Precise parameter control of multicycle terahertz generation in PPLN using flexible pulse trains.

The low (sub %) efficiencies so-far demonstrated for nonlinear optical down-conversion to terahertz (THz) frequencies are a primary limiting factor in the generation of high-energy, high-field THz-radiation pulses (in particular narrowband, multicycle pulses) needed for many scientific fields. However, simulations predict that far higher conversion efficiencies are possible by use of suitably-optimized optical sources. Here we implement a customized optical laser system producing highly-tunable trains of infrared pulses and systematically explore the experimental optimization of the down-conversion process. Our setup, which allows tuning of the energy, duration, number and periodicity of the pulses in the train, provides a unique capability to test predictions of analytic theory and simulation on the parameter dependences for the optical-to-THz difference-frequency generation process as well as to map out, with unprecedented precision, key properties of the nonlinear crystal medium. We discuss the agreements and deviations between simulation and experimental results which, on the one hand, shed light on limitations of the existing theory, and on the other hand, provide the first steps in a recipe for development of practical, high-field, efficiency-optimized THz sources.

Characteristic Timescales of the Local Moment Dynamics in Hund's Metals.

We study the characteristic timescales of the fluctuating local moments in Hund's metal systems for different degrees of correlation. By analyzing the dynamical spin susceptibility in the real-time domain, we determine the timescales controlling oscillation and damping of on-site fluctuations-a crucial factor for the detection of local moments with different experimental probes. We apply this procedure to different families of iron pnictides or chalcogenides, explaining the material trend in the discrepancies reported between experimental and theoretical estimates of their magnetic moments.

Antenatal glucocorticoid treatment is associated with diurnal cortisol regulation in term-born children.

Due to the rapid developmental changes that occur during the fetal period, prenatal influences can affect the developing central nervous system with lifelong consequences for physical and mental health. Glucocorticoids are one of the proposed mechanisms by which fetal programing occurs. Glucocorticoids pass through the blood-brain barrier and target receptors throughout the central nervous system. Unlike endogenous glucocorticoids, synthetic glucocorticoids readily pass through the placental barrier to reach the developing fetus. The synthetic glucocorticoid, betamethasone, is routinely given prenatally to mothers at risk for preterm delivery. Over 25% of the fetuses exposed to betamethasone will be born at term. Few studies have examined the lasting consequences of antenatal treatment of betamethasone on the regulation of the hypothalamic-pituitary-adrenal (HPA) axis. The purpose of this study is to examine whether antenatal exposure to betamethasone alters circadian cortisol regulation in children who were born full term. School-aged children prenatally treated with betamethasone and born at term (n=19, mean (SD)=8.1 (1.2) years old) were compared to children not treated with antenatal glucocorticoids (n=61, mean (SD)=8.2 (1.4) years old). To measure the circadian release of cortisol, saliva samples were collected at awakening; 30, 45, and 60min after awakening; and in the evening. Comparison children showed a typical diurnal cortisol pattern that peaked in the morning (the cortisol awakening response) and gradually decreased throughout the day. In contrast, children exposed to antenatal betamethasone lacked a cortisol awakening response and had a flatter diurnal slope (p's<0.01). These data suggest that antenatal glucocorticoid treatment may disrupt the circadian regulation of the HPA axis among children born at term. Because disrupted circadian regulation of cortisol has been linked to mental and somatic health problems, future research is needed to determine whether children exposed to antenatal synthetic glucocorticoids are at risk for poor mental and physical health.

[Medical and vocational rehabilitation in rehabilitation facilities for people with mental illnesses in Germany: Analysis of admission and discharge data]. / Medizinisch-berufliche Rehabilitation in Rehaeinrichtungen für psychisch Kranke in Deutschland : Analyse der Aufnahme- und Entlassungsdaten.

