MOSPD2 is a therapeutic target for the treatment of CNS inflammation.

In multiple sclerosis and experimental autoimmune encephalomyelitis (EAE), myeloid cells comprise a major part of the inflammatory infiltrate in the central nervous system (CNS). We previously described that motile sperm domain-containing protein 2 (MOSPD2) is expressed on human myeloid cells and regulates monocyte migration in vitro. The role of MOSPD2 in EAE pathogenesis was studied by generating MOSPD2 knock-out (KO) mice and monoclonal antibodies directed against MOSPD2. We found that EAE development in MOSPD2 KO mice was significantly suppressed. While frequency representation of leukocyte subsets in lymphoid tissues was comparable, the ratio of inflammatory monocytes in the blood was markedly reduced in MOSPD2 KO mice. In addition, T cells from MOSPD2 KO mice displayed reduced secretion of proinflammatory cytokines and increased production of interleukin (IL)-4. Prophylactic and post-onset treatment using monoclonal antibodies (mAbs) generated against MOSPD2 abrogated development and reduced EAE severity. These results suggest that MOSPD2 is key in regulating migration of inflammatory monocytes, and that anti-MOSPD2 mAbs constitute a potential therapy for the treatment of CNS inflammatory diseases.

First evaluation of the Behavioral Addiction Indoor Tanning Screener (BAITS) in a nationwide representative sample.

BACKGROUND: Evidence suggests that indoor tanning may have addictive properties. However, many instruments for measuring indoor tanning addiction show poor validity and reliability. Recently, a new instrument, the Behavioral Addiction Indoor Tanning Screener (BAITS), has been developed. OBJECTIVES: To test the validity and reliability of the BAITS by using a multimethod approach. METHODS: We used data from the first wave of the National Cancer Aid Monitoring on Sunbed Use, which included a cognitive pretest (August 2015) and a Germany-wide representative survey (October to December 2015). In the cognitive pretest 10 users of tanning beds were interviewed and 3000 individuals aged 14-45 years were included in the representative survey. Potential symptoms of indoor tanning addiction were measured using the BAITS, a brief screening survey with seven items (answer categories: yes vs. no). Criterion validity was assessed by comparing the results of BAITS with usage parameters. Additionally, we tested internal consistency and construct validity. RESULTS: A total of 19·7% of current and 1·8% of former indoor tanning users were screened positive for symptoms of a potential indoor tanning addiction. We found significant associations between usage parameters and the BAITS (criterion validity). Internal consistency (reliability) was good (Kuder-Richardson-20, 0·854). The BAITS was shown to be a homogeneous construct (construct validity). CONCLUSIONS: Compared with other short instruments measuring symptoms of a potential indoor tanning addiction, the BAITS seems to be a valid and reliable tool. With its short length and the binary items the BAITS is easy to use in large surveys.

Prevalence of sun-protective behaviour and intentional sun tanning in German adolescents and adults: results of a nationwide telephone survey.

BACKGROUND: The incidence rate of melanoma in the Caucasian population is rising worldwide. One of the major environmental risk factors for melanoma is the exposure to ultraviolet (UV) radiation. To prevent skin damage caused by UV exposure, several organizations recommend wearing protective clothing, staying in the shade, avoiding the outdoors during midday and using sunscreen. OBJECTIVE: To provide representative data on factors associated with sun-protective behaviours and intentional sun exposure during summertime in the German population. METHODS: A population-based sample of 3000 German residents aged 14-45 years (response: 32.1%) was interviewed via telephone from October to December 2015. Survey participants provided data on the use of recommended sun-protective measures on a sunny summer day and their intentional sun exposure during summertime. Data were weighted by age, sex, educational level and federal state to ensure the national representativeness of the sample. RESULTS: Wearing long-sleeved clothes was the most frequently reported protective measure (53.9%), while wearing headgear was the least common (17.9%). Significantly lower frequencies of almost all recommended sun-protective measures were identified for males, participants between 14 and 25 years, those with an immigrant background and those with low levels of education. Using sun protection was positively associated with female gender (OR = 1.62), higher levels of education (ORhigh = 1.27), sunburn during childhood (OR = 1.33) and paying attention to healthy nutrition (OR = 1.64; all P < 0.05). Sun tanning behaviour was associated with female gender (OR = 1.42), younger age, lower level of education, sunbed use (OR = 5.24) and smoking status (OR = 1.50; all P < 0.001). CONCLUSION: As individual sun-protective measures are easy to implement and provide effective protection against high-risk UV exposure, campaigns on skin cancer prevention in Germany should put a stronger focus on young adults, men, less educated individuals and those with immigration background.

