratory tests were performed at baseline and at 1‐month FU. Results: 3D PRIMOS and ultrasound measurements revealed highly significant and stable reductions in height (baseline mean score: 4.0 ± 1.7 mm, 1‐month FU mean score: 1.5 ± 0.8 mm, 12‐month FU mean score: 1.8 ± 0.9 mm, P = <0.0001), volume (baseline mean score: 1,105 ± 911.5 mm3, 1‐month FU mean score: 416.1 ± 218.1 mm3, 12‐month FU mean sore: 431.2 ± 253.6 mm3, P = <0.0001, respectively) and penetration depth of keloids (relative reduction between baseline and 12‐month FU of 74.4%, P = <0.0001). The POSAS and DLQI scales confirmed significant objective and subjective improvements in scar appearance in all categories. The life quality associated with keloid appearance improved from a 'moderate effect' to a 'small effect' throughout the course of the study. Conclusions: Results of this study confirm the efficacy and safety of the combination of 5‐FU and TAC in keloids. Treatments were well tolerated and demonstrated stable results at 12‐month FU. [ABSTRACT FROM AUTHOR]

Background: Demodex spp. mites are the most complex member of the human skin microbiome. Mostly they are commensals, although their pathophysiological role in inflammatory dermatoses is recognized. Demodex mites cannot be cultivated in vitro, so only little is known about their life cycle, biology and physiology. Different bacterial species have been suggested to be the endobacterium of Demodex mites, including Bacillus oleronius, B. simplex, B. cereus and B. pumilus. Objectives: Our aim was to find the true endobacterium of human Demodex mites. Methods: The distinct genetic and phenotypic differences and similarities between the type strain and native isolates are described by DNA sequencing, PCR, MALDI‐TOF, DNA‐DNA hybridization, fatty and mycolic acid analyses, and antibiotic resistance testing. Results: We report the true endobacterium of Demodex folliculorum, independent of the sampling source of mites or life stage: Corynebacterium kroppenstedtii subsp. demodicis. Conclusions: We anticipate our finding to be a starting point for more in‐depth understanding of the tripartite microbe–host interaction between Demodex mites, its bacterial endosymbiont and the human host. [ABSTRACT FROM AUTHOR]

Background: Chronic viral infections caused by highly contagious human papillomaviruses (HPVs) from the alpha genus are a substantial risk factor for tumour diseases. Objectives: The goal of this study was to compare the HPV infection pattern with histology in a patient group of immunocompromised HIV+ and non‐immunocompromised patients with anal intraepithelial neoplasia. Materials and Methods: Tissue samples (n = 210) from the anogenital area of 121 patients underwent retrospective histological and molecular examination for HPV DNA prevalence by chip analysis. The study was part of a cancer screening from the Dermatology Department of the LMU Munich, Germany. All data were collected and processed anonymously. Results: HPV 6 or 11 are more abundant in tissue samples from histologically diagnosed condylomata acuminata (47.7%) compared to grade 1, 2, and 3 intraepithelial neoplasias (IN 1‐3). Detection of high‐risk (hr) alpha‐HPV DNA was significantly higher in tissue samples from IN 3 (67.5%) compared to IN 1 and 2 (12.9%), and compared to condylomata acuminata (29.5%). No HPV types were detected in histologically unremarkable tissue samples. There was a significant association between the prevalence of HPV 16 and the classifications IN 1 to IN 3 (χ2 (2) = 13.62, P = 0.001). We identified a significant correlation between the prevalence of high‐risk and low‐risk (lr) HPV types and HIV, especially mixed infections of different HPV types correlated with high‐grade IN. Based on the present data, we suggest the risk of carcinoma in HIV+/− patients (RICH) score and test it in the 121 patients. Conclusions: hr alpha‐HPVs, mainly HPV 16, are associated with increased oncogenic potential of premalignant lesions (IN 1‐3), especially in HIV+ patients. Based on the combination of HIV/HPV‐testing and histological analysis, we identified correlations that could potentially forecast the risk of malignant transformation and summarized them in the form of RICH score. [ABSTRACT FROM AUTHOR]