BACKGROUND: Integrative medical and vocational rehabilitation has been implemented in Germany in rehabilitation facilities for people with mental illnesses (RPK). MATERIAL AND METHODS: In all 52 RPK facilities in Germany the admission and discharge data of all rehabilitation patients are collected and accumulated at facility level before they are combined at the registration office of the Federal Association of RPKs (BAG RPK). This study is based on a descriptive analysis of admission and discharge data of 1311 rehabilitation patients in the year 2010. RESULTS: Nearly two thirds of the 1311 RPK rehabilitation patients met the diagnostic criteria for schizophrenia or affective disorders. A subgroup of 39.1 % of all patients participated in vocational RPK measures (programs for participation in working life, LTA) after having received medical RPK measures. After completion of the vocational RPK measures 38 % of the rehabilitation patients were employed and 26 % were in education and retraining, i.e. 64 % of the patients were employed in the labor market or in educational measures. The housing and living conditions of the majority of patients changed in the direction of increased autonomy after completion of the RPK measures. DISCUSSION AND CONCLUSION: For people with severe mental illnesses, RPKs can be a place of successful rehabilitative measures facilitating participation in community life. Future studies need to investigate predictors of outcome.

Production of folate in oat bran fermentation by yeasts isolated from barley and diverse foods.

AIMS: The focus of the research was to identify yeasts from barley kernels in order to study their folate production capability while maintaining high viscosity caused by soluble fibres in oat bran fermentation. METHODS AND RESULTS: The 65 isolated yeasts were characterized by API carbohydrate utilization tests, and assays for extracellular enzyme activities were the following: amylase, beta-glucanase, cellulase or CMCase, lipase, protease and xylanase. Yeasts were identified by partial DNA sequencing of the 25S D1/D2 and ITS1-5.8S-ITS2 regions. They belonged to the genera Aureobasidium, Cryptococcus, Pseudozyma and Rhodotorula. Folate production was determined from supernatant and cells grown in a rich laboratory medium or directly from oat bran solution inoculated with the appropriate yeast. Food yeasts, Saccharomyces cerevisiae, Candida milleri, Kluyveromyces marxianus and Galactomyces geotrichum, were used for comparison. Most of the yeasts isolated from barley destroyed the solid, viscous structure of the oat bran solution, indicating that they degraded the viscosity-generating soluble fibres, considered to be nutritionally advantageous. The best folate producers were S. cerevisiae, followed by Pseudozyma sp., Rhodotorula glutinis and K. marxianus. The yeasts maintaining high viscosity were used together with lactic acid bacteria (LAB) Streptococcus thermophilus or Lactobacillus rhamnosus to ferment oat bran solution. None of the yeasts isolated from barley, contrary to S. cerevisiae and C. milleri, produced together with LAB significant amounts of folate. CONCLUSIONS: Fermentative yeasts together with LAB are potential for use in developing novel high folate content healthy foods and snacks from oat bran. SIGNIFICANCE AND IMPACT OF THE STUDY: High soluble fibre content and high natural folate content but low energy content food and snack products with pleasant fermentation aroma provide possibilities for new developments in the food industry.

Late spontaneous recanalization of a symptomatically occluded internal carotid artery two years after extra-intracranial bypass. Case report and review of the literature.

Spontaneous recanalization of the internal carotid artery (ICA) is rarely observed. Mainly case reports are published. Most often early recanalization occurs within days or weeks and only a few cases of late recanalization months or years after detected occlusion are reported. Symptomatic bilateral ICA occlusion is regarded as an acceptable indication for extra-intracranial (EC-IC) bypass. The authors report on a case with bilateral symptomatic ICA occlusion and EC-IC bypass >2 years prior to detected spontaneous leftsided recanalization. Spontaneous recanalization unmasking a high degree ICA stenosis at the carotid bifurcation allowed a successful subsequent surgical recanalization in this patients. Mechanisms of early and late recanalization as well as treatment options are discussed.

Organ-cocultures (COCs) for long term in vitro studies of lung cancer using 2-photon microscopy.

