Metabolic Signature of Atypical Fibroxanthoma and Pleomorphic Dermal Sarcoma: Expression of Hypoxia-inducible Factor-1α and Several of Its Downstream Targets

Metabolic reprogramming mediated by hypoxia-inducible factors play a crucial role in many human cancers. HIF-1α is activated under hypoxic conditions and is considered a key regulator of oxygen homoeostasis during tumor proliferation under hypoxia. Aim of this research was to analyze the immunohistochemical expression of HIF-1α, VEGF-A, Glut-1, MCT4, and CAIX in atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS). 21 paraffin-embedded AFX and 22 PDS were analysed by immunohistochemis-try, namely HIF-1α, VEGF-A (referred to as VEGF throughout the manuscript), Glut-1, MCT4, and CAIX. To quantify the protein expression, we considered the percentage of positive tumor cells (0: 0%, 1: up to 1%, 2: 2-10%, 3: 11-50%, 4: >50%) in relation to the staining intensity (0: negative, 1: low, 2: medium, 3: strong). HIF-1α expression (mean ± SD) in AFX (9.33±2.92) was significantly stronger than that in PDS (5.90±4.38; P= 0.007), whereas the expression of VEGF, Glut-1, MCT4, and CAIX did not show differences between AFX and PDS. When comparing all tumors without subgroup stratification, the expression of HIF-1α (P= 0.044) and MCT4 (P= 0.036) was significantly stronger in ulcerated tumors than in tumors without ulceration. Our findings provide the first evidence that HIF-1α-induced metabolic reprogramming may contribute to the pathogenesis of AFX and PDS. HIF-1α expression seems to be higher in AFX than in PDS, and ulcerated tumors show higher expression levels of HIF-1α and MCT4 irrespective of the diagnosis

Differences in healthcare costs in youths with conduct disorders in rural vs. urban regions: an analysis of German health insurance data

Abstract Background For children and adolescents with mental health problems, there is a lack of data as to whether the type of residential area (urban vs. rural) influences healthcare costs for affected individuals. The aim of this study was therefore to explore potential urban vs. rural healthcare cost differences in children and adolescents with conduct disorder (CD), one of the most frequent and cost-intensive child and adolescent psychiatric disorders. Additionally, we aimed to compare healthcare costs of youths with CD, and of youths without this diagnosis. Methods We analysed data from a German health insurance company, extracting all youths with a CD diagnosis in 2011 (CD group; N = 6337), and an age- and sex-matched group without this diagnosis (control group). For both groups, annual costs per person for outpatient and inpatient healthcare were aggregated, stratified by area of residence (urban vs. rural). Results While mean annual overall costs in the CD group did not differ significantly between urban and rural areas of residence (2785 EUR vs. 3557 EUR, p = 0.253), inpatient treatment costs were significantly higher in rural areas (2166 EUR (60.9% of overall costs) vs. 1199 EUR (43.1% of overall costs), p < 0.0005). For outpatient healthcare costs, the reverse effect was found, with significantly higher costs in individuals from urban areas of residence (901 EUR (32.3% of overall costs) vs. 581 EUR (16.3% of overall costs), p < 0.0005). In the control group, no significant rural vs. urban difference was found for either overall health costs, inpatient or outpatient costs. Mean overall costs in the CD group were four times higher than in the control group (3162 (±5934) EUR vs. 795 (±4425) EUR). Conclusions This study is the first to demonstrate urban vs. rural differences in healthcare costs among youths with CD. The higher costs of inpatient treatment in rural regions may indicate a need for alternative forms of service provision and delivery in rural settings

Use of ICDAS-II, Fluorescence-Based Methods, and Radiography in Detection and Treatment Decision of Occlusal Caries Lesions: An In Vitro Study

Aim. To use visual inspection (ICDAS-II), laser fluorescence (LF), fluorescence based camera (FC) and radiographic examination (BW) for detection of caries and for treatment decision. Methods. The occlusal sites of 84 extracted permanent teeth were examined using all methods and treatment decisions (preventive or operative care) were recorded based on each method independently. For validation of the findings, fissures were opened with rotating instruments and clinical depth was determined as gold standard. Correlations (), sensitivity, specificity and AUC were calculated. McNemar test was used to show whether different methods led to significant changes in treatment decisions. Results. Highest correlation was found between ICDAS-II and FC ( 0.84), ICDAS-II and gold standard (0.82) and FC and gold standard (0.81). ICDAS-II provided the highest performance (AUC 1.0), followed by FC (0.95) and LF (0.88). The greatest difference was found for treatment planning of dentine lesions, where the use of FC (cut-offs according to the literature) had the greatest agreement between operative treatment and dentine lesions, followed by use of ICDAS-II. Conclusion. ICDAS-II may have high potential for detection and treatment planning, and other devices, especially the fluorescence camera, can add substantial information to the visual examination, enabling examiners plan treatment more accurately

Agreement of Bioluminescence Measurements and Visual Assessment in Monitoring Occlusal Surfaces of Permanent Teeth

