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Tactile sensation and vision are often both utilized for the exploration of objects that are within reach though it is not known whether or how these two distinct sensory systems combine such information. Here in mice, we used a combination of stereo photogrammetry for 3D reconstruction of the whisker array, brain-wide anatomical tracing and functional connectivity analysis to explore the possibility of tacto-visual convergence in sensory space and within the circuitry of the primary visual cortex (VISp). Strikingly, we find that stimulation of the contralateral whisker array suppresses visually evoked activity in a tacto-visual sub-region of VISp whose visual space representation closely overlaps with the whisker search space. This suppression is mediated by local fast-spiking interneurons that receive a direct cortico-cortical input predominantly from layer 6 neurons located in the posterior primary somatosensory barrel cortex (SSp-bfd). These data demonstrate functional convergence within and between two primary sensory cortical areas for multisensory object detection and recognition. Where and how the brain integrates discrete sensory inputs is not fully understood. Here authors show that a multisensory zone in the mouse anterior primary visual cortex integrates tactile and visual inputs from a shared sensory space through interareal feedforward inhibition. [ABSTRACT FROM AUTHOR]

Although DNA methylation data yields highly accurate age predictors, little is known about the dynamics of this quintessential epigenomic biomarker during lifespan. To narrow the gap, we investigate the methylation trajectories of male mouse colon at five different time points of aging. Our study indicates the existence of sudden hypermethylation events at specific stages of life. Precisely, we identify two epigenomic switches during early-to-midlife (3-9 months) and mid-to-late-life (15-24 months) transitions, separating the rodents' life into three stages. These nonlinear methylation dynamics predominantly affect genes associated with the nervous system and enrich in bivalently marked chromatin regions. Based on groups of nonlinearly modified loci, we construct a clock-like classifier STageR (STage of aging estimatoR) that accurately predicts murine epigenetic stage. We demonstrate the universality of our clock in an independent mouse cohort and with publicly available datasets. DNA methylation is an age biomarker, but nonlinear aspects of its age-related dynamics are not well characterized. Here, the authors identify loci that undergo sudden methylation changes at specific life stages in the aging colon of male mice. [ABSTRACT FROM AUTHOR]

Copyright of Die Urologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This article compares the long-term outcomes of two different strategies for coronary revascularization: conventional off-pump total arterial revascularization with bilateral internal mammary arteries (BIMA) and hybrid coronary revascularization (HCR). The study retrospectively analyzed patients who received either BIMA (n = 542) or HCR (n = 123) at a single institute. After adjusting for baseline differences, the study found that patients who received BIMA had better 10-year survival and freedom from repeat revascularization compared to those who received HCR. However, the HCR group had a higher incidence of chronic obstructive lung disease, while the BIMA group had a higher incidence of three-vessel coronary artery disease and left main disease. Overall, the study suggests that for otherwise fit patients, conventional off-pump revascularization with BIMA may be the preferred strategy. [Extracted from the article]

This article discusses the use of Minimal Invasive Total Arterial Coronary Artery Bypass Grafting (MICS-CABG) as a surgical approach for treating coronary artery disease in obese patients. The study compared the outcomes of MICS-CABG in obese (BMI >30) and nonobese (BMI<30) patients. The results showed that MICS-CABG is safe and feasible for both obese and nonobese patients, with no significant differences in perioperative and mid-term outcomes. The authors conclude that obesity should not be an exclusion criterion for MICS-CABG in high volume centers. [Extracted from the article]

Aims To examine the diversity of Staphylococcus aureus isolated from nasal swabs of ruminants in Rwanda. Methods and results A total of 454 nasal swabs from 203 cows, 170 goats, and 81 sheep were examined for the presence of S. aureus , and 30 S. aureus isolates were detected and characterized pheno- and genotypically. Resistance to penicillin and/or tetracycline was observed. The isolates were assigned to eight different spa types (t21057 (novel), t10103, t18853, t20842, t318, t355, t458, and t9432) belonging to six clonal complexes (CCs) (CC152, CC30, CC3591, CC3666, CC522, and CC97). Panton–Valentine leukocidin (PVL) genes (lukF-PV/lukS-PV), the bovine leukocidin genes (lukM/lukF-P83), and the human and bovine variants of the toxic shock syndrome toxin gene tst-1 variants were detected. Conclusion These findings demonstrate that the nares of ruminants in Rwanda are colonized with mastitis-associated S. aureus , including lineages that are also carried by humans, underscoring the zoonotic risk, especially for livestock keepers. These results highlight the crucial importance of hygiene measures when handling livestock. [ABSTRACT FROM AUTHOR]

In this randomized controlled intervention trial, we investigated whether intense visual stimulation through television watching can enhance visual information processing and motor learning performance. 74 healthy young adults were trained in a motor skill with visual information processing demands while being accommodated in a controlled environment for five days. The experimental manipulation (n = 37) consisted of prolonged television watching (i.e., 8 h/day, + 62.5% on average) to induce intense exposure to visual stimulation. The control group (n = 37) did not consume visual media. The groups were compared by motor learning performance throughout the study as well as pre/post visual attention parameters and resting-state network connectivity in functional MRI. We found that the intervention group performed significantly better in the motor learning task (+ 8.21% (95%-CI[12.04, 4.31], t(70) = 4.23, p < 0.001) while showing an increased capacity of visual short-term memory (+ 0.254, t(58) = − 3.19, p = 0.002) and increased connectivity between visual and motor-learning associated resting-state networks. Our findings suggest that the human brain might enter a state of accentuated visuomotor integration to support the implementation of motor learning with visual information processing demands if challenged by ample input of visual stimulation. Further investigation is needed to evaluate the persistence of this effect regarding participants exposed to accustomed amounts of visual media consumption. Clinical Trials Registration: This trial was registered in the German Clinical Trials Register/Deutsches Register klinischer Studien (DRKS): DRKS00019955. [ABSTRACT FROM AUTHOR]