Background: High‐risk α‐genus human papillomaviruses (α‐HPVs) are linked to cervical and genital carcinomas; however, their correlation with cutaneous squamous cell carcinoma (cuSCC) or premalignant skin lesions remains controversial. Objective: We evaluated the contribution of high‐risk α‐HPV to the occurrence of cuSCC, Bowen's disease and actinic keratosis (AK), and the distribution of high‐risk α‐HPV genotypes in these cutaneous tumours. Methods: HPV genotypes were determined using a commercial PCR‐based microarray on skin tissue samples collected from 76 [38 young (<60 years) and 38 elderly (>60 years)] cuSCC, 34 Bowen's disease, 48 AK patients and 10 young controls. Associations between α‐HPV prevalence and relevant risk factors were analysed. Results: High‐risk α‐HPV was more frequently detected in cuSCC patients (57.9%) than in the patients with Bowen's disease (38.2%), AK (0.0%) and control patients (10.0%). The high‐risk α‐HPV prevalence was higher in young than in elderly cuSCC patients (65.8% vs. 50.0%, P = 0.031). The most common HPV type was 16, present in 90.9% of all HPV‐carrying cuSCC patients. Multiple infections with different high‐risk α‐HPV types were found in 20.5% of HPV‐related cuSCC, whereas only single infection with type 16 was found in Bowen's disease. Although sun exposure is known as a major risk factor for cuSCC, high‐risk α‐HPVs were more frequently found in non‐exposed sites rather than in sun‐exposed sites of cuSCC. Conclusion: Multiple infections, as well as single infection with high‐risk α‐HPV may link to cuSCC. In spite of the involvement of high‐risk α‐HPV at high levels in cuSCC and Bowen's disease, no high‐risk α‐HPV was detected in AK patients, suggesting that Bowen's disease rather than AK might be involved in the development of HPV‐related cuSCC as a precursor. [ABSTRACT FROM AUTHOR]

Background and objective: Striae distensae (SD) represent therapeutically challenging forms of dermal atrophic scarring. In addition to topical ointments, medical needling and various energy‐based devices, non‐ablative fractional lasers have been suggested for their improvement. However, objective evaluations of their efficacy are widely missing. In this study, we aimed to assess the clinical improvement of SD albae after three treatments with a non‐ablative fractional 1565 nm Er: glass laser by employing three‐dimensional analysis and several questionnaires. Methods: A total of 16 Caucasians suffering from SD albae were included in this prospective study. Every patient received three treatments – one every 4 weeks – using a non‐ablative, fractional 1565 nm laser (two passes: 300 μbeams/cm2, 40 mJ inside the SD; 150 μbeams/cm2, 50 mJ inside the SD and within the surrounding area). Questionnaires (DLQI, POSAS), digital photography and three‐dimensional analysis employing PRIMOS® software and VECTRA® camera system were taken at baseline, 1 and 6 months after the last treatment. Results: Evaluation of objective measurements at 6‐month follow‐up (FU) showed a significant reduction in depth of atrophic lesions by 31.7% and less skin irregularities with Smax at baseline of 621.2 μm decreasing to 411.6 μm (P < 0.01, respectively). Improvement in objective measurements was supported by significant changes in patients' rating of skin appearance. POSAS patient total score declined from 33.5 points to 17.5 points throughout the study (P < 0.001). From baseline to 6‐month FU, patients' life quality improved by 68.0% (DLQI score). Procedures showed no lasting negative side‐effects and little to no down time. Conclusion: The use of a fractional non‐ablative 1565 nm laser represents a safe approach for the treatment of SD albae. Clinically observed improvements were supported by significant data from objective measurements. The results achieved at 1‐month FU represented at 6‐month FU, showing stable clinical improvements. [ABSTRACT FROM AUTHOR]

Cryoglobulinemic vasculitis associated with chronic hepatitis C: a case of skin lesions/purpura in a 49-year-old Caucasian male patient Dear Editor, Cryoglobulinemia is a rare disease in humans (incidence ~1: 100,000) and may cause vasculitis in small vessels affecting the skin, kidneys, and peripheral nervous system. In treatment-resistant patients, a monotherapy with the B-cell depleting agent rituximab, potentially in combination with systemic corticosteroids, represents a viable treatment option for severe cryoglobulinemic vasculitis. [Extracted from the article]