Interval cancers after skin cancer screening: incidence, tumour characteristics and risk factors for cutaneous melanoma.

BACKGROUND: The rate of interval cancers is an established indicator for the performance of a cancer-screening programme. METHODS: We examined the incidence, tumour characteristics and risk factors of melanoma interval cancers that occurred in participants of the SCREEN project, which was carried out 2003/2004 in Schleswig-Holstein, Germany. Data from 350 306 SCREEN participants, who had been screened negative for melanoma, were linked to data of the state cancer registry. Melanoma interval cancers were defined as melanomas diagnosed within 4-24 months after SCREEN examination. Results were compared with melanomas of the pre-SCREEN era (1999-2002), extracted from the cancer registry. RESULTS: The overall relative incidence of melanoma interval cancers in terms of observed/expected ratio was 0.93 (95% CI: 0.82-1.05; in situ: 1.61 (1.32-1.95), invasive: 0.71 (0.60-0.84)). Compared with melanomas of the pre-SCREEN era, the interval melanomas were thinner and had a slightly greater proportion of lentigo maligna melanomas whereas nodular melanomas were less frequent. INTERPRETATION: The results indicate a moderate performance of the SCREEN intervention with an excess of in situ melanomas. In part, the findings might be due to specifics of the SCREEN project, in particular a short-term follow-up of patients at high risk for melanoma.

[Prevalence, risk groups, and reasons for sunbed use in Germany]. / Prävalenz, Risikogruppen und Motive der Solariennutzung in Deutschland.

BACKGROUND: Ultraviolet (UV) radiation of sunbeds has been classified carcinogenic by the International Agency for Research on Cancer (IARC). Unlike in other countries the available data on the important risk factor has been lacking until recently in Germany. OBJECTIVES: The SUN-Study 2012 (Sunbed-Use: Needs for Action Study) aimed at identifying epidemiological prevalence data concerning this completely preventable risk factor. MATERIALS AND METHODS: A total of 4,851 participants aged 14-45 years were selected from the German population in a representative manner and were surveyed via standardized telephone interviews. The survey period was split into a summer and a winter wave in order to take possible season effects into account. RESULTS: Four out of 10 Germans aged 14-45 years (39.2 %; 95 % CI 37.8-40.6 %) have ever used a sunbed. Within the last year 14.6 % (95 % CI 13.6-15.6 %) visited a sunbed. Current users reported six visits per year on average and every twentieth reported a family history of cutaneous malignant melanoma in first-degree relatives. More than 5 % of minors currently used sunbeds despite the nationwide ban, mostly at unsupervised locations. Half of those minors did not know about the legal ban of sunbed use for minors. CONCLUSIONS: Our study proves that sunbed use which is an important risk factor for skin cancer is widely used. Moreover, considerable information deficits about health risks exist among the German population.

VB-201, an oxidized phospholipid small molecule, inhibits CD14- and Toll-like receptor-2-dependent innate cell activation and constrains atherosclerosis.

Atherosclerosis is an inflammatory disease of the vascular wall. Activated monocytes and dendritic cells (DC) in the intima layer of the vasculature promote atherogenesis. Toll-like receptor (TLR)-2 and TLR-4, which are predominantly expressed on these cells and mediate their activation, are essential for atherosclerosis development. In this study we demonstrate that VB-201, an oxidized phospholipid (Ox-PL) small molecule, inhibits TLR signalling restricted to TLR-2 and TLR-4 in human and mouse monocytes and DC. Mechanistically, we show that VB-201 binds directly to TLR-2 and CD14, the TLR-4 co-receptor, to impair downstream cues and cytokine production. In a rabbit model, oral administration of VB-201 constrained atherosclerosis progression. This effect was not due to reduced cholesterol abundance, as hyperlipidaemia was sustained. We suggest that VB-201 may counter inflammation where TLR-2 and/or CD14 complicity is essential, and is therefore beneficial for the treatment of atherosclerosis.

