Impulsivity mediates the association between narcissism and substance-related problems beyond the degree of substance use: a longitudinal observational study.

BACKGROUND: Narcissism has been implied as a putative risk factor for substance use disorders (SUDs). However, previous research did not disentangle the degree of substance use from substance-related problems, the symptoms of SUDs. This preregistered study addressed the open question whether grandiose and vulnerable narcissism and their constituent traits convey specific SUD risk, that is, explain substance-related problems beyond the degree of use. Furthermore, we tested whether impulsivity or substance use motives linked to narcissistic self-regulation mediate this association. METHODS: Narcissism, impulsivity, substance use motives, past-year substance use, and substance-related problems were assessed in 139 (poly-)substance users, 121 of whom completed a one-year follow-up. For significant longitudinal associations between narcissism factors and substance-related problems controlled for the degree of use, we tested impulsivity and substance use motives as mediators. RESULTS: Grandiose narcissism (r =.24, p =.007) and its constituent factors antagonistic (r =.27, p =.003) and agentic narcissism (r =.18, p =.050), but not vulnerable narcissism, prospectively predicted substance-related problems beyond the degree of substance use. Associations of grandiose narcissism and antagonistic narcissism with substance-related problems were fully mediated by impulsivity, but not substance use motives. Impulsivity explained roughly one third of the association of both grandiose (P̂M = 0.30) and antagonistic narcissism (P̂M = 0.26) with substance-related problems. DISCUSSION: We demonstrate that grandiose narcissism- particularly antagonistic but also agentic narcissism- is specifically linked to substance-related problems beyond the degree of substance use. The mediating effect of impulsivity but not substance use motives suggests that impulsivity may be a more important mechanism than narcissistic self-regulation in promoting SUD in narcissism. However, future studies may use more targeted measures than substance use motives to further probe the role of self-regulation. Similar result patterns for alcohol compared to all substances together indicate that mechanisms may be alike across substances. In conclusion, narcissistic individuals may not use substances more but have a higher SUD risk, informing prevention and treatment.

Can gadolinium contrast agents be replaced with saline for direct MR arthrography of the hip? A pilot study with arthroscopic comparison.

OBJECTIVE: To compare image quality and diagnostic performance of preoperative direct hip magnetic resonance arthrography (MRA) performed with gadolinium contrast agent and saline solution. METHODS: IRB-approved retrospective study of 140 age and sex-matched symptomatic patients with femoroacetabular impingement, who either underwent intra-articular injection of 15-20 mL gadopentetate dimeglumine (GBCA), 2.0 mmol/L ("GBCA-MRA" group, n = 70), or 0.9% saline solution ("Saline-MRA" group, n = 70) for preoperative hip MRA and subsequent hip arthroscopy. 1.5 T hip MRA was performed including leg traction. Two readers assessed image quality using a 5-point Likert scale (1-5, excellent-poor), labrum and femoroacetabular cartilage lesions. Arthroscopic diagnosis was used to calculate diagnostic accuracy which was compared between groups with Fisher's exact tests. Image quality was compared with the Mann-Whitney U tests. RESULTS: Mean age was 33 years ± 9, 21% female patients. Image quality was excellent (GBCA-MRA mean range, 1.1-1.3 vs 1.1-1.2 points for Saline-MRA) and not different between groups (all p > 0.05) except for image contrast which was lower for Saline-MRA group (GBCA-MRA 1.1 ± 0.4 vs Saline-MRA 1.8 ± 0.5; p < 0.001). Accuracy was high for both groups for reader 1/reader 2 for labrum (GBCA-MRA 94%/ 96% versus Saline-MRA 96%/93%; p > 0.999/p = 0.904) and acetabular (GBCA-MRA 86%/ 83% versus Saline-MRA 89%/87%; p = 0.902/p = 0.901) and femoral cartilage lesions (GBCA-MRA 97%/ 99% versus Saline-MRA 97%/97%; both p > 0.999). CONCLUSION: Diagnostic accuracy and image quality of Saline-MRA and GBCA-MRA is high in assessing chondrolabral lesions underlining the potential role of non-gadolinium-based hip MRA. KEY POINTS: • Image quality of Saline-MRA and GBCA-MRA was excellent for labrum, acetabular and femoral cartilage, ligamentum teres, and the capsule (all p > 0.18). • The overall image contrast was lower for Saline-MRA (Saline-MRA 1.8 ± 0.5 vs. GBCA-MRA 1.1 ± 0.4; p < 0.001). • Diagnostic accuracy was high for Saline-MRA and GBCA-MRA for labrum (96% vs. 94%; p > 0.999), acetabular cartilage damage (89% vs. 86%; p = 0.902), femoral cartilage damage (97% vs. 97%; p > 0.999), and extensive cartilage damage (97% vs. 93%; p = 0.904).