Three-dimensional organ cultures allow performing research in vitro in a complex multi-cellular environment. We aimed at developing a long term coculture system (COC) for the study of lung cancer to repeatedly measure tumor volume. Organ cultures of bronchial mucosa with 1-2 mm diameter were embedded in agarose and bisected with a tissue slicer so that the organ culture within was cut into halves uncovering the connective tissue of the stroma of each half. A cell suspension of GFP-transfected EPLC 32M1 lung tumor cells was brought in contact with the connective tissue of the wounded surface. Adherent tumor cells grew invasively into the organ culture. Using 2-Photon microscopy, Z-stacks were recorded, reconstructed with appropriate analysis software, and the tumor volume was calcvulated. Tumor cells were identified by GFP-fluorescence. Repeated measurements of the same COC could be performed over up to 8 weeks. The tumor volume increased continually with the growth rate becoming slower towards the end of culture. A comparison of two clones of tumor cells which had shown different rates of proliferation in monolayer culture demonstrated that the clone with the higher rate of proliferation in monoculture produced tumors with more rapid growth in the COC model. In this study we present a coculture system for the study of lung cancer using 2-Photon microscopy. COCs are particularly appropriate for long term in vitro treatment studies.

Loss of autophagy in erythroid cells leads to defective removal of mitochondria and severe anemia in vivo.

Timely elimination of damaged mitochondria is essential to protect cells from the potential harm of disordered mitochondrial metabolism and release of proapoptotic proteins. In mammalian red blood cells, the expulsion of the nucleus followed by the removal of other organelles, such as mitochondria, are necessary differentiation steps. Mitochondrial sequestration by autophagosomes, followed by delivery to the lysosomal compartment for degradation (mitophagy), is a major mechanism of mitochondrial turnover. Here we show that mice lacking the essential autophagy gene Atg7 in the hematopoietic system develop severe anemia. Atg7(-/-) erythrocytes accumulate damaged mitochondria with altered membrane potential leading to cell death. We find that mitochondrial loss is initiated in the bone marrow at the Ter119(+)/CD71(High) stage. Proteomic analysis of erythrocyte ghosts suggests that in the absence of autophagy other cellular degradation mechanisms are induced. Importantly, neither the removal of endoplasmic reticulum nor ribosomes is affected by the lack of Atg7. Atg7 deficiency also led to severe lymphopenia as a result of mitochondrial damage followed by apoptosis in mature T lymphocytes. Ex vivo short-lived hematopoietic cells such as monocytes and dendritic cells were not affected by the loss of Atg7. In summary, we show that the selective removal of mitochondria by autophagy, but not other organelles, during erythropoeisis is essential and that this is a necessary developmental step in erythroid cells.

Ankylosing spondylitis monocytes show upregulation of proteins involved in inflammation and the ubiquitin proteasome pathway.

OBJECTIVES: To determine if peripheral blood monocytes from patients with ankylosing spondylitis (AS) differed in protein expression compared to rheumatoid arthritis (RA) and healthy controls (HC). METHODS: Monocyte protein expression was characterised by 2D gel electrophoresis and by label-free quantitative expression profiling, using nano-ultra performance liquid chromatography coupled to electrospray ionisation mass spectrometry (ESI-MS(E), where (E) refers to low/high collision energy switching). Data sets were analysed using the Waters expression profiling system and Ingenuity pathway analysis (IPA). RESULTS: Two-dimensional gel electrophoresis showed upregulation of proteasomal constituents in AS monocytes, including the beta subunit of proteasome activator (PA)28. Monocyte expression profiling and IPA showed that significant changes in protein expression within the ubiquitin proteasome pathway (UPP) were restricted to AS monocytes. Statistically significant differences in protein expression involving the leucocyte extravasation, vascular endothelial growth factor, integrin and Toll-like receptor signalling pathways were seen in AS and RA monocytes compared to healthy controls. No evidence of upregulation of proteins involved in the endoplasmic reticulum stress response pathway was found in either AS or RA monocytes. Finally, the PA28 complex was shown to increase the generation of human leucocyte antigen (HLA)-B27 antigenic epitopes by the proteasome in vitro. CONCLUSIONS: Our proteomic analyses support the hypothesis that monocytes play an important role in the pathogenesis of AS and RA, and further suggest a specific role in AS for the UPP. Quantitative proteomic expression profiling constitutes a powerful new tool for rheumatology research.