Single-cell RNA sequencing (scRNA-seq) provides a powerful tool to evaluate the transcriptomic landscape and heterogeneity of thousands of cells in parallel. However, complex study designs or the unavailability of in-house instruments require the temporal disconnection between sample preparation and library construction, raising the need for efficient sample preservation methods which are compatible with scRNA-seq downstream analysis. Several studies evaluated the effect of methanol fixation as preservation method, yet none of them deeply assessed its effect on adult primary dissociated brain tissue. Here, we evaluated its effect on murine dentate gyrus (DG) single cell suspensions and on subsequent scRNA-seq downstream analysis by performing SOrting and Robot-assisted Transcriptome SEQuencing (SORT-seq), a partially robotized version of the CELseq2 protocol. Our results show that MeOH fixation preserves RNA integrity and has no apparent effects on cDNA library construction. They also suggest that fixation protects from sorting-induced cell stress and increases the proportion of high-quality cells. Despite evidence of mRNA leakage in fixed cells, their relative gene expression levels correlate well with those of fresh cells and fixation does not significantly affect the variance of the dataset. Moreover, it allows the identification of all major DG cell populations, including neural precursors, granule neurons and different glial cell types, with a tendency to preserve more neurons that are underrepresented in fresh samples. Overall, our data show that MeOH fixation is suitable for preserving primary neural cells for subsequent single-cell RNA profiling, helping to overcome challenges arising from complex workflows, improve experimental flexibility and facilitate scientific collaboration. [ABSTRACT FROM AUTHOR]

Introduction: By 2050, the worldwide percentage of people 65 years and older is assumed to have doubled compared to current numbers. Therefore, finding ways of promoting healthy (cognitive) aging is crucial. Physical activity is considered an effective approach to counteract not only physical but also cognitive decline. However, the underlying mechanisms that drive the benefits of regular physical activity on cognitive function are not fully understood. This randomized controlled trial aims to analyze the effect of an eight-week standardized physical activity training program in older humans on cognitive, brain, and gut-barrier function as well as the relationship between the resulting changes. Methods and analysis: One-hundred healthy participants aged 60 to 75 years will be recruited. First, participants will undergo an extensive baseline assessment consisting of neurocognitive tests, functional and structural brain imaging, physical fitness tests, and gut-microbiome profiling. Next, participants will be randomized into either a multi-component physical activity group (experimental condition) or a relaxation group (active control condition), with each training lasting 8 weeks and including an equal number and duration of exercises. The whole intervention will be online-based, i.e., participants will find their intervention schedule and all materials needed on the study website. After the intervention phase, participants will have their post-intervention assessment, which consists of the same measures and tests as the baseline assessment. The primary outcome of this study is the change in the cognitive parameter of visual processing speed from baseline to post-measurement, which will on average take place 10 weeks after the randomization. Secondary outcomes related to cognitive, brain, and microbiome data will be analyzed exploratory. [ABSTRACT FROM AUTHOR]

Background: Numerous genes, including SOD1, mutated in familial and sporadic amyotrophic lateral sclerosis (f/sALS) share a role in DNA damage and repair, emphasizing genome disintegration in ALS. One possible outcome of chromosomal instability and repair processes is extrachromosomal circular DNA (eccDNA) formation. Therefore, eccDNA might accumulate in f/sALS with yet unknown function. Methods: We combined rolling circle amplification with linear DNA digestion to purify eccDNA from the cervical spinal cord of 9 co-isogenic symptomatic hSOD1G93A mutants and 10 controls, followed by deep short-read sequencing. We mapped the eccDNAs and performed differential analysis based on the split read signal of the eccDNAs, referred as DifCir, between the ALS and control specimens, to find differentially produced per gene circles (DPpGC) in the two groups. Compared were eccDNA abundances, length distributions and genic profiles. We further assessed proteome alterations in ALS by mass spectrometry, and matched the DPpGCs with differentially expressed proteins (DEPs) in ALS. Additionally, we aligned the ALS-specific DPpGCs to ALS risk gene databases. Results: We found a six-fold enrichment in the number of unique eccDNAs in the genotoxic ALS-model relative to controls. We uncovered a distinct genic circulome profile characterized by 225 up-DPpGCs, i.e., genes that produced more eccDNAs from distinct gene sequences in ALS than under control conditions. The inter-sample recurrence rate was at least 89% for the top 6 up-DPpGCs. ALS proteome analyses revealed 42 corresponding DEPs, of which 19 underlying genes were itemized for an ALS risk in GWAS databases. The up-DPpGCs and their DEP tandems mainly impart neuron-specific functions, and gene set enrichment analyses indicated an overrepresentation of the adenylate cyclase modulating G protein pathway. Conclusions: We prove, for the first time, a significant enrichment of eccDNA in the ALS-affected spinal cord. Our triple circulome, proteome and genome approach provide indication for a potential importance of certain eccDNAs in ALS neurodegeneration and a yet unconsidered role as ALS biomarkers. The related functional pathways might open up new targets for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Individuals with grandiose narcissism exhibit enhanced antagonism and a defensive pattern of discordance between their emotional and physiological reactions to self‐threatening evaluations. Although theoretical perspectives link narcissistic defensiveness to negative emotions, empirical evidence linking grandiose narcissism to emotional reactivity remains mixed. The current study used self‐reported affect, electrocardiography, and facial electromyography (fEMG) to examine whether people scoring high in grandiose narcissism show amplified physiological and self‐reported emotional reactivity to negative social evaluation. Following two challenging cognitive tasks, participants received negative and neutral feedback in a face‐to‐face evaluation situation. Receiving negative feedback decreased self‐reported positive affect and dominance, slowed heart rate, and amplified fEMG activity related to frowning and eye constriction. Although self‐reported emotional reactions were unrelated to grandiose narcissism, fEMG activity associated with negative affect was significantly enhanced by grandiose narcissism. In conclusion, individuals with higher levels of grandiose narcissism may not be willing to report overt emotional reactivity to self‐threatening feedback, but physiological responses "beneath their thin skin" reveal amplified threat‐related facial muscle activity suggestive of a negative emotional state. Although grandiose narcissism is often linked with strong negative emotional reactions to social evaluations, direct evidence of the reactions remains mixed. We show that while narcissistic recipients do not report stronger negative emotions when receiving feedback on their performance than others do, their facial muscle responses to negative feedback are amplified. The findings align with theoretical accounts on narcissistic defensiveness and demonstrate a discordance in narcissistic individuals' self‐reported and physiological reactions to social evaluation. [ABSTRACT FROM AUTHOR]

