[Progressive maculopathy despite discontinuation of chloroquine treatment-multimodal imaging and review of the literature]. / Progressive Makulopathie trotz Absetzen der Chloroquin-Therapie ­ Multimodale Bildgebung und Review der Literatur.

This case report presents a pictorially well-documented case with multimodal images of a progression of maculopathy despite discontinuation of chloroquine treatment in a long-term follow-up over 6 years. Additionally, the current detection methods in screening for early recognition of maculopathy and their prognostic significance are reviewed.

[Which learning methods are expected for ultrasound training? Blended learning on trial]. / Welche Lehrmethoden werden für die Ultraschallausbildung erwartet? : "Blended learning" auf dem Prüfstand.

BACKGROUND: Current teaching methods in graduate and postgraduate training often include frontal presentations. Especially in ultrasound education not only knowledge but also sensomotory and visual skills need to be taught. This requires new learning methods. AIM: This study examined which types of teaching methods are preferred by participants in ultrasound training courses before, during and after the course by analyzing a blended learning concept. It also investigated how much time trainees are willing to spend on such activities. MATERIAL AND METHODS: A survey was conducted at the end of a certified ultrasound training course. Participants were asked to complete a questionnaire based on a visual analogue scale (VAS) in which three categories were defined: category (1) vote for acceptance with a two thirds majority (VAS 67-100%), category (2) simple acceptance (50-67%) and category (3) rejection (< 50%). RESULTS: A total of 176 trainees participated in this survey. Participants preferred an e-learning program with interactive elements, short presentations (less than 20 min), incorporating interaction with the audience, hands-on sessions in small groups, an alternation between presentations and hands-on-sessions, live demonstrations and quizzes. For post-course learning, interactive and media-assisted approaches were preferred, such as e-learning, films of the presentations and the possibility to stay in contact with instructors in order to discuss the results. Participants also voted for maintaining a logbook for documentation of results. CONCLUSION: The results of this study indicate the need for interactive learning concepts and blended learning activities. Directors of ultrasound courses may consider these aspects and are encouraged to develop sustainable learning pathways.

Prevalence, Trend and Determining Factors of Gestational Diabetes in Germany.

Purpose: The true prevalence of gestational diabetes in Germany is unknown. Thus, the study's purposes were to estimate the prevalence of gestational diabetes as well as to describe the temporal prevalence trend and to identify determinants. Material and Methods: We calculated prevalence estimates based on two datasets: the register-based German perinatal statistic (n = 650 232) and the maternal self-reports from the German children and youth health survey (KiGGS; n = 15 429). Differences between prevalence estimates were analysed using χ2 and trend tests, and determinants were identified using logistic regression. Results: According to the perinatal statistic, gestational diabetes was present in 3.7 % of pregnant women in Germany in 2010. The prevalence across the years 2001 to 2006 was estimated at 1.9 % which differed significantly from the prevalence estimate derived from the KiGGS dataset for the same period of time (5.3 %; 95 % confidence interval: 4.6-6.1 %). Both datasets show an increasing trend of gestational diabetes (p < 0.001). The risk for gestational diabetes was mainly associated with age, BMI and social class of pregnant women as well as with multiple pregnancies. Conclusion: The lack of significant screening studies among representative samples hampers a sound estimation of the true prevalence of gestational diabetes in Germany. The increasing trend in gestational diabetes might continue due to the projected increase of important risk factors (e.g., maternal age, obesity). Our analyses support the current consensus recommendations regarding standardised gestational diabetes screening.

[Card-based age control mechanisms at tobacco vending machines. Effect and consequences]. / Die kartenbasierte Alterskontrolle an Zigarettenautomaten. Wirkung und Folgen.

Until recently, 700,000 tobacco vending machines provided uncontrolled access to cigarettes for children and adolescents in Germany. On January 1, 2007, a card-based electronic locking device was attached to all tobacco vending machines to prevent the purchase of cigarettes by children and adolescents under 16. Starting in 2009, only persons older than 18 are able to buy cigarettes from tobacco vending machines. The aim of the present investigation (SToP Study: "Sources of Tobacco for Pupils" Study) was to assess changes in the number of tobacco vending machines after the introduction of these new technical devices (supplier's reaction). In addition, the ways smoking adolescents make purchases were assessed (consumer's reaction). We registered and mapped the total number of tobacco points of sale (tobacco POS) before and after the introduction of the card-based electronic locking device in two selected districts of the city of Cologne. Furthermore, pupils from local schools (response rate: 83%) were asked about their tobacco consumption and ways of purchase using a questionnaire. Results indicated that in the area investigated the total number of tobacco POSs decreased from 315 in 2005 to 277 in 2007. The rates of decrease were 48% for outdoor vending machines and 8% for indoor vending machines. Adolescents reported circumventing the card-based electronic locking devices (e.g., by using cards from older friends) and using other tobacco POSs (especially newspaper kiosks) or relying on their social network (mainly friends). The decreasing number of tobacco vending machines has not had a significant impact on cigarette acquisition by adolescent smokers as they tend to circumvent the newly introduced security measures.

