Species composition, geographical distribution and seasonal abundance of the Anopheles maculipennis complex along the Upper Rhine, Germany.

Between May and September 2016, mosquitoes were collected on a biweekly basis at 55 locations with CO2-baited encephalitis vector surveillance traps along the Upper Rhine, Germany, to evaluate the species composition, geographical distribution and abundance of the Anopheles maculipennis complex, some members of this complex being considered vectors of historical malaria in Germany. A total of 2115 Anopheles maculipennis complex specimens were collected during the season, of which a sample of 1252 individuals was determined to species level by amplification of species-specific internal transcribed spacer 2 (ITS2) sequences. A total of 856 individuals of Anopheles daciae (68.37%), 394 Anopheles messeae (31.47%) and 2 Anopheles maculipennis s.s. (0.16%) were recorded. The number and proportion of A. daciae was remarkably higher in the northern meandering zone of the Upper Rhine (843 specimens, 79.90%), than in the more canalised southern furcation zone where A. messeae with 183 collected specimens represented 92.89% of 197 classified individuals. The average number of collected A. maculipennis s.l. individuals per trapping site was 38.45, equalling 0.64% of the total mosquito collection. Despite an increase in imported malaria cases, this comparatively low abundance of A. maculipennis s.l. may indicate a low risk of endemic malaria transmission by members of the A. maculipennis complex today. The proportionally dominance of A. daciae suggests that this species could be suspected the main historical vector of malaria in the Upper Rhine region. Sequence analyses of the ITS2 fragment revealed intraindividual polymorphisms within 3 of 5 diagnostic nucleotides in all specimens of A. daciae, raising the question if additional loci should be considered, to gain further insight into the taxonomical relation to A. messeae.

The relationship between sense of coherence and post-traumatic stress: a meta-analysis.

Background: Antonovsky's concept of sense of coherence (SOC) - as a global orientation reflecting an individual's feeling of confidence in both the predictability of their internal and external environment and their ability to cope with stressful and challenging situations in life - shows a negative association with symptoms of post-traumatic stress. However, single studies varying in study characteristics provide heterogeneous effect size estimations. Objective: The purpose of the current study is to investigate the relationship between SOC and post-traumatic stress disorder (PTSD) symptom severity for the first time on a meta-analytical level. Method: The random-effects meta-analysis is based on zero-order correlations (r) and consists of 47 independent samples out of 45 studies (N = 10,883). Results: After correcting for sampling error, the mean correlation between SOC and PTSD symptoms was M(r) = -.41 (excluding four outliers: -.39). However, this effect could not be generalized to all types of PTSD samples owing to substantial remaining heterogeneity. Subsequent moderator analyses investigating the influence of different SOC and PTSD measures, trauma type and duration, mean age and gender imbalances per sample did not reveal significant moderating effects. Conclusions: The meta-analysis reveals a substantial correlation between SOC and PTSD symptom severity: higher SOC levels are associated with lower symptom severity. Thus, future research should progress to the question of whether the relationship between SOC and post-traumatic stress is causal, and by which factors it is moderated. Abbreviations: CD, Cook's distance; DSM, Diagnostic and Statistical Manual of Mental Disorders; (G)RR, general (and specific) resistance resources; IES(-R), Impact of Event Scale (Revised); PDS, Posttraumatic Stress Diagnostic Scale; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; PTSD, post-traumatic stress disorder; SDR, standard deleted residual; SOC, sense of coherence; SOC-R, Sense of Coherence Scale - Revised.