Are degenerative findings detected on traction MR arthrography of the hip associated with failure of arthroscopic femoroacetabular impingement surgery?

OBJECTIVES: To identify preoperative degenerative features on traction MR arthrography associated with failure after arthroscopic femoroacetabular impingement (FAI) surgery. METHODS: Retrospective study including 102 patients (107 hips) undergoing traction magnetic resonance arthrography (MRA) of the hip at 1.5 T and subsequent hip arthroscopic FAI surgery performed (01/2016 to 02/2020) with complete follow-up. Clinical outcomes were assessed using the International Hip Outcome Tool (iHOT-12) score. Clinical endpoint for failure was defined as an iHOT-12 of < 60 points or conversion to total hip arthroplasty. MR images were assessed by two radiologists for presence of 9 degenerative lesions including osseous, chondrolabral/ligamentum teres lesions. Uni- and multivariate Cox regression analysis was performed to assess the association between MRI findings and failure of FAI surgery. RESULTS: Of the 107 hips, 27 hips (25%) met at least one endpoint at a mean 3.7 ± 0.9 years follow-up. Osteophytic changes of femur or acetabulum (hazard ratio [HR] 2.5-5.0), acetabular cysts (HR 3.4) and extensive cartilage (HR 5.1) and labral damage (HR 5.5) > 2 h on the clockface were univariate risk factors (all p < 0.05) for failure. Three risk factors for failure were identified in multivariate analysis: Acetabular cartilage damage > 2 h on the clockface (HR 3.2, p = 0.01), central femoral osteophyte (HR 3.1, p = 0.02), and femoral cartilage damage with ligamentum teres damage (HR 3.0, p = 0.04). CONCLUSION: Joint damage detected by preoperative traction MRA is associated with failure 4 years following arthroscopic FAI surgery and yields promise in preoperative risk stratification. CLINICAL RELEVANCE STATEMENT: Evaluation of negative predictors on preoperative traction MR arthrography holds the potential to improve risk stratification based on the already present joint degeneration ahead of FAI surgery. KEY POINTS: • Osteophytes, acetabular cysts, and extensive chondrolabral damage are risk factors for failure of FAI surgery. • Extensive acetabular cartilage damage, central femoral osteophytes, and combined femoral cartilage and ligamentum teres damage represent independent negative predictors. • Survival rates following hip arthroscopy progressively decrease with increasing prevalence of these three degenerative findings.

Highly infectious prions are not directly neurotoxic.

Prions are infectious agents which cause rapidly lethal neurodegenerative diseases in humans and animals following long, clinically silent incubation periods. They are composed of multichain assemblies of misfolded cellular prion protein. While it has long been assumed that prions are themselves neurotoxic, recent development of methods to obtain exceptionally pure prions from mouse brain with maintained strain characteristics, and in which defined structures-paired rod-like double helical fibers-can be definitively correlated with infectivity, allowed a direct test of this assertion. Here we report that while brain homogenates from symptomatic prion-infected mice are highly toxic to cultured neurons, exceptionally pure intact high-titer infectious prions are not directly neurotoxic. We further show that treatment of brain homogenates from prion-infected mice with sodium lauroylsarcosine destroys toxicity without diminishing infectivity. This is consistent with models in which prion propagation and toxicity can be mechanistically uncoupled.

Playful mouth-to-mouth interactions of belugas (Delphinapterus leucas) in managed care.