The first novel coronavirus (SARS-CoV-2) cases occurred in Germany after contact with a Chinese business delegate between 19 and 22 January 2020 near the city of Munich, Bavaria. Likewise, classical outpatient care involves face-to-face contact with patients and clustering of patients before the consultation in confined waiting rooms. It is likely, in times of learning on demand and home learning as well as increased demand for rapid and remote dermatological diagnosis and therapy, that even after the current SARS-CoV-2 pandemic, these available resources will be of great value. [Extracted from the article]

Demodex spp. mites are an often neglected member of the human skin microbiome. Mostly they are commensals, although their pathophysiological role in rosacea, spinulosis folliculorum, and other skin diseases is recognized. Little is known about their life cycle, biology, and physiology. Demodex mites cannot be cultivated in vitro, thereby complicating research immensely. The manual extraction from human sebum is laborious and death can only be detected by surrogate markers like ceased movement or loss of fluorescence. Here we present a new approach for the extraction of larger mite numbers and the hitherto most precise way to detect death. The extraction of mites from sebum and debris by hand can be accelerated by a factor 10 using sucrose gradient centrifugation, which is well tolerated by the mites. Staining with propidium iodide allows for easy identification of dead mites, excluding frail mites that stopped moving, and has no negative effect on overall mite survival. We anticipate our methods to be a starting point for more sophisticated research and ultimately in vitro cultivation of Demodex spp. mites. [ABSTRACT FROM AUTHOR]

Copyright of Der Internist is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Rosacea is a common chronic inflammatory skin disorder that typically occurs in adults and affects the face. Synonyms of rosacea include 'acne rosacea', 'couperose' and 'facial erythrosis', in German also 'Kupferfinne' and 'Rotfinne'. The disorder is characterised by a chronic and flaring course and is caused by a genetically predisposed, multifactorial process. A higher incidence is seen in people with fair skin and a positive family history. The characteristic rosacea symptoms manifest primarily, but not exclusively centrofacially, with forehead, nose, chin and cheeks significantly affected. Based on the various main symptoms a classification of the individual clinical pictures can be performed. However, a classification often does not reflect the clinical reality, since the various symptoms commonly coexist. The present review provides an introduction on pathogenesis and clinical manifestations of rosacea and prefers a symptom-oriented therapy approach. [ABSTRACT FROM AUTHOR]

Zusammenfassung Rosazea ist eine häufige chronisch-entzündliche Hauterkrankung, die typischerweise bei Erwachsenen vorkommt und das Gesicht betrifft. Synonyme der Rosazea sind Acne rosacea, Kupferfinne, Rotfinne, Couperose und Rosacea. Die Erkrankung ist durch einen chronischen und schubartigen Verlauf gekennzeichnet und wird durch ein genetisch prädisponiertes, multifaktorielles Geschehen bedingt. Ein vermehrtes Auftreten wird bei hellem Hauttyp und positiver Familienanamnese verzeichnet. Die charakteristischen Rosazea-Symptome manifestieren sich vorwiegend, aber nicht ausschließlich zentrofazial, wobei Stirn, Nase, Kinn und die Wangen maßgeblich betroffen sind. Dabei werden unterschiedliche Hauptsymptome voneinander unterschieden, anhand derer eine Klassifikation der verschiedenen klinischen Bilder vorgenommen werden kann. Eine Klassifizierung wird oftmals jedoch nicht der klinischen Realität gerecht, da die verschiedenen Symptome häufig gemeinsam auftreten. Diese Übersichtarbeit führt in die Pathogenese und Klinik der Rosazea ein und plädiert für einen symptomorientierten Therapieansatz. [ABSTRACT FROM AUTHOR]

