Konzentrische Sklerose Baló - eine differentialdiagnostische Betrachtung anhand von bildmorphologischen Kriterien von 7 Tesla Magnetresonanztomographie Aufnahmen und klinischen Gesichtspunkten im Vergleich zu Multipler Sklerose

Hintergrund: Die Konzentrische Sklerose Baló (Baló concentric sclerosis, BCS) ist eine seltene, atypisch demyelinisierende Erkrankung, die durch Läsionen der weißen Substanz mit alternierenden Schichten von hoher und geringer Signalintensität in der Magnetresonanztomographie (MRT) gekennzeichnet ist. Bisher wurde angenommen, dass BCS eine Variante der Multiplen Sklerose (MS) ist. Des Weiteren wird vermutet, dass neben der BCS Läsion auftretende MS typische Läsionen einen Hinweis auf weitere Krankheitsaktivität geben. Ziel dieser Arbeit ist es, die Ähnlichkeiten und Unterschiede zwischen BCS und MS durch Beschreibung der Läsionsmorphologie und -lokalisierung in hochauflösenden 7 Tesla (7T) MRT Scans darzustellen. Außerdem wird von den charakteristischen klinischen Verläufen von BCS Patienten berichtet und diese mit denen von MS Patienten verglichen, um die bisherigen Annahmen einer Zuordnung zur MS wissenschaftlich zu prüfen und bildmorphologische Parameter zum prospektiv beobachteten klinischen und paraklinischen Krankheitsverlauf zu untersuchen und zu vergleichen. Methoden: Zehn Patienten mit Läsionen vom Baló-Typ und zehn Patienten mit schubförmig remittierender MS erhielten eine 7T MRT Untersuchung. Zusätzlich wurden neun BCS Patienten mittels 3T MRT untersucht und bei vier von diesen erfolgte ein 3T MRT Follow-up nach einem Jahr. Des Weiteren wurden von allen Patienten klinische Daten erhoben. Ergebnisse: In neun von zehn Baló-Typ Läsionen waren im Zentrum intraläsionale Venen zu finden. Im Gegensatz zu den MS Läsionen konnten in vier Läsionen vom Baló-Typ inhomogene intraläsionale T2*w-Signalintensitäten gefunden werden, welche auf Mikroblutungen oder kleine ektatische Venulen hindeuten. Neben der Baló-Typ Läsion konnten in acht von zehn BCS-Patienten 97 weitere Läsionen gefunden werden, von denen 36 (37%) eine zentrale Vene hatten und damit MS typisch sind. Im Gegensatz dazu wiesen 77% aller MS Läsionen eine zentrale Vene auf. Bei BCS Patienten wurden im Vergleich zu MS Patienten keine Läsionen der kortikalen grauen Substanz und der U-Faser festgestellt. Vier von zehn BCS Patienten erfüllten die MS Kriterien nach McDonald, wobei alle drei BCS Patienten mit schubförmigen Verlauf enthalten waren. Schlussfolgerung: Die Ergebnisse zeigen Gemeinsamkeiten, aber auch starke bildmorphologische und klinische Unterschiede von BCS und MS. Die zentrale Vene, die sowohl in Baló-Typ Läsionen als auch in MS Läsionen zu finden ist, spricht für eine mögliche ähnliche pathophysiologische Initiierung der entzündlichen Läsionen. Die Läsionsausbreitung ist jedoch verschieden. Eine mögliche Hypothese für diese aufgewiesenen Ähnlichkeiten sowie auch differenten Läsionen kann die Hypoxie-induzierte Gewebsverletzung sein, welche die Läsionsmorphologie von MS in BCS Läsionen transformieren kann. Des Weiteren könnten erfüllte MS Kriterien nach McDonald bei BCS Patienten ein möglicher Indikator für weitere Krankheitsaktivität sein.Background: Concentric sclerosis Baló (Baló concentric sclerosis, BCS) is a rare, atypical demyelinating disease characterized by white matter lesions of the cortex with alternating layers of high and low signal intensity in magnetic resonance imaging (MRI). So far, it has been assumed that BCS is a variant of multiple sclerosis (MS). Furthermore, it is suggested that typical MS lesions in addition to the BCS lesion give an indication of further disease activity. The aim of this work is to demonstrate the similarities and differences between BCS and MS by describing the lesion morphology and localization in high resolution 7 Tesla (7T) MRI scans. In addition, clinical courses of BCS are reported and compared with those of MS patients to validate previous assumptions of association with MS and to examine and compare morphological parameters of the prospectively observed clinical and paraclinical disease course. Methods: Ten patients with Baló-type lesions and ten patients with relapsing-remitting MS received a 7T MRI scan. In addition, nine BCS patients were examined by 3T MRI and four of these were followed up at one year. Furthermore, clinical data were collected from all patients. Results: In nine of ten Baló-type lesions intralesional veins were found in the center. In contrast to the MS lesions, inhomogeneous intralesional T2*w signal intensities were found in four lesions of the Baló type, indicating microhemorrhages or small ectatic venules. In addition to the Baló-type lesion, 97 additional lesions were found in eight out of ten BCS patients, of which 36 (37%) had a central vein and are therefore typical of MS. In contrast, 77% of all MS lesions had a central vein. In BCS patients, no lesions of cortical gray matter and U-fiber were detected compared to MS patients. Four of ten BCS patients met McDonald's MS criteria, with all three BCS patients being relapsing-remitting. Conclusion: The results show similarities, but also strong morphological and clinical differences between BCS and MS. The central vein, which can be found both in Baló-type lesions and in MS lesions, suggests a possible similar pathophysiological initiation of the lesions. However, the spread of lesions is different. A possible hypothesis for these demonstrated similarities as well as different lesions may be hypoxia-induced tissue injury, which may transform the lesion morphology of MS into BCS lesions. In addition, fulfilled McDonald MS criteria in BCS patients may be a possible indicator of further disease activity