This letter, published in the Annals of Hematology, discusses the detection of a rare JAK2exon13InDel-mutation in a patient with chronic eosinophilic leukemia (CEL), Löffler endocarditis, and bilateral cerebral infarctions. The patient presented with bilateral cerebral infarctions, leukocytosis with eosinophilia, and extensive hepatosplenomegaly. The JAK2exon13InDel-mutation, as well as a DNMT3A mutation, were detected in the patient. The letter highlights the association between hypereosinophilia and subendocardial fibrosis, as well as the increased risk of thromboembolic complications in patients with JAK2 mutations. The authors emphasize the importance of early treatment initiation in patients with JAK2exon13InDel-mutation-associated MPN. [Extracted from the article]

Copyright of Western North American Naturalist is the property of Monte L. Bean Life Science Museum and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Western North American Naturalist is the property of Monte L. Bean Life Science Museum and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Capturing disease progression in amyotrophic lateral sclerosis (ALS) is challenging and refinement of progression markers is urgently needed. This study introduces new motor unit number index (MUNIX), motor unit size index (MUSIX) and compound muscle action potential (CMAP) parameters called M50, MUSIX200 and CMAP50. M50 and CMAP50 indicate the time in months from symptom onset an ALS patient needs to lose 50% of MUNIX or CMAP in relation to the mean values of controls. MUSIX200 represents the time in months until doubling of the mean MUSIX of controls. We used MUNIX parameters of Musculi abductor pollicis brevis (APB), abductor digiti minimi (ADM) and tibialis anterior (TA) of 222 ALS patients. Embedded in the D50 disease progression model, disease aggressiveness and accumulation were analyzed separately. M50, CMAP50 and MUSIX200 significantly differed among disease aggressiveness subgroups (p < 0.001) regardless of disease accumulation. ALS patients with a low M50 had a significantly shorter survival compared to high M50 (median 32 versus 74 months). M50 preceded the loss of global function (median of about 14 months). M50, CMAP50 and MUSIX200 characterize the disease course in ALS in a new way and may be applied as early measures of disease progression. [ABSTRACT FROM AUTHOR]

Aging is accompanied by macro-structural alterations in the brain that may relate to age-associated cognitive decline. Animal studies could allow us to study this relationship, but so far it remains unclear whether their structural aging patterns correspond to those in humans. Therefore, by applying magnetic resonance imaging (MRI) and deformation-based morphometry (DBM), we longitudinally screened the brains of male RccHan:WIST rats for structural changes across their average lifespan. By combining dedicated region of interest (ROI) and voxel-wise approaches, we observed an increase in their global brain volume that was superimposed by divergent local morphologic alterations, with the largest aging effects in early and middle life. We detected a modality-dependent vulnerability to shrinkage across the visual, auditory, and somato-sensory cortical areas, whereas the piriform cortex showed partial resistance. Furthermore, shrinkage emerged in the amygdala, subiculum, and flocculus as well as in frontal, parietal, and motor cortical areas. Strikingly, we noticed the preservation of ectorhinal, entorhinal, retrosplenial, and cingulate cortical regions, which all represent higher-order brain areas and extraordinarily grew with increasing age. We think that the findings of this study will further advance aging research and may contribute to the establishment of interventional approaches to preserve cognitive health in advanced age. [ABSTRACT FROM AUTHOR]

Here we present the case of a patient with simultaneous CD, solitary plasmacytoma with minimal bone marrow involvement, and POEMS syndrome followed by progression into multiple myeloma (MM). In CD without clonal plasma cell disorder, the Castleman disease variant of POEMS syndrome may occur and usually presents as a less severe and sensory polyneuropathy [[4]]. The diagnosis of POEMS syndrome requires the two mandatory criteria polyneuropathy and monoclonal plasma cell proliferation as well as one of the three other major criteria (Castleman disease [CD], sclerotic bone lesion, and elevated vascular endothelial growth factor [VEGF]) and one of the six minor criteria [[1]]. [Extracted from the article]

