Cerebral vasomotor reactivity in neurodegenerative diseases

Small-caliber cerebral vessels change their diameters in response to alterations of key metabolite concentrations such as carbon dioxide or oxygen. This phenomenon, termed the cerebral vasomotor reactivity (CVMR), is the basis for blood flow regulation in the brain in accordance with its metabolic status. Typically, CVMR is determined as the amount of change in cerebral blood flow in response to a vasodilating stimulus, which can be measured by various neuroimaging methods or by transcranial Doppler. It has been shown that CVMR is impaired in cerebrovascular diseases, but there is also evidence of a similar dysfunction in neurodegenerative disorders. Here, we review studies that have investigated CVMR in the common neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and multiple sclerosis. Moreover, we discuss potential neurodegenerative mechanisms responsible for the impairment of CVMR

Substantial disease exacerbation in a patient with relapsing-remitting multiple sclerosis after withdrawal from siponimod

Among patients with multiple sclerosis, discontinuing highly effective disease-modifying treatments can potentially lead to severe disease recurrence, especially cessation of natalizumab and fingolimod. Similar to fingolimod, siponimod is a sphingosine-1-phosphate receptor modulator that inhibits the egress of a lymphocyte subpopulation from lymph nodes. In the present case report, we describe a patient with MS who experienced substantial disease exacerbation after withdrawal from siponimod

Severe disease exacerbations in patients with multiple sclerosis after discontinuing fingolimod

Discontinuation of fingolimod in patients with multiple sclerosis (MS) can lead to disease reactivation. In this review, we describe cases of severe exacerbations in patients with MS following discontinuation of fingolimod, including three cases from our center. We consider potential mechanisms of disease reactivation after cessation of fingolimod, and the evidence supporting this rebound effect. We conclude that discontinuation of fingolimod results in the return of disease activity, which then leads to severe exacerbations (i.e., rebounds) in a clinically significant proportion of patients. Lastly, we consider disease-modifying treatment options for patients who discontinue fingolimod

The Maternal and Fetal Outcomes of Pregnancy in Wilson’s Disease: A Systematic Literature Review and Meta-Analysis

Wilson’s disease (WD) is a rare, treatable genetic disorder with multi-organ symptoms related mainly to copper accumulation. Most patients become aware of the disease as young adults, thus knowledge on fertility, pregnancy course and outcome is very important both for patients and physicians. The aim of this study was to perform a systematic review and meta-analysis of pregnancy outcomes in women with WD. This systematic literature review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were identified by searching the PubMed database (up to 12 January 2022) and by screening reference lists. We found 49 publications, including 13 retrospective studies and 36 series and case reports on pregnancy outcomes in WD patients. In total, descriptions of 449 pregnant women with 822 pregnancies were retrieved. Successful deliveries were achieved in 78.3% (644/822) of all pregnancies. Spontaneous abortions were observed in 21.7% (178/822) of pregnancies, more frequently in patients who were untreated 68.6% (96/140). Analyzing maternal outcome, 2.2% (18/822) of pregnancies were associated with the aggravation of neurological symptoms. Symptoms of hepatic deterioration were observed in 4.6% (38/822) of cases. These were usually transient and recovered after pregnancy; however, death due to liver failure was observed in 0.2% (2/822) of cases. Birth defects occurred in 4.7% (39/822) of pregnancies. The available meta-analysis showed statistically significant positive associations between anti-copper treatment and pregnancy outcome. Our results document the significance of anti-copper treatment as the main factor leading to successful pregnancy, as well as positive outcomes for women with WD

Transcriptomic Profiling of Femoral Veins in Deep Vein Thrombosis in a Porcine Model

Deep vein thrombosis (DVT) is a severe disease affecting the human venous system, accompanied by high morbidity and mortality rates caused by early and late complications. The study aimed at analyzing the changes in the transcriptome of the femoral vein caused by DVT in the porcine model based on the formation of the thrombus in vivo. The study was performed on 11 castrated male pigs: A thrombus was formed in each left femoral vein in six animals; the remaining five served as a control group. Total RNA was isolated from the left femoral veins of the experimental and control animals. High-throughput RNA sequencing was used to analyze the global changes in the transcriptome of veins with induced DVT. Applied multistep bioinformatics revealed 1474 differentially expressed genes (DEGs): 1019 upregulated and 455 downregulated. Functional Gene Ontology annotated 1220 of DEGs into 225 biological processes, 30 molecular functions and 40 cellular components categories. KEGG analysis disclosed TNF, NF-κB and apoptosis pathways’ overexpression in DVT samples. A thorough analysis of the detected DEGs indicated that a dysregulated inflammatory response and disturbed balance between clotting and anti-clotting factors play a crucial role in the process of DVT

Pulmonary artery embolism: comprehensive transcriptomic analysis in understanding the pathogenic mechanisms of the disease

