Lipoprotein (a) Lp(a) serum levels are highly genetically determined and promote atherogenesis. High Lp(a) levels are associated with increased cardiovascular morbidity. Serum Lp(a) levels have ...recently been associated with large artery atherosclerosis (LAA) stroke. We aimed to externally validate this association in an independent cohort.
This study stems from the prospective multicentre CoRisk study (CoPeptin for Risk Stratification in Acute Stroke patients NCT00878813), conducted at the University Hospital Bern, Switzerland, between 2009 and 2011, in which Lp(a) plasma levels were measured within the first 24 hours after stroke onset. We assessed the association of Lp(a) with LAA stroke using multivariable logistic regression and performed interaction analyses to identify potential effect modifiers.
Of 743 patients with ischaemic stroke, 105 (14%) had LAA stroke aetiology. Lp(a) levels were higher for LAA stroke than non-LAA stroke patients (23.0 nmol/l vs 16.3 nmol/l, p = 0.01). Multivariable regression revealed an independent association of log10and#xA0;Lp(a) with LAA stroke aetiology (aOR 1.47 95% CI 1.03and#x2013;2.09, p = 0.03). The interaction analyses showed that Lp(a) was not associated with LAA stroke aetiology among patients with diabetes.
In a well-characterised cohort of patients with ischaemic stroke, we validated the association of higher Lp(a) levels with LAA stroke aetiology, independent of traditional cardiovascular risk factors. These findings may inform randomised clinical trials investigating the effect of Lp(a) lowering agents on cardiovascular outcomes. The CoRisk (CoPeptin for Risk Stratification in Acute Patients) study is registered on ClinicalTrials.gov.
NCT00878813.
Simultaneous motor-cognitive training is considered promising for preventing the decline in cognitive functioning in older adults with mild neurocognitive disorder (mNCD) and can be highly motivating ...when applied in the form of exergaming. The literature points to opportunities for improvement in the application of exergames in individuals with mNCD by developing novel exergames and exergame-based training concepts that are specifically tailored to patients with mNCD and ensuring the implementation of effective training components.
This study systematically explores the effectiveness of a newly developed exergame-based motor-cognitive training concept (called "Brain-IT") targeted to improve cognitive functioning in older adults with mNCD.
A 2-arm, parallel-group, single-blinded randomized controlled trial with a 1:1 allocation ratio (ie, intervention: control), including 34 to 40 older adults with mNCD will be conducted between May 2022 and December 2023. The control group will proceed with the usual care provided by the (memory) clinics where the patients are recruited. The intervention group will perform a 12-week training intervention according to the "Brain-IT" training concept, in addition to usual care. Global cognitive functioning will be assessed as the primary outcome. As secondary outcomes, domain-specific cognitive functioning, brain structure and function, spatiotemporal parameters of gait, instrumental activities of daily living, psychosocial factors, and resting cardiac vagal modulation will be assessed. Pre- and postintervention measurements will take place within 2 weeks before starting and after completing the intervention. A 2-way analysis of covariance or the Quade nonparametric analysis of covariance will be computed for all primary and secondary outcomes, with the premeasurement value as a covariate for the predicting group factor and the postmeasurement value as the outcome variable. To determine whether the effects are substantive, partial eta-squared (η
) effect sizes will be calculated for all primary and secondary outcomes.
Upon the initial submission of this study protocol, 13 patients were contacted by the study team. Four patients were included in the study, 2 were excluded because they were not eligible, and 7 were being informed about the study in detail. Of the 4 included patients, 2 already completed all premeasurements and were in week 2 of the intervention period. Data collection is expected to be completed by December 2023. A manuscript of the results will be submitted for publication in a peer-reviewed open-access journal in 2024.
This study contributes to the evidence base in the highly relevant area of preventing disability because of cognitive impairment, which has been declared a public health priority by the World Health Organization.
ClinicalTrials.gov NCT05387057; https://clinicaltrials.gov/ct2/show/NCT05387057.
DERR1-10.2196/41173.
Summary Focal cortical dysplasias (FCDs) represent a prominent cause of pharmacologically intractable epilepsy. In FCD, the decrease of parvalbumin immunoreactive (PV+) inhibitory interneurons has ...been repeatedly documented. Here, we wanted to show whether another interneuronal population, the calretinin immunoreactive (CR+) neurons, exhibits any change in human FCD. We also investigated samples of morphologically normal temporal neocortex resected together with sclerotic hippocampus (nHSTN), where decrease of PV+ interneurons was previously documented as well. Brain tissue from 24 patients surgically treated for pharmacoresistant epilepsy was examined. Calretinin immunoreactivity was qualitatively evaluated and the density of CR+ neuronal profiles was quantified. As a control, post-mortem acquired neocortical samples of nine patients without any brain affecting disease were used. CR+ neurons were located predominantly in superficial cortical layers both in controls and pathological samples. Similarly, the morphology of CR+ neurons was unaffected in pathological samples. The overall density of CR+ neurons was significantly decreased in FCD type I (to approximately 70% of control values) and even more in FCD type II (to approximately 50% of controls). In nHSTN, no change compared to controls was found in CR+ neuronal density. Our results may contribute to the better understanding of the role of individual interneuronal populations in epileptogenesis.
...two genetically engineered mouse lines were crossed: a Cre-dependent reporter mouse line expressing the red fluorescent protein tdTomato (tdTom) with a CR-ires-Cre mouse line, which expresses the ...enzyme Cre-recombinase in a fashion similar to endogenous CR expression. ...the exclusive expression of CR or PV (but never both of them) in adult cortical neurons well-known across all studied species including mouse (Xu et al., 2010) seems to be also valid during the ontogeny of the cortical neurons in the mouse visual cortex. ...coming back to the VRPs of tdTom+ cells, it has to be acknowledged that the heterogeneity of the tdTom+ population (transitory CR+ pyramidal neurons and adult CR+ interneurons) complicates the interpretation of the results with regard to the VRPs of these cells. GABAergic neurons are less selective to stimulus orientation than excitatory neurons in layer II/III of visual cortex, as revealed by in vivo functional Ca2+ imaging in transgenic mice.