Cognitive decline is one of the greatest health threats of old age and the maintenance of optimal brain function across a lifespan remains a big challenge. The hippocampus is considered particularly vulnerable but there is cross-species consensus that its functional integrity benefits from the early and continuous exercise of demanding physical, social and mental activities, also referred to as environmental enrichment (EE). Here, we investigated the extent to which late-onset EE can improve the already-impaired cognitive abilities of lifelong deprived C57BL/6 mice and how it affects gene expression in the hippocampus. To this end, 5- and 24-month-old mice housed in standard cages (5mSC and 24mSC) and 24-month-old mice exposed to EE in the last 2 months of their life (24mEE) were subjected to a Barnes maze task followed by next-generation RNA sequencing of the hippocampal tissue. Our analyses showed that late-onset EE was able to restore deficits in spatial learning and short-term memory in 24-month-old mice. These positive cognitive effects were reflected by specific changes in the hippocampal transcriptome, where late-onset EE affected transcription much more than age (24mSC vs. 24mEE: 1311 DEGs, 24mSC vs. 5mSC: 860 DEGs). Remarkably, a small intersection of 72 age-related DEGs was counter-regulated by late-onset EE. Of these, Bcl3, Cttnbp2, Diexf, Esr2, Grb10, Il4ra, Inhba, Rras2, Rps6ka1 and Socs3 appear to be particularly relevant as key regulators involved in dendritic spine plasticity and in age-relevant molecular signaling cascades mediating senescence, insulin resistance, apoptosis and tissue regeneration. In summary, our observations suggest that the brains of aged mice in standard cage housing preserve a considerable degree of plasticity. Switching them to EE proved to be a promising and non-pharmacological intervention against cognitive decline. [ABSTRACT FROM AUTHOR]

Background and purpose: Fatigue and low sleep quality in multiple sclerosis (MS) are closely related symptoms. Here, the associations between the brain's functional connectivity (FC) and fatigue and low sleep quality were investigated to determine the degree of neural distinctiveness of these symptoms. Method: A hundred and four patients with relapsing–remitting MS (age 38.9 ± 10.2 years, 66 females) completed the Modified Fatigue Impact Scale and the Pittsburgh Sleep Quality Index and underwent resting‐state functional magnetic resonance imaging. FC was analyzed using independent‐component analysis in sensorimotor, default‐mode, fronto‐parietal and basal‐ganglia networks. Multiple linear regression models allowed us to test the association between FC and fatigue and sleep quality whilst controlling for one another as well as for demographic, disease‐related and imaging variables. Results: Higher fatigue correlated with lower sleep quality (r = 0.54, p < 0.0001). Higher fatigue was associated with lower FC of the precentral gyrus in the sensorimotor network, the precuneus in the posterior default‐mode network and the superior frontal gyrus in the left fronto‐parietal network, independently of sleep quality. Lower sleep quality was associated with lower FC of the left intraparietal sulcus in the left fronto‐parietal network, independently of fatigue. Specific associations were found between fatigue and the sensorimotor network's global FC and between low sleep quality and the left fronto‐parietal network's global FC. Conclusion: Despite the high correlation between fatigue and low sleep quality in the clinical picture, our findings clearly indicate that, on the neural level, fatigue and low sleep quality in MS are associated with decreased FC in distinct functional brain networks. [ABSTRACT FROM AUTHOR]

Small Island Developing States (SIDS) share high burdens of nutrition-related conditions, including non-communicable diseases, associated with an increasing reliance on imported, processed foods. Improving health through increasing the production and consumption of local, nutritious foods is a policy objective of many SIDS governments. This study aimed to understand contemporary challenges and opportunities to strengthening local food systems in two case study settings, Fiji and St. Vincent and the Grenadines. Fifty-two in-depth, semi-structured interviews were conducted with key stakeholders involved in local food production. Interviews were analysed by both country teams using thematic analysis. Local food production networks in both settings included formal governance bodies as well as more informal connections through civil society and communities. Their main function was the sharing of resources and knowledge, but levels of trust and cooperation between the stakeholders varied in a market open to intense competition from imports. Local food production was hindered by few and slow investments by local governments, dated technology, and lack of knowledge. Stakeholders believed this marginalisation was occurring against a background of rising preferences for imported foods in the population, and increasing disinterest in employment in the sector. Despite the challenges, strong narratives of resilience and opportunity were highlighted such as national pride in local produce for commercialisation and local diets. Efforts to support local food production in SIDS should focus on strengthening governance structures to prioritise local produce over corporate and import markets, assist collaboration and co-learning, and support alternative agro-food practices. [ABSTRACT FROM AUTHOR]

The neurophysiological technique motor unit number index (MUNIX) is increasingly used in clinical trials to measure loss of motor units. However, the heterogeneous disease course in amyotrophic lateral sclerosis (ALS) obfuscates robust correlations between clinical status and electrophysiological assessments. To address this heterogeneity, MUNIX was applied in the D50 disease progression model by analyzing disease aggressiveness (D50) and accumulation (rD50 phase) in ALS separately. 237 ALS patients, 45 controls and 22 ALS-Mimics received MUNIX of abductor pollicis brevis (APB), abductor digiti minimi (ADM) and tibialis anterior (TA) muscles. MUNIX significantly differed between controls and ALS patients and between ALS-Mimics and controls. Within the ALS cohort, significant differences between Phase I and II revealed in MUNIX, compound muscle action potential (CMAP) and motor unit size index (MUSIX) of APB as well as in MUNIX and CMAP of TA. For the ADM, significant differences occurred later in CMAP and MUNIX between Phase II and III/IV. In contrast, there was no significant association between disease aggressiveness and MUNIX. In application of the D50 disease progression model, MUNIX can demonstrate disease accumulation already in early Phase I and evaluate effects of therapeutic interventions in future therapeutic trials independent of individual disease aggressiveness. [ABSTRACT FROM AUTHOR]