UVA-induced DNA double-strand breaks result from the repair of clustered oxidative DNA damages.

UVA (320-400 nm) represents the main spectral component of solar UV radiation, induces pre-mutagenic DNA lesions and is classified as Class I carcinogen. Recently, discussion arose whether UVA induces DNA double-strand breaks (dsbs). Only few reports link the induction of dsbs to UVA exposure and the underlying mechanisms are poorly understood. Using the Comet-assay and γH2AX as markers for dsb formation, we demonstrate the dose-dependent dsb induction by UVA in G(1)-synchronized human keratinocytes (HaCaT) and primary human skin fibroblasts. The number of γH2AX foci increases when a UVA dose is applied in fractions (split dose), with a 2-h recovery period between fractions. The presence of the anti-oxidant Naringin reduces dsb formation significantly. Using an FPG-modified Comet-assay as well as warm and cold repair incubation, we show that dsbs arise partially during repair of bi-stranded, oxidative, clustered DNA lesions. We also demonstrate that on stretched chromatin fibres, 8-oxo-G and abasic sites occur in clusters. This suggests a replication-independent formation of UVA-induced dsbs through clustered single-strand breaks via locally generated reactive oxygen species. Since UVA is the main component of solar UV exposure and is used for artificial UV exposure, our results shine new light on the aetiology of skin cancer.

[Prevention of skin cancer: considerations on strategic communication]. / Prävention von Hautkrebs : Kommunikationsstrategische Überlegungen.

In recent decades the numbers of cases of skin cancer have been increasing worldwide in light skinned populations. In Germany skin cancer is the most common form of cancer. To reduce the burden of skin cancer protection from ultraviolet radiation (primary prevention) and early detection (secondary prevention) of the disease play a decisive role. In this context information to the population about preventive behavior and the support of informed decision-making in skin cancer screening are important aspects in communication. This paper gives an overview about communicational aspects in the promotion of skin cancer prevention. In the development of communicational interventions it is important to identify the relevant target groups. Relevant key opinion leaders have to be included in the information process. Additionally, interventions should be based on a theoretical framework and be designed for the respective target group. Furthermore, different forms of communication and communication tools are provided for the realization of an information intervention. To appraise the intervention elements of summative and formal evaluation are available. The current results provide important findings about different effects of communicational aspects on knowledge and behavior of the population; however, due to the complexity of information interventions a particular effect cannot be explained by a single communicational element.

Sunbed use in Germany: trends, user histories and factors associated with cessation and readiness to change.

BACKGROUND: Sunbed use is considered carcinogenic in humans. Studies that examine behavioural patterns related to sunbed use over time are needed for developing skin cancer prevention strategies. OBJECTIVES: To explore age-related trends in the initiation age, to investigate individual histories of sunbed use and to identify characteristics associated with cessation. METHODS: We analysed cross-sectional data of 4851 sunbed users and nonusers from a representative sample of Germans, aged 14-45 years, interviewed in 2011/2012. Biographical data were reconstructed based on reported tanning frequency/duration and changes in sunbed use over time. We used survival analysis to model the initiation age and created birth cohorts to assess age-related trends. Characteristics associated with sunbed use cessation were identified using logistic regression. RESULTS: Among sunbed users, median sunbed exposure was 180 min per year. Annual exposure remained constant in 85·6% of this subgroup with no changes over time during periods of sunbed use. Age at initiation decreased significantly across birth cohorts from 25 to 19 years (25th percentile; cohorts 1966-75 to 1986-93). Characteristics associated with sunbed use cessation included educational level [odds ratios (OR) 1·53 and 1·71 for medium and high education, respectively], greater awareness of skin cancer risk (OR 2·41) and immigrant background (OR 0·54; all P < 0·01). CONCLUSIONS: Initiation of sunbed use at an increasingly younger age suggests the need for interventions targeted at young adults. Approaches that increase general skin cancer risk awareness and that are sensitive to participants' educational level and immigrant background may also be helpful.