It is in general well appreciated that the cortical interneurons play various important roles in cortical neuronal networks both in normal and pathological states. Based on connectivity pattern, ...developmental, morphological and electrophysiological properties, distinct subgroups of GABAergic interneurons can be differentiated in the neocortex as well as in the hippocampal formation. In this E-Book, we are focusing our attention on inhibitory interneurons expressing calcium-binding protein calretinin (CR). The aim of the E-Book is to consolidate the knowledge about this interneuronal population and to inspire further research on the function and malfunction of these neurons, which – functionally – seem to stand "at the top of the pyramid" of cortical interneuronal types.
In this prospective study, we aimed to assess the haemodynamic changes before and after haemodialysis (HD) in cardiac healthy subjects on chronic HD by imaging methods and endocrine markers of fluid ...balance.
Mid-regional pro-atrial natriuretic peptide (MR-proANP), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), vasopressin (AVP) and copeptin (CT-proAVP), metanephrines and normetanephrines, renin and aldosterone, standard transthoracic echocardiography and diameter of vena cava inferior (VCID) were performed in 20 patients with end stage renal disease (CKD5D) before and after HD and were stratified in residual excretion (RE, less or more 0.5 l) and ultrafiltration rate (UF, less or more 2 l).
Copeptin was significantly higher in patients before HD. Copeptin was inversely correlated with haemodialysis treatment adequacy (KT/v), RE and UF, but was not significantly influenced by age, gender and body mass index (BMI). MR-proANP was significantly reduced by haemodialysis by 27% and was inversely correlated with KT/v, but there was a significant influence by UF, RE, age, gender and BMI. NT-proBNP was significantly higher in patients before HD and was not influenced by RE and UF. Renin, aldosterone, metanephrines and normetanephrines did not demonstrate significant differences. Echocardiographic parameters and VCID were significantly correlated with RE, UF and copeptin.
Modern biomarkers will provide cardiovascular risk assessment, but elimination (UF), RE and other factors may influence the serum concentrations, e.g. in patients with renal impairment. The interpretation will be limited by altered reference ranges, and will be restricted to individual courses combined with clinical and echocardiographic data.
Abstract Expression of urokinase-type plasminogen activator (uPA) is increased after brain injury, suggesting that, like in cancer tissue, uPA plays roles in brain remodeling. Here we injured brain ...with intrahippocampal kainic acid (KA) injection in adult Wt and uPA−/− mice. At 20 days post-injury, uPA−/− mice had more severe loss of contralateral pyramidal ( p < 0.05) and hilar neurons ( p < 0.05) than Wt mice. The number of doublecortin (DCX)-positive newly born neurons was also reduced in uPA−/− mice as compared to Wt ( p < 0.01). No difference was observed in granule cell dispersion or distribution of DCX-positive neurons in the dentate gyrus. uPA deficiency did not affect the total length of hippocampal blood vessels or vessel density. No differences were observed in the severity of status epilepticus or consequent epilepsy between the genotypes. These data indicate that uPA deficiency can unfavorably modulate both delayed neurodegeneration and neurogenesis but has little effect on post-injury neuronal migration and vascular density. Our results favor the idea that elevated uPA during the post-injury phase is neuroprotective.
The main aim was to describe interneuronal population expressing calcium binding proteins calretinin (CR) and parvalbumin (PV) in the perirhinal (PRC) and retrosplenial (RSC) cortex of the rat. These ...two cortical areas differ strikingly in their connectivity and function, which could be caused also by different structure of the interneuronal populations. Having a precise knowledge of the cellular composition of any cerebral area forms one of the basic input parameters and tenets for computational modelling of neuronal networks and for understanding some pathological conditions, like generating and spreading of epileptic activity. PRC possesses higher absolute and relative densities of CR+ and PV+ neurons than RSC, but the CR : PV ratio is higher in the RSC, which is similar to the neocortex. The bipolar/bitufted neurons are most common type of CR+ population, while the majority of PV+ neurons show multipolar morphology. Current results indicate that main difference between analysed areas is in density of CR+ neurons, which was significantly higher in the PRC. Our results coupled with works of other authors show that there are significant differences in the interneuronal composition and distribution of heretofore seemingly similar transitional cortical areas. These results may contribute to the better understanding of the mechanism of function of this cortical region in normal and diseased states.
The mild behavioral impairment (MBI) syndrome is defined by the emergence in later life of persistent neuropsychiatric symptoms. The MBI checklist (MBI-C) can be used for systematic detection and ...documentation of such symptoms.
Development of a German version of the MBI‑C and assessment of its application in a clinical setting.
The MBI‑C was translated from English into German in collaboration with the main author of the original version, and its practical application was then tested on a study population (n = 21) in a gerontopsychiatric inpatient clinic. Patient compliance, understanding of questions, time effort, evaluation procedure and possible discrepancy between patient and family member evaluations were assessed.
The German translation of the original MBI‑C obtained certification as an official version and can be downloaded at https://mbitest.org . All 34 questions were fully completed by the study population, the level of understanding of questions was good, with the mean time effort being 16 min. In some cases, significant differences between patients' and family members' responses were found.
The presence of MBI may indicate the development of an otherwise presymptomatic neurodegenerative dementia syndrome. Hence, the MBI‑C could aid in the early detection of neurodegenerative dementia. By means of the translated version of the MBI‑C presented in this study, this hypothesis can now be tested in German-speaking countries.
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