Background Anhidrotic ectodermal dysplasia ( AED) is an inherited syndrome, which originates mainly from genetic alteration of the ectodysplasin A ( EDA) gene. It regularly affects the adnexa of the skin which results in a characteristic phenotype of the patients including hypo- or anhidrosis leading to severe disturbances in the regulation of body temperature. Objectives To prevent the development of the symptoms in early childhood promising therapeutic approaches are currently under clinical investigation. In this context, timely diagnosis of this genetic syndrome is crucial. The purpose of our study was the investigation of modern non-invasive imaging methods such as optical coherence tomography ( OCT) and reflectance confocal microscopy ( RCM) in the immediate diagnosis of AED. Methods We examined a 3-year-old boy with the suspicion for an AED syndrome and his family members with RCM and OCT to document presence and characteristic features of sweat glands in comparison to non-affected individuals. Results The patient and the affected brother showed significantly reduced sweat glands in the imaging compared to the controls. The genetic analysis revealed a mutation of the EDA gene for hemizygosity previously associated with AED and the mother was revealed as the conductor of the genetic alteration. Conclusions With the help of non-invasive imaging, we were able to detect sweat gland dysplasia in the affected family members without performing a biopsy which led us to the diagnosis of an AED. The application of modern dermatological imaging techniques might serve as valuable supplementary tools in the immediate, non-invasive diagnosis of genetic syndromes especially in newborns when early therapeutic approaches are planned. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a commonly used and effective treatment option for nonmelanoma skin cancer. Apart from local side-effects such as pain, oedema and erythema, no major adverse events occur in the majority of cases. Here we report on five patients who developed memory deficits such as transient global amnesia immediately after PDT for actinic keratosis. All PDT treatments were performed according to standard therapy protocols. The reported patients had a memory gap for the entire procedure, as well as for the consecutive emergency medical care. Other common neurological causes such as stroke or epileptic seizures were excluded. No focal neurological deficits were detectable. The symptoms had a fairly rapid onset following red-light illumination and were reversible without sequelae within 1-24 h. No correlation of the condition and pain during the illumination could be revealed. Magnetic resonance imaging of the brain revealed punctuated lesions in the hippocampus as a potential morphological correlate in one patient. The association between amnestic syndromes and PDT is novel and has not previously been reported. Even though PDT is considered a safe treatment modality, the possibility of neurological adverse events, albeit rare, should be kept in mind. [ABSTRACT FROM AUTHOR]

Background Measuring quality of life through questionnaires is a common method to evaluate the impact of different afflictions on the patient's well-being, especially in the field of dermatology where appearance changing afflictions are common. Objectives A variety of questionnaires has been used to distinguish different skin conditions like psoriasis, atopic dermatitis and scars. Using the Dermatology Life Quality Index ( DLQI), we investigated different scar types regarding their impact on quality of life. Methods We assessed the quality of life in 130 patients presenting to our outpatient scar clinic for the first time using the DLQI. Scars were analysed according to their clinical appearance (physiological scars, keloids, hypertrophic scars, atrophic scars, self-harm scars). Physiological scars were established as a baseline for further comparison between groups. Results Patients in the physiological scar group scored a mean DLQI score of 2.07 ± 3.56, patients in the keloid-, hypertrophic scar-, atrophic scar- and self-harm scar group scored values of 6.06 ± 4.00, 2.53 ± 2.48, 7.26 ± 6.72 and 12.00 ± 3.85 respectively. When compared to the baseline group the difference in the overall score for keloids was +3.99 ( P < 0.001), hypertrophic scars scored +0.45 (ns), atrophic scars +5.19 ( P < 0.01) and self-harm scars +9.93 ( P < 0.001). Conclusion Using the DLQI, we could demonstrate that different subsets of pathological scars do affect patients in a different magnitude. The DLQI provides a promising adjunct for quantifying the quality of life in patients suffering from keloids, atrophic- and self-harm scars and may constitute an interesting additional tool for monitoring the progress of scar treatments. [ABSTRACT FROM AUTHOR]

Background Human papillomavirus ( HPV) are responsible for a broad spectrum of mucocutaneous infections and may cause squamous cell carcinoma following long-standing infection . Oncogenic HPV, most commonly HPV 16, are detectable in over 90% of cervical intraepithelial neoplasia and anal intraepithelial neoplasia ( AIN). Human immunodeficiency virus ( HIV) infection is strongly associated with a higher prevalence of chronic HPV infection, a higher incidence of AIN and an increased risk for anal cancer ( AC). In September 2013, guidelines concerning prevention, screening and treatment of AIN for patients affected by HIV were issued by the German AIDS society. Objective In order to validate the suggested screening procedure, we analysed data from 123 male and female patients with HIV infection that regularly present in our outpatient clinic. Methods Anal cytology, HPV typing and high-resolution anoscopy ( HRA) were performed. Results Our results show that screening by anal cytology only identifies a minority of patients with high grade AIN ( AIN 3) histology. Patients with normal cytology ( NILM, cytology graded negative for intraepithelial lesion or malignancy; n = 5, 29.4%), atypical squamous cells of undetermined significance ( ASCUS; n = 5, 71.4%) and low grade squamous intraepithelial lesion ( LSIL; n = 8, 44.5%) showed highly dysplastic lesions ( AIN 2 and 3) in the histological workup more frequently than expected. Additionally, high-grade squamous intraepithelial lesion ( HSIL) was strongly associated with detection of high-risk oncogenic HPV. Conclusion Anal cytology as the solitary screening tool for anal cancer fails to detect anal dysplasia in a considerable number of patients. Additionally, HPV typing and possibly further biomarkers might be applied to identify those patients with a higher risk of developing anal carcinoma, in order to monitor them more closely or directly transfer them to HRA. [ABSTRACT FROM AUTHOR]