Antecedentes: El concepto de sentido de coherencia (SOC) de Antonovsky- como una orientación global reflejando el sentimiento de seguridad de un individuo, tanto en la previsibilidad de su ambiente interno y externo y su habilidad para enfrentar situaciones estresantes y desafiantes en su vida- muestra una asociación negativa con el estrés postraumático. Sin embargo, estudios individuales que varían en las características proporcionan estimaciones del tamaño del efecto heterogéneo.Objetivo: El propósito de este estudio es investigar la relación entre SOC y severidad de los síntomas de TEPT por primera vez a un nivel metaanalítico.Método: El metanálisis de efectos aleatorios se basa en correlaciones de orden cero (r) y consta de 47 muestras independientes de 45 estudios (N= 10.883).Resultados: Después de corregir por error de muestreo, la correlación media entre SOC y síntomas de TEPT fue M(r) =−.41 (excluyendo cuatro valores atípicos: −.39). Sin embargo, este efecto podría no ser generalizado a todos los tipos de muestras de TEPT debido a la importante heterogeneidad restante. Los siguientes análisis del moderador investigan la influencia de diferentes mediciones de SOC y TEPT, tipo de trauma y duración, edad media y desbalance de género por muestra no revela efectos moderados significativos.Conclusiones: El metanálisis revela una importante correlación entre SOC y severidad de los síntomas de TEPT: Niveles más altos de SOC están asociados con menor severidad de los síntomas. De este modo, las investigaciones futuras deberían progresar a la pregunta de si la relación entre SOC y estrés postraumático es causal, y por cuáles factores es moderada.

Standard urotherapy as first-line intervention for daytime incontinence: a meta-analysis.

According to the International Children's Continence Society (ICCS) guidelines for the treatment of daytime urinary incontinence (DUI) in children and adolescents, the first-line intervention for all types of DUI is standard urotherapy (SU). Despite this recommendation there is still no meta-analysis available on the effectiveness of SU. The aim of this study is to provide a meta-analytic evaluation of the intervention. This meta-analysis is based on Odds Ratios (OR) and consists of 26 patient samples out of 19 studies (N = 1609), collected from well-established medical databases. Remission rates after SU are compared to spontaneous remission rates, which are matched to the individual follow-up period. The meta-analysis shows that SU is an effective treatment of DUI. Compared to a spontaneous remission rate of 15.40% per year, urotherapy increases the probability to recover by a factor of 7.27 (6.57 if corrected for publication bias). After exclusion of three outlying samples this effect can be generalized for all types of SU and all patient populations. Moderator analyses cannot identify variables which significantly influence the variance of effect sizes. However, RCTs seem to be associated with lower effects, even when the control group is not considered for effect size calculation. Based on the present meta-analysis, SU is an effective intervention for treating DUI in children and adolescents. Of 100 patients in 1 year, approximately 56 patients (54 if corrected for publication bias) remit after being treated with SU, while only 15 out of 100 remit spontaneously. However, to further quantify the effect size of SU in comparison to spontaneous remission rates and other treatments, additional RCTs are still needed.

Transplant-associated thrombotic microangiopathy is an endothelial complication associated with refractoriness of acute GvHD.

There is increasing evidence that endothelial dysfunction is involved in refractoriness of acute GvHD (aGvHD). Here we investigated the hypothesis that another endothelial complication, transplant-associated thrombotic microangiopathy (TMA), contributes to the pathogenesis of aGvHD refractoriness. TMA was retrospectively assessed in 771 patients after allogeneic stem cell transplantation (alloSCT). Incidences of TMA and refractory aGvHD were correlated with biomarkers of endothelial damage obtained before alloSCT for patients receiving or not receiving statin-based endothelial prophylaxis (SEP). Diagnostic criteria for TMA and refractory aGvHD were met by 41 (5.3%) and 76 (10%) patients, respectively. TMA was overrepresented in patients with refractory aGvHD (45.0 vs 2.3% in all other patients, P<0.001). TMA independently increased mortality. Elevated pretransplant suppressor of tumorigenicity-2 and nitrates along with high-risk variants of the thrombomodulin gene were associated with increased risk of TMA. In contrast, SEP abolished the unfavorable outcome predicted by pretransplant biomarkers on TMA risk. Patients on SEP had a significantly lower risk of TMA (P=0.001) and refractory aGvHD (P=0.055) in a multivariate multistate model. Our data provide evidence that TMA contributes to the pathogenesis of aGvHD refractoriness. Patients with an increased TMA risk can be identified pretransplant and may benefit from pharmacological endothelium protection.