Background: Caries lesion activity is typically assessed by visual–tactile criteria. Regular monitoring is required to detect the transition of lesions and to ensure that the initial assessment was valid. This clinical study aimed to evaluate the agreement of bioluminescence measurements (Calcivis imaging system, Cis) with visual examination to assess caries lesion activity and to monitor occlusal surfaces. Methods: The occlusal surfaces of ninety-one permanent posterior teeth were assessed for the presence or absence of active caries lesions with ICCMS criteria and Cis measurements at three visit times: baseline (t1) and six months (t2) and 12 months (t3) after baseline. Results: At the baseline visit, 70% of the included occlusal sites were assessed visually as active lesions (ICCMS codes 1 and 2). At t3, 64.8% of the sites showed signs of an active lesion. The percentage agreements between the visual and Cis methods were 87.8% (t1), 89.9% (t2) and 88.6% (t3). The corresponding κ-values were 0.71 (95% CI 0.52;0.87), 0.75 (95% CI 0.59;0.89) and 0.77 (95% CI 0.61;0.90), respectively. No significant difference between the visual and bioluminescence systems was found at any visit (p > 0.05). The results based on cluster randomization (generalized estimation equations) showed no significant differences between the visual and Cis findings for all visits (p = 0.108, Wald Χ2 with 1 df = 2.587). Conclusion: The bioluminescence system demonstrated substantial agreement for the activity assessment of occlusal lesions compared to the findings obtained by visual assessment over twelve months

Women's Media Use and Preferences of Media-Based Interventions on Lifestyle-Related Risk Factors in Gynecological and Obstetric Care: A Cross-Sectional Multi-Center Study in Germany

This study aimed to investigate factors affecting (1) women’s media use regarding health-related behaviors during pregnancy and lactation, (2) women’s preferences for media format, and (3) the content of media-based interventions on lifestyle-related risk factors during pregnancy and lactation. A cross-sectional observational multi-center study of pregnant and lactating women and women of childbearing age was carried out in 14 randomly selected obstetric and gynecologic care settings in the 12 most populated cities in Baden-Wuerttemberg, South-West Germany. Data from 219 surveyed women showed that older women, pregnant women, and lactating women have a higher probability of using media during pregnancy and lactation, respectively. The majority of women preferred a combination of analog and digital media-based interventions in gynecological (46.9%) and obstetric (47.1%) care settings and at home (73.0%). Women would like to see information brochures and flyers on health-related behaviors during pregnancy and lactation for use in gynecological and obstetric care settings, and for media use at home, they would like to have books. The probability of preferring the favored media formats in gynecological and obstetric care settings and at home were associated with pregnancy status, relationship status, socioeconomic status (SES), ethnicity, and health insurance status. About 80% of the surveyed women preferred media content regarding recommendations for a healthy lifestyle and healthy behavior during pregnancy and lactation. All of the independent variables were associated with the probability of preferring a specific media content. The SES was found to play a major role in the probability of preferring a specific media content, followed by pregnancy status, ethnicity, and health insurance status. The results from our study provide a basis for tailored preventive interventions in gynecological and obstetric care settings and for use at home. The results imply that a woman can be reached before conception, during pregnancy, or during lactation with preventive measures tailored to their requirements; however, acceptance may vary across personal attributes, such as SES, ethnicity, and others

Performance of a new fluorescence camera for detection of occlusal caries in vitro

The aim of this study was firstly to assess inter- and intra- examiner reproducibility and accuracy in the detection of occlusal caries in extracted human teeth using the newly developed fluorescence-based camera VistaCam iX and secondly to compare the performance to the established fluorescence device VistaProof. The occlusal surfaces of 101 teeth were assessed. The distribution of the lesions were characterized first visually using ICDAS-II (consensus score). The investigation sites were assessed by two examiners with different levels of experience in cariology (one experienced dentist, one final-year dental student) by both fluorescence-based cameras VistaCam iX (FC1) and VistaProof (FC2). The teeth were hemisectioned and assessed for lesion depth. Intra-class-correlation coefficients for inter- and intra-examiner reproducibility were 0.88–0.97 (FC1) and 0.82–0.98 (FC2), respectively. There was significant positive correlation (r(s), p  0.05). Both fluorescence cameras demonstrated high reproducibility and good performance for the detection of occlusal caries at various stages of the disease process. The novice and the experienced examiner were able to apply both systems for detection of lesions. The in vitro performance of both devices was comparable to each other, although there was a tendency of a better performance for the FC2. Thus, within the limitations of an in vitro study, measurements with the FC2 can be continued by the new fluorescence camera (FC1) and data formerly assessed can be compared without significant loss of information

Caries Experience and Increment in Children Attending Kindergartens with an Early Childhood Caries Preventive Program Compared to Basic Prophylaxis Measures—A Retrospective Cohort Study

Dental caries constitutes a public health challenge. As preventive strategies are desirable, this retrospective cohort study aimed to assess the caries experience and increment in children attending kindergartens with an early childhood caries (ECC) preventive program (intervention group, IG) compared to basic prophylaxis measures (control group, CG) located in areas of different socioeconomic status (SES) within Marburg (Germany). The long-term caries experience (2009–2019) of these 3–5-year-old kindergarten children was evaluated. For the caries increment, dental records of 2019 were screened for the availability of a minimum of two dental examinations at least 8 months apart. Caries was scored according to the WHO criteria (dmf–t). The data were split by observation period (300–550 and >550 days). Overall, 135 children (Ø 3.7 years) attended IG, and 132 children (Ø 3.6 years) attended CG. After 300–550 days, no significant differences were found between both groups regarding mean caries increment and experience (p > 0.05). After >550 days, IG with low SES exhibited a high caries experience. Fluoride varnish applications could not reduce the caries increment compared to CG in the short-term but slightly decreased the long-term caries experience. Comprehensive ECC prevention measures actively involving parents are needed to overcome the caries burden