Copyright of HNO is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background:Epidermal growth factor receptor (EGFR) has been hypothesised to modulate the effectiveness of anti-HER2 therapy. We used a standardised, quantitative immunofluorescence assay and a novel EGFR antibody to evaluate the correlation between EGFR expression and clinical outcome in the North Central Cancer Treatment Group (NCCTG) N9831 trial.Methods:Tissue microarrays were constructed that allowed analysis of 1365 patients randomly assigned to receive chemotherapy alone (Arm A), sequential trastuzumab after chemotherapy (Arm B) and chemotherapy with concurrent trastuzumab (Arm C). Measurement of EGFR was performed using the EGFR antibody, D38B1, on the fluorescence-based AQUA platform. The result was validated using an independent retrospective metastatic breast cancer cohort (n=130).Results:Epidermal growth factor receptor assessed as a continuous (logarithmic transformed) variable shows an association with disease-free survival in Arm C (P=0.009) but not in Arm A or B. High EGFR expression was associated with worse outcome (Hazard ratio (HR)=2.15; 95% CI 1.28-3.60, P=0.004). Validation in a Greek metastatic breast cancer cohort showed an HR associated with high EGFR expression of 1.92 (P=0.0073).Conclusions:High expression of EGFR appears to be associated with decreased benefit from adjuvant concurrent trastuzumab. Since other treatment options exist for HER2-driven tumours, further validation of these data may select patients for alternative or additive therapy. [ABSTRACT FROM AUTHOR]

Human papillomaviruses (HPV) are double-stranded DNA viruses, which selectively infect keratinocytes in stratified epithelia. After an initial infection, many patients clear HPV. In some patients, however, HPV persist, and dysfunctional innate immune responses to HPV infection could be involved in the ineffective clearing of these viruses. In this study, the mechanisms of HPV-induced immune responses in keratinocytes were investigated. Binding of viral DNA leads to AIM2 inflammasome activation and IL-1β release, while IFI16 activation results in IFN-β release. Using immunohistochemistry, AIM2 and IFI16-two recently identified sensors for cytosolic DNA-were also detected in HPV positive skin lesions. CISH stainings further confirmed the presence of cytosolic HPV16 DNA in biopsy samples. Moreover, active IL-1β and cleaved caspase-1 were detected in HPV infected skin, suggesting inflammasome activation by viral DNA. In subsequent functional studies, HPV16 DNA triggered IL-1β and IL-18 release via the AIM2 inflammasome in normal human keratinocytes. Although HPV DNA did not induce IFN-β in keratinocytes, IFN-β secretion was observed when AIM2 was blocked. Meanwhile, blocking of IFI16 increased HPV16 DNA-induced IL-1β, but not IL-18, secretion. These findings suggest crosstalk between IFI16 and AIM2 in the immune response to HPV DNA. In sum, novel aspects concerning HPV-induced innate immune responses were identified. Eventually, understanding the mechanisms of HPV-induced inflammasome activation could lead to the development of novel strategies for the prevention and treatment of HPV infections. [ABSTRACT FROM AUTHOR]