Adaptive Dose Escalation using Serial Four-dimensional Positron Emission Tomography/Computed Tomography Scans during Radiotherapy for Locally Advanced Non-small Cell Lung Cancer.

AIMS: Computed tomography (CT)-based radiotherapy dose escalation for locally advanced non-small cell lung cancer (LA-NSCLC) has had limited success. In this planning study, we investigated the potential for adaptive dose escalation using respiratory-gated 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography scans (4DPET/4DCT) acquired before and during a course of chemoradiotherapy (CRT). MATERIALS AND METHODS: We prospectively enrolled patients with LA-NSCLC receiving curative intent CRT. Radiotherapy was delivered using intensity-modulated radiotherapy (IMRT) using the week 0 4DCT scan. Three alternative, dose-escalated IMRT plans were developed offline based on the week 0, 2 and 4 4DPET/4DCT scans. The FDG-avid primary (PET-T) and nodal disease (PET-N) volumes defined by the 50% of maximum standard uptake value threshold were dose escalated to as high as possible while respecting organ at risk constraints. RESULTS: Thirty-two patients were recruited, 27 completing all scans. Twenty-five patients (93%) were boosted successfully above the clinical plan doses at week 0, 23 (85%) at week 2 and 20 (74%) at week 4. The median dose received by 95% of the planning target volume (D95) at week 0, 2 and 4 to PET-T were 74.4 Gy, 75.3 Gy and 74.1 Gy and to PET-N were 74.3 Gy, 71.0 Gy and 69.5 Gy. CONCLUSIONS: Using 18F-FDG-4DPET/4DCT, it is feasible to dose escalate both primary and nodal disease in most patients. Choosing week 0 images to plan a course with an integrated boost to PET-avid disease allows for more patients to be successfully dose escalated with the highest boost dose.

[Prerequisites for a successful lung cancer screening program]. / Voraussetzungen für ein erfolgreiches Lungenkrebsscreeningprogramm.

The American national lung cancer screening trial (NLST) has provided the first confirmation of a reduction in lung cancer mortality by using low-dose multislice computed tomography (MSCT). Preliminary evaluations of smaller European trials could not confirm such a reduction. The final evaluation of the larger Dutch-Belgian NELSON trial and five other European trials are expected within the next 1-2 years. The results of the completed rounds of screening in all these studies indicate that the margin between a positive and a negative benefit-to-harm balance will be narrow. In such a scenario it will be crucial to optimize the definition of the target population for screening as a high-risk group for lung cancer, the quality of screening in terms of high sensitivity and specificity as well as high quality treatment and an effective ongoing control of program quality. Not all healthcare systems are suitable to fulfill these prerequisites.

Effect of smoking cessation counseling within a randomised study on early detection of lung cancer in Germany.

INTRODUCTION: In the German lung cancer screening trial LUSI, smoking cessation counseling (SCC) was offered to all participants at time of randomization, and smoking habits were asked for within annual questionnaire inquiries. We analyzed the smoking habits of the participants within the first 2 years of follow-up and especially the potential effect of the SCC on these habits. MATERIALS AND METHODS: We used the smoking data of the initial inquiry on which the decision on invitation to the study was based, the socio-economic data of the questionnaire filled-in at time of randomization, the psycho-social data obtained during the SCC, and the annual questionnaire data of the first two annual follow-up screening rounds. RESULTS: Smoking prevalence decreased in the entire cohort significantly by 4 %, whereby the decrease was with 4.5 % statistically not significantly higher in the control arm than in the screening arm with 3.4 %. The decline was much stronger in the subgroup of attendees to stop-smoking counseling and mounted up therein to 10 %. In some participants, an increase of readiness to quit smoking was observed during the counseling hour, but did not show effects on smoking status 2 years later. DISCUSSION: We did not see a tendency to increased smoking among participants of the intervention arm or the entire study. The decline of smoking prevalence among the attendees of the counseling might be due to self-selection. Since the issue of effectiveness of smoking cessation counseling is important, further research with randomization into offering counseling or no intervention should be taken into consideration.