[Collection and processing of personal data to evaluate cancer screening programmes - results of a survey of the German population in light of the bill 'early detection of cancer and cancer registries']. / Erfassung und Verarbeitung von persönlichen Daten zur Evaluation von Krebsfrüherkennungsprogrammen - Ergebnisse einer Bevölkerungsbefragung im Kontext des Krebsfrüherkennungs- und -registergesetzes.

In a representative German sample, 62.1% of participants of cancer screening interventions indicated willingness to provide personal data for data-linkage with cancer registries. An agreement of over 90% is deemed necessary to conduct a meaningful population-based evaluation. The 'early detection of cancer and cancer regis-tries' bill proposed a procedure based on the use of pseudonyms only. This way personal consent is not required but participants are granted the right to object.

[Current dermatology guidelines in Germany-selected recommendations from 2021 and 2022]. / Aktuelle dermatologische Leitlinien in Deutschland ­ Ausgewählte Empfehlungen aus den Jahren 2021 und 2022.

Guidelines are systematically developed decision-making aids to ensure appropriate clinical care for specific medical conditions. In Germany, dermatological guidelines are developed under the aegis of the German Dermatological Society (DDG) and the Professional Association of German Dermatologists (BVDD), while European and international guidelines are published by organisations such as the European Centre for Guidelines Development (EuroGuiDerm), founded by the European Dermatology Forum (EDF) in cooperation with the Division of Evidence-Based Medicine at Charité-Universitätsmedizin Berlin. In 2021 and 2022, the German guidelines were revised or developed on topics such as the management of anticoagulation during dermatological procedures, chronic pruritus, contact dermatitis, laser therapy of the skin, psoriasis vulgaris, rosacea, extracorporeal photopheresis, onychomycosis, mucous membrane pemphigoid and prevention of skin cancer. A selection of the most important recommendations and innovations in the guidelines is summarized here.

Skin cancer screening participation and impact on melanoma incidence in Germany--an observational study on incidence trends in regions with and without population-based screening.

BACKGROUND: The SCREEN (Skin Cancer Research to provide Evidence for Effectiveness of Screening in Northern Germany) project involved population-wide skin cancer screening with whole-body examination by general physicians and dermatologists. It was conducted in the German state of Schleswig-Holstein (July 2003-June 2004), but not in the German state of Saarland. METHODS: The population-based registries of Schleswig-Holstein and Saarland provided data on melanoma incidence before, during, and after SCREEN to assess the association of skin cancer screening with incidence. RESULTS: Approximately 19% of the Schleswig-Holstein population participated in SCREEN (women: 27%, men: 10%). A total of 52% of all melanomas diagnosed during SCREEN in Schleswig-Holstein were detected as part of the project. Melanoma incidence increased during SCREEN (invasive melanoma in women: +8.9 per 100,000 (95% confidence intervals (CI): 6.1; 11.7); men: +4.0 per 100,000 (95% CI: 1.6; 6.4)) and decreased afterwards (women: -10.6 per 100,000 (95% CI: -13.3; -7.9); men: -4.1 per 100,000 (95% CI: -6.5; -1.7)). Similar changes were not observed in Saarland that had no such project. The differences between the two states were greatest among women, the group with the greater SCREEN participation. CONCLUSION: The SCREEN project had a substantial impact on melanoma incidence. This is consistent with the impact of effective screening for other cancers.

Effectiveness of skin cancer screening programmes.

Skin cancer, nonmelanoma skin cancer (NMSC) and cutaneous malignant melanoma (CMM), is the most frequent cancer worldwide. It is amenable to early detection, and screening for skin cancer has the potential to reduce mortality and morbidity. However, there are no recommendations for population-based skin cancer screening programmes due to the lack of evidence for the effectiveness from epidemiological studies. In 2008 the first nationwide screening programme for NMSC and CMM in the world was established in Germany. The decision for implementing such a programme was based on the results and evidence of a pilot study that was conducted from 2003 to 2004. The pilot study revealed that a population-based screening programme for skin cancer is feasible and effective. Careful evaluation of the nationwide programme is crucial to generate strong evidence for long-term public health benefits.

