Avian haemosporidian parasites in captive and free-ranging, wild birds from zoological institutions in Switzerland: Molecular characterization and clinical importance.

Avian haemosporidian parasites are widespread and infect birds from a broad variety of avian families with diverse consequences ranging from subclinical infections to severe and fatal disease. This study aimed to determine the occurrence and diversity of avian haemosporidia including associated clinical signs and pathomorphological lesions in captive and free-ranging, wild birds from two zoos and the near environment in Switzerland. Blood samples from 475 birds, including 230 captive and 245 free-ranging, wild individuals belonging to 42 different avian species from 15 orders were examined for the presence of avian haemosporidian DNA by a one-step multiplex PCR designed to simultaneously detect and discriminate the genera Plasmodium, Haemoproteus and Leucocytozoon by targeting mitochondrial genome sequences. Positive samples were additionally tested using a nested PCR targeting the cytochrome b gene of Plasmodium and Haemoproteus. The obtained amplicons were bidirectionally sequenced. This study revealed haemosporidian DNA in 42 samples, belonging to ten host species. The most commonly detected lineage was Plasmodium relictum SGS1, which was identified in 29 birds (Phoenicopterus roseus: n = 24, Alectoris graeca: n = 1, Lamprotornis superbus: n = 1, Somateria mollissima: n = 1, Spheniscus demersus: n = 1, Tetrao urogallus crassirostris: n = 1), followed by Haemoproteus sp. STRURA03 in six avian hosts (Bubo bubo: n = 5, Bubo scandiacus = 1), Plasmodium relictum GRW11 in four individuals (Phoenicopterus roseus: n = 3, Spheniscus demersus: n = 1) and Plasmodium elongatum GRW06 in one Alectura lathami lathami. A Phalacrocorax carbo was infected with Plasmodium relictum, but the exact lineage could not be determined. One mixed infection with P. relictum and Haemoproteus sp. was detected in a Bubo scandiacus. Only five individuals (Spheniscus demersus: n = 2, Somateria mollissima: n = 1, Bubo scandiacus: n = 1, Alectoris graeca: n = 1) showed clinical and pathomorphological evidence of a haemosporidian infection.

Syngamus trachea in free-ranging white stork (Ciconia ciconia) nestlings in Switzerland.

Syngamosis is a disease caused by the strongylid nematode Syngamus trachea, which infects the respiratory tract of various bird species around the world. The parasite appears to be harmful for a wide variety of avian orders, occasionally leading to a fatal outcome, particularly in young birds. The aim of this study was to examine the parasitic fauna in deceased or euthanized, free-ranging white storks nesting at the Zoo Basel in 2019 and 2020; and to assess the extent to which these parasites contributed to the wild birds' death. In five out of 24 necropsied white storks, an infection with S. trachea was diagnosed based on morphological analysis of adult nematode stages and eggs, in combination with PCR amplification and sequencing of DNA extracted from female worms. The main pathological changes affected the white storks' respiratory tract and a mixed cell tracheitis was diagnosed in the histopathological examination of three of the five infected birds. Some birds displayed additional lesions compatible with syngamosis, namely partially degenerated parasitic structures with concurrent granulomatous inflammation in the lung and multifocal acute hemorrhages in the bronchi and parabronchi. Coprological examinations (fecal flotation technique, fecal sedimentation technique, sodium acetate acetic acid formalin procedure and Ziehl-Neelsen staining) from the intestinal content as well as a PCR for Toxoplasma gondii on brain, lung, heart, liver, and spleen tissue yielded negative results in all examined individuals. In the absence of further major pathological findings, S. trachea was assumed to have significantly contributed to the death of the infected birds.

Causes of Abortions in South American Camelids in Switzerland-Cases and Questionnaire.

Over the last decade, South American camelids (SAC) have gained increasing popularity in Switzerland. They are used for several purposes such as fiber and meat production, as companion or guard animals and for trekking activities. The purpose of this study was to investigate the frequency and reasons for pregnancy loss and perinatal death in SAC herds. Within the scope of this study, early embryonic losses could not be identified, as pregnancy examinations by ultrasonography are not performed routinely. Aborted and stillborn fetuses were collected, necropsied and analyzed for infectious abortifacients. A nationwide survey among breeders was carried out. During a 1.5-year period, only eight cases of aborted or stillborn alpaca and llama (out of a population of 6550 animals) were reported by the breeders, and their causes were subsequently analyzed. In half of the cases, Coxiella burnetii was identified in the fetoplacental material. Abortions and stillbirths were reported to be rare in Swiss herds. As a conclusion, recording of embryonic losses through ultrasound training of veterinarians should be impaired and breeders motivated to have abortions and perinatal mortality examined. Special focus should be laid on C. burnetii due to its zoonotic risk.