Distribution of individual members of the mosquito Anopheles maculipennis complex in Germany identified by newly developed real-time PCR assays.

Owing to their role as vectors of malaria parasites, species of the Anopheles maculipennis complex (Diptera: Culicidae) Meigen were intensively studied in the past, but with the disappearance of malaria in Germany in the middle of the last century, the interest in this field of research declined. A comprehensive ecological analysis of the current species distribution for Germany is lacking. Between 2010 and 2013, a total of 1445 mosquitoes of the An. maculipennis complex were collected at 72 different sites in Germany. The samples comprise 722 single individuals as well as 723 individuals in 90 pools of up to 25 mosquitoes. All samples were analysed with newly developed species-specific qPCR assays for the identification of the four German species using nucleotide differences within the internal transcribed spacer 2 (ITS2) ribosomal DNA. All gathered data were used for species distribution modelling. The overall prevalence of An. messeae s.l. was highest with 98.89% of all pools; An. daciae with 6.93% of all individuals and An. messeae s.s. with 69.53%. The prevalence of the other two species was relatively low: An. maculipennis s.s. with 13.30% of all individuals (6.67% of all pools) and An. atroparvus with 1.80% of all individuals (1.11% of all pools).

Evaluation of a structured expert elicitation estimating the proportion of illness acquired by foodborne transmission for nine enteric pathogens in Australia.

Estimates of the proportion of illness transmitted by food for different enteric pathogens are essential for foodborne burden-of-disease studies. Owing to insufficient scientific data, a formal synthesis of expert opinion, an expert elicitation, is commonly used to produce such estimates. Eleven experts participated in an elicitation to estimate the proportion of illnesses due to food in Australia for nine pathogens over three rounds: first, based on their own knowledge alone; second, after being provided with systematic reviews of the literature and Australian data; and finally, at a workshop where experts reflected on the evidence. Estimates changed significantly across the three rounds (P = 0·002) as measured by analysis of variance. Following the workshop in round 3, estimates showed smoother distributions with significantly less variation for several pathogens. When estimates were combined to provide combined distributions for each pathogen, the width of these combined distributions reflected experts' perceptions of the availability of evidence, with narrower intervals for pathogens for which evidence was judged to be strongest. Our findings show that the choice of expert elicitation process can significantly influence final estimates. Our structured process - and the workshop in particular - produced robust estimates and distributions appropriate for inclusion in burden-of-disease studies.

Gene-specific regulation of hepatic selenoprotein expression by interleukin-6.

Sepsis is a severe inflammatory disease resulting in excessive production of pro-inflammatory cytokines including interleukin-6 (IL-6), causing oxidative stress, tissue damage and organ dysfunction. Health benefits have been observed upon selenium (Se) supplementation in severe sepsis. Selenium is incorporated into selenoproteins implicated in anti-oxidative defence, thyroid hormone metabolism and immunoregulation. Selenium metabolism is controlled by hepatocytes synthesizing and secreting the Se transporter selenoprotein P (SePP). The circulating SePP declines in sepsis causing low serum Se levels. Dysregulation of the hepatic selenoenzyme deiodinase type 1 (DIO1) potentially contributes to the low T3 (thyroid hormone) syndrome observed in severe diseases. We hypothesized that IL-6 affects hepatic selenoprotein biosynthesis directly. Testing human hepatocytes in culture, IL-6 reduced the concentrations of SePP mRNA and secreted SePP in a dose-dependent manner. In parallel, expression of DIO1 declined at the mRNA, protein and enzyme activity level. The effects of IL-6 on glutathione peroxidase (GPX) expression were isozyme-specific; GPX1 remained unaffected, while transcript concentrations of GPX2 increased and those of GPX4 decreased. This pattern of IL-6-dependent effects was mirrored in reporter gene experiments with SePP, DIO1, GPX1, and GPX2 promoter constructs pointing to direct transcriptional effects of IL-6. The redirection of hepatic selenoprotein biosynthesis by IL-6 may represent a central regulatory circuit responsible for the decline of serum Se and low T3 concentrations in sepsis. Accordingly, therapeutic IL-6 targeting may be effective for improving the Se and thyroid hormone status, adjuvant Se supplementation success and survival in sepsis.

