Profile of Basal Cell Carcinoma Mutations and Copy Number Alterations - Focus on Gene-Associated Noncoding Variants.

Basal cell carcinoma (BCC) of the skin is the most common cancer in humans, characterized by the highest mutation rate among cancers, and is mostly driven by mutations in genes involved in the hedgehog pathway. To date, almost all BCC genetic studies have focused exclusively on protein-coding sequences; therefore, the impact of noncoding variants on the BCC genome is unrecognized. In this study, with the use of whole-exome sequencing of 27 tumor/normal pairs of BCC samples, we performed an analysis of somatic mutations in both protein-coding sequences and gene-associated noncoding regions, including 5'UTRs, 3'UTRs, and exon-adjacent intron sequences. Separately, in each region, we performed hotspot identification, mutation enrichment analysis, and cancer driver identification with OncodriveFML. Additionally, we performed a whole-genome copy number alteration analysis with GISTIC2. Of the >80,000 identified mutations, ~50% were localized in noncoding regions. The results of the analysis generally corroborated the previous findings regarding genes mutated in coding sequences, including PTCH1, TP53, and MYCN, but more importantly showed that mutations were also clustered in specific noncoding regions, including hotspots. Some of the genes specifically mutated in noncoding regions were identified as highly potent cancer drivers, of which BAD had a mutation hotspot in the 3'UTR, DHODH had a mutation hotspot in the Kozak sequence in the 5'UTR, and CHCHD2 frequently showed mutations in the 5'UTR. All of these genes are functionally implicated in cancer-related processes (e.g., apoptosis, mitochondrial metabolism, and de novo pyrimidine synthesis) or the pathogenesis of UV radiation-induced cancers. We also found that the identified BAD and CHCHD2 mutations frequently occur in melanoma but not in other cancers via The Cancer Genome Atlas analysis. Finally, we identified a frequent deletion of chr9q, encompassing PTCH1, and unreported frequent copy number gain of chr9p, encompassing the genes encoding the immune checkpoint ligands PD-L1 and PD-L2. In conclusion, this study is the first systematic analysis of coding and noncoding mutations in BCC and provides a strong basis for further analyses of the variants in BCC and cancer in general.

The Role of Circular RNAs in Keratinocyte Carcinomas.

Keratinocyte carcinomas (KC) include basal cell carcinomas (BCC) and cutaneous squamous cell carcinomas (cSCC) and represents the most common cancer in Europe and North America. Both entities are characterized by a very high mutational burden, mainly UV signature mutations. Predominately mutated genes in BCC belong to the sonic hedgehog pathway, whereas, in cSCC, TP53, CDKN2A, NOTCH1/2 and others are most frequently mutated. In addition, the dysregulation of factors associated with epithelial to mesenchymal transition (EMT) was shown in invasive cSCC. The expression of factors associated with tumorigenesis can be controlled in several ways and include non-coding RNA molecules, such as micro RNAs (miRNA) long noncoding RNAs (lncRNA) and circular RNAs (circRNA). To update findings on circRNA in KC, we reviewed 13 papers published since 2016, identified in a PubMed search. In both BCC and cSCC, numerous circRNAs were identified that were differently expressed compared to healthy skin. Some of them were shown to target miRNAs that are also dysregulated in KC. Moreover, some studies confirmed the biological functions of individual circRNAs involved in cancer development. Thus, circRNAs may be used as biomarkers of disease and disease progression and represent potential targets of new therapeutic approaches for KC.

Comparison of the Skin Cancer Quality of Life Impact Tool and the Skin Cancer Index Questionnaire in Measurement of Health-Related Quality of Life and the Effect of Patient Education Brochures in Patients with Actinic Keratosis, Non-melanoma Skin Cancer, and Cutaneous Melanoma.