Effects of a Brief Web-Based "Social Norms"-Intervention on Alcohol, Tobacco and Cannabis Use Among German University Students: Results of a Cluster-Controlled Trial Conducted at Eight Universities.

Background and Aim: "Social norms" (SN)-interventions are aimed at changing existing misperceptions regarding peer substance use by providing feedback on actual norms, thereby affecting personal substance use. It is unknown whether SN-intervention effects previously demonstrated in US students can be replicated in German students. The aim of the INSIST-study was to examine the effects of a web-based SN-intervention on substance use. Design: Cluster-controlled trial. Setting: Eight Universities in Germany. Participants and Measurements: Students were recruited at four intervention vs. four delayed intervention control Universities. 4,463 students completed baseline, 1,255 students (59% female) completed both baseline and 5-months follow-up web-based surveys on personal and perceived peer substance use. Intervention participants received feedback contrasting personal and perceived peer use with previously assessed use and perceptions of same-sex, same-university peers. Intervention effects were assessed via multivariable mixed logistic regression models. Findings: Relative to controls, reception of SN-feedback was associated with higher odds for decreased alcohol use (OR: 1.91, 95% CI 1.42-2.56). This effect was most pronounced in students overestimating peer use at baseline and under or accurately estimating it at follow-up (OR: 6.28, 95% CI 2.00-19.8). The OR was 1.33 (95% CI 0.67-2.65) for decreased cannabis use in students at intervention Universities and was statistically significant at 1.70 (95% CI 1.13-2.55) when contrasting unchanged and decreased with increased use. Regarding tobacco use and episodes of drunkenness, no intervention effects were found. Conclusions: This study was the first cluster-controlled trial suggesting beneficial effects of web-based SN-intervention on alcohol and cannabis use in a large sample of German University students. Clinical Trial Registration: The trial registration number of the INSIST-study is DRKS00007635 at the "German Clinical Trials Register."

A Review of the Parasite Fauna of the Black-Bellied Pangolin, Phataginus tetradactyla LIN. (Manidae), From Central Africa with the Description of Intraproboscis sanghae n. gen., n. sp. (Acanthocephala: Gigantorhynchidae).

A new archiacanthocephalan in the family Gigantorhynchidae, Intraproboscis sanghae n. gen., n. sp. is described from females collected from the African black-bellied pangolin Phataginus tetradactyla Linn. (Manidae) in the Central African Republic. A dichotomous key to the genera of Gigantorhynchidae is provided. The specimens presented are distinct from those of the genus Gigantorhynchus Hamann, 1892 that have only 1 or 2 circles of hooks (crowns) at the apical end of the proboscis and are found in South American mammals, except for Gigantorhynchus pesteri Tadros, 1966 from baboons in Rhodesia (Zimbabwe), Africa (Amin, 2013). They superficially resemble those of the other gigantorhynchid genus Mediorhynchus Van Cleave, 1916, especially in the organization of the truncate-cone proboscis and the position of the receptacle. Species of Mediorhynchus are bird parasites. The new genus, Intraproboscis, now the third genus in Gigantorhynchidae; however, is distinguished from Mediorhynchus by having a simple proboscis receptacle that is completely suspended within the proboscis, the passage of the retractor muscles through the receptacle into the body cavity posteriorly, absence of neck, and presence of a parareceptacle structure (first finding in the Archiacanthocephala) and a uterine vesicle; among other features, including the differential dorsoventral thickness of the body wall. The receptacle in Mediorhynchus is complex, with many accessory muscles and retractor muscles passing into the body cavity dorsally and ventrally. Our specimens reached 180 mm in length and the proboscis had 34-36 rows of 6-7 ventrally lamellated, rooted hooks each anteriorly, and 15-17 spinelike hooks each posteriorly. Micropores extended into the anterior and posterior proboscis and energy dispersive x-ray analysis (EDXA) of anterior hooks showed high levels of calcium and phosphorus but negligible traces of sulfur. Spinelike hooks in the posterior proboscis had lower levels of Ca and P and slightly higher levels of S. Molecular and phylogenetic analyses based on the 18S rDNA gene placed I. sanghae in a clade with the archiacanthocephalans Mediorhynchus, Moniliformis, Macracanthorhynchus, Oncicola, and Oligacanthorhynchus.