Mild motor abnormalities can herald the beginning of Parkinson´s disease but their diagnostic value is limited by multifactorial ageing‐related influences on motor function. We characterized mild motor abnormalities in different motor domains by conducting a systematic motor assessment in 20 patients with clinically isolated REM sleep behaviour disorder (iRBD) without parkinsonian motor signs and 20 healthy controls. We addressed the influence of lifestyle factors and age on motor function, which needs to be distinguished from neurodegenerative motor features, and assessed the diagnostic value of innovative and established quantitative motor tests in iRBD. Patients with iRBD showed abnormalities in perceptual motor speed (falling stick test), trunk movement coordination (bend, twist and touch test) and dynamic balance (line walk test) without alterations in simple motor speed (alternate tap test), dexterity (grooved pegboard), static balance (force plate) and gait (timed up and go test). The falling stick test showed the highest diagnostic accuracy in identifying subjects with RBD (ROC‐AUC 0.85, p ≤ 0.001). Multivariate analysis revealed physical activity and age as additional determinants of motor test performance. iRBD comprises a wide spectrum of mild motor abnormalities which cannot be verified by established tests for motor speed, gait and balance. The falling stick test, an innovative screening test for perceptual motor speed, provides high diagnostic potential in identifying subjects with subclinical neurodegenerative symptoms before parkinsonian motor signs become apparent. Normative data for physical activity and age need to be obtained to ensure correct interpretation of motor test results in prodromal Parkinson‐related disease. [ABSTRACT FROM AUTHOR]

Efficient purification of viable neural cells from the mature CNS has been historically challenging due to the heterogeneity of the inherent cell populations. Moreover, changes in cellular interconnections, membrane lipid and cholesterol compositions, compartment-specific biophysical properties, and intercellular space constituents demand technical adjustments for cell isolation at different stages of maturation and aging. Though such obstacles are addressed and partially overcome for embryonic premature and mature CNS tissues, procedural adaptations to an aged, progeroid, and degenerative CNS environment are underrepresented. Here, we describe a practical workflow for the acquisition and phenomapping of CNS neural cells at states of health, physiological and precocious aging, and genetically provoked neurodegeneration. Following recent, unprecedented evidence of post-mitotic cellular senescence (PoMiCS), the protocol appears suitable for such de novo characterization and phenotypic opposition to classical senescence. Technically, the protocol is rapid, efficient as for cellular yield and well preserves physiological cell proportions. It is suitable for a variety of downstream applications aiming at cell type-specific interrogations, including cell culture systems, Flow-FISH, flow cytometry/FACS, senescence studies, and retrieval of omic-scale DNA, RNA, and protein profiles. We expect suitability for transfer to other CNS targets and to a broad spectrum of engineered systems addressing aging, neurodegeneration, progeria, and senescence. [ABSTRACT FROM AUTHOR]

Learning from errors as the main mechanism for motor adaptation has two fundamental prerequisites: a mismatch between the intended and performed movement and the ability to adapt motor actions. Many neurological patients are limited in their ability to transfer an altered motor representation into motor action due to a compromised motor pathway. Studies that have investigated the effects of a sustained and unresolvable mismatch over multiple days found changes in brain processing that seem to optimize the potential for motor learning (increased drive for motor adaptation and a weakening of the current implementation of motor programs). However, it remains unclear whether the observed effects can be induced experimentally and more important after shorter periods. Here, we used task-based and resting-state fMRI to investigate whether the known pattern of cortical adaptations due to a sustained mismatch can be induced experimentally by a short (20 min), but unresolvable, sensory–motor mismatch by impaired facial movements in healthy participants by transient facial tapping. Similar to long-term mismatch, we found plastic changes in a network that includes the striatal, cerebellar and somatosensory brain areas. However, in contrast to long-term mismatch, we did not find the involvement of the cerebral motor cortex. The lack of the involvement of the motor cortex can be interpreted both as an effect of time and also as an effect of the lack of a reduction in the motor error. The similar effects of long-term and short-term mismatch on other parts of the sensory–motor network suggest that the brain-state caused by long-term mismatch can be (at least partly) induced by short-term mismatch. Further studies should investigate whether short-term mismatch interventions can be used as therapeutic strategy to induce an altered brain-state that increase the potential for motor learning. [ABSTRACT FROM AUTHOR]

Copyright of Jahrbuch der Europäischen Integration is the property of Nomos Verlagsgesellschaft mbH & Co. KG and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Ischemic stroke is a major cause of death and long-term disability. We demonstrate that middle cerebral artery occlusion (MCAO) in mice leads to a strong decline in dendritic arborization of penumbral neurons. These defects were subsequently repaired by an ipsilateral recovery process requiring the actin nucleator Cobl. Ischemic stroke and excitotoxicity, caused by calpain-mediated proteolysis, significantly reduced Cobl levels. In an apparently unique manner among excitotoxicity-affected proteins, this Cobl decline was rapidly restored by increased mRNA expression and Cobl then played a pivotal role in poststroke dendritic arbor repair in peri-infarct areas. In Cobl knockout (KO) mice, the dendritic repair window determined to span day 2 to 4 poststroke in wild type (WT) strikingly passed without any dendritic regrowth. Instead, Cobl KO penumbral neurons of the primary motor cortex continued to show the dendritic impairments caused by stroke. Our results thereby highlight a powerful poststroke recovery process and identified causal molecular mechanisms critical during poststroke repair. Ischemic stroke is a major cause of death and long-term disability. This study reveals that, in mice, stroke-induced damage to dendritic arborization in the area around an infarct is rapidly repaired via dendritic regrowth; this plasticity requires the actin nucleator Cobl. [ABSTRACT FROM AUTHOR]