Abstract Background Pulmonary embolism (PE) is a severe disease that usually originates from deep vein thrombosis (DVT) of the lower extremities. This study set out to investigate the changes in the transcriptome of the pulmonary artery (PA) in the course of the PE in the porcine model. Methods The study was performed on 11 male pigs: a thrombus was formed in each right femoral vein in six animals, and then was released to induce PE, the remaining five animals served as a control group. In the experimental animals total RNA was isolated from the PA where the blood clot lodged, and in the control group, from the corresponding PA segments. High-throughput RNA sequencing was used to analyse the global changes in the transcriptome of PA with induced PE (PA-E). Results Applied multistep bioinformatics revealed 473 differentially expressed genes (DEGs): 198 upregulated and 275 downregulated. Functional Gene Ontology annotated 347 DEGs into 27 biological processes, 324 to the 11 cellular components and 346 to the 2 molecular functions categories. In the signaling pathway analysis, KEGG ‘protein processing in endoplasmic reticulum’ was identified for the mRNAs modulated during PE. The same KEGG pathway was also exposed by 8 differentially alternative splicing genes. Within single nucleotide variants, the 61 allele-specific expression variants were localised in the vicinity of the genes that belong to the cellular components of the ‘endoplasmic reticulum’. The discovered allele-specific genes were also classified as signatures of the cardiovascular system. Conclusions The findings of this research provide the first thorough investigation of the changes in the gene expression profile of PA affected by an embolus. Evidence from this study suggests that the disturbed homeostasis in the biosynthesis of proteins in the endoplasmic reticulum plays a major role in the pathogenesis of PE

A Reliability of Active and Passive Knee Joint Position Sense Assessment Using the Luna EMG Rehabilitation Robot

Joint position sense (JPS) is the awareness of joint location in space, indicating accuracy and precision of the movement. Therefore, the aim of the present study is to determine the reliability of active and passive JPS assessment regarding the knee joint. This was carried out using the Luna EMG rehabilitation robot. Further analysis assessed whether the examination of only the dominant site is justified and if there are differences between sites. The study comprised 24 healthy male participants aged 24.13 ± 2.82 years, performing sports at a recreational level. Using the Luna EMG rehabilitation robot, JPS tests were performed for the right and left knees during flexion and extension in active and passive mode, in two separate sessions with a 1-week interval. Both knee flexion and extension in active and passive modes demonstrated high reliability (ICC = 0.866–0.982; SEM = 0.63–0.31). The mean JPS angle error did not differ significantly between the right and left lower limbs (p < 0.05); however, no between-limb correlation was noted (r = 0.21–0.34; p > 0.05). The Bland–Altman plots showed that the between-limb bias was minimal, with relatively wide limits of agreement. Therefore, it was concluded that the Luna EMG rehabilitation robot is a reliable tool for active and passive knee JPS assessment. In our study, JPS angle error did not differ significantly between left and right sides; however, the slight asymmetry was observed (visible in broad level of agreement exceeding 5° in Bland–Altman plots), what may suggest that in healthy subjects, e.g., active athletes, proprioception should always be assessed on both sides

A pan-Baltic assessment of temporal trends in coastal pike populations

The northern pike (Esox lucius) is an iconic predatory fish species of significant recreational value and ecological role in the Baltic Sea. Some earlier studies indicate local declines of pike in the region, but a thorough spatial evaluation of regional population trends of pike in the Baltic Sea is lacking. In this study, we collate data from 59 unique time-series from fisheries landings and fishery-independent monitoring programs to address temporal trends in pike populations since the mid-2000′s in eight countries surrounding the Baltic Sea. In a common analysis considering all time-series in concert, we found indications of an overall regional temporal decline of pike in the Baltic Sea, but trends differed among countries. Individual negative trends in time-series were moreover found in several regions of the Baltic Sea, but predominantly so in the central and southern parts, while positive trends were only found in Estonia and northern Finland. The mix of data used in this study is inherently noisy and to some extent of uncertain quality, but as a result of the overall negative trends, together with the socioeconomic and ecological importance of pike in coastal areas of the Baltic Sea, we suggest that actions should be taken to protect and restore pike populations. Management measures should be performed in combination with improved fishery-independent monitoring programs to provide data of better quality and development of citizen-science approaches as a data source for population estimates. Possible measures that could strengthen pike populations include harvest regulations (including size limits, no-take areas and spawning closures), habitat protection and restoration, and an ecosystem-based approach to management considering also the impact of natural predators

A pan-Baltic assessment of temporal trends in coastal pike populations

The northern pike (Esox lucius) is an iconic predatory fish species of significant recreational value and ecological role in the Baltic Sea. Some earlier studies indicate local declines of pike in the region, but a thorough spatial evaluation of regional population trends of pike in the Baltic Sea is lacking. In this study, we collate data from 59 unique time-series from fisheries landings and fishery-independent monitoring programs to address temporal trends in pike populations since the mid-2000′s in eight countries surrounding the Baltic Sea. In a common analysis considering all time-series in concert, we found indications of an overall regional temporal decline of pike in the Baltic Sea, but trends differed among countries. Individual negative trends in time-series were moreover found in several regions of the Baltic Sea, but predominantly so in the central and southern parts, while positive trends were only found in Estonia and northern Finland. The mix of data used in this study is inherently noisy and to some extent of uncertain quality, but as a result of the overall negative trends, together with the socioeconomic and ecological importance of pike in coastal areas of the Baltic Sea, we suggest that actions should be taken to protect and restore pike populations. Management measures should be performed in combination with improved fishery-independent monitoring programs to provide data of better quality and development of citizen-science approaches as a data source for population estimates. Possible measures that could strengthen pike populations include harvest regulations (including size limits, no-take areas and spawning closures), habitat protection and restoration, and an ecosystem-based approach to management considering also the impact of natural predators