Fatal avian malaria in captive Atlantic puffins (Fratercula arctica) in Switzerland.

Avian malaria is a vector-borne disease caused by Plasmodium species, which may affect a broad spectrum of bird families worldwide. In most endemic and migratory birds, Plasmodium infections seem not to cause severe harm; however, non-indigenous species kept in human care such as penguins may experience high morbidity and mortality rates. Fatal avian malaria may also occur in other non-native seabirds such as puffins (Fratercula spp.), but reported cases are scarce. The aim of this study was to analyze seven cases of sudden death in captive Atlantic puffins (Fratercula arctica) at Berne Animal Park in Switzerland between 2010 and 2020, and to determine the involvement of haemosporidian parasites in the fatal outcome. In all cases, lymphoplasmacytic inflammation, necrotic lesions in several organs and presence of protozoan stages within tissues/erythrocytes or accumulation of iron-based pigment were observed histologically. A one-step multiplex PCR designed to simultaneously detect and discriminate haemosporidia belonging to the genera Plasmodium, Haemoproteus and Leucocytozoon, and a nested PCR detecting Plasmodium and Haemoproteus infections were performed on DNA extracted from formalin-fixed and paraffin-embedded (FFPE) or fresh liver and spleen tissues from five and two birds, respectively. Plasmodium spp. DNA was detected in the tissues from six of seven birds by the one-step multiplex PCR and in five of seven individuals by the nested PCR protocol. Direct sequencing of the amplification products allowed the molecular identification of Plasmodium relictum SGS1 as the involved species in three individuals and Plasmodium matutinum LINN1 in two of these fatal cases. In one bird, no haemosporidian DNA could be amplified from FFPE tissues despite of suggestive histopathological findings. These results indicate that avian malaria represents an important cause of death in captive puffins and it should be considered as a differential diagnosis in unclear or fatal cases in this threatened bird species.

An experimental genetically attenuated live vaccine to prevent transmission of Toxoplasma gondii by cats.

Almost any warm-blooded creature can be an intermediate host for Toxoplasma gondii. However, sexual reproduction of T. gondii occurs only in felids, wherein fertilisation of haploid macrogametes by haploid microgametes, results in diploid zygotes, around which a protective wall develops, forming unsporulated oocysts. Unsporulated oocysts are shed in the faeces of cats and meiosis gives rise to haploid sporozoites within the oocysts. These, now infectious, sporulated oocysts contaminate the environment as a source of infection for people and their livestock. RNA-Seq analysis of cat enteric stages of T. gondii uncovered genes expressed uniquely in microgametes and macrogametes. A CRISPR/Cas9 strategy was used to create a T. gondii strain that exhibits defective fertilisation, decreased fecundity and generates oocysts that fail to produce sporozoites. Inoculation of cats with this engineered parasite strain totally prevented oocyst excretion following infection with wild-type T. gondii, demonstrating that this mutant is an attenuated, live, transmission-blocking vaccine.

RNA-Seq analysis during the life cycle of Cryptosporidium parvum reveals significant differential gene expression between proliferating stages in the intestine and infectious sporozoites.

Cryptosporidium parvum is a major cause of diarrhoea in humans and animals. There are no vaccines and few drugs available to control C. parvum. In this study, we used RNA-Seq to compare gene expression in sporozoites and intracellular stages of C. parvum to identify genes likely to be important for successful completion of the parasite's life cycle and, thereby, possible targets for drugs or vaccines. We identified 3774 protein-encoding transcripts in C. parvum. Applying a stringent cut-off of eight fold for determination of differential expression, we identified 173 genes (26 coding for predicted secreted proteins) upregulated in sporozoites. On the other hand, expression of 1259 genes was upregulated in intestinal stages (merozoites/gamonts) with a gene ontology enrichment for 63 biological processes and upregulation of 117 genes in 23 metabolic pathways. There was no clear stage specificity of expression of AP2-domain containing transcription factors, although sporozoites had a relatively small repertoire of these important regulators. Our RNA-Seq analysis revealed a new calcium-dependent protein kinase, bringing the total number of known calcium-dependent protein kinases (CDPKs) in C. parvum to 11. One of these, CDPK1, was expressed in all stages, strengthening the notion that it is a valid drug target. By comparing parasites grown in vivo (which produce bona fide thick-walled oocysts) and in vitro (which are arrested in sexual development prior to oocyst generation) we were able to confirm that genes encoding oocyst wall proteins are expressed in gametocytes and that the proteins are stockpiled rather than generated de novo in zygotes. RNA-Seq analysis of C. parvum revealed genes expressed in a stage-specific manner and others whose expression is required at all stages of development. The functional significance of these can now be addressed through recent advances in transgenics for C. parvum, and may lead to the identification of viable drug and vaccine targets.