Energy Requirement and Food Intake Behaviour in Young Adult Intact Male Cats with and without Predisposition to Overweight

Obesity is a common problem in cats. In the experimental cat family of the institute of animal nutrition besides a “normal” lean phenotype, cats with predisposition to an overweight phenotype are present. To investigate energy requirements and food intake behaviour of intact male cats of different phenotypes, six “normal” lean cats (GL) and six cats disposed to overweight (GO) were used. At the beginning of the experiment, all cats had an ideal body condition score of 5. To reach this the GO cats had to pass a weight-loss program. Energy requirements of the cats were determined using respiration chambers, whereas the amount and frequency of food intake was measured with a feeding station recording the data automatically. Energy requirement at weight constancy of the GO cats was even on fat-free mass (FFM) significantly (P = 0.02) lower (162.6 kJ/kg FFM/d) than that of the “normal” lean cats (246 kJ/kg FFM/d). The GO cats also showed a higher food intake 34.5 ± 1.5 g dry matter/kg body weight0.67 compared to the GL cats (24.0 ± 2.1 g dry matter/kg body weight0.67)(P = 0.001). In conclusion quantifiable differences in food intake and behaviour in cats predisposed to overweight compared to “normal” lean cats were found

Pediatric asthma attack and home paint exposure

Although asthma mortality has been declining for the past several decades, asthma mor-bidity is on the rise, largely due to deteriorating indoor air quality and comorbidities, such as aller-gies. Consumer products and building materials including paints emit volatile organic compounds (VOCs), such as propylene glycol (PG), which is shown to dehydrate respiratory tracts and can con-tributor to airway remodeling. We hypothesize that paint exposure increases the risk of asthma attacks among children because high levels of VOCs persist indoors for many weeks after painting. Children 1–15 years old visiting two of the University of Miami general pediatric clinics were screened for their history of asthma and paint exposure by interviewing their parents and/or guard-ians accompanying them to the clinic. They were also asked questions about asthma diagnosis, severity of asthma and allergies and their sociodemographics. The risk of asthma attack among asthmatic children was modeled with respect to paint exposure adjusting for potential confounders using multivariate logistic regressions. Of 163 children, 36 (22%) reported physician-diagnosed asthma and of these, 13 (33%) had an asthma attack during the last one year. Paint exposure was marginally significant in the univariate analysis (OR = 4.04; 95% CI = 0.90–18.87; p \u3c 0.1). However, exposed asthmatic children were 10 times more likely to experience an asthma attack than unex-posed asthmatic children (OR = 10.49; CI = 1.16–94.85, p \u3c 0.05) when adjusted for other risk factors. Given paint is one of the sources of indoor VOCs, multiple strategies are warranted to manage the health effects of VOC exposure from paint, including the use of zero-VOC water-based paint, exposure avoidance and clinical interventions