Histological and histochemical analysis of the gastrointestinal tract of the common pipistrelle bat (Pipistrellus pipistrellus).

Bats have a very high mass-specific energy demand due to small size and active flight. European bat species are mostly insectivorous and the morphology of the gastrointestinal tract should be adapted accordingly. This study investigated the general anatomy by histology and the function by analysing carbohydrate distribution in particular of the mucus of the GI tract of the insectivorous bat Pipistrellus pipistrellus. The GI tracts of three individuals were dissected, fixed in formaldehyde, and embedded in paraffin wax. The tissues and cells of the GI tract of P. pipistrellus were analysed by classical (Acid Alizarin Blue, Haematoxylin-Eosin, and Masson Goldner Trichrome), histochemical (periodic acid-Schiff, Alcian blue at pH 2.5) and lectin histochemical (lectins WGA and HPA) staining procedures. The GI tract of P. pipistrellus was organised into the typical mammalian layers. The short, narrow, and thin-walled esophagus was simple with a folded stratified squamous epithelium without glands but mucous surface cells secreting neutral mucus. The stomach was globular shaped without specialisation. Mucous surface cells produced neutral mucus whereas neck and parietal cells secreted a mixture of neutral and acid mucus. Chief cell surface was positive for N-acetylglucosamine and the cytoplasm for N-acetylgalactosamine residues. The intestine lacked a caecum and appendix. The small intestine was divided into duodenum, jejunum­ileum and ileum­colon. The epithelium consisted of columnar enterocytes and goblet cells. The large intestine was short, only represented by the descending colon-rectum. It lacked villi and the mucosa had only crypts of Lieberkühn. Towards the colon-rectum, goblet cells produced mucus with N-acetylglucosamine residues increasing in acidity except in colon-rectum where acidity was highest in the base of crypts. Along the tube the surface of enterocytes was positive for N-acetylglucosamine and N-acetylgalactosamine. All over the mucus filling the lumen of the GI tract was positive for N-acetylglucosamine and increased in acidity in all parts except of the stomach. In conclusion, the simple GI tract showed an anatomical reduction of tissue enabling for a short retention time and a reduction of the load carried during flight: short GI tract, lack of lymphoid tissue, missing of glands in certain regions, and a distinct pattern of mucus distribution, indicating different physiological functions of these areas. The GI tract of P. pipistrellus was typical for an insectivorous species probably representing the ancestral condition.

Improved detection of anterior fibromuscular stroma and transition zone prostate cancer using biparametric and multiparametric MRI with MRI-targeted biopsy and MRI-US fusion guidance.