INTRODUCTION: Few studies have evaluated patient-reported outcome measures and the effect of patient educational materials in German patients with skin cancer. We conducted a prospective study to measure the impact of treatment on health-related quality of life in German patients with skin cancer, identify variables that may contribute to changes in health-related quality of life, and evaluate the effect of providing additional information through a patient education brochure. METHODS: A total of 461 patients diagnosed with actinic keratosis, nonmetastatic nonmelanoma skin cancer, melanoma in situ, or nonmetastatic cutaneous melanoma treated between August 2018 and July 2020 were included. Ninety-seven patients were randomly selected to receive an additional patient education brochure ("Hautkrebs"). The patients completed a Skin Cancer Quality of Life Index Tool (n = 324) or a Skin Cancer Index Questionnaire (n = 137) 1 week after surgical treatment. RESULTS: Ninety-seven patients were provided an additional patient education brochure. We found statistical correlation between sociodemographic factors (young age and female gender) and the location of the skin cancer (head and face) and impairment of health-related quality of life in patients with skin cancer (p < 0.05). Moreover, we found that patients who were presented a brochure showed significantly higher awareness concerning direct sun exposure (p < 0.05). CONCLUSION: Impaired health-related quality of life is correlated with a patient with skin cancer's age, gender, and the location of the lesion. Physicians should consider these factors in clinical practice and advocate the use of patient education brochures as effective assets in preventing the reoccurrence of skin cancer.

Patched 1 expression in Merkel cell carcinoma.

The relevance of Hedgehog signaling in Merkel cell carcinoma has only been addressed by a few studies with conflicting results. Thus, we aimed to establish the expression of Hedgehog signaling molecules in Merkel cell carcinoma to characterize causes of aberrant expression and to correlate these findings with the clinical course of the patients. Immunohistochemistry was performed for Sonic, Indian, Patched 1 (PTCH1) and Smoothened on patients' tumor tissue. Respective mRNA expression was analyzed in 10 Merkel cell carcinoma cell lines using quantitative real-time polymerase chain reaction. PTCH1 sequencing and DNA methylation microarray analyses were carried out on tumor tissues as well as cell lines. PTCH1 immunoreactivity in Merkel cell carcinoma was similar to that of basal cell carcinomas, which both significantly differed from PTCH1 immunoreactivity in healthy skin. Most PTCH1 mutations found were synonymous or without known functional impact. However, on average, the promoter regions of both PTCH1 were hypomethylated independently from PTCH1 gene expression or Merkel cell polyomavirus status. PTCH1 and GLI1/2/3 genes were differently expressed in different cell lines; notably, there was a significant correlation between GLI2 and PTCH1 mRNA expression. Similar to PTCH1 protein expression in patient tissues, PTCH1 gene expression in Merkel cell carcinoma cell lines is highly variable, but due to the similar methylation pattern across Merkel cell carcinoma cell lines, effects other than methylation seem to be the reason for the differential expression and PTCH1 appears to be upregulated by GLI as a classical Hedgehog target gene.

Dicer Sequencing, Whole Genome Methylation Profiling, mRNA and smallRNA Sequencing Analysis in Basal Cell Carcinoma.

BACKGROUND/AIMS: Perturbations in the expression of microRNAs (miRNAs) and their maturing machinery components such as Dicer have been previously described for basal cell carcinoma (BCC). However, the mutational status of Dicer in BCC is unclear. Further, the sclerodermiform subtype of BCC (sBCC) has not been previously investigated regarding its methylation profile or its smallRNA expression profile via RNA sequencing. We conducted this study to investigate the mutational status of Dicer in BCC. METHODS: Dicer sequencing was performed on the Illumina MiSeq System in a total of 16 BCC samples (8 nodular BCCs, 8 sBCCs) and mapped against the human reference genome (i.e., hg19). Dicer sequencing was performed in all 16 BCC samples. We performed whole genome methylation profiling with Infinium MethylationEPIC BeadChips as well as mRNA and smallRNA sequencing in 5 sBCCs with the Illumina NextSeq500 next-generation sequencing system. RESULTS: Compared to the wildtype Dicer sequence, we found 5 to 7 variants per sBCC sample including insertion, deletion, and multiple nucleotide variants. Global methylation profiles were highly similar between groups. mRNA sequencing revealed S100A9, KRT14, KRT10, S100A8, S100A7, COX1, KRT1, COX3, and smallRNA sequencing analysis miR-21, miR-99a, miR26-a-2, let-7f, let-7g, let-7i, miR-100, and miR-205 were the most strongly expressed in sBCCs. CONCLUSION: We identified a variety of Dicer mutations that could play a role in aberrant miRNA expression in BCC. The noted RNA sequences should be further evaluated in functional studies to explore their potential pathogenetic role in sBCC.