Belugas (Delphinapterus leucas) engage in many forms of play (e.g., object, water, locomotor), but no play is quite as curious as the unusual form of cooperative social play involving mouth-to-mouth interactions. These playful interactions are characterized by two belugas approaching each other head-to-head and interlocking their jaws, clasping one another, as if they were shaking hands. Observed in belugas both in the wild and in managed care, it is seemingly an important type of social play that offers a unique way of socializing with conspecifics. To describe this unusual behavior, a group of belugas in managed care was observed from 2007 to 2019. Although adults participated in mouth-to-mouth interactions, most were initiated and received by young belugas. Both males and females engaged in mouth-to-mouth interactions and did so at similar frequencies. Individual differences in how many mouth-to-mouth interactions were initiated among calves were also observed. Due to the unique, cooperative nature of mouth-to-mouth interactions, which require both social and motor skills, it is hypothesized that these interactions may be used to test social and motor competency.

Humanized Transgenic Mice Are Resistant to Chronic Wasting Disease Prions From Norwegian Reindeer and Moose.

Chronic wasting disease (CWD) is the transmissible spongiform encephalopathy or prion disease affecting cervids. In 2016, the first cases of CWD were reported in Europe in Norwegian wild reindeer and moose. The origin and zoonotic potential of these new prion isolates remain unknown. In this study to investigate zoonotic potential we inoculated brain tissue from CWD-infected Norwegian reindeer and moose into transgenic mice overexpressing human prion protein. After prolonged postinoculation survival periods no evidence for prion transmission was seen, suggesting that the zoonotic potential of these isolates is low.

Structural mapping of GABRB3 variants reveals genotype-phenotype correlations.

PURPOSE: Pathogenic variants in GABRB3 have been associated with a spectrum of phenotypes from severe developmental disorders and epileptic encephalopathies to milder epilepsy syndromes and mild intellectual disability (ID). In this study, we analyzed a large cohort of individuals with GABRB3 variants to deepen the phenotypic understanding and investigate genotype-phenotype correlations. METHODS: Through an international collaboration, we analyzed electro-clinical data of unpublished individuals with variants in GABRB3, and we reviewed previously published cases. All missense variants were mapped onto the 3-dimensional structure of the GABRB3 subunit, and clinical phenotypes associated with the different key structural domains were investigated. RESULTS: We characterized 71 individuals with GABRB3 variants, including 22 novel subjects, expressing a wide spectrum of phenotypes. Interestingly, phenotypes correlated with structural locations of the variants. Generalized epilepsy, with a median age at onset of 12 months, and mild-to-moderate ID were associated with variants in the extracellular domain. Focal epilepsy with earlier onset (median: age 4 months) and severe ID were associated with variants in both the pore-lining helical transmembrane domain and the extracellular domain. CONCLUSION: These genotype-phenotype correlations will aid the genetic counseling and treatment of individuals affected by GABRB3-related disorders. Future studies may reveal whether functional differences underlie the phenotypic differences.

High prevalence of hip lesions secondary to arthroscopic over- or undercorrection of femoroacetabular impingement in patients with postoperative pain.

OBJECTIVES: To compare the prevalence of pre- and postoperative osseous deformities and intra-articular lesions in patients with persistent pain following arthroscopic femoroacetabular impingement (FAI) correction and to identify imaging findings associated with progressive cartilage damage. METHODS: Retrospective study evaluating patients with hip pain following arthroscopic FAI correction between 2010 and 2018. Pre- and postoperative imaging studies were analyzed independently by two blinded readers for osseous deformities (cam-deformity, hip dysplasia, acetabular overcoverage, femoral torsion) and intra-articular lesions (chondro-labral damage, capsular lesions). Prevalence of osseous deformities and intra-articular lesions was compared with paired t-tests/McNemar tests for continuous/dichotomous data. Association between imaging findings and progressive cartilage damage was assessed with logistic regression. RESULTS: Forty-six patients (mean age 29 ± 10 years; 30 female) were included. Postoperatively, 74% (34/46) of patients had any osseous deformity including 48% (22/46) acetabular and femoral deformities. Ninety-six percent (44/46) had an intra-articular lesion ranging from 20% (9/46) for femoral to 65% (30/46) for acetabular cartilage lesions. Prevalence of hip dysplasia increased (2 to 20%, p = 0.01) from pre- to postoperatively while prevalence of cam-deformity decreased (83 to 28%, p < 0.001). Progressive cartilage damage was detected in 37% (17/46) of patients and was associated with extensive preoperative cartilage damage > 2 h, i.e., > 60° (OR 7.72; p = 0.02) and an incremental increase in postoperative alpha angles (OR 1.18; p = 0.04). CONCLUSION: Prevalence of osseous deformities secondary to over- or undercorrrection was high. Extensive preoperative cartilage damage and higher postoperative alpha angles increase the risk for progressive degeneration. KEY POINTS: • The majority of patients presented with osseous deformities of the acetabulum or femur (74%) and with intra-articular lesions (96%) on postoperative imaging. • Prevalence of hip dysplasia increased (2 to 20%, p = 0.01) from pre- to postoperatively while prevalence of a cam deformity decreased (83 to 28%, p < 0.001). • Progressive cartilage damage was present in 37% of patients and was associated with extensive preoperative cartilage damage > 2 h (OR 7.72; p = 0.02) and with an incremental increase in postoperative alpha angles (OR 1.18; p = 0.04).

