The retinal origin of congenital nystagmus

This thesis describes a revolutionary retinal mechanism leading to nystagmus in mouse models for CSNB. In patients with CSNB and nystagmus, mutations were found that are specifically present in the photoreceptor to ON-bipolar cell synapse, both pre- and postsynaptically. Here, we studied one presynaptic (Cav1.4) and two postsynaptic mutations (mGluR6nob3, Nyxnob) that cause CSNB. We found that all three mouse models show nystagmus and oscillating RGCs, but that they varied phenotypically between the three genotypes. All three mutations lead to an altered membrane potential of the ON-BCs and consequently of the AII ACs as well. The latter are then outside their normal working range and start to intrinsically oscillate. These oscillations are passed on to the RGCs, which also start to oscillate. This includes the ON-DSRGCs, that send an oscillatory retinal slip signal to the AOS, which consequently leads to compensatory, oscillatory eye movements, the nystagmus. The different phenotypes can thereby be explained by the difference in depolarization levels of the ON-BCs due to the different mutations

Population-based patient care study for breast cancer

Background: Different approaches for an effective quality management are funded by the Ministry of Health to verify, to assess and, if necessary to optimize the quality of health care using the tracer diagnoses of breast, rectal, and lung cancer in eight regions in Germany. The conception of these observational studies and initial findings are shown here, using breast cancer in the region of Munich (population 2.4 million) as an example. Patients and Methods: The study started on April 1, 1996. The recruitment phase for all primary boast cancer patients in this region is planned for 2 years with a 3-5-year follow-up. Established documentation sheets are used to document basic medical information of each patient, along with the original reports (pathology: radiotherapy, doctors' reports, etc.), follow-up reports and quality of life questionnaires (QLQ, including the EORTC QLQ C30). Results: In 1996, the Munich region has a crude incidence of 125/100,000 women (world standard 71.5). After almost complete documentation the incidence is 10-15% higher. In the period from April 1 1996 to June 30, 1997 1,360 patients have been recruited into the study. 79% of the patients were 50 years of age or older. pT stages are distributed as follows: pTIS 5%, pT1 54%, pT2 32%, pT3 4%, pT4 6%. 4.5% had primary metastases. Breast-conserving therapy (BCT) was performed in 57% of patients. Five of the 46 departments involved recruited more than 50 patients each within these 14 months. These larger departments treat 59% of all patients. The proportion of older patients and pT4 stages is significantly higher in the smaller departments. BCT is performed significantly more often in the larger departments. First results of quality of life show dependencies on age, but no differences between mastectomy and BCT 3 months after operation. Not only the addressed patients (response rate to QLQ over 80%) but also almost all hospitals and many physicians are milling to support and to partake in quality assurance. 35 hospitals, 46 surgical departments. 80 heads of department and surgically: active general practioners, 330 general practioners. 7 radiotherapy departments, and 13 pathology departments have so far documented for this study. Conclusions: An effective quality management in oncology needs a modern cancer registry which uses documentation sheets as well as original reports and organizes the complicated infrastructure for an interdisciplinary cooperation. To be able to evaluate the health care reality it is necessary to carry out a data analysis and assess each individual case. A feedback of the results have to be available for each physician and each department. The cost of this information management is approximately 0.3% of the health care cost for this group of patients

Risk of basal cell carcinoma after Hodgkin's disease

Background: Basal cell cancer is a common skin cancer, yet studies of second tumors after Hodgkin's disease tend to exclude basal cell cancers as second malignant tumors from analysis. Basal cell carcinomas (BCC) are possibly more common in immunosuppressed patients and were recently implicated as indicators of subsequent malignancies. Materials and Methods: Our database of 1,120 patients with Hodgkin's disease (derived from the tumor registry) was investigated for the occurrence of later BCCs. Kaplan-Meier curves were calculated. Results: A total of 9 cases of BCC were observed 0-20 years after the diagnosis of Hodgkin's disease, One case relapsed after excision. The probability of second BCC was 2.1% after 15 years of follow-up and 7.1% after 20 years. Statistically, the risk for second BCC was increased only in younger patients and with prolonged follow-up, but not in the total group of patients with Hodgkin's disease. Conclusion: BCC is not a major threat: for the survivors of Hodgkin's disease, but continued follow-up is necessary

Changes in prognostic and therapeutic parameters in prostate cancer from an epidemiological view over 20 years

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; The study objective was to examine changes in prognosis and treatment of prostate cancer patients over 20 years and to evaluate their impact on survival. &lt;b&gt;&lt;i&gt;Patients and Methods:&lt;/i&gt;&lt;/b&gt; 38,861 prostate cancer patients diagnosed between 1990 and 2010 and living in the catchment area of the Munich Cancer Registry were analysed. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Pre-therapeutic prostate-specific antigen (PSA) testing increased substantially in the early 1990s. A shift from capsule-exceeding tumours to capsule-limited tumours also took place especially in the 1990s. The proportion of radical prostatectomy increased continuously over the last 20 years from 20% to almost 50% whereas hormone therapy decreased from 55% to 18%. Radiation therapy and transurethral resection of the prostate increased slightly from about 5% to 10%. The 5- and 10-year relative survival rates increased from 92% to 97% and from 86% to 92%, respectively. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; 2 reasons may account for the rise in survival rates over 20 years: First, the establishment of widely used PSA testing resulted in a shift towards more favourable T categories due to the detection of many additional small tumours as well as the noticeable change in initial treatment strategy towards more radical prostatectomies. The second factor that likely increased survival was improvements in the therapies themselves.</jats:p

Organic vs. Conventional Grassland Management: Do 15N and 13C Isotopic Signatures of Hay and Soil Samples Differ?