Reduced ten-eleven translocation and isocitrate dehydrogenase expression in inflammatory hidradenitis suppurativa lesions.

BACKGROUND: As environmental factors appear to predispose patients to hidradenitis suppurativa (HS), studying epigenetic modifications is of interest to further understand the pathogenesis of HS. OBJECTIVES: To study the expression of DNA hydroxymethylation regulators, namely the ten-eleven translocation (TET) and isocitrate dehydrogenase (IDH) family, in the skin of HS patients. MATERIALS & METHODS: Twenty patients with HS and 12 healthy subjects were recruited. We analysed the expression of TET1, TET2, TET3, IDH1, IDH2, IDH3a, and IDH3b in lesional and perilesional HS tissue as well as tissue from healthy controls by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). In addition, immunohistochemistry was performed for TET1, TET2, and TET3. RESULTS: RT-PCR analysis showed that mRNA of all the studied genes was significantly under-expressed in lesional HS skin compared to healthy skin. IDH1 and IDH2 mRNA expression was also significantly lower in perilesional HS skin compared to healthy skin, and TET3 mRNA expression was significantly lower in lesional HS skin compared to perilesional HS skin. RT-PCR analysis for TET1, TET2, and TET3 mRNA expression was confirmed by immunohistochemical analysis. Correlation analysis revealed a significant positive correlation between TET and IDH gene expression in perilesional and lesional HS skin. CONCLUSIONS: Our results suggest that epigenetic changes occur in HS tissue and that aberrant expression of the DNA hydroxymethylation regulators may play a role in the pathogenesis of HS. As epigenetic modifications are reversible, further research into the cause of these aberrant expression patterns is warranted in order to develop possible novel therapeutic approaches.

Circulating Cell-Free miR-375 as Surrogate Marker of Tumor Burden in Merkel Cell Carcinoma.

PURPOSE: Merkel cell carcinoma (MCC) is an aggressive skin cancer with neuroendocrine differentiation. There is an unmet need for MCC-specific blood-based surrogate biomarkers of tumor burden; circulating cell-free miRNA may serve this purpose. EXPERIMENTAL DESIGN: Expression of miR-375 was quantified in 24 MCC and 23 non-MCC cell lines, 67 MCC and 58 non-MCC tumor tissues, sera of 2 preclinical MCC models, and sera of 109 patients with MCC and 30 healthy controls by nCounter human-v2-miRNA expression or miR-375-specific real-time PCR assays. The patients' sera consisted of two retrospective (discovery and training) and two prospective (validation) cohorts. RESULTS: miR-375 expression was high in MCC cell lines and tissues compared with non-MCCs. It was readily detected in MCC-conditioned medium and sera of preclinical models bearing MCC xenografts. miR-375 levels were higher in sera from tumor-bearing patients with MCC than in tumor-free patients or healthy controls (P < 0.0005). Moreover, miR-375 serum levels correlated with tumor stage in tumor-bearing (P = 0.037) but not in tumor-free (P = 0.372) patients with MCC. miR-375 serum level showed high diagnostic accuracy to discriminate tumor-bearing and tumor-free patients with MCC as demonstrated by ROC curve analysis in the retrospective cohorts (AUC = 0.954 and 0.800) as well as in the prospective cohorts (AUC = 0.929 and 0.959). miR-375 serum level reflected dynamic changes in tumor burden of patients with MCC during therapeutic interventions. CONCLUSIONS: Circulating cell-free miR-375 proved as a surrogate marker for tumor burden in MCC without restriction to polyomavirus positivity; it thus appears to be useful for therapy monitoring and the follow-up of patients with MCC.