Brain activation during social cognition predicts everyday perspective-taking: A combined fMRI and ecological momentary assessment study of the social brain.

Identifying distinct neural networks underlying social affect (empathy, compassion) and social cognition (Theory of Mind) has advanced our understanding of social interactions. However, little is known about the relation of activation in these networks to psychological experience in daily life. This study (N = 122) examined the ecological validity of neural activation patterns induced by a laboratory paradigm of social affect and cognition with respect to social interactions in everyday life. We used the EmpaToM task, a naturalistic video-based paradigm for the assessment of empathy, compassion, and Theory of Mind, and combined it with a subsequent 14-day ecological momentary assessment protocol on social interactions. Everyday social affect was predicted by social affect experienced during the EmpaToM task, but not by related neural activation in regions of interest from the social affect network. In contrast, everyday social cognition was predicted by neural activation differences in the medial prefrontal cortex - a region of interest from the social cognition network - but not by social cognition performance in the EmpaToM task. The relationship between medial prefrontal cortex activation and everyday social cognition was stronger for spontaneous rather than deliberate perspective taking during the EmpaToM task, pointing to a distinction between propensity and capacity in social cognition. Finally, this neural indicator of Theory of Mind explained variance in everyday social cognition to a similar extent as an established self-report scale. Taken together, this study provides evidence for the ecological validity of lab-based social affect and cognition paradigms when considering relevant moderating factors.

Disentangling substance use and related problems: urgency predicts substance-related problems beyond the degree of use.

BACKGROUND: Substance use disorders are reliably associated with high impulsivity and sensation seeking. Importantly, both precede problematic substance use, implicating them as risk factors. Individuals with substance use disorders show variable degrees of substance use (combined quantity and frequency) and substance-related problems and differ in both aspects from healthy controls. Dimensional research has indicated differential associations of impulsivity-related traits as well as sensation seeking with the degree of substance use and substance-related problems. The current study aimed to clarify whether impulsivity-related traits and sensation seeking predict substance-related problems above and beyond the degree of substance use and are thus specifically linked to problems, the dimension that characterizes substance use disorders. METHOD: We assessed impulsivity-related traits and sensation seeking using self-report, as well as delay discounting, a behavioral indicator of impulsivity, in a sample of 258 substance-using adults. RESULTS: Sensation seeking and impulsivity-related traits significantly predicted the degree of substance use, with sensation seeking explaining the largest portion of variance. In contrast, self-reported impulsivity, in particular when experiencing negative emotions (urgency), but not sensation seeking or delay discounting, predicted substance-related problems when controlling for the degree of substance use. CONCLUSIONS: This suggests that urgency, but not sensation seeking, may be specifically linked to substance-related problems and thus especially relevant for substance use disorders. Taken together, this study underlines the necessity to assess and control for the degree of substance use in risk factor research concerning substance-related problems. Thus, it may inform future research improving targeted prevention and therapy.

In-vitro sonothrombolysis using thick-shelled polymer microbubbles - a comparison with thin-shelled microbubbles.