BACKGROUND: The objective of this study was to analyze the potential of prostate magnetic resonance imaging (MRI) and MRI/transrectal ultrasound-fusion biopsies to detect and to characterize significant prostate cancer (sPC) in the anterior fibromuscular stroma (AFMS) and in the transition zone (TZ) of the prostate and to assess the accuracy of multiparametric MRI (mpMRI) and biparametric MRI (bpMRI) (T2w and diffusion-weighted imaging (DWI)). METHODS: Seven hundred and fifty-five consecutive patients underwent prebiopsy 3 T mpMRI and transperineal biopsy between October 2012 and September 2014. MRI images were analyzed using PIRADS (Prostate Imaging-Reporting and Data System). All patients had systematic biopsies (SBs, median n=24) as reference test and targeted biopsies (TBs) with rigid software registration in case of MRI-suspicious lesions. Detection rates of SBs and TBs were assessed for all PC and sPC patients defined by Gleason score (GS)⩾3+4 and GS⩾4+3. For PC, which were not concordantly detected by TBs and SBs, prostatectomy specimens were assessed. We further compared bpMRI with mpMRI. RESULTS: One hundred and ninety-one patients harbored 194 lesions in AFMS and TZ on mpMRI. Patient-based analysis detected no difference in the detection of all PC for SBs vs TBs in the overall cohort, but in the repeat-biopsy population TBs performed significantly better compared with SBs (P=0.004 for GS⩾3+4 and P=0.022 for GS⩾4+3, respectively). Nine GS⩾4+3 sPCs were overlooked by SBs, whereas TBs missed two sPC in men undergoing primary biopsy. The combination of SBs and TBs provided optimal local staging. Non-inferiority analysis showed no relevant difference of bpMRI to mpMRI in sPC detection. CONCLUSIONS: MRI-targeted biopsies detected significantly more anteriorly located sPC compared with SBs in the repeat-biopsy setting. The more cost-efficient bpMRI was statistically not inferior to mpMRI in sPC detection in TZ/AFMS.

Occupational exposure to endocrine disruptors and lymphoma risk in a multi-centric European study.

BACKGROUND: Incidence rates of lymphoma are usually higher in men than in women, and oestrogens may protect against lymphoma. METHODS: We evaluated occupational exposure to endocrine disrupting chemicals (EDCs) among 2457 controls and 2178 incident lymphoma cases and subtypes from the European Epilymph study. RESULTS: Over 30 years of exposure to EDCs compared to no exposure was associated with a 24% increased risk of mature B-cell neoplasms (P-trend=0.02). Associations were observed among men, but not women. CONCLUSIONS: Prolonged occupational exposure to endocrine disruptors seems to be moderately associated with some lymphoma subtypes.

Randomized Study on Early Detection of Lung Cancer with MSCT in Germany: Results of the First 3 Years of Follow-up After Randomization.

INTRODUCTION: The German Lung Cancer Screening Intervention Trial (LUSI) is one of the European randomized trials investigating the efficacy of low-dose multislice computed tomography (MSCT) as a screening tool for lung cancer. In the evaluation of the first (prevalence) screening round, we observed exceptionally high early recall rates, which made the routine application of MSCT screening questionable. Because screening may behave differently in subsequent (incidence) screening rounds, we analyzed (a) basic characteristics for the annual rounds 2 to 4, which have now also been completed, and (b) the first 3 years with complete follow-up since time of randomization. METHODS: Data material was the data record of LUSI after the fourth screening round and the 3-year follow-up had been completed. Basic characteristics of screening, e.g., early recall rate, detection rate, and interval cancers as well of proportion of advanced cancers, were descriptively evaluated and, if informative, group differences were tested for statistical significance. RESULTS: Early recall rates were significantly lower in the subsequent screening rounds than in the first one if the MSCT information from the previous screening rounds was available. Detection and biopsy rates were approximately 1% or lower, ratio of benign:malignant biopsies: 1:1.6 to 1:3. CONCLUSION: Our recent data may not only settle one concern regarding high recall rates in routine MSCT screening but also indicate that screening must be strictly organized to be effective. Performance indicators are similar to those in mammography screening. Nevertheless, possible consequences for the participants (diagnostic workup of suspicious findings, biopsies) are more invasive than in mammography screening.

Genetic variants in DNA repair genes as potential predictive markers for oxaliplatin chemotherapy in colorectal cancer.