Purpose: The most common protocols in the initial diagnostic of acute ischemic stroke do not assess cardiogenic or aortic causes of embolism. These are usually evaluated later by transthoracic (TTE) or transesophageal (TEE) echocardiography. This study aimed to evaluate the feasibility of a diagnostic tool for thoracic cardiovascular thrombi according to the first experience with a new extended cardio-stroke protocol (Big 5—Jena eCS protocol) in acute stroke patients. Methods: Retrospective analyses of the tomography scans database of the Jena University Hospital were performed. We included a total of 67 patients in the feasibility analyses, based on the evaluation of three outcomes. Results: Primary outcome: the Big 5—Jena eCS protocol was able to detect thoracic cardiovascular thrombi in a total of 20 patients in different locations including the arch of the aorta, the aortic valve, the left atrium, the left atrial appendage, the left ventricle, and the pulmonary arteries. Secondary outcome: implementating the protocol did not result in a significant elevation of the radiation exposure compared to traditional protocols. Tertiary outcome: the new protocol identified seven cases that were considered negative by echocardiography. Conclusion: The implementation of an extended cardio-stroke protocol is feasible, no significantly time-consuming, acquiring assessable imaging, and maintaining radiation exposure acceptable. The Big 5—Jena eCS protocol was also able to detect some thrombi not reported by TTE or TEE; however, due to our data's explorative character, a conclusive comparison with cardiac ultrasound is not possible. A prospective pilot study and clinical trials should be conducted to assess the diagnostic accuracy of this protocol compared to echocardiography and determine the potential impact on diagnostic and treatment decisions. [ABSTRACT FROM AUTHOR]

Visually induced motion sickness (VIMS) is a relevant limiting factor in the use of virtual reality (VR) devices. Understanding the origin of this problem might help to develop strategies to circumvent this limitation. Previous studies have attributed VIMS to a mismatch between visual, and vestibular information, causing ambiguity of the position of the body in relation to its surrounding. Studies using EEG have shown a shift of the power spectrum to lower frequencies while VIMS is experienced. However, little is known about the relationship between the intensity of the VIMS and the changes in these power spectra. Moreover, the effect of different varieties of VIMS on the causal relationship between brain areas is largely unknown. Here, we used EEG to study 14 healthy subjects in a VR environment who were exposed to increasing levels of mismatch between vestibular and visual information. The frequency power and the bivariate transfer entropy as a measure for the information transfer were calculated. We found a direct association between increasing mismatch levels and subjective VIMS. With increasing VIMS, the proportion of slow EEG waves (especially 1–10 Hz) increases, especially in temporo-occipital regions. Furthermore, we found a general decrease in the information flow in most brain areas but especially in brain areas involved in the processing of vestibular signals and the detection of self-motion. We hypothesize that the general shift of frequency power and the decrease in information flow while experiencing high intensity VIMS represent a brain state of a reduced ability to receive, transmit and process information. We further hypothesize that the mechanism of reduced information flow is a general reaction of the brain to an unresolvable mismatch of information. This reaction aims on transforming a currently unstable model with a high prediction error into a stable model in an environment of minimal contradictory information. [ABSTRACT FROM AUTHOR]

Objectives: There is a lack of data on patients' and diagnostic factors for prognostication of complete recovery in patients with non-idiopathic peripheral facial palsy (FP). Methods: Cohort register-based study of 264 patients with non-idiopathic peripheral FP and uniform diagnostics and standardized treatment in a university hospital from 2007 to 2017 (47% female, median age: 57 years). Clinical data, facial grading, electrodiagnostics, motor function tests, non-motor function tests, and onset of prednisolone therapy were assessed for their impact on the probability of complete recovery using univariable and multivariable statistics. Results: The most frequent reason for a non-idiopathic peripheral FP was a reactivation of Varicella Zoster Virus (VZV; 36.4%). Traumatic origin had a higher proportion of complete FP (52.9%). Furthermore, in traumatic FP, the mean interval between onset and start of prednisolone therapy was longer than in other cases (5.6 ± 6.2 days). Patients with reactivation of VZV, Lyme disease or otogenic FP had a significant higher recovery rate (p = 0.002, p < 0.0001, p = 0.018, respectively), whereas patients with post-surgery FP and other reasons had a significant lower recovery rate (p < 0.0001). After multivariate analyses voluntary activity in first EMG, Lyme disease and post-surgery cause were identified as independent diagnostic and prognostic factors on the probability of complete recovery (all p < 0.05). Conclusion: Infectious causes for non-idiopathic FP like VZV reactivation and Lyme disease had best probability for complete recovery. Post-surgery FP had a worse prognosis. Level of evidence: 2 [ABSTRACT FROM AUTHOR]

In the aftermath of an acute stroke, numerous signaling cascades that reshape the brain both in the perilesional zone as well as in more distal regions are activated. Despite continuous improvement in the acute treatment of stroke and the sustained research efforts into the pathophysiology of stroke, we critically lag in our integrated understanding of the delayed and chronic responses to ischemic injury. As such, the beneficial or maladaptive effect of some stroke-induced cellular responses is unclear, restricting the advancement of therapeutic strategies to target long-term complications. A prominent delayed effect of stroke is the robust increase in adult neurogenesis, which raises hopes for a regenerative strategy to counter neurological deficits in stroke survivors. In the adult brain, two regions are known to generate new neurons from endogenous stem cells: the subventricular zone (SVZ) and the dentate subgranular zone (SGZ) of the hippocampus. While both niches respond with an increase in neurogenesis post-stroke, there are significant regional differences in the ensuing stages of survival, migration, and maturation, which may differently influence functional outcome. External interventions such as rehabilitative training add a further layer of complexity by independently modulating the process of adult neurogenesis. In this review we summarize the current knowledge regarding the effects of ischemic stroke on neurogenesis in the SVZ and in the SGZ, and the influence of exogenous stimuli such as motor activity or enriched environment (EE). In addition, we discuss the contribution of SVZ or SGZ post-stroke neurogenesis to sensory, motor and cognitive recovery. [ABSTRACT FROM AUTHOR]