[The practical application of the International Classification of Functioning, Disability and Health (ICF) in medical rehabilitation of psychiatric patients]. / Praxisorientierte Anwendung der Internationalen Klassifikation der Funktionsfähigkeit, Behinderung und Gesundheit (ICF) in der medizinischen Rehabilitation von psychisch erkrankten und behinderten Menschen.

The WHO Classification of Functioning, Disability and Health enables the description of functional health, disability and impairment on an international and interdisciplinary level in a common language. The fundamental underlying assumption of this Classification, which is orientated around a bio-psycho-social model of health and impairment, has been accepted by rehabilitation scientists in general. Unfortunately, the WHO does not make any recommendations as to how this classification could be applied in practice. In this article, various problems are outlined which could occur when the ICF is applied. Furthermore an example from a psychiatric rehabilitation institution illustrates the way the ICF could serve as an instrument for an extensive rehabilitation management programme. Here, Stucki's use will be made of Rehab-Cycle model. This describes a comprehensive sequence of steps which help analyse the patients problems from a patient-centred standpoint, to set up a schedule for treatment and to evaluate the results. Within Stucki's model the ICF is used as a system to analyse problems upon which intervention can be set. This method is illustrated with an example from a rehabilitation case. Summarizing, it is pointed out that through easier communication (as a result of the ICF) interdisciplinary productivity and efficiency will increase. On this basis it is possible to achieve a more comprehensive multimodal approach in the treatment of people suffering from psychic impairments or disability.

Cell cycle effects of radiation on human bronchial epithelium and lung carcinoma cells in monolayer cultures and a three-dimensional co-culture system.

The aim of this study was to investigate whether the three-dimensional structure of the bronchial tissue and the contact of non-malignant with malignant cells influence the effectiveness of radiotherapy. Monolayer cultures of cells of the human bronchial epithelial cell line BEAS 2B, monolayer co-cultures of BEAS 2B cells and cells of the GFP-transfected lung carcinoma cell line EPLC 32M1, organ cultures of human bronchial epithelium, and organ co-cultures with EPLC 32M1 cells were irradiated with 10 Gy, and the DNA content was analyzed using flow cytometry. In non-malignant epithelial cells, BEAS 2B monolayer cultures without tumor cells were highly radiosensitive. However, contact with tumor cells in monolayer co-cultures markedly reduced radiosensitivity. Non-malignant cells in three-dimensional organ cultures and organ co-cultures with tumor cells showed moderate radiosensitivity. In EPLC 32M1 tumor cells, proliferation was increased without irradiation when the cells were in contact with epithelial cells in both organ and monolayer co-cultures. Radiosensitivity was higher in organ co-cultures than in monolayer cultures and monolayer co-cultures. These data indicate that organ co-cultures in combination with flow cytometry allow investigation of the effects of radiation in an in vivo-like environment and that both the spatial organization and the interaction of non-malignant and tumor cells are crucial for the effectiveness of radiotherapy.

5-Aminolevulinic acid-induced fluorescence in bronchial tumours: dependency on the patterns of tumour invasion.

5-ALA-induced protoporphyrin IX (PPIX) fluorescence kinetics was quantified by fluorescence microscopy in three-dimensional organ co-cultures of human bronchial epithelium, which were infiltrated by four different lung tumour cell lines (EPLC-M31, LCLC-103H, NCI-H125 and NCI-H841). Corresponding fluorescence measurements were performed in monolayer cultures of these tumour cell lines and BEAS-2B cells as a model for normal bronchial epithelium by flow cytometry. Significant differences of fluorescence intensities (FI) between the tumours were detected in organ co-cultures as well as in single cell measurements. Relative FI values in organ co-cultures (FI(EPLC-32M1)>FI(LCLC-H103)>FI(NCI-H125)>FI(NCI-H841)) did not correspond to the measurements in single cells (FI(LCLC-H103)>FI(NCI-H125)>FI(NCI-H841)>FI(EPLC-32M1)). Histology of organ co-cultures revealed different patterns of invasion and tumour cell densities depending on the tumour type. After correction of FI in the co-cultures to tumour cell density the correlation coefficient for fluorescence values between both models increased considerably. Thus, additionally to distinctive features of 5-ALA metabolism, patterns of tumour invasion may be a factor determining 5-ALA-induced fluorescence. Considering these results, a pronounced heterogeneity of 5-ALA-induced fluorescence might be expected in different bronchial tumours in vivo. This could interfere with the diagnostic reliability of 5-ALA-induced fluorescence for early tumour detection.