[Digital electroencephalography in brain death diagnostics : Technical requirements and results of a survey on the compatibility with medical guidelines of digital EEG systems from providers in Germany]. / Digitale Elektroenzephalographie in der Hirntoddiagnostik : Technische Anforderungen und Ergebnisse einer Umfrage zur Richtlinienkompatibilität digitaler EEG-Systeme bei Anbietern in Deutschland.

BACKGROUND: The guidelines of the German Medical Association and the German Society for Clinical Neurophysiology and Functional Imaging (DGKN) require a high procedural and technical standard for electroencephalography (EEG) as an ancillary method for diagnosing the irreversible cessation of brain function (brain death). Nowadays, digital EEG systems are increasingly being applied in hospitals. So far it is unclear to what extent the digital EEG systems currently marketed in Germany meet the guidelines for diagnosing brain death. METHODS: In the present article, the technical und safety-related requirements for digital EEG systems and the EEG documentation for diagnosing brain death are described in detail. On behalf of the DGKN, the authors sent out a questionnaire to all identified distributors of digital EEG systems in Germany with respect to the following technical demands: repeated recording of the calibration signals during an ongoing EEG recording, repeated recording of all electrode impedances during an ongoing EEG recording, assessability of intrasystem noise and galvanic isolation of measurement earthing from earthing conductor (floating input). RESULTS: For 15 of the identified 20 different digital EEG systems the specifications were provided by the distributors (among them all distributors based in Germany). All of these EEG systems are provided with a galvanic isolation (floating input). The internal noise can be tested with all systems; however, some systems do not allow repeated recording of the calibration signals and/or the electrode impedances during an ongoing EEG recording. CONCLUSION: The majority but not all of the currently available digital EEG systems offered for clinical use are eligible for use in brain death diagnostics as per German guidelines.

[Can treatment with anesthetic anticonvulsive drugs worsen outcome in status epilepticus?] / Kann der Einsatz anästhetisierender Antikonvulsiva beim Status epilepticus das Outcome verschlechtern?

BACKGROUND AND OBJECTIVES: Nowadays, there is an ongoing discussion about the risks and benefits of anesthetic treatment concerning outcome in status epilepticus (SE). Therefore, we performed a retrospective database analysis to examine the influence of treatment with anesthetic drugs and narcosis in SE on mortality and disability. METHODS: All treatment episodes of SE at the Department of Neurology of the University of Rostock between 01 January 2000 and 31 December 2009 were evaluated. SE severity before treatment, mortality, and disability at discharge were taken into account. RESULTS: Of 167 treatment episodes of SE, 34 included treatment with anesthetic anticonvulsive drugs and narcosis. In the treatment episodes with use of anesthetic anticonvulsive drugs and narcosis, there was a more than twofold increased risk for death compared to the other treatment episodes. However, due to sample size this difference was not significant (p = 0.09). Cardiopulmonary complications were the cause of death in 4 of 5 patients dying during treatment episodes with anesthetic anticonvulsive drugs and narcosis. At discharge, disability as measured with the Modified Rankin Scale was higher in patients treated with anesthetic anticonvulsive drugs and narcosis than in the others (p = 0.03). A subgroup analysis revealed that especially in patients with nonconvulsive SE with impaired consciousness treatment with narcosis was associated with a higher rate of new deficits or mortality (p = 0.012). CONCLUSIONS: Especially when considering narcosis for treatment of nonconvulsive SE, risks and benefits should be carefully weighed. When treating SE with anesthetic drugs and narcosis, everything has to be done to avoid cardiopulmonary complications.

The measuring of substantia nigra hyperechogenicity in an Italian cohort of Parkinson disease patients: a case/control study (NOBIS Study).