Expression of oncogenic miR-17-92 and tumor suppressive miR-143-145 clusters in basal cell carcinoma and cutaneous squamous cell carcinoma.

BACKGROUND: A variety of cancers are associated with the expression of the oncogenic miR-17-92 cluster (Oncomir-1) and tumor suppressor miR-143-5p/miR-145-5p. Epidermal skin cancer has not been investigated for the expression of miR-17-92 and miR-143-145 clusters, despite being extensively studied regarding global microRNA profiles. The goal of this study was to investigate the expression and possible correlation of expression of miR17-92 and miR-143-145 cluster members in epidermal skin cancer. METHODS: We evaluated punch biopsies from patients with cutaneous squamous cell carcinoma (cSCC, n=15) and basal cell carcinoma (BCC, n=16), along with control specimens from non-lesional epidermal skin (n=16). Expression levels of the miR17-92 cluster (including miR-17-5p, miR-17-3p, miR-18a-3p, miR-18a-5p, miR-19a-3p, miR-19a-5p, miR-19b-3p, miR-19b-1-5p, miR-20a-3p, miR-20a-5p, miR-92a-3p, and miR-92a-5p) and the tumor-suppressive cluster miR-143-145 (including miR-143-5p and miR-145-5p) were detected by quantitative real-time reverse transcriptase polymerase chain reaction. RESULTS: We noted a highly significant increased expression of the miR-17-92 members miR-17-5p, miR-18a-5p, miR19a-3p, and miR-19b-3p and tumor suppressor miR-143-5p (p<0.01) in cSCC. miR-145-5p had a significantly decreased expression (p<0.05) for in BCC. A correlation analysis revealed multiple correlating miRNA-pairs within and between the investigated clusters. CONCLUSION: This study marks the first evidence for the participation of members of the miR-17-92 cluster in cSCC and miR-143-145 cluster in BCC.

Quality of life in caregivers with and without chronic disease: Welsh Health Survey, 2013.

Background: The aim of the present study was to investigate and compare quality of life after regular care provision in people with and without currently treated chronic disease in a country-wide and population-based setting. Methods: Data were retrieved from Welsh Health Survey, 2013. Information on demographics, lifestyle factors, health conditions, regular care provision and quality of life was obtained by household interview. Chi-square test, t-test and survey-weighted multi-nominal regression modelling were performed. Results: Of 15 007 Welsh adults aged 16 and above, 2751 (19.1%) people reported that they have been giving care for any sick, disabled or frail person. They tended to be aged 40-74, being female, education 25, physically active, current smokers and living in second-hand smoking households. In caregivers with current chronic disease (n = 1562), they have experienced physical health limits, bodily pains, emotional problems, less calm and less cheerful. In caregivers without current chronic diseases (n = 1151), they have experienced physical health limits, bodily pains, less cheerful, downhearted and unhappiness. Conclusions: This is the first study to examine quality of life in caregivers both with and without currently treated chronic disease. Longitudinal monitoring and increasing education, training and support to lessen caregiving burden would be suggested.

Expression of PIWIL3 in primary and metastatic melanoma.