Distinguishing organic and conventional products is a major issue of food security and authenticity. Previous studies successfully used stable isotopes to separate organic and conventional products, but up to now, this approach was not tested for organic grassland hay and soil. Moreover, isotopic abundances could be a powerful tool to elucidate differences in ecosystem functioning and driving mechanisms of element cycling in organic and conventional management systems. Here, we studied the δ15N and δ13C isotopic composition of soil and hay samples of 21 organic and 34 conventional grasslands in two German regions. We also used Δδ15N (δ15N plant - δ15N soil) to characterize nitrogen dynamics. In order to detect temporal trends, isotopic abundances in organic grasslands were related to the time since certification. Furthermore, discriminant analysis was used to test whether the respective management type can be deduced from observed isotopic abundances. Isotopic analyses revealed no significant differences in δ13C in hay and δ15N in both soil and hay between management types, but showed that δ13C abundances were significantly lower in soil of organic compared to conventional grasslands. Δδ15N values implied that management types did not substantially differ in nitrogen cycling. Only δ13C in soil and hay showed significant negative relationships with the time since certification. Thus, our result suggest that organic grasslands suffered less from drought stress compared to conventional grasslands most likely due to a benefit of higher plant species richness, as previously shown by manipulative biodiversity experiments. Finally, it was possible to correctly classify about two third of the samples according to their management using isotopic abundances in soil and hay. However, as more than half of the organic samples were incorrectly classified, we infer that more research is needed to improve this approach before it can be efficiently used in practice

Mycobacterium avium subsp. paratuberculosis Proteome Changes Profoundly in Milk

Mycobacterium avium subspecies paratuberculosis (MAP) are detectable viable in milk and other dairy products. The molecular mechanisms allowing the adaptation of MAP in these products are still poorly understood. To obtain information about respective adaptation of MAP in milk, we differentially analyzed the proteomes of MAP cultivated for 48 h in either milk at 37 °C or 4 °C or Middlebrook 7H9 broth as a control. From a total of 2197 MAP proteins identified, 242 proteins were at least fivefold higher in abundance in milk. MAP responded to the nutritional shortage in milk with upregulation of 32% of proteins with function in metabolism and 17% in fatty acid metabolism/synthesis. Additionally, MAP upregulated clusters of 19% proteins with roles in stress responses and immune evasion, 19% in transcription/translation, and 13% in bacterial cell wall synthesis. Dut, MmpL4_1, and RecA were only detected in MAP incubated in milk, pointing to very important roles of these proteins for MAP coping with a stressful environment. Dut is essential and plays an exclusive role for growth, MmpL4_1 for virulence through secretion of specific lipids, and RecA for SOS response of mycobacteria. Further, 35 candidates with stable expression in all conditions were detected, which could serve as targets for detection. Data are available via ProteomeXchange with identifier PXD027444

Temporal and small-scale spatial variation in grassland productivity, biomass quality, and nutrient limitation

Characterization of spatial and temporal variation in grassland productivity and nutrition is crucial for a comprehensive understanding of ecosystem function. Although within-site heterogeneity in soil and plant properties has been shown to be relevant for plant community stability, spatiotemporal variability in these factors is still understudied in temperate grasslands. Our study aimed to detect if soil characteristics and plant diversity could explain observed small-scale spatial and temporal variability in grassland productivity, biomass nutrient concentrations, and nutrient limitation. Therefore, we sampled 360 plots of 20 cm × 20 cm each at six consecutive dates in an unfertilized grassland in Southern Germany. Nutrient limitation was estimated using nutrient ratios in plant biomass. Absolute values of, and spatial variability in, productivity, biomass nutrient concentrations, and nutrient limitation were strongly associated with sampling date. In April, spatial heterogeneity was high and most plots showed phosphorous deficiency, while later in the season nitrogen was the major limiting nutrient. Additionally, a small significant positive association between plant diversity and biomass phosphorus concentrations was observed, but should be tested in more detail. We discuss how low biological activity e.g., of soil microbial organisms might have influenced observed heterogeneity of plant nutrition in early spring in combination with reduced active acquisition of soil resources by plants. These early-season conditions are particularly relevant for future studies as they differ substantially from more thoroughly studied later season conditions. Our study underlines the importance of considering small spatial scales and temporal variability to better elucidate mechanisms of ecosystem functioning and plant community assembly