Transcranial sonography (TCS) shows an increased echogenic area of the substantia nigra (SN) in patients with Parkinson disease (PD). It has been increasingly used in the diagnosis of PD and its differentiation from atypical parkinsonian syndromes. Here, we studied the diagnostic accuracy of SN TCS in Italian patients. In this blinded cross-sectional study (NOBIS study), two expert neuro-sonologists performed TCS in 25 PD patients and 29 age- and sex-matched controls. The study participants were completely hidden to the TCS investigators using large drapery. One month later, the SN TCS recordings were re-read by the initial investigator, and cross-read by the second reader. Diagnostic accuracy was estimated on the first reading, intra-reader reliability on re-reading, and inter-reader reliability on cross-readings. The mean SN echogenic area was larger in the patients (0.24 cm2) than in the controls (0.15 cm2; Mann-Whitney test, p < 0.001). SN measures did not differ between right and left, or between ipsilateral and contralateral to the clinically more affected side. There was no correlation between SN echogenicity and PD severity or duration. High intra-reader (concordance correlation coefficient 0.93) and inter-reader (0.98) agreement of SN measurements was found. The diagnostic accuracy for the detection of PD was high (area under receiver-operating characteristic curve 0.91; 95% CI 0.83-1.00) with an optimum cut-off value for SN echogenic area of 0.18 cm2 with the device used here (specificity 0.83-0.90; sensitivity 0.72-0.92). This study supports the use of SN TCS in the diagnostic workup of PD if performed by trained readers.

[Helpful instrumental examinations in idiopathic Parkinson's disease]. / Hilfreiche Zusatzuntersuchungen beim idiopathischen Parkinson-Syndrom.

BACKGROUND: The clinical diagnosis of idiopathic Parkinson's disease (iPD) can be challenging. In these cases, additional diagnostic methods are available that can help to improve diagnostic accuracy. OBJECTIVES, MATERIAL AND METHODS: This article provides an overview of currently available and promising novel ancillary methods for the early and differential diagnosis of iPD. RESULTS: Imaging tools, such as 1.5 Tesla magnetic resonance imaging (MRI) and computed tomography (CT) are mainly used for the differentiation between iPD and symptomatic parkinsonian syndromes (PS). High-resolution diffusion tensor imaging and iron and neuromelanin-sensitive high-field MRI sequences can become important in the future, particularly for earlier diagnosis. Transcranial B­mode sonography of the substantia nigra and basal ganglia is established for early and differential diagnostics, especially in the combination of diagnostic markers but necessitates an adequately trained investigator and the use of validated digital image analysis instruments. DATScan can discriminate iPD from essential tremor, medication-induced parkinsonism and psychogenic movement disorder but not iPD from atypical PS. For the latter differential diagnosis, fluorodeoxyglucose positron emission tomography and myocardial metaiodobenzylguanidine scintigraphy can be helpful. Olfactory testing should preferably be used in combination with other diagnostic tests. Genetic, biochemical and histopathological tests are currently not recommended for routine use. Novel sensor-based techniques have a high potential to support clinical diagnosis of iPD but have not yet reached a developmental stage that is sufficient for clinical use. Novel sensor-based techniques have high potential to support clinical diagnosis of iPD, but have not yet reached a development stage that is sufficient for clinical use. CONCLUSION: Ancillary diagnostic methods can support the early and differential diagnosis of iPD.

[Diagnostics of clinical and prodromal idiopathic Parkinson's disease : New criteria]. / Diagnostik des klinischen und prodromalen idiopathischen Parkinson-Syndroms : Neue Kriterien.

BACKGROUND: Recently, the Movement Disorder Society (MDS) published an adaptation of the previous United Kingdom Brain Bank Society (UKBBS) criteria for the diagnosis of idiopathic Parkinson's disease (iPD). OBJECTIVES: This article presents the changes in the current clinical diagnostic criteria for IPD. Furthermore, the new MDS criteria for prodromal iPD are discussed. RESULTS: The recently introduced MDS criteria for the clinical diagnosis of iPD include useful novel features (e.g. postural instability is no longer listed as a cardinal symptom, familiar history of iPD and intake of neuroleptics at the first visit no longer lead to exclusion of the diagnosis) and red flags do not lead to exclusion of the diagnosis; however, they must be counterbalanced by the presence of supportive criteria for iPD. The criteria for identification of persons in the prodromal stage are currently established only for scientific investigations. CONCLUSION: The new MDS criteria for the diagnostics of iPD should help to improve the sensitivity and specificity.