PURPOSE: The PIWI-interacting RNA machinery in malignant melanoma (MM) has not been sufficiently studied. We aimed to investigate the PIWIL3 expression profiles in primary melanomas and metastases of MM including a correlation with clinical data. METHODS: We studied 161 primary melanomas, 45 lymph node metastases, and 16 distant metastases of 183 patients with MM. We used immunohistochemistry to assess PIWIL3 protein expression in situ. The relationship between the immunoreactivity of PIWIL3 and clinical data was statistically evaluated. RESULTS: We observed a significantly (P = 0.000059) higher median immunoreactivity score in primary melanomas (4.9; range, 0.1-6), lymph node metastases (5.1; range, 3.3-6), and distant metastases (5.6; range, 4.5-6). PIWIL3 was expressed significantly higher (P = 0.0002) in primary nodular melanomas and acral melanomas (5.2; range, 3.4-6) when compared to other melanoma subtypes (4.7; range, 0.1-6). On univariate analysis, a significant positive correlation was observed between primary melanoma PIWIL3 expression and tumor thickness (r = 0.2; P = 0.014). On univariate and multivariate analysis, PIWIL3 did not prove to be an independent predictor for melanoma relapse or death. CONCLUSIONS: Our data indicate that PIWIL3 protein expression is elevated in more aggressive primary MM and metastatic disease. As also observed in other malignancies, PIWIL3 seems to play a role in MM progression.

Microbial Profile and Antimicrobial Susceptibility of Bacteria Found in Inflammatory Hidradenitis Suppurativa Lesions.

BACKGROUND: The role of bacterial colonization in hidradenitis suppurativa (HS) lesions is poorly understood. To date, data on the related microbial profile and especially on bacterial resistance rates are scarce. METHODS: The results of bacterial cultures and susceptibility patterns of the isolated microorganisms obtained from deep portions of HS lesions from patients who underwent surgery at our HS Centre between 2010 and 2015 were retrospectively evaluated. RESULTS: Analyses of 113 bacterial samples from 113 HS patients revealed bacterial growth in 95 samples (84.1%). Polymicrobial growth was found in 51 samples (45.1%). Coagulase-negative staphylococci and Staphylococcus aureus were the most commonly isolated bacteria, followed by Proteus mirabilis and Escherichia coli. Data on susceptibility testing were available for 68 samples, which yielded 129 isolates. The isolated strains were primarily resistant to penicillin G, followed by erythromycin, clindamycin and ampicillin. The highest effectiveness against isolates was observed for fosfomycin, imipenem, fluoroquinolones (moxifloxacin, ciprofloxacin, levofloxacin), and cotrimoxazole. CONCLUSIONS: Our findings on bacterial species and their topographical distribution revealed that the microbial flora in HS lesions reflects commensal flora of the skin. Due to the susceptibility rate and immunomodulatory and anti-inflammatory properties, cotrimoxazole may represent an alternative antibiotic agent and should be considered for therapy in HS patients.

Circular RNA expression in cutaneous squamous cell carcinoma.

BACKGROUND: CircularRNAs (circRNAs) are a reinvented class of abundant, stable, and evolutionary conserved non-coding RNAs with pivotal impacts on the cellular regulatory network and epigenetics by sequestering microRNAs (miRNAs) like a sponge. OBJECTIVE: Purpose of the present study was to investigate circRNA expression in cutaneous squamous cell carcinoma (cSCC). METHODS: A total of six cSCC and six non-lesional skin (control) biopsies were harvested. Microarray based circRNA expression was determined in the cSCC (n=3) and compared with the non-lesional skin (n=3) from a group of 13,617 distinct human circRNAs found in the Arraystar circRNA Array V2.0 (Arraystar, Rockville, USA). Microarray data were validated by quantitative real-time reverse transcription polymerase chain reaction in a separate group (cSCC, n=3 and non-lesional skin, n=3). miRNA binding to miRNA response elements (MREs) sequence data were acquired bioinformatically. Further data mining was performed to identify circRNAs containing MRE sequences that interacted with previously described miRNAs playing a role in cSCC formation. RESULTS: A total of 322 circRNAs (143 up- and 179 down-regulated; fold change ≥2 and p<0.05) were identified as differentially expressed in cSCC. Furthermore, we identified a total of 1603 MREs that were part of the differentially expressed circRNAs. Among those circRNAs, a complementary MRE sequence was identified in 23 miRNAs previously known to be cSCC relevant. CONCLUSION: This study showed that circRNAs are differentially expressed in cSCC and play an important role in tumor formation by interfering with cSCC relevant miRNAs through miRNA sequence complementary MREs participating in epigenetic control.