7 Tesla MRI of Balo's concentric sclerosis versus multiple sclerosis lesions

Background: Baló’s concentric sclerosis (BCS) is a rare condition characterized by concentrically layered white matter lesions. While its pathogenesis is unknown, hypoxia-induced tissue injury and chemotactic stimuli have been proposed as potential causes of BCS lesion formation. BCS has been suggested to be a variant of multiple sclerosis (MS). Here, we aimed to elucidate similarities and differences between BCS and MS by describing lesion morphology and localization in high-resolution 7 Tesla (7 T) magnetic resonance imaging (MRI) scans. Methods: Ten patients with Baló-type lesions underwent 7 T MRI, and 10 relapsing remitting MS patients served as controls. The 7 T MR imaging protocol included 3D T1-weighted (T1w) magnetization-prepared rapid gradient echo, 2D high spatial resolution T2*-weighted (T2*w) fast low-angle shot and susceptibility-weighted imaging. Results: Intralesional veins were visible in the center of all but one Baló-type lesion. Four Baló-type lesions displayed inhomogeneous intralesional T2*w signal intensities, which are suggestive of microhemorrhages or small ectatic venules. Eight of 10 BCS patients presented with 97 additional lesions, 36 of which (37%) had a central vein. Lesions involving the cortical gray matter and the U-fibers were not detected in BCS patients. Conclusion: Our findings support the hypothesis that BCS and MS share common pathogenetic mechanisms but patients present with different lesion phenotypes

Moderating Readers and Reading Online

Despite the proliferation of online forums for the discussion of literary texts, very little has been written to date on the management of these spaces and how this helps frame the kinds of discussion and interpretative work that take place. This article draws on a series of interviews with moderators of online book-related sites, alongside close analysis of online interactions between moderators and users to consider issues of authority, hierarchy, power and control, asking how these act to structure or facilitate acts of interpretation taking place online. We begin by outlining the moderator's role before conducting a brief review of existing scholarship on offline reading groups and online communities, to identify how social infrastructures are established and negotiated. The main body of the article draws upon interviews with moderators of two online literary forums – The Republic of Pemberley and The Guardian’s online Reading Group – to explore the ways in which each of the respective moderators frames his or her role. This is accompanied by an in-depth exploration of how the forms of interpretation we find on the two sites are shaped and directed by the moderators. The article concludes by reflecting upon some of the issues raised by this study and its methodology, particularly with regards to digital dualism and the blurring of the boundaries between the public and the private in online spaces

Keep It Real: Selecting Realistic Sets of Urban Green Space Indicators

With increasing urbanisation, urban green spaces are expected to be crucial for urban resilience and sustainability, through the delivery of ecological, economic and social benefits. In practice, however, planning, management and evaluation of urban green spaces are rarely structured and evidence-based. This represents a missed opportunity to account for, track and foster the multiple benefits that green spaces are expected to deliver. To gain insight into this gap, this study assesses the availability and uptake of relevant evidence by city governments. Interviews, focus groups and quantitative surveys were applied in four medium-sized European cities: Coimbra (Portugal), Genk (Belgium), Leipzig (Germany), and Vilnius (Lithuania), covering the main governance and climatic gradients in Europe. Using straightforward data exploration and regression, we analyse which ecological, economic and social indicators are typically chosen by cities and why. Together with the city stakeholders, we derived a common set of benefit categories and key performance indicators which can be adapted to diverse local contexts. We conclude that cities tend to make pragmatic decisions when composing their indicator sets, but nevertheless cover multiple urban green space dimensions. Finally, we explore how indicator choice could be optimised towards a complementary and credible indicator set, taking into account a realistically feasible monitoring effort undertaken by the cities

Exposure and Effect Assessment of Aerosolized Red Tide Toxins (Brevetoxins) and Asthma

addresses: National Science Foundation National Institute of Environmental Health Sciences Oceans and Human Health Center, University of Miami Rosenstiel School of Marine and Atmospheric Sciences, Miami, Florida 33136, USA. [email protected]: PMCID: PMC2717136types: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.'Reproduced with permission from Environmental Health Perspectives'Copyright © 2009 National Institute of Environmental Health SciencesIn previous studies we demonstrated statistically significant changes in reported symptoms for lifeguards, general beach goers, and persons with asthma, as well as statistically significant changes in pulmonary function tests (PFTs) in asthmatics, after exposure to brevetoxins in Florida red tide (Karenia brevis bloom) aerosols

Serum amyloid A: high-density lipoproteins interaction and cardiovascular risk

Aims High-density lipoproteins (HDLs) are considered as anti-atherogenic. Recent experimental findings suggest that their biological properties can be modified in certain clinical conditions by accumulation of serum amyloid A (SAA). The effect of SAA on the association between HDL-cholesterol (HDL-C) and cardiovascular outcome remains unknown. Methods and results We examined the association of SAA and HDL-C with mortality in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study, which included 3310 patients undergoing coronary angiography. To validate our findings, we analysed 1255 participants of the German Diabetes and Dialysis study (4D) and 4027 participants of the Cooperative Health Research in the Region of Augsburg (KORA) S4 study. In LURIC, SAA concentrations predicted all-cause and cardiovascular mortality. In patients with low SAA, higher HDL-C was associated with lower all-cause and cardiovascular mortality. In contrast, in patients with high SAA, higher HDL-C was associated with increased all-cause and cardiovascular mortality, indicating that SAA indeed modifies the beneficial properties of HDL. We complemented these clinical observations by in vitro experiments, in which SAA impaired vascular functions of HDL. We further derived a formula for the simple calculation of the amount of biologically ‘effective' HDL-C based on measured HDL-C and SAA from the LURIC study. In 4D and KORA S4 studies, we found that measured HDL-C was not associated with clinical outcomes, whereas calculated ‘effective' HDL-C significantly predicted better outcome. Conclusion The acute-phase protein SAA modifies the biological effects of HDL-C in several clinical conditions. The concomitant measurement of SAA is a simple, useful, and clinically applicable surrogate for the vascular functionality of HD