BACKGROUND: Vascular thrombosis can be treated pharmacologically, however, serious shortcomings such as bleeding may occur. Several studies suggest that sonothrombolysis can induce lysis of the clots using ultrasound. Moreover, intravenously injected thin-shelled microbubbles (MBs) combined with ultrasound can further improve clot lysis. Thick-shelled MBs have been used for drug delivery, targeting and multimodal imaging. However, their capability to enhance sonothrombolysis is unknown. In this study, using an in-vitro set-up, the enhancement of clot lysis using ultrasound and thick-shelled MBs was investigated. Thin-shelled MBs was used for comparison. METHOD: The main components in the in-vitro set-up was a vessel mimicking phantom, a pressure mearing system and programmable ultrasound machine. Blood clots were injected and entrapped on a pore mesh in the vessel phantom. Four different protocols for ultrasound transmission and MB exposure (7 blood clots/protocol) were considered together with a control test were no MBs and ultrasound were used. For each protocol, ultrasound exposure of 20 min was used. The upstream pressure of the partially occluded mesh was continuously measured to assess clot burden. At the end of each protocol blood clots were removed from the phantom and the clot mass loss was computed. RESULTS: For the thick-shelled MBs no difference in clot mass loss compared with the control tests was found. A 10% increase in the clot mass loss compared with the control tests was found when using thin-shelled MBs and low pressure/long pulses ultrasound exposure. Similarly, in terms of upstream pressure over exposure time, no differences were found when using the thick-shelled MBs, whereas thin-shelled MBs showed a 15% decrease achieved within the first 4 min of ultrasound exposure. CONCLUSION: No increase in clot lysis was achieved using thick-shelled MBs as demonstrated by no significant change in clot mass or upstream pressure. Although thick-shelled MBs are promising for targeting and drug delivery, they do not enhance clot lysis when considering the ultrasound sequences used in this study. On the other hand, ultrasound in combination with thin-shelled MBs can facilitate thrombolysis when applying long ultrasound pulses with low pressure.

Occurrence of canine and feline lungworms in Arion vulgaris in a park of Vienna: First report of autochthonous Angiostrongylus vasorum, Aelurostrongylus abstrusus and Troglostrongylus brevior in Austria.

So far, neither the feline lungworms Aelurostrongylus abstrusus and Troglostrongylus brevior nor the canine lungworm Angiostrongylus vasorum was reported in wildlife or intermediate hosts from Austria. The slug Arion vulgaris represents an invasive species in Europe and serves as intermediate host for several lungworm species. This study aimed to analyse the occurrence of metastrongyloid lungworm larvae in slugs in Vienna, Austria. Therefore, 193 A. vulgaris were collected in the central Prater park in summer 2016. Specimens were artificially digested, analysed microscopically for lungworm larvae, and species were confirmed via PCR and sequencing. Out of 193, five slugs were positive to lungworms (2.6%), one for A. vasorum, two for A. abstrusus (genotypes A and B) and one for T. brevior, and one slug had a mixed infection of A. abstrusus and T. brevior larvae. The current study is the first evidence on the endemicity of these metastrongyloid lungworm species in Austria.

Fatal pulmonary hemorrhage in a horse during bronchoalveolar lavage - single case report.

BACKGROUND: Pulmonary hemorrhage is a rare cause of death in horses. Hemorrhage within the respiratory tract has many causes, including mycosis of the guttural pouch, invasive procedures causing serious trauma to nasal conchae, or lung biopsy. We report on a rare case of a fatal pulmonary hemorrhage in a horse after a severe cough during bronchoalveolar lavage. To the best of our knowledge, this is the first report of spontaneous hemorrhage in a horse during bronchoalveolar lavage. CASE PRESENTATION: A 21-year-old mare which belonged to the didactic herd of The Faculty of Veterinary Medicine underwent BAL procedure for training purposes. Clinical examination prior to the procedure did not reveal any abnormalities and the horse had been classified as healthy. The horse was sedated with 0.01 mg/kg of detomidine and 0.01 mg/kg of butorphanol. The silicon BAL catheter was passed through the nasal passage into the trachea and then into the bronchus. Before catheter was wedged, the mare began to cough heavily and massive haemorrhage from mouth and nostrils occurred. Despite fluid therapy, shock occurred within 15 min and the mare was euthanized. Upon necropsy, site of hemorrhage was identified in the left lobar caudal bronchi, from a large blood vessel running directly beneath the bronchial wall. Upon histology, a chronic lympho-plasmocytic inflammatory process in left bronchi was identified. Moreover, Masson's trichrome staining revealed severe, perivascular fibrosis. CONCLUSION: Although BAL is a relatively safe procedure, and such complications should be treated as extremely rare, this case indicates that, in some individuals with specific subclinical problems, even mild physical force such as a cough can lead to rupture of the artery.