Background: Most spontaneous subarachnoid hemorrhages (SAH) occur unexpectedly and independently of classical risk factors. In the light of increasing climate variability and change, we investigated weather and rapid weather changes as possible short-term risk factors for SAH.Methods: Seven hundred ninety one patients admitted to three major hospitals in Germany for non-traumatic SAH with a determinable onset of SAH symptoms were included in this hospital-based, case-crossover study. The effects of atmospheric pressure, relative air humidity, and ambient temperature and their 24 h changes on the onset of SAH under temperate climate conditions were estimated.Results: There was no association between the risk of SAH and 24 h weather changes, mean daily temperature or mean relative air humidity in the overall population. For every 11.5 hPa higher mean daily atmospheric pressure, the risk of SAH increased by 15% (OR 1.15, 95% confidence interval (CI) 1.01-1.30) in the entire study population with a lag time of three days.Conclusion: Our results suggest no relevant association between 24 h-weather changes or absolute values of ambient temperature and relative humidity and the risk of SAH. The medical significance of the statistically weak increase in SAH risk three days after exposure to high atmospheric pressure is unclear. However, as the occurrence of stable high-pressure systems will increase with global warming and potentially affect SAH risk, we call for confirming studies in different geographical regions to verify our observations. [ABSTRACT FROM AUTHOR]

Neuroinflammation significantly contributes to Amyotrophic Lateral Sclerosis (ALS) pathology. In lieu of this, reports of elevated chitinase levels in ALS are interesting, as they are established surrogate markers of a chronic inflammatory response. While post-mortem studies have indicated glial expression, the cellular sources for these moieties remain to be fully understood. Therefore, the objective of this pilot study was to examine whether the peripheral immune system also contributes to chitinase dysregulation in ALS. The temporal expression of CHIT1, CHI3L1, and CHI3L2 in non-polarized monocyte-derived macrophages (MoMas) from ALS patients and healthy controls (HCs) was examined. We demonstrate that while CHIT1 and CHI3L1 display similar temporal expression dynamics in both groups, profound between-group differences were noted for these targets at later time-points i.e., when cells were fully differentiated. CHIT1 and CHI3L1 expression were significantly higher in MoMas from ALS patients at both the transcriptomic and protein level, with CHI3L1 levels also being influenced by age. Conversely, CHI3L2 expression was not influenced by disease state, culture duration, or age. Here, we demonstrate for the first time, that in ALS, circulating immune cells have an intrinsically augmented potential for chitinase production that may propagate chronic neuroinflammation, and how the ageing immune system itself contributes to neurodegeneration. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive neurodegenerative disorder. As previous therapeutic trials in ALS have been severely hampered by patients' heterogeneity, the identification of biomarkers that reliably reflect disease progression represents a priority in ALS research. Here, we used the D50 disease progression model to investigate correlations between cerebrospinal fluid (CSF) neurofilament light chain (NfL) levels and disease aggressiveness. The D50 model quantifies individual disease trajectories for each ALS patient. The value D50 provides a unified measure of a patient's overall disease aggressiveness (defined as time taken in months to lose 50% of functionality). The relative D50 (rD50) reflects the individual disease covered and can be calculated for any time point in the disease course. We analyzed clinical data from a well-defined cohort of 156 patients with ALS. The concentration of NfL in CSF samples was measured at two different laboratories using the same procedure. Based on patients' individual D50 values, we defined subgroups with high (<20), intermediate (20–40), or low (>40) disease aggressiveness. NfL levels were compared between these subgroups via analysis of covariance, using an array of confounding factors: age, gender, clinical phenotype, frontotemporal dementia, rD50-derived disease phase, and analyzing laboratory. We found highly significant differences in NfL concentrations between all three D50 subgroups (p < 0.001), representing an increase of NfL levels with increasing disease aggressiveness. The conducted analysis of covariance showed that this correlation was independent of gender, disease phenotype, and phase; however, age, analyzing laboratory, and dementia significantly influenced NfL concentration. We could show that CSF NfL is independent of patients' disease covered at the time of sampling. The present study provides strong evidence for the potential of NfL to reflect disease aggressiveness in ALS and in addition proofed to remain at stable levels throughout the disease course. Implementation of CSF NfL as a potential read-out for future therapeutic trials in ALS is currently constrained by its demonstrated susceptibility to (pre-)analytical variations. Here we show that the D50 model enables the discovery of correlations between clinical characteristics and CSF analytes and can be recommended for future studies evaluating potential biomarkers. [ABSTRACT FROM AUTHOR]

NKCC1 is the primary transporter mediating chloride uptake in immature principal neurons, but its role in the development of in vivo network dynamics and cognitive abilities remains unknown. Here, we address the function of NKCC1 in developing mice using electrophysiological, optical, and behavioral approaches. We report that NKCC1 deletion from telencephalic glutamatergic neurons decreases in vitro excitatory actions of γ-aminobutyric acid (GABA) and impairs neuronal synchrony in neonatal hippocampal brain slices. In vivo, it has a minor impact on correlated spontaneous activity in the hippocampus and does not affect network activity in the intact visual cortex. Moreover, long-term effects of the developmental NKCC1 deletion on synaptic maturation, network dynamics, and behavioral performance are subtle. Our data reveal a neural network function of NKCC1 in hippocampal glutamatergic neurons in vivo, but challenge the hypothesis that NKCC1 is essential for major aspects of hippocampal development. [ABSTRACT FROM AUTHOR]