[Municipal Health Promotion in Germany: Duties, Rights and Potential]. / Kommunale Prävention und Gesundheitsförderung in Deutschland: Pflichten, Rechte und Potenziale im Kontext der kommunalen Daseinsvorsorge.

Municipalities have an overarching structure in health promotion. Due to the right to self-government, municipalities are in charge of both voluntary and obligatory tasks. Some of the original and fundamental tasks can be summarized as "services to the public". Current common definitions do not include the term "health promotion". In the present study, a sub-target of a joint project, legal acts, requirements and recommendations were researched and analyzed. The results show substantive cornerstones of health promotion in various regulations of different disciplines. Based on these findings, health promotion can be interpreted as being part of services to the public. Currently the regulations for education, social tasks, environmental and consumer protection constitute the legal framework for community health promotion, but also include constitutions. They range from public international law to municipal resolutions. Quality management and also quality development are already an integral part in some communal departments. The management of structures, processes and results arises from commitments or measurable targets. In contrast, quality management for health promotion is not based on binding requirements. Specifications of other neighboring sectors (e. g. education, social sector) demonstrate the potential and effectiveness of legal policy guidelines, seen as a frame. A transparent communication about the current regulations is indispensable for formulating future guidelines. The German National Prevention Act opens opportunities for municipalities. However, its interpretation and local engagement will still guide the practice of communal health promotion.

Doppler and Duplex Sonography for the Diagnosis of the Irreversible Cessation of Brain Function ("Brain Death"): Current Guidelines in Germany and Neighboring Countries.

Extra- and transcranial sonography of brain-supplying arteries is accepted worldwide in brain death protocols as a valid "ancillary" method of proving brain circulatory arrest. Color-coded duplex sonography and CT angiography have been newly incorporated in the fourth update of the German Medical Association's guidelines for the determination of the irreversible cessation of brain function ("brain death"), effective July 2015. The updated guidelines address in more detail the diagnostic procedures and the required qualifications of the examiners. The present article summarizes the guidelines and the recommendations regarding the application and documentation of ultrasound findings for the diagnosis of brain circulatory arrest in children and adults, as valid in Germany. The method, limitations, and procedure in the case of inconclusive findings are described. Age-related minimum values of mean arterial pressure for the diagnosis of cerebral circulatory arrest in children are presented. A concise overview of the respective regulations for the use of sonography for diagnosing brain death in other countries, especially in the countries neighboring Germany, is given.

Transcranial Sonography of the Insula: Digitized Image Analysis of Fusion Images with Magnetic Resonance.

Purpose: Transcranial B-mode sonography (TCS) of brain parenchyma is increasingly used as a diagnostic tool for movement disorders. Accordingly, experimental B-Mode Assist software was developed to enable digitized analysis of the echogenicity of predefined brain regions. The aim of the study was to assess the reproducibility of digitized TCS image analysis of the insula. Materials and Methods: A total of 130 patients with an indication for neurosonological examination were screened for participation in the study. The insula was imaged from the right temporal bone window using Virtual Navigator and TCS-MRI (magnetic resonance imaging) fusion imaging. All subjects were examined three times by two experienced sonographers. Corresponding images of the insula in the axial thalamic plane were encoded and digitally analyzed. Interclass correlation coefficient (ICC) and Spearman's rank correlation coefficient were used for the assessment of intra- and inter-reader as well as intra- and inter-investigator reliabilities. Results: TCS images of 114 patients were evaluated (21 patients with TIA, 53 patients with headache, 18 patients with essential tremor, 22 patients with neurodegerative disease). 16 patients were excluded from analysis due to insufficient bone window. The intra-reader, inter-reader, intra-investigator and inter-investigator ICCs/Spearman's rank correlation coefficients were 0.995/0.993, 0.937/0.921, 0.969/0.961 and 0.875/0.858, resp. Conclusion: The present study demonstrates a high reliability to reproduce echogenicity values of the insula using digitized image analysis and TCS-MRI fusion images with almost perfect intra-reader, inter-reader, intra-investigator and inter-investigator agreement.

Accuracy of transcranial brain parenchyma sonography in the diagnosis of dementia with Lewy bodies.