Expression profiles of long noncoding RNAs in cutaneous squamous cell carcinoma.

BACKGROUND: Despite there being over 35,000 different long noncoding RNA (lncRNA) sequences described little is known regarding their molecular-pathological role in cutaneous squamous cell carcinoma (cSCC). MATERIALS & METHODS: In this pilot study, lncRNA and mRNA expression profiles were determined in cSCC and control (n = 6) by an Arraystar human lncRNA Microarray. Kyoto Encyclopedia of Genes and Genomes pathway enrichment and gene ontology analysis of mRNAs was performed. RESULTS: Analysis of differential expression revealed 1516 upregulated lncRNAs and 2586 downregulated lncRNAs in cSCC compared with controls. Data analysis identified known oncogenic lncRNAs, such as the HOX transcript antisense RNA HOTAIR, among the differentially expressed lncRNA sequences. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that focal adhesion, extracellular matrix and the oncogenic phosphatidylinositol 3'-kinase-Akt signaling pathway had the highest enrichment scores. CONCLUSION: This study provides the first evidence for differential expression of lncRNA in cSCC and serves as a template for further, larger functional in-depth analyses regarding cSCC molecular lncRNAs.

Circular RNA expression in basal cell carcinoma.

AIM: Circular RNAs (circRNAs), are nonprotein coding RNAs consisting of a circular loop with multiple miRNA, binding sites called miRNA response elements (MREs), functioning as miRNA sponges. This study was performed to identify differentially expressed circRNAs and their MREs in basal cell carcinoma (BCC). MATERIALS & METHODS: Microarray circRNA expression profiles were acquired from BCC and control followed by qRT-PCR validation. Bioinformatical target prediction revealed multiple MREs. Sequence analysis was performed concerning MRE interaction potential with the BCC miRNome. RESULTS: We identified 23 upregulated and 48 downregulated circRNAs with 354 miRNA response elements capable of sequestering miRNA target sequences of the BCC miRNome. CONCLUSION: The present study describes a variety of circRNAs that are potentially involved in the molecular pathogenesis of BCC.

Reconstruction of nasal tip support in primary, open approach septorhinoplasty : A retrospective analysis between the tongue-in-groove technique and the columellar strut.

The reconstruction of the nasal tip support is one of the most essential issues in septorhinoplasty. A comparison of the results after using the tongue-in-groove technique and the columellar strut technique was the target of this study. Thirty-three patients who underwent a primary, open approach septorhinoplasty using the above-mentioned techniques were retrospectively analyzed. The gain in tip rotation postoperatively, the sensitivity and the rigidity of the nasal tip and the aesthetic outcome after surgery were examined and evaluated. Both techniques led to an increase in nasal tip rotation postoperatively. The gain in rotation was higher in patients, treated with the tongue-in-groove technique (p = 0.0052). The sensitivity of the tip region in the tongue-in-groove group of patients was significantly lower than that in the columellar strut group of patients (p = 0.0424). Both techniques led to high percentages of tip rigidity after surgery with satisfactory aesthetic results though. The tongue-in-groove technique and the columellar strut technique are both reliable techniques for reconstructing the nasal tip support and correcting a droopy tip. Although the tongue-in-groove technique might result in a more significant increase in tip rotation, it leads to less sensitivity in the tip region.

Long-noncoding RNAs in basal cell carcinoma.