Background: In patients with Parkinson's disease (PD), depression has a strong impact on quality of life (QoL). However, little is known about the influence of subthreshold depression (STD) on QoL in PD patients.Methods: A total of 230 hospitalized PD patients with normal and impaired cognitive status were included in this observational study. We collected the following data for analysis: Beck Depression Inventory level, Montreal Cognitive Assessment (MOCA) score, non-motor symptoms questionnaire score, PD questionnaire-39 (PDQ-39) score, Hoehn-Yahr stage, and Movement Disorder Society-sponsored revision of the unified PD rating scale III (MDS-UPDRS III) score. To study the impact of STD on the PDQ-39 summary index (SI) and its domains, we used multivariate analysis of variance and multivariate analysis of covariance.Results: In this cohort, 80 (34.8%) patients had STD [44 (32.3%) with high MOCA score (> 21) and 36 (38.3%) with low MOCA score (< 21)]. In PDQ-39 SI, there was a significant effect on depression level. In patients with higher MOCA score, STD was associated with worse PDQ-39 domains emotional well-being and cognition, whereas in patients with lower MOCA score, STD had no significant effect on PDQ-39 SI or its subdomains.Conclusion: In PD patients, QoL is significantly affected by STD, and thus, more attention in medical care should be focused on treating STD. However, the impact is only observable in PD patients with normal cognitive function. STD patients show more reduced QoL than non-depressed patients, indicating that STD should be treated as a transition zone between normal mood and depression. [ABSTRACT FROM AUTHOR]

Numerous neuroimaging studies in amyotrophic lateral sclerosis (ALS) have reported links between structural changes and clinical data; however phenotypic and disease course heterogeneity have occluded robust associations. The present study used the novel D50 model, which distinguishes between disease accumulation and aggressiveness, to probe correlations with measures of diffusion tensor imaging (DTI). DTI scans of 145 ALS patients and 69 controls were analyzed using tract‐based‐spatial‐statistics of fractional anisotropy (FA), mean‐ (MD), radial (RD), and axial diffusivity (AD) maps. Intergroup contrasts were calculated between patients and controls, and between ALS subgroups: based on (a) the individual disease covered (Phase I vs. II) or b) patients' disease aggressiveness (D50 value). Regression analyses were used to probe correlations with model‐derived parameters. Case–control comparisons revealed widespread ALS‐related white matter pathology with decreased FA and increased MD/RD. These affected pathways showed also correlations with the accumulated disease for increased MD/RD, driven by the subgroup of Phase I patients. No significant differences were noted between patients in Phase I and II for any of the contrasts. Patients with high disease aggressiveness (D50 < 30 months) displayed increased AD/MD in bifrontal and biparietal pathways, which was corroborated by significant voxel‐wise regressions with D50. Application of the D50 model revealed associations between DTI measures and ALS pathology in Phase I, representing individual disease accumulation early in disease. Patients' overall disease aggressiveness correlated robustly with the extent of DTI changes. We recommend the D50 model for studies developing/validating neuroimaging or other biomarkers for ALS. [ABSTRACT FROM AUTHOR]

Copyright of Neuroforum is the property of De Gruyter and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Neuroforum is the property of De Gruyter and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Open in new tab Download slide Open in new tab Download slide OBJECTIVES Cardiac surgery in patients with infective endocarditis (IE) and preoperative intracranial haemorrhage (pre-ICH) is a highly debatable issue, and guidelines are still not well defined. The goal of this study was to investigate the effect of cardiac surgery and its timing on the clinical outcomes of patients with IE and pre-ICH. METHODS We did a single-centre retrospective analysis of data from patients with preoperative brain imaging who had surgery for left-sided IE between January 2007 and May 2018. RESULTS Among the 363 patients included in the study, 34 had pre-ICH. Hospital mortality was similar between the patients with and without pre-ICH (29% vs 27%, respectively; P  = 0.84). Unadjusted, postoperative neurological deterioration appeared higher in patients with pre-ICH (24% vs 17%; P  = 0.35). In multivariable analysis, pre-ICH did not qualify as an independent predictor for either postoperative neurological deterioration [odds ratio 1.10, 95% confidence interval (CI) 0.44–2.73; P  = 0.84] or hospital mortality (odds ratio 1.02, 95% CI 0.43–2.40; P  = 0.96). Postoperative partial thromboplastin time was significantly elevated in 4 patients with relevant post-ICH compared with those patients without relevant post-ICH (65.5 vs 37.6, respectively; P  = 0.004). CONCLUSIONS Pre-ICH was not an independent predictor for postoperative neurological deterioration or hospital mortality in patients with IE. Postoperative coagulation management seems to be crucial in patients with IE with ICH. Although this is to date the largest monocentric study addressing surgical decision and timing, the number of patients with pre-ICH was low. Therefore, these conclusions should be regarded with caution; randomized clinical trials are needed. [ABSTRACT FROM AUTHOR]

The integral membrane zinc metalloprotease ZMPSTE24 plays a key role in the proteolytic processing of farnesylated prelamin A, the precursor of the nuclear scaffold protein lamin A. Failure of this processing step results in the accumulation of permanently farnesylated forms of prelamin A which cause the premature aging disease Hutchinson-Gilford Progeria Syndrome (HGPS), as well as related progeroid disorders, and may also play a role in physiological aging. ZMPSTE24 is an intriguing and unusual protease because its active site is located inside of a closed intramembrane chamber formed by seven transmembrane spans with side portals in the chamber permitting substrate entry. The specific features of prelamin A that make it the sole known substrate for ZMPSTE24 in mammalian cells are not well-defined. At the outset of this work it was known that farnesylation is essential for prelamin A cleavage in vivo and that the C-terminal region of prelamin A (41 amino acids) is sufficient for recognition and processing. Here we investigated additional features of prelamin A that are required for cleavage by ZMPSTE24 using a well-established humanized yeast system. We analyzed the 14-residue C-terminal region of prelamin A that lies between the ZMPSTE24 cleavage site and the farnesylated cysteine, as well 23-residue region N-terminal to the cleavage site, by generating a series of alanine substitutions, alanine additions, and deletions in prelamin A. Surprisingly, we found that there is considerable flexibility in specific requirements for the length and composition of these regions. We discuss how this flexibility can be reconciled with ZMPSTE24's selectivity for prelamin A. [ABSTRACT FROM AUTHOR]