[Hernia repair--which technique? Help in making the decision]. / Hernienrepair--welche Technik? Hilfen zur Entscheidungsfindung.

Operation of the inguinal hernia is the most common operation in general surgery. Many criteria influence the kind of operation the surgeon will perform. Detailed anatomic knowledge of the inguinal region, standardised tactical and technical performance of the operation team, careful preparation and a minimum of blood loss reduce complications to low levels. These items are the same for all operation methods. The Shouldice procedure has been the golden standard for many years, nowadays (1998) in America in more than 80% of operations a mesh is implanted in the abdominal wall. A Cochran review of EBM showed advantages for mesh repair compared to nonmesh repair. Patient oriented decision making in choosing a method for inguinal hernia repair should be the new standard of modern general surgery.

[Ambulatory laparoscopic cholecystectomy]. / Die ambulante laparoskopische Cholecystektomie.

A total of 140 patients underwent outpatient laparoscopic cholecystectomy in an outpatient clinic. Evaluation and follow-up of the patients were done prospectively. Population and preoperative data were comparable to published studies of patients operated on in hospitals. There were no serious intra- or postoperative complications. Postoperatively, patients needed less pain medication, were less tired and returned to work earlier than patients after clinical laparoscopic cholecystectomies. Outpatient laparoscopic cholecystectomy offers a good alternative to patients with moderate operative risks (ASA 1-3). It could reduce costs in the German health system and would be therefore highly cost effective.

[Sprain of the cervical spine: early functional vs. immobilization treatment]. / Die Distorsion der Halswirbelsäule: frühfunktionelle vs. ruhigstellende Behandlung.

Neck sprains are very common injuries often treated with immobilisation of different duration. The treatment with collars was tested against physiotherapy in a prospective randomised trial. Endpoints were defined as state of health, pain and costs. Ninety-seven patients with whiplash injuries were splitted by randomisation into two groups. One group was treated with a certain scheme of physiotherapy. Another group was treated with collar immobilisation for 3 weeks. Concerning symptoms at the time of admittance, age and sex distribution the groups were comparable. Fifty healthy persons with the same age and sex distribution served as a control group. Regarding to physical state of health and pain, which were examined by valid questionnaires, significant advantages of physiotherapy after two weeks were found. After 12 weeks the physical state of health corresponds to that of the control group. No influence on psychical state of health was seen. Physiotherapy for treatment of neck sprain is highly recommended. It has clear advantages over the treatment with collars with regard to state of health and pain, and it seems to be economically favourable.

[Effectiveness and economics of private practice established surgeons, exemplified by ambulatory laparoscopic cholecystectomy in 1994 and 1996]. / Effizienz und Okonomie in der Praxis niedergelassener Chirurgen, dargestellt an der ambulanten laparoskopischen Cholecystektomie in den Jahren 1994 und 1996.

Ambulatory laparoscopic cholecystectomy is a safe procedure providing high patient satisfaction if performed by an experienced surgeon. These are the results of a prospective documentation of 150 outpatients to undergo laparoscopic cholecystectomy between 1994 and 1996. Patients returned to work early (mean 13.2 days off). No patient had to be admitted to hospital following ambulatory operation. All patients declared that they would have the operation performed in the same way a second time if necessary at all. Looking at the money earned for the ambulatory operation compared to the costs, there is a deficit of nearly DM 800 with each performance. Despite the good results and the great satisfaction on the part of the patients, outpatient laparoscopic cholecystectomy will not be widely performed until and unless the surgeons costs are at least covered.