Oxaliplatin-based chemotherapy exerts its effects through generating DNA damage. Hence, genetic variants in DNA repair pathways could modulate treatment response. We used a prospective cohort of 623 colorectal cancer patients with stage II-IV disease treated with adjuvant/palliative chemotherapy to comprehensively investigate 1727 genetic variants in the DNA repair pathways as potential predictive markers for oxaliplatin treatment. Single nucleotide polymorphisms (SNP) associations with overall survival and recurrence-free survival were assessed using a Cox regression model. Pathway analysis was performed using the gamma method. Patients carrying variant alleles of rs3783819 (MNAT1) and rs1043953 (XPC) experienced a longer overall survival after treatment with oxaliplatin than patients who did not carry the variant allele, while the opposite association was found in patients who were not treated with oxaliplatin (false discovery rate-adjusted P-values for heterogeneity 0.0047 and 0.0237, respectively). The nucleotide excision repair (NER) pathway was found to be most likely associated with overall survival in patients who received oxaliplatin (P-value=0.002). Our data show that genetic variants in the NER pathway are potentially predictive of treatment response to oxaliplatin.

Strong induction of iodothyronine deiodinases by chemotherapeutic selenocompounds.

The biological activity of thyroid hormones (TH) is regulated by selenoenzymes of the iodothyronine deiodinase (DIO) family catalysing TH activating and inactivating reactions. Besides TH metabolism, several studies indicate an important role of DIO isoenzymes in tumorigenesis and cancer growth. It is therefore of therapeutic importance to identify modulators of DIO expression. We have synthesized and studied a series of selenocompounds containing a methyl- or benzyl-imidoselenocarbamate backbone. One of these novel compounds had chemotherapeutic activities in a murine xenograft tumour model by an unknown mechanism. Therefore, we tested their effects on DIO expression in vitro. In HepG2 hepatocarcinoma cells, DIO1 activity was strongly (up to 10-fold) increased by the methyl- but not by the corresponding benzyl-imidoselenocarbamates. Steady-state mRNA levels remained unaltered under these conditions indicating a post-transcriptional mode of action. The effects were further characterized in HEK293 cells stably expressing DIO1, DIO2 or DIO3. Even within the artificial genetic context of the expression vectors, all three DIO isoenzymes were up-regulated by the methyl- and to a lesser extent by the benzyl-imidoselenocarbamates. Consistent stimulating effects were observed with methyl-N,N'-di(quinolin-3-ylcarbonyl)-imidoselenocarbamate (EI201), a selenocompound known for its anti-tumour activity. DIO inducing effects were unrelated to the intracellular accumulation of selenium, yet the precise mode of action remains elusive. Collectively, our data highlight that these selenocompounds may constitute interesting pharmacological compounds for modifying DIO expression potentially affecting the balance between cell differentiation and proliferation.

[Implementing an Organised Colorectal Cancer Screening Programme in Germany: Opportunities and Challenges]. / Einführung eines organisierten Darmkrebs-Screenings in Deutschland: Chancen und Herausforderungen.

BACKGROUND: Each year in Germany, about 65,000 people are diagnosed with colorectal cancer (CRC) and more than 25,000 people die of the disease. The majority of these cases could be avoided by a more effective screening programme. Recently, a law came into force that offers a great opportunity in this regard. It calls for introducing an organised CRC screening programme in Germany, which includes an invitation system as well as further measures for quality assurance and programme evaluation. To realise this opportunity, challenges of implementation need to be considered. The aim of this review article is to elaborate the challenges of an organised CRC screening in Germany in order to derive the need for action regarding successful implementation. METHODS: This review article is based on a selective literature search, including current guidelines and recommendations. RESULTS AND CONCLUSION: In the context of CRC screening, but also by colonoscopies performed for other indications (e.g., due to symptoms), precancerous lesions (adenomas) are detected and removed in a relevant proportion of the target population, which requires a surveillance examination after 3 or 5 years according to current recommendations. Therefore, an efficient invitation system for CRC screening should be designed to allow for a flexible interval depending on previous findings, which differs from mammography screening with its fixed interval. A prerequisite would be the standardised documentation of all colonoscopies irrespective of the indication, given that a substantial proportion of colonoscopies in Germany are performed outside of the screening program. Still, the work load regarding documentation could be less than for mammography screening. Another challenge in terms of organisation results from the parallel offer of 2 different screening tools (colonoscopy and faecal occult blood test). To realise the potential of an organised CRC screening, it seems important to devote sufficient time and resources for developing an efficient and feasible concept, while there might be interim options to avoid further delay regarding the initial invitation of the target population. Given that expertise from, amongst others, gastroenterology, epidemiology, clinical chemistry and health communication is required, an interdisciplinary approach appears essential.