Specific induction of tumor neovasculature death by modified murine PPE-1 promoter armed with HSV-TK.

BACKGROUND: One strategy to increase tissue specificity of gene therapy is to use promoters or enhancers. OBJECTIVES: (1) To enhance the selectivity of a murine preproendothelin-1 (PPE-1) promoter in tumor angiogenesis by using a positive endothelial transcription-binding element. (2) To test the specificity and efficiency of the modified PPE-1 promoter [PPE-1(3X)] in vitro and in vivo by using reporter genes, and the therapeutic gene herpes simplex virus-thymidine kinase (HSV-TK) in a mouse model of Lewis lung carcinoma (LLC). RESULTS: The modified PPE-1 promoter specifically induced expression in the tumor angiogenic vascular bed with a 35-fold higher expression compared to the normal vasculare bed of the lung. Thus, when the HSV-TK gene controlled by the modified PPE-1 promoter was used systemically, it induced tumor-specific necrosis, apoptosis and mononuclear infiltrates, leading to massive destruction of the neovasculature of the pulmonary metastasis, which suppressed metastasis development. CONCLUSIONS: These results show that an adenoviral vector armed with HSV-TK controlled by the endothelial-selective murine PPE-1(3X) promoter is efficient and safe to target tumor neovasculature.

Effectiveness of information campaigns.

Skin cancer represents the most common type of cancer in the white population worldwide and the incidence has dramatically increased during the last decades. UV-radiation is believed to be the most important risk factor responsible for this trend. The prominent role of UV-radiation renders skin cancer most suitable for primary prevention, because the main risk factor can easily be avoided by sticking to simple rules for the behaviour in the sun or under artificial UV (e.g. sunbeds). Since UV-exposure cannot and should not be avoided totally especially due to the beneficial health effects of UV-irradiation like Vitamin D(3)-production, recommendations and information for the public should be as clear and as weighted as possible, through adequate messages, such as: "Love the sun and protect your skin". For that purpose the Association of Dermatological Prevention in Germany (ADP) developed the period of life programme (POLP) that defines certain age-specific target groups, with the aim to give well adapted prevention messages to the population during lifetime. Evaluation of primary prevention campaigns in Germany showed that due to continuous intervention programs during the last 16 years changes in the "sun-behaviour" of the population have been achieved leading to a reduced but sufficient exposure to solar UV-irradiation. This will then contribute to the aim of decreasing morbidity and mortality of skin cancer.

Discrimination between benign and malignant cells of melanocytic lineage by two novel antigens, a glycoprotein with a molecular weight of 113,000 and a protein with a molecular weight of 76,000.

The present study describes two novel antigens, a glycoprotein with a molecular weight of 113,000 and a protein with a molecular weight of 76,000, which are associated with the transformed phenotype of melanocytes. The monoclonal antibodies (MoAb) MUC18 and MUC54, raised against human malignant melanoma, were selected for differential reactivity with normal and neoplastic cells of melanocyte lineage. The antigen defined by MoAb MUC18 is a membrane bound monomeric sialylated glycoprotein with an apparent molecular weight of 113,000. In contrast to the broad reactivity with melanomas, isolated nevus nests were stained in only 1 of 55 nevi investigated. No staining of MoAb MUC18 was observed in a large variety of surgically removed normal and tumor tissues except for smooth muscle cells of the blood vessel wall and hair follicles. MoAb MUC54 immunoprecipitated a cytoplasmic monomeric protein with an apparent molecular weight of 76,000. By immunoperoxidase staining, the antigen was demonstrated on a large number of melanomas and in addition on 1 of 36 nevocellular, 3 of 4 Spitz, and 5 of 14 dysplastic nevi. The Mr 76,000 protein was found in a number of epithelial tissues and various types of neoplasms. Both antibodies presented in this study define structural changes in the antigenic profile of melanocytes occurring during carcinogenesis.

Effects of chronic low-dose ultraviolet B radiation on DNA damage and repair in mouse skin.