Long noncoding RNAs (lncRNAs) are fundamental regulators of pre- and post-transcriptional gene regulation. Over 35,000 different lncRNAs have been described with some of them being involved in cancer formation. The present study was initiated to describe differentially expressed lncRNAs in basal cell carcinoma (BCC). Patients with BCC (n = 6) were included in this study. Punch biopsies were harvested from the tumor center and nonlesional epidermal skin (NLES, control, n = 6). Microarray-based lncRNA and mRNA expression profiles were identified through screening for 30,586 lncRNAs and 26,109 protein-coding transcripts (mRNAs). The microarray data were validated by RT-PCR in a second set of BCC versus control samples. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of mRNAs were performed to assess biologically relevant pathways. A total of 1851 lncRNAs were identified as being significantly up-regulated, whereas 2165 lncRNAs were identified as being significantly down-regulated compared to nonlesional skin (p < 0.05). Oncogenic and/or epidermis-specific lncRNAs, such as CASC15 or ANRIL, were among the differentially expressed sequences. GO analysis showed that the highest enriched GO targeted by up-regulated transcripts was "extracellular matrix." KEGG pathway analysis showed the highest enrichment scores in "Focal adhesion." BCC showed a significantly altered lncRNA and mRNA expression profile. Dysregulation of previously described lncRNAs may play a role in the molecular pathogenesis of BCC and should be subject of further analysis.

Mutation Scanning of D1705 and D1709 in the RNAse IIIb Domain of MicroRNA Processing Enzyme Dicer in Cutaneous Melanoma.

Since the discovery of microRNAs (miRNAs) there have been performed several studies showing perturbations in the expression of miRNAs and the miRNA expression machinery in cutaneous melanoma. Dicer, a pivotal cytosolic enzyme of miRNA maturation has shown to be affected by both somatic and germline mutations in a variety of cancers. Recent studies have shown that recurrent somatic mutations of Dicer frequently affect the metal-ion-binding sites D1709 and D1705 of its RNase IIIb domain, therefore called hot spot mutations. The present study investigates metal-ion-binding sites D1709 and D1705 of the Dicer RNase IIIb domain in cutaneous melanomas and melanoma metastasis by Sanger sequencing. All investigated samples showed wildtype sequence and no single mutation was detected. The miRNA processing enzyme Dicer of melanoma and melanoma metastasis does not appear to be affected by mutation in the metal-ion-binding sites D1709 and D1705 of its RNase IIIb domain.

A pilot study of quality of life in German prehospital emergency care physicians.

BACKGROUND: Quality of life in patients represents an important area of assessment. However, attention to health professionals should be equally important. The literature on the quality of life (QOL) of emergency physicians is scarce. This pilot study investigated QOL in emergency physicians in Germany. MATERIALS AND METHODS: We conducted a cross-sectional study from January to June in 2015. We approached the German Association of Emergency Medicine Physicians and two of the largest recruitment agencies for emergency physicians in Germany and invited their members to participate. We used the WHO Q-BREF to obtain QOL scores in four domains that included physical, mental, social, and environmental health. RESULTS: The 478 German emergency physicians included in the study held board certifications in general medicine (n = 40; 8.4%), anesthesiology (n = 243; 50.8%), surgery (n = 63; 13.2%), internal medicine (n = 81; 17.0%), or others (n = 51; 10.7%). The women surveyed tended to report a better QOL but worse general health than the men. Regarding specific domains, women scored worse in physical health, particularly energy during everyday work (relative risk ratio [RRR]: 1.98 [1.21-3.24]). Both men and women scored worse in psychological health than general health, particularly young women. Women were also more likely to view their safety (RRR: 1.87 [1.07-3.28]) and living place (RRR: 2.51 [1.10-5.73]) as being poor than their male counterparts. CONCLUSION: QOL in German prehospital emergency care physicians is satisfactory for the included participants; however, there were some negative effects in the psychological health domain. This is particularly obvious in young female emergency physicians.