Trends in Mortality Due to Myocardial Infarction, Stroke, and Pulmonary Embolism in Patients Receiving Dialysis

IMPORTANCE During the past decades, improvements in the prevention and management of myocardial infarction, stroke, and pulmonary embolism have led to a decline in cardiovascular mortality in the general population. However, it is unknown whether patients receiving dialysis have also benefited from these improvements. OBJECTIVE To assess the mortality rates for myocardial infarction, stroke, and pulmonary embolism in a large cohort of European patients receiving dialysis compared with the general population. DESIGN, SETTING, AND PARTICIPANTS In this cohort study, adult patients who started dialysis between 1998 and 2015 from 11 European countries providing data to the European Renal Association Registry were and followed up for 3 years. Data were analyzed from September 2020 to February 2022. EXPOSURES Start of dialysis. MAIN OUTCOMES AND MEASURES The age- and sex-standardized mortality rate ratios (SMRs) with 95% CIs were calculated by dividing the mortality rates in patients receiving dialysis by the mortality rates in the general population for 3 equal periods (1998-2003, 2004-2009, and 2010-2015). RESULTS In total, 220 467 patients receiving dialysis were included in the study. Their median (IQR) age was 68.2 (56.5-76.4) years, and 82 068 patients (37.2%) were female. During follow-up, 83 912 patients died, of whom 7662 (9.1%) died because of myocardial infarction, 5030 (6.0%) died because of stroke, and 435 (0.5%) died because of pulmonary embolism. Between the periods 1998 to 2003 and 2010 to 2015, the SMR of myocardial infarction decreased from 8.1 (95% CI, 7.8-8.3) to 6.8 (95% CI, 6.5-7.1), the SMR of stroke decreased from 7.3 (95% CI, 7.0-7.6) to 5.8 (95% CI, 5.5-6.2), and the SMR of pulmonary embolism decreased from 8.7 (95% CI, 7.6-10.1) to 5.5 (95% CI, 4.5-6.6). CONCLUSIONS AND RELEVANCE In this cohort study of patients receiving dialysis, mortality rates for myocardial infarction, stroke, and pulmonary embolism decreased more over time than in the general population.Peer reviewe

Evaluation of Variation in the Performance of GFR Slope as a Surrogate End Point for Kidney Failure in Clinical Trials that Differ by Severity of CKD

BACKGROUND: The GFR slope has been evaluated as a surrogate end point for kidney failure in meta-analyses on a broad collection of randomized controlled trials (RCTs) in CKD. These analyses evaluate how accurately a treatment effect on GFR slope predicts a treatment effect on kidney failure. We sought to determine whether severity of CKD in the patient population modifies the performance of GFR slope. METHODS: We performed Bayesian meta-regression analyses on 66 CKD RCTs to evaluate associations between effects on GFR slope (the chronic slope and the total slope over 3 years, expressed as mean differences in ml/min per 1.73 m2/yr) and those of the clinical end point (doubling of serum creatinine, GFR &lt;15 ml/min per 1.73 m2, or kidney failure, expressed as a log-hazard ratio), where models allow interaction with variables defining disease severity. We evaluated three measures (baseline GFR in 10 ml/min per 1.73 m2, baseline urine albumin-to-creatinine ratio [UACR] per doubling in mg/g, and CKD progression rate defined as the control arm chronic slope, in ml/min per 1.73 m2/yr) and defined strong evidence for modification when 95% posterior credible intervals for interaction terms excluded zero. RESULTS: There was no evidence for modification by disease severity when evaluating 3-year total slope (95% credible intervals for the interaction slope: baseline GFR [-0.05 to 0.03]; baseline UACR [-0.02 to 0.04]; CKD progression rate [-0.07 to 0.02]). There was strong evidence for modification in evaluations of chronic slope (95% credible intervals: baseline GFR [0.02 to 0.11]; baseline UACR [-0.11 to -0.02]; CKD progression rate [0.01 to 0.15]). CONCLUSIONS: These analyses indicate consistency of the performance of total slope over 3 years, which provides further evidence for its validity as a surrogate end point in RCTs representing varied CKD populations.</p