Hyperinsulinism and cerebral microangiopathy.

BACKGROUND AND PURPOSE: High insulin levels are a recognized risk factor for atherosclerosis. Microvascular endothelium is more susceptible to metabolic and mitogenic effects of insulin than large-vessel endothelium. Besides their atherogenic effect, high insulin levels impair fibrinolysis by enhancing plasminogen activator inhibitor-1. We undertook this study to evaluate the hypothesis that elevated serum insulin and C-peptide levels are related to cerebral small-vessel disease rather than large-vessel pathology. METHODS: One hundred ninety-four consecutive patients presenting with symptomatic cerebrovascular disease were assigned to three subgroups that were differentiated by clinical presentations, brain imaging studies, and extracranial as well as transcranial vascular ultrasound findings: (1) patients with lacunes (n = 20), (2) patients with subcortical arteriosclerotic encephalopathy (n = 35), and (3) patients with strokes due to large-vessel disease (n = 99). Patients who had suffered a cryptogenic (n = 9) or cardioembolic (n = 16) stroke or who showed characteristics of the microangiopathy and macroangiopathy groups (n = 15) were not further evaluated. Thirty patients without manifestations of cerebrovascular disease were also examined. Fasting blood glucose, insulin, and C-peptide levels were determined in all subjects. RESULTS: There were no significant differences in age or sex among the three groups and control patients. Insulin levels were significantly higher in the lacunar group compared with the subcortical arteriosclerotic encephalopathy group, the macroangiopathy group, and the control patients (median [interquartile range]: 103.8 [198.6], 72.0 [103.2], 66.0 [57.0], and 52.2 [57.0] pmol/L, respectively; all P < .05, Mann-Whitney test). There was a statistically significant difference in insulin concentrations between the microangiopathy group (subcortical arteriosclerotic encephalopathy and lacunes) and the macroangiopathy and control groups (81.0 [110.4], 66.0 [57.0], and 55.2 [57.0] pmol/L, respectively; all P < .05, Mann-Whitney). The same was true for the distribution of C-peptide levels and to a minor extent blood glucose values, but these differences failed to reach statistical significance. CONCLUSIONS: Elevated insulin levels potentially represent a pathogenetic factor in the development of cerebral small-vessel disease, predominantly in patients presenting with lacunes. Whether this is due solely to atherosclerotic changes of the small penetrating arteries or whether changes in hemorheology are operative as well remains to be evaluated.

A comparison of long term results of the standard Whipple procedure and the pylorus preserving pancreatoduodenectomy.

The standard Whipple procedure involves intestinal disturbances, such as dumping, diarrhea, dyspeptic complaints and the occurrence of ulcers of the anastomoses. A postoperative weight loss was observed ranging between 10 and 40 kilograms. Only a few patients were able to compensate after several months. It was thought that preservation of the intact stomach would prevent the complications arising from a loss of gastric reservoir function and thus the malnutrition could be improved postoperatively. Between 1985 and March 1992, we performed the pylorus-preserving Whipple procedure and treated a group of 43 patients with this method. In the same period, 15 patients were operated upon with the standard Whipple procedure. The present evaluation of the accumulated patient data, including extensive functional studies, led to the following results comparing the pylorus preserving Whipple procedure with the standard Whipple procedure. First, the capacity for food uptake and the development of body weight postoperatively is significantly better. Second, gastric or jejunal ulcers were not observed. Third, there were no clinical signs of digestive disorders, such as different forms of dumping. Nutrition and digestion were not impeded by the preserved opening mechanism of the pylorus. Fourth, the postoperative exocrine function was only slightly decreased. Fifth, glucose metabolism postoperatively was influenced only slightly by preservation of the pylorus. In taking the results of all the examinations into consideration, it can be said that the restricted organ loss in the Whipple procedure with pylorus preservation leaves the secretory and functional capacity of the upper part of the gastrointestinal tract almost unchanged.