["Why not?"--content analysis of answers from more than 700 pupils about their motives for not smoking]. / "Warum nicht?"-- Inhaltsanalyse der Motivangaben zum Rauchverzicht von über 700 Schülern.

BACKGROUND AND OBJECTIVE: In spite of declining smoking prevalence nothing is known about the motives of adolescents in Germany who abstain from smoking. If one knows what motives prevent youngsters from ever starting to smoke it would make it possible to adjust future preventive strategies that would reach the "hard core" of smoking adolescents. This study investigated the true motives of non-smokers and also focused on possible gender and social background as well as age differences in the structure of their motivation. METHOD: In the SToP-Study ("Sources of Tobacco for Pupils" Study 2008) 780 pupils, of whom 709 were non-smokers from 32 school classes, grades 7-9, were interviewed about their smoking experience. In anonymized answers to the questions pupils wrote down their motives for being non-smokers. A total of 1,329 free text statements, some of them very elaborate, were categorized and evaluated in a qualitative analysis. RESULTS: The most important and frequently mentioned motives for not smoking were health related (78,1%). But the most significant health risks of tobacco consumption (cardiac and cerebrovascular disease, chronic obstructive pulmonary disease), except cancer risk, were hardly appreciated. Other important reasons for not smoking were aesthetic aversion (38.6%), lacking perception of a benefit (25.1%) and economic motives (20.9%). It was especially female grammar school pupils who most frequently expressed health and aesthetic reasons (such as disgust, smell and taste aversion, dental and finger discolorations) as motives for not smoking. CONCLUSION: Extrinsic reasons (legal restrictions, smoking bans imposed by parents and schools, age limits etc.) are not important reasons to abstain for young non-smokers. Specifically, arguments about health, participation in sports and being in good physical condition should be central to any advice given to young smokers within the setting of general medical practice.

Embedded ferroelectric nanostructure arrays.

Ferroelectrics hold promise for high-density non-volatile data storage device use. Their eventual performance will strongly depend on the available displacement current, which primarily scales with the area but might to some extent be enhanced by substrate-induced homogeneous strain while the interface at the same time controls the coercive field. As the lateral dimensions persistently decrease, the only way to keep track of the real figures of merit with realistic electrodes is to use a macroscopic configuration instead of scanning probe approaches with undefined interfaces. We report on a novel approach to integrating arbitrarily patterned, highly registered ferroelectric nanoislands fabricated by a template controlled chemical solution deposition approach into a matrix of a low-k dielectric spin-on glass. These structures with a narrow lateral size distribution below 100 nm are subsequently polished in a chemical-mechanical polishing step to expose their very tops, whose piezoelectrically active area depends on the polishing time. At this stage our findings indicate a full piezoelectric functionality of the locally exposed nanoislands. The structures are ready for macroscopic top electrodes to average the displacement current over hundreds of almost identical structures, to provide a nanoscale scaling behaviour of the individual ferroelectric capacitors.

Effects of a physical exercise session on state body image: The influence of pre-experimental body dissatisfaction and concerns about weight and shape.

The effects of a physical exercise session on state body image and mood were examined. In a cross-over design, participants were randomised to two groups starting either with physical exercise (PE; experimental condition) or with reading a newspaper (RN; control condition). Before and after PE and RN, participants (N = 65) rated their body dimensions using a digital photo distortion technique and indicated their attitudinal body image and mood. Participants' judgements of their 'felt' body dimensions and attitudes toward their own body were affected differently by PE and RN, indicating that participants felt slightly slimmer and were more satisfied with their bodies after PE. Exercise-induced changes in body perception were greater, the higher the pre-experimental drive for thinness, body dissatisfaction and weight/shape concerns were. Especially in those participants with higher body image disturbances, physical exercise can have a reinforcing effect on immediate body image and mood improvement.

[Optimization of perioperative management in laparoscopic hernioplasty]. / Optimierung des perioperativen Managements am Beispiel der laparoskopischen Leistenbruchoperation.