BACKGROUND AND PURPOSE: Transcranial sonography (TCS) of the brain parenchyma is used to visualize alterations in the substantia nigra (SN) and it is applied for early diagnosis of Parkinson's disease. Our aim was to explore specific echogenic alterations of the SN in dementia with Lewy bodies (DLB) compared to Alzheimer's disease (AD). METHODS: Seventy-one subjects underwent TCS: 22 DLB, 28 AD and 21 healthy elderly controls. Cognitive impairment, extrapyramidal signs, visual hallucinations, fluctuations and rapid eye movement sleep behaviour symptoms were investigated. TCS assessed SN hyperechogenicity and symmetry. RESULTS: Transcranial sonography revealed SN hyperechogenicity in 100% of DLB compared to 50% of AD and 30% of controls. Mean SN echogenic area (cm(2) ) was 0.22 ± 0.03 in DLB, 0.15 ± 0.03 in AD and 0.14 ± 0.03 in controls (P < 0.0001). More than 50% of DLB presented a marked hyperechogenicity (cutoff value >0.22 cm(2) ) compared to only 10% of AD (P < 0.0003). DLB had symmetrical SN enlargement, whereas AD were mostly asymmetrical (P = 0.015). A combination of SN echogenic area and asymmetry index had a sensitivity of 88.9% and a specificity of 81.2% in discriminating DLB from AD (positive predictive value 85.7%, negative predictive value 85.7%). No association was found between SN hyperechogenicity and Unified Parkinson's Disease Rating Scale part III, Mini Mental State Examination or the presence of visual hallucinations. CONCLUSIONS: Transcranial sonography may be a valid supportive tool in the diagnostic workup of neurodegenerative dementia helping clinicians to distinguish DLB from AD even at the early stages.

Cofactor-independent human antiphospholipid antibodies induce venous thrombosis in mice.

UNLABELLED: Essentials Cofactor-independent antiphospholipid antibodies (CI-aPL) are generally considered non-pathogenic. We analyzed the effects of human monoclonal CI-aPL in a mouse model of venous thrombosis. As shown in vitro, CI-aPL induce a procoagulant state in vivo by activation of endosomal NADPH-oxidase. Contrary to common belief, CI-aPL induce venous thrombosis in vivo. SUMMARY: Background There is general consensus that the antiphospholipid syndrome (APS) is caused by antiphospholipid antibodies (aPL) with antibodies against ß2-glycoprotein-I being the most relevant. aPL that bind phospholipids in the absence of protein cofactors are generally considered pathogenetically irrelevant. We showed that cofactor-independent human monoclonal aPL isolated from APS patients induce proinflammatory and procoagulant cellular responses by activating endosomal NADPH-oxidase 2 (NOX2). Similar aPL were detected in all IgG fractions from APS patients analyzed. Objectives We aimed to clarify if cofactor-independent aPL can be thrombogenic in vivo and, if so, whether these effects are mediated via activation of NOX2. Methods Two cofactor-independent human monoclonal aPL, HL5B and RR7F, were tested in a mouse model of venous thrombosis. Genetically modified mice and in vitro assays were used to delineate the mechanisms underlying thrombus induction. Results HL5B and RR7F dramatically accelerate thrombus formation in this mouse model. Thrombus formation depends on tissue factor activation. It cannot be induced in NOX2-deficient mice. Bone marrow chimeras of C57BL/6J mice reconstituted with NOX2-deficient bone marrow showed that leukocyte activation plays a major role in thrombus formation. Neither TLR4 signaling nor platelet activation by our aPL is required for venous thrombus formation. Conclusions Cofactor-independent aPL can induce thrombosis in vivo. This effect is mainly mediated by leukocyte activation, which depends on the previously described signal transduction via endosomal NOX2. Because most APS patients have been shown to harbor aPL with similar activity, our data are of general relevance for the APS.

[Changing structures--Integrating health]. / Strukturen ändern--Gesundheit integrieren.

Changes in (municipal) structures for the improvement of health are often required but, in contrast to behavioural measures, less frequently implemented and scientifically evaluated. Results on this subject for Germany are scarce. In recent years, municipal prevention and health promotion programmes received new impetus from the expansion of the German "Early Assistance" initiative. Early assistance programmes to help children grow up healthy initiated municipal processes such as the establishment of networks between health services and youth welfare services, prevention chains and nationwide initiatives. This has moved issues such as equal opportunities for health into the centre of politically driven structural development efforts. Neighbourhood management groups and municipal round tables on prevention-specific topics etc. have been established throughout Germany. Regarding this structural development, 6 projects from the field of prevention research give a good indication as to how the structure of municipal concepts can be effectively implemented.