Chronic exposure to sunlight causes skin cancer in humans, yet little is known about how habitual exposure to low doses of ultraviolet B radiation (UVB) affects DNA damage in the skin. We treated Skh-1 hairless mice with daily doses of suberythemal UVB for 40 days and analyzed the amount and distribution of DNA photodamage using RIAs and immunofluorescence micrography. We found that DNA damage accumulated in mouse skin as a result of chronic irradiation and that this damage persisted in the dermis and epidermis for several weeks after the chronic treatment was terminated. Although the persistent damage was evenly distributed throughout the dermis, it remained in the epidermis as a small number of heavily damaged cells at the dermal-epidermal boundary. Rates of DNA damage induction and repair were determined at different times over the course of chronic treatment in response to a higher challenge dose of UVB light. The amount of damage induced by the challenge dose increased in response to chronic exposure, and excision repair of cyclobutane pyrimidine dimers and pyrimidine(6-4)pyrimidone dimers was significantly reduced. The sensitization of mouse epidermal DNA to photoproduct induction, the reduction in excision repair, and the accumulation of nonrepairable DNA damage in the dermis and epidermis suggest that chronic low-dose exposure to sunlight may significantly enhance the predisposition of mammalian skin to sunlight-induced carcinogenesis.

Identification of a non-dividing subpopulation of mouse and human epidermal cells exhibiting high levels of persistent ultraviolet photodamage.

The distribution and persistence of cyclobutane pyrimidine dimers were investigated in mouse skin after chronic and acute exposures to ultraviolet-B radiation. We found that DNA damage accumulated in response to chronic irradiation and persisted in a unique set of epidermal cells located at the basal layer. Treatment with a tumor promoter caused the heavily damaged epidermal cells to divide and p53-immunopositive clusters to form within 24 h suggesting that these cells may be progenitors of the mutant p53 clusters associated with actinic keratoses and squamous cell carcinomas. In contrast to low fluence chronic irradiation, daily treatment with a higher fluence of ultraviolet-B produced extensive hyperplasia and considerably reduced penetration of photodamage. Exposure of chronically irradiated skin to an acute "sunburn dose" of ultraviolet-B also produced significant epidermal hyperplasia and resulted in complete loss of heavily damaged basal cells within 4 d postirradiation. The occurrence and distribution of cyclobutane dimers in human skin correlated well with putative sunlight exposure and resembled that observed in ultraviolet-B-irradiated mice. Heavily damaged basal cells were observed at various sites, including those receiving sporadic sunlight exposure, suggesting that these cells may play an important role in carcinoma formation in humans.

Lipoxygenase activity in heart cells.

Arachidonic acid (AA) metabolism via the lipoxygenase (LOX) pathway in rat hearts and in cultured rat cardiomyocytes was investigated using 1-[14C]AA. LOX activity was detected in the microsomal fraction, in the high speed supernatant prepared from rat hearts and in rat cardiomyocyte supernatant. LOX products from all fractions comigrated in thin layer chromatography as 12-hydroxyeicosatetraenoic acid (12-HETE) and 15-HETE. Enzyme linked immunosorbent assay for 12-HETE showed its formation by the microsomal fraction, the ammonium sulfate (AS) pellet, and by rat cardiomyocyte supernatant, while radioimmunoassay for 15-HETE showed its formation only by the AS pellet. The properties of LOX in each fraction are reported here.

Increased numbers of spontaneous micronuclei in blood lymphocytes and cultures fibroblasts of individuals with familial cutaneous malignant melanoma.

In vitro detection of micronuclei was used to determine spontaneous chromosomal instability in cultured fibroblasts of 28 healthy normal controls, 28 individuals with nonfamilial cutaneous malignant melanoma (CMM) and 14 people with familial occurrence of CMM. Lymphocytes from 40 healthy controls, 40 CMM patients and 6 individuals with familial CMM were also compared for spontaneous expression of micronuclei in vitro. In the familial cases micronucleus frequency was found to be higher, both in cultured fibroblasts (P less than 0.005) and in lymphocytes (P less than 0.001) as compared to normal controls. There was no significant difference between nonfamilial cases and normal controls. We conclude that chromosomal instability may contribute to a genetic risk for development of cutaneous malignant melanoma.