INTRODUCTION: Although about 150,000-200,000 hernia repair procedures are performed every year in Germany alone, fast-track concepts are mainly ignored for this type of surgery. Therefore, this study was designed to analyze the perioperative management of patients undergoing laparoscopic hernia repair, performed as transabdominal preperitoneal patch hernioplasty (TAPP). Based on these results, the clinical management was optimized in order to shorten the length of stay without affecting the quality of treatment or the complication rate, and the effects of the optimization strategies were reanalyzed. METHODS: With ethics committee approval 249 patients undergoing TAPP procedures were investigated. In the first two study sections, problems of the perioperative management were identified first retrospectively (n=129) and then prospectively (n=60). Based on these results, the clinical management was then redesigned and optimized. A TAPP score was developed including the parameters age, ASA physical status, extent and severity of the procedure and postoperative pain level. Patients were scored 24 h after surgery, and clear-cut criteria were defined for discharge home on the second postoperative day. Furthermore, all patients received 10 mg of sodium picosulfate to avoid postoperative constipation. In the third study section (n=60) the impact of the optimization strategies on length of stay, need for pain medication, complication rate and patient satisfaction (based on the PPP33 questionnaire) was evaluated. RESULTS: Patients were on average approximately 60 years old (range 22-92 years), and demographic data were comparable within the study sections. As a result of the optimization process, 72% of the patients could be discharged home on the second postoperative day whereas previously that had only been possible in 5%. Accordingly, the postoperative length of stay (including the day of surgery) was significantly reduced from 4.2+/-0.6 to 3.3+/-0.6 days. By the administration of sodium picosulfate, 92% of all patients reported defecation on the first day after surgery, whereas previously the majority of patients (60%) had complained of constipation at this time. No serious complications were observed. The number of minor complications was very low in total and neither complication rate nor patient satisfaction was affected by earlier discharge. The second day after surgery was judged to be the ideal time point for discharge by 81% of all patients. CONCLUSIONS: This study demonstrates that the length of stay after laparoscopic hernia repair can be reduced by one day by relatively simple means without affecting patient satisfaction or the complication rate. Most important is the introduction of clear-cut criteria that allow an early decision-making for discharge home. Moreover, many patients complain of constipation after laparoscopic surgery, and this may prolong the length of stay. This problem can be solved completely by the standardized use of sodium picosulfate, administered on the evening after surgery.

Influence of a continuous prednisolone medication on the time course of neuromuscular block of atracurium in patients with chronic inflammatory bowel disease.

BACKGROUND: Corticosteroids interact with neuromuscular blocking agents. However, experimental data are contradictory: enhancement and attenuation of the neuromuscular block has been observed. This study tested the influence of long-term medication with prednisolone on atracurium-induced neuromuscular block. METHODS: Sixty patients with chronic inflammatory bowel disease undergoing elective abdominal surgery were investigated. Thirty patients received a long-term medication with prednisolone (Group A) and 30 were without corticoid medication (Group B). Additionally, another 30 patients without inflammatory bowel disease and without corticoid medication served as control (Group C). The following parameters of an atracurium-induced neuromuscular block (0.25 mg kg(-1)) were measured: onset time, maximum block, recovery to 25% first twitch height, recovery index (time from 25% until 75% recovery of first twitch), duration to recovery to a train-of-four (TOF) rate of 0.7 and 0.9. RESULTS: The groups did not differ with regard to onset time, maximum block, and recovery index. The duration to 25% twitch height was significantly lower in Group A [18.1 (0-30.7) min] compared with Group B [23.5 (0-36.7) min; P<0.05]. Duration to a TOF rate of 0.7 and 0.9, respectively, were significantly reduced in Group A [36.1 (7.9) and 40.9 (9.0 min)] compared with Group B [47.9 (7.6) and 53.4 (9.2) min; P<0.001]. CONCLUSIONS: Long-term medication with prednisolone resulted in a shorter duration of an atracurium-induced neuromuscular block in patients with Crohn's disease or ulcerative colitis. The presence of the inflammatory bowel disease did not influence the time course of the neuromuscular block.

Endogenous brain-derived neurotrophic factor and neurotrophin-3 antagonistically regulate survival of axotomized corticospinal neurons in vivo.