Novel approach to study gastropod-mediated innate immune reactions against metastrongyloid parasites.

The anthropozoonotic metastrongyloid nematodes Angiostrongylus cantonensis and Angiostrongylus costaricensis, as well as Angiostrongylus vasorum, Crenosoma vulpis, Aelurostrongylus abstrusus and Troglostrongylus brevior are currently considered as emerging gastropod-borne parasites and have gained growing scientific attention in the last years. However, the knowledge on invertebrate immune responses and on how metastrongyloid larvae are attacked by gastropod immune cells is still limited. This work aims to describe an in vitro system to investigate haemocyte-derived innate immune responses of terrestrial gastropods induced by vital axenic metastrongyloid larvae. We also provide protocols on slug/snail management and breeding under standardized climate conditions (circadian cycle, temperature and humidity) for the generation of parasite-free F0 stages which are essential for immune-related investigations. Adult slug species (Arion lusitanicus, Limax maximus) and giant snails (Achatina fulica) were maintained in fully automated climate chambers until mating and production of fertilized eggs. Newly hatched F0 juvenile specimens were kept under parasite-free conditions before experimental use. An improved protocol for gastropod haemolymph collection and haemocyte isolation was established. Giemsa-stained haemolymph preparations showed adequate haemocyte isolation in all three gastropod species. Additionally, a protocol for the production of axenic first and third stage larvae (L1, L3) was established. Haemocyte functionality was tested in haemocyte-nematode-co-cultures. Scanning electron microscopy (SEM) and light microscopy analyses revealed that gastropod-derived haemocytes formed clusters as well as DNA-rich extracellular aggregates catching larvae and decreasing their motility. These data confirm the usefulness of the presented methods to study haemocyte-mediated gastropod immune responses to better understand the complex biology of gastropod-borne diseases.

Prion propagation and toxicity in vivo occur in two distinct mechanistic phases.

Mammalian prions cause fatal neurodegenerative conditions including Creutzfeldt-Jakob disease in humans and scrapie and bovine spongiform encephalopathy in animals. Prion infections are typically associated with remarkably prolonged but highly consistent incubation periods followed by a rapid clinical phase. The relationship between prion propagation, generation of neurotoxic species and clinical onset has remained obscure. Prion incubation periods in experimental animals are known to vary inversely with expression level of cellular prion protein. Here we demonstrate that prion propagation in brain proceeds via two distinct phases: a clinically silent exponential phase not rate-limited by prion protein concentration which rapidly reaches a maximal prion titre, followed by a distinct switch to a plateau phase. The latter determines time to clinical onset in a manner inversely proportional to prion protein concentration. These findings demonstrate an uncoupling of infectivity and toxicity. We suggest that prions themselves are not neurotoxic but catalyse the formation of such species from PrP(C). Production of neurotoxic species is triggered when prion propagation saturates, leading to a switch from autocatalytic production of infectivity (phase 1) to a toxic (phase 2) pathway.

A novel prion disease associated with diarrhea and autonomic neuropathy.

BACKGROUND: Human prion diseases, although variable in clinicopathological phenotype, generally present as neurologic or neuropsychiatric conditions associated with rapid multifocal central nervous system degeneration that is usually dominated by dementia and cerebellar ataxia. Approximately 15% of cases of recognized prion disease are inherited and associated with coding mutations in the gene encoding prion protein (PRNP). The availability of genetic diagnosis has led to a progressive broadening of the recognized spectrum of disease. METHODS: We used longitudinal clinical assessments over a period of 20 years at one hospital combined with genealogical, neuropsychological, neurophysiological, neuroimaging, pathological, molecular genetic, and biochemical studies, as well as studies of animal transmission, to characterize a novel prion disease in a large British kindred. We studied 6 of 11 affected family members in detail, along with autopsy or biopsy samples obtained from 5 family members. RESULTS: We identified a PRNP Y163X truncation mutation and describe a distinct and consistent phenotype of chronic diarrhea with autonomic failure and a length-dependent axonal, predominantly sensory, peripheral polyneuropathy with an onset in early adulthood. Cognitive decline and seizures occurred when the patients were in their 40s or 50s. The deposition of prion protein amyloid was seen throughout peripheral organs, including the bowel and peripheral nerves. Neuropathological examination during end-stage disease showed the deposition of prion protein in the form of frequent cortical amyloid plaques, cerebral amyloid angiopathy, and tauopathy. A unique pattern of abnormal prion protein fragments was seen in brain tissue. Transmission studies in laboratory mice were negative. CONCLUSIONS: Abnormal forms of prion protein that were found in multiple peripheral tissues were associated with diarrhea, autonomic failure, and neuropathy. (Funded by the U.K. Medical Research Council and others.).