Pharmaceutical industry interactions of psychiatric trainees from 20 European countries.

BACKGROUND: Interactions between the pharmaceutical industry (PI) and psychiatrists have been under scrutiny recently, though there is little empirical evidence on the nature of the relationship and its intensity at psychiatry trainee level. We therefore studied the level of PI interactions and the underlying beliefs and attitudes in a large sample of European psychiatric trainees. METHODS: One thousand four hundred and forty-four psychiatric trainees in 20 European countries were assessed cross-sectionally, with a 62-item questionnaire. RESULTS: The total number of PI interactions in the preceding two months varied between countries, with least interactions in The Netherlands (M (Mean)=0.92, SD=1.44, range=0-12) and most in Portugal (M=19.06, SD=17.44, range=0-100). Trainees were more likely to believe that PI interactions have no impact on their own prescribing behaviour than that of other physicians (M=3.30, SD=1.26 vs. M=2.39, SD=1.06 on a 5-point Likert scale: 1 "completely disagree" to 5 "completely agree"). Assigning an educational role to the pharmaceutical industry was associated with more interactions and higher gift value (IRR (incidence rate ratio)=1.21, 95%CI=1.12-1.30 and OR=1.18, 95%CI=1.02-1.37). CONCLUSIONS: There are frequent interactions between European psychiatric trainees and the PI, with significant variation between countries. We identified several factors affecting this interaction, including attribution of an educational role to the PI. Creating alternative educational opportunities and specific training dedicated to PI interactions may therefore help to reduce the impact of the PI on psychiatric training.

[Cross stability in conventional shoes by the use of spring steel insoles: a pedobarographic effect study with observational application]. / Querstabilität im Konfektionsschuh durch Federstahleinlagen: Eine pedobarographische Wirkungsstudie mit Anwendungsbeobachtung.

BACKGROUND: From an orthopedic point of view, wearing conventional ready to wear shoes negatively affects the front transverse arch of the human foot by forcing it into an unnatural inverted position. OBJECTIVES: The aim of the present orthopedic application study was to conduct a standardized assessment of the biomechanical effect of a newly developed, longitudinally flexible and cross stable spring steel insole by means of pedobarographic measurements and by means of a supplementary questioning of the participants. MATERIAL AND METHODS: In order to do this a total of 33 healthy adult participants were recruited in summer 2013. The randomized, blinded and controlled main study compared the cross stable insole made from spring steel with a flat, ordinary control insole made from ethylene vinyl acetate by means of pedobarographic in-shoe measurements at the forefoot. Additionally, the subjectively perceived effect of the steel insole with respect to comfort, restricted mobility and pain was assessed in a randomized, blinded and controlled ancillary study, using a cross-over design. RESULTS: Both the plantar peak pressure and the plantar force-time integral were significantly higher with the spring steel insole, especially in the central forefoot. In the subsequent test phase lasting several weeks during which the participants were asked to wear the spring steel insole, they rarely complained about problems and in particular did not report negative effects regarding comfort, restricted mobility and pain compared to the ordinary control insoles. CONCLUSION: The present study was conducted according to high methodological standards and proved for the first time that the tested spring steel insoles have a positive effect on the human forefoot. The cross stability increases the pressure in the median ball area, prevents the unnatural inverted position of the forefoot and thus creating an effect which is comparable to walking barefoot. As the participants did not judge this orthopedic effect of the cross stability as being uncomfortable, such an insole could be used a millionfold as a primary prevention in conventional shoes.