Neuronal growth factors regulate the survival of neurons by their survival and death-promoting activity on distinct populations of neurons. The neurotrophins nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) promote neuronal survival via tyrosine kinase (Trk) receptors, whereas NGF and BDNF can also induce apoptosis in developing neurons through p75(NTR) receptors in the absence of their respective Trk receptors. Using mutant mice and inactivation of neurotrophins and their receptors with antibodies in rats, we show that endogenous NT-3 induces death of adult BDNF-dependent, axotomized corticospinal neurons (CSNs). When NT-3 is neutralized, the neurons survive even without BDNF, suggesting complete antagonism. Whereas virtually all unlesioned and axotomized CSNs express both trkB and trkC mRNA, p75 is barely detectable in unlesioned CSNs but strongly upregulated in axotomized CSNs by day 3 after lesion, the time point when cell death occurs. Blocking either cortical TrkC or p75(NTR) receptors alone prevents death, indicating that the opposing actions of NT-3 and BDNF require their respective Trk receptors, but induction of death depends on p75(NTR) cosignaling. The results show that neuronal survival can be regulated antagonistically by neurotrophins and that neurotrophins can induce neuronal death in the adult mammalian CNS. We further present evidence that signaling of tyrosine kinase receptors of the trk family can be crucially involved in the promotion of neuronal death in vivo.

An axotomy model for the induction of death of rat and mouse corticospinal neurons in vivo.

To study trophic dependencies of rat and mouse corticospinal neurons (CSN), we established a lesion model for the induction of death of analogous populations of CSN in these rodent species. Before lesion, CSN were retrogradely labeled with Fast Blue (FB). A stereotaxic cut lesion through the entire internal capsule (ICL) was used to axotomize CSN. The extent of axotomy was determined by application of a control tracer. In both species, FB-labeled CSN were localized in three major areas: (1) the sensory motor cortex; (2) the supplementary motor and medial prefrontal cortex; and (3) the somatosensory cortex. ICL does not lead to complete axotomy of CSN of the rat and mouse somatosensory cortex. In rats, ICL results in complete axotomy of CSN of the sensory motor cortex and incomplete axotomy of the caudal portion of the supplementary motor and medial prefrontal cortex. In mice, the area of axotomized CSN extends significantly further frontally. In both species, axotomy-induced death of CSN is observed in the center of the sensory motor cortex. This lesion model is useful for investigations on the response of CSN of the sensory motor cortex to lesion and therapeutic drugs.

The Caenorhabditis elegans Ldb/NLI/Clim orthologue ldb-1 is required for neuronal function.

LIM homeodomain (LIM-HD) and nuclear LIM-only proteins play important roles in a variety of developmental processes in animals. In some cases their activities are modulated by a nuclear LIM binding protein family called Ldb/NLI/Clim. Here we characterize the Ldb/NLI/Clim orthologue ldb-1 of the nematode Caenorhabditis elegans. Two alternatively spliced variants exist, which differ in their amino-termini. The ldb-1 orthologue of Caenorhabditis briggsae has the same structure as that of C. elegans and is highly conserved throughout the open reading frame, while conservation to fly and vertebrate proteins is restricted to specific domains: the dimerization domain, the nuclear localization sequence, and the LIM interaction domain. C. elegans ldb-1 is expressed in neurogenic tissues in embryos, in all neurons in larval and adult stages, and in vulval cells, gonadal sheath cells, and some body muscle cells. C. elegans LDB-1 is able to specifically bind LIM domains in yeast two-hybrid assays. RNA inactivation studies suggest that C. elegans ldb-1 is not required for the differentiation of neurons that express the respective LIM-HD genes or for LIM-HD gene autoregulation. In contrast, ldb-1 is necessary for several neuronal functions mediated by LIM-HD proteins, including the transcriptional activation of mec-2, the mechanosensory neuron-specific stomatin.

Presenilin is required for proper morphology and function of neurons in C. elegans.

Mutations in the human presenilin genes cause the most frequent and aggressive forms of familial Alzheimer's disease (FAD). Here we show that in addition to its role in cell fate decisions in non-neuronal tissues, presenilin activity is required in terminally differentiated neurons in vivo. Mutations in the Caenorhabditis elegans presenilin genes sel-12 and hop-1 result in a defect in the temperature memory of the animals. This defect is caused by the loss of presenilin function in two cholinergic interneurons that display neurite morphology defects in presenilin mutants. The morphology and function of the affected neurons in sel-12 mutant animals can be restored by expressing sel-12 only in these cells. The wild-type human presenilin PS1, but not the FAD mutant PS1 A246E, can also rescue these morphological defects. As lin-12 mutant animals display similar morphological and functional defects to presenilin mutants, we suggest that presenilins mediate their activity in postmitotic neurons by facilitating Notch signalling. These data indicate cell-autonomous and evolutionarily conserved control of neural morphology and function by presenilins.

Protein interaction surface of the POU transcription factor UNC-86 selectively used in touch neurons.