Analysis of polyvinyl alcohol microbubbles in human blood plasma using capillary electrophoresis.

Recently, a new type of ultrasound contrast agent that consists of air-filled microbubbles stabilized with a shell of polyvinyl alcohol was developed. When superparamagnetic nanoparticles of iron oxide are incorporated in the polymer shell, a multimodal contrast agent can be obtained. The biodistribution and elimination pathways of the polyvinyl alcohol microbubbles are essential to investigate, which is limited with today's techniques. The aim of the present study was, therefore, to develop a method for qualitative and quantitative analysis of microbubbles in biological samples using capillary electrophoresis with ultraviolet detection. The analysis parameters were optimized to a wavelength at 260 nm and pH of the background electrolyte ranging between 11.9 and 12. Studies with high-intensity ultrasonication degraded microbubbles in water showed that degraded products and intact microbubbles could be distinguished, thus it was possible to quantify the intact microbubbles solely. Analysis of human blood plasma spiked with either plain microbubbles or microbubbles with nanoparticles demonstrated that it is possible to separate them from biological components like proteins in these kinds of samples.

The potential clinical value of contrast-enhanced echocardiography beyond current recommendations.

BACKGROUND: Contrast agents are used in resting echocardiography to opacify the left ventricular (LV) cavity and to improve LV endocardial border delineation in patients with suboptimal image quality. If a wider use of contrast-enhanced echocardiography would be adopted instead of the current selective approach, diagnoses such as myocardial ischemia and LV structural abnormalities could potentially be detected earlier. The aim was therefore to retrospectively investigate if contrast-enhanced echocardiography beyond the current recommendations for contrast agent usage affects assessment of wall motion abnormalities, ejection fraction (EF) and detection of LV structural abnormalities. A secondary aim was to evaluate the user dependency during image analysis. METHODS: Experienced readers (n = 4) evaluated wall motion score index (WMSI) and measured EF on greyscale and contrast-enhanced images from 192 patients without indications for contrast-enhanced echocardiography. Additionally, screening for LV structural abnormalities was performed. Repeated measurements were performed in 20 patients by the experienced as well as by inexperienced (n = 2) readers. RESULTS: Contrast analysis resulted in significantly higher WMSI compared to greyscale analysis (p < 0.003). Of the 83 patients, classified as healthy by greyscale analysis, 55% were re-classified with motion abnormalities by contrast analysis. No significant difference in EF classification (≥55%, 45-54%, 30-44%, < 30%) was observed. LV structural abnormalities, such as increased trabeculation (n = 21), apical aneurysm (n = 4), hypertrophy (n = 1) and thrombus (n = 1) were detected during contrast analysis. Intra- and interobserver variability for experienced readers as well as the variability between inexperienced and experienced readers decreased for WMSI and EF after contrast analysis. CONCLUSIONS: Contrast-enhanced echocardiography beyond current recommendations for contrast agent usage increased the number of detected wall motion and LV structural abnormalities. Moreover, contrast-enhanced echocardiography increased reproducibility for assessment of WMSI and EF.

N-terminal domain of prion protein directs its oligomeric association.

The self-association of prion protein (PrP) is a critical step in the pathology of prion diseases. It is increasingly recognized that small non-fibrillar ß-sheet-rich oligomers of PrP may be of crucial importance in the prion disease process. Here, we characterize the structure of a well defined ß-sheet-rich oligomer, containing ∼12 PrP molecules, and often enclosing a central cavity, formed using full-length recombinant PrP. The N-terminal region of prion protein (residues 23-90) is required for the formation of this distinct oligomer; a truncated form comprising residues 91-231 forms a broad distribution of aggregated species. No infectivity or toxicity was found using cell and animal model systems. This study demonstrates that examination of the full repertoire of conformers and assembly states that can be accessed by PrP under specific experimental conditions should ideally be done using the full-length protein.