Background Following allergen exposure, cytokines and other pro-inflammatory signals play an important role in the immunological cascade leading to allergic sensitization. Inflammasomes sense exogenous and endogenous danger signals and trigger IL-1β and IL-18 activation which in turn shape Th2 responses. Honey bee venom ( BV) allergies are very common; however, the local inflammatory cascade leading to the initiation of allergic sensitization is poorly understood. In this study, the local inflammatory cascades in skin after exposure to BV were investigated. Methods The mechanisms of inflammasome activation in human skin and in cultured keratinocytes upon BV exposure were analyzed by ELISA, Western blot, flow cytometry, si RNA techniques, and immunofluorescence. Results In an ex vivo bee sting model, BV induced IL-1β release suggesting the activation of inflammasomes. Indeed, in cultured keratinocytes, the BV component melittin triggered IL-1β and IL-18 release via the AIM2 inflammasome. AIM2 is a cytosolic DNA receptor, and mitochondrial as well as genomic DNA was detected in the cytosol of melittin-treated keratinocytes as triggers of inflammasome activation. As a mechanism, melittin mediated destruction of mitochondrial membranes leading to the leakage of mitochondrial DNA into the cytosolic compartment. Conclusion These data suggest that upon BV exposure, keratinocytes are involved in an innate immune response by the activation of the AIM2 inflammasome and subsequent IL-1β and IL-18 release triggered by endogenous DNA. As IL-1β and IL-18 are involved in Th2- and IgE-mediated immune reactions, these results could add to the understanding of the role of the tissue microenvironment to subsequent allergic responses. [ABSTRACT FROM AUTHOR]

In Western countries, the incidence of atopy and allergic diseases is high and further rising. While genetic factors certainly play a role, epigenetic or even nutritional factors might also be important in the pathogenesis of allergies. Vitamin D – the 'sunshine hormone' – exerts profound effects on both adaptive and innate immune functions involved in the development and course of allergic diseases. As also the incidence of vitamin D insufficiency is surprisingly high in the general population, clinical and experimental studies have started to investigate if correcting vitamin D levels [measured as serum 25 hydroxy vitamin D -25(OH)D] is beneficial or even protective in patients with allergies or children at risk. This review highlights current data on the effects of vitamin D on the allergy-mediating immune system and the vitamin D status in atopic patients. Furthermore, the benefits and risks of vitamin D supplementation during pregnancy, childhood and in adults with respect to the development and course of allergic disease are discussed. [ABSTRACT FROM AUTHOR]

The article discusses the case of patient with keratitis-ichthyosis-deafness (KID) syndrome who developed cutaneous vegetating candidiasis. Topics discussed include the clinical presentation of the patient, antimycotic treatment using fluconazole, and the treatment of ichthyosis with acitretin. Also mentioned are the management of hyperkeratotic skin lesions with salicylic acid and the improvement in the patient's condition following treatment.

In this study, we establish an MCF-7 xenograft model that mimics the progression of human breast carcinomas typified by loss of p53 integrity, development of centrosome amplification, acquired estrogen receptor (ERα) heterogeneity, overexpression of Mdm2 and metastatic spread from the primary tumor to distant organs. MCF-7 cells with abrogated p53 function (vMCF-7Dnp53) maintained nuclear ERα expression and normal centrosome characteristics in vitro. However, following mitogen stimulation, they developed centrosome amplification and a higher frequency of aberrant mitotic spindles. Centrosome amplification was dependent on cdk2/cyclin activity since treatment with the small molecule inhibitor SU9516 suppressed centriole reduplication. In contrast to the parental MCF-7 cells, when introduced into nude mice as xenografts, tumors derived from the vMCF-7DNp53 cell line developed a strikingly altered phenotype characterized by increased tumor growth, higher tumor histopathology grade, centrosome amplification, loss of nuclear ERα expression, increased expression of Mdm-2 oncoprotein and resistance to the antiestrogen tamoxifen. Importantly, while MCF-7 xenografts did not develop distant metastases, primary tumors derived from vMCF-7DNp53 cells gave rise to lung metastases. Taken together, these observations indicate that abrogation of p53 function and consequent deregulation of the G1/S cell cycle transition leads to centrosome amplification responsible for breast cancer progression.Oncogene (2008) 27, 3901–3911; doi:10.1038/onc.2008.18; published online 11 February 2008 [ABSTRACT FROM AUTHOR]

The article presents several case studies of patients with photoallergic contact dermatitis due to treatment of pulmonary fibrosis with pirfenidone. Topics discussed include 57-year-old patient being put on pirfenidone treatment due to methotrexate induced lung fibrosis who was prescribed Lung transplantation and therapy with cyclosporine, a 67-year-old patient was given pirfenidone due to idiopathic pulmonary fibrosis and had itchy skin lesions and drugs causing photoallergic reactions.

ORIGINAL ARTICLE, p 1358 [ABSTRACT FROM AUTHOR]