The Caenorhabditis elegans POU protein UNC-86 specifies the HSN motor neurons, which are required for egg-laying, and six mechanosensory neurons. To investigate how UNC-86 controls neuronal specification, we characterized two unc-86 mutants that do not respond to touch but show wild-type egg-laying behavior. Residues P145 and L195, which are altered by these mutations, are located in the POU-specific domain and abolish the physical interaction of UNC-86 with the LIM homeodomain protein, MEC-3. This results in a failure to maintain mec-3 expression and in loss of expression of the mechanosensory neuron-specific gene, mec-2. unc-86-dependent expression of genes in other neurons is not impaired. We conclude that distinct residues in the POU domain of UNC-86 are involved in modulating UNC-86 activity during its specification of different neurons. A structural model of the UNC-86 POU domain, including base pairs and amino acid residues required for MEC-3 interaction, revealed that P145 and L195 are part of a hydrophobic pocket which is similar to the OCA-B-binding domain of the mammalian POU protein, Oct-1.

Identification of amino acid residues in the Caenorhabditis elegans POU protein UNC-86 that mediate UNC-86-MEC-3-DNA ternary complex formation.

The POU homeodomain protein UNC-86 and the LIM homeodomain protein MEC-3 are essential for the differentiation of the six mechanoreceptor neurons in the nematode Caenorhabditis elegans. Previous studies have indicated that UNC-86 and MEC-3 bind cooperatively to at least three sites in the mec-3 promoter and synergistically activate transcription. However, the molecular details of the interactions of UNC-86 with MEC-3 and DNA have not been investigated so far. Here we used a yeast system to identify the functional domains in UNC-86 required for transcriptional activation and to characterize the interaction of UNC-86 with MEC-3 in vivo. Our results suggest that transcriptional activation is mediated by the amino terminus of UNC-86, whereas amino acids in the POU domain mediate DNA binding and interaction with MEC-3. By random mutagenesis, we identified mutations that only affect the DNA binding properties of UNC-86, as well as mutations that prevent coactivation by MEC-3. We demonstrated that both the POU-specific domain and the homeodomain of UNC-86, as well as DNA bases adjacent to the proposed UNC-86 binding site, are involved in the formation of a transcriptionally active complex with MEC-3. These data suggest that some residues involved in the contact of UNC-86 with MEC-3 also contribute to the interaction of the functionally nonrelated POU protein Oct-1 with Oca-B, whereas other positions have different roles.

Caspase-mediated cleavage is not required for the activity of presenilins in amyloidogenesis and NOTCH signaling.

The Alzheimer's disease (AD) associated presenilin (PS) proteins are proteolytically processed. One of the processing pathways involves cleavage by caspases. Pharmacological inhibition of caspases is currently being discussed as a treatment for a variety of neurodegenerative diseases, including AD. We therefore inhibited caspase mediated processing of PS-1 and PS-2 in cells transfected with wt and mutant PS by mutagenizing the substrate recognition site or by using specific peptide aldehydes known to block caspases. We found that the inhibition of caspase mediated processing of PS proteins does not decrease its amyloidogenic activity. PS cDNA constructs with mutations in the caspase cleavage site are biologically active in Caenorhabditis elegans such as the wt human PS proteins, demonstrating that caspase-mediated cleavage is not required for the physiological PS function in NOTCH signaling.

[Infection with hepatitis viruses HAV, HBV and HCV as well as with AIDS virus HIV in drug addicts of the Zurich street scene--a prevalence study]. / Infektionen mit den Hepatitisviren HAV, HBV und HCV sowie mit dem Aidsvirus HIV bei Drogenabhängigen der Gassenszene Zürichs--eine Prävalenzstudie.

382 i.v. drug abusers were tested for a past or ongoing infection with the hepatitis viruses A (HAV), B (HBV), the newly discovered C (HCV) and with the Aids virus HIV. The cohort studied was representative for i.v. drug users of the Zurich street scene including occasional users, weekend users and severe drug addicts. 56% of the drug users tested showed HBV markers. 21% had an ongoing infection. 32% were naturally HBV immune and 4% showed immunity due to vaccination. HAV markers were detected in 50% of the individuals tested, with an ongoing infection present in 8%. 48% of the individuals tested showed signs of HCV contact. 15% of the i.v. drug users were HIV infected. 22% of these individuals were HIV-antigen positive. The data confirm that i.v. drug users have the highest rates of infection within the total population. The prevalence of viral markers correlated positively with the duration and intensity of i.v. drug use and with the practice of needle sharing. In comparison to comparable earlier studies, the present viral prevalence data were lower. This is thought to be due to an Aids prevention campaign undertaken in the Zurich street drug scene, including free distribution of injection material and condoms.