The Relevance of Reperfusion Stroke Therapy for miR-9-3p and miR-9-5p Expression in Acute Stroke-A Preliminary Study.

Reperfusion stroke therapy is a modern treatment that involves thrombolysis and the mechanical removal of thrombus from the extracranial and/or cerebral arteries, thereby increasing penumbra reperfusion. After reperfusion therapy, 46% of patients are able to live independently 3 months after stroke onset. MicroRNAs (miRNAs) are essential regulators in the development of cerebral ischemia/reperfusion injury and the efficacy of the applied treatment. The first aim of this study was to examine the change in serum miRNA levels via next-generation sequencing (NGS) 10 days after the onset of acute stroke and reperfusion treatment. Next, the predictive values of the bioinformatics analysis of miRNA gene targets for the assessment of brain ischemic response to reperfusion treatment were explored. Human serum samples were collected from patients on days 1 and 10 after stroke onset and reperfusion treatment. The samples were subjected to NGS and then validated using qRT-PCR. Differentially expressed miRNAs (DEmiRNAs) were used for enrichment analysis. Hsa-miR-9-3p and hsa-miR-9-5p expression were downregulated on day 10 compared to reperfusion treatment on day 1 after stroke. The functional analysis of miRNA target genes revealed a strong association between the identified miRNA and stroke-related biological processes related to neuroregeneration signaling pathways. Hsa-miR-9-3p and hsa-miR-9-5p are potential candidates for the further exploration of reperfusion treatment efficacy in stroke patients.

The protective effect of low-dose minocycline on brain microvascular ultrastructure in a rodent model of subarachnoid hemorrhage.

The multifaceted nature of subarachnoid hemorrhage (SAH) pathogenesis is poorly understood. To date, no pharmacological agent has been found to be efficacious for the prevention of brain injury when used for acute SAH intervention. This study was undertaken to evaluate the beneficial effects of low-dose neuroprotective agent minocycline on brain microvascular ultrastructures that have not been studied in detail. We studied SAH brain injury using an in vivo prechiasmatic subarachnoid hemorrhage rodent model. We analyzed the qualitative and quantitative ultrastructural morphology of capillaries and surrounding neuropil in the rodent brains with SAH and/or minocycline administration. Here, we report that low-dose minocycline (1 mg/kg) displayed protective effects on capillaries and surrounding cells from significant SAH-induced changes. Ultrastructural morphology analysis revealed also that minocycline stopped endothelial cells from abnormal production of vacuoles and vesicles that compromise blood-brain barrier (BBB) transcellular transport. The reported ultrastructural abnormalities as well as neuroprotective effects of minocycline during SAH were not directly mediated by inhibition of MMP-2, MMP-9, or EMMPRIN. However, SAH brain tissue treated with minocycline was protected from development of other morphological features associated with oxidative stress and the presence of immune cells in the perivascular space. These data advance the knowledge on the effect of SAH on brain tissue ultrastructure in an SAH rodent model and the neuroprotective effect of minocycline when administered in low doses.

The three-dimensional conformation and activity of mitochondria in syncytial male germ line-cysts of medicinal leeches.

We studied the spatial conformation and activity of mitochondria in the developing syncytial male germline cysts during spermatogenesis of the medicinal leeches using light, fluorescent, transmission electron microscopy, and serial block-face scanning electron microscopy. In cysts with spermatogonia and spermatocytes, mitochondria form networks and are in a dynamic hyperfusion state, while in cysts with spermatids, a single huge mitochondrion is observed. As spermiogenesis progresses, this huge mitochondrion is finally located in the future midpiece. The highest activity, in terms of membrane potential, of the mitochondria in H. medicinalis germline cysts was observed in cysts with spermatocytes; the lowest was in cysts with late elongated spermatids.

A Simple Synthesis of Reduction-Responsive Acrylamide-Type Nanogels for miRNA Delivery.

MicroRNAs (miRNAs) have great therapeutic potential; however, their delivery still faces huge challenges, especially given the short half-life of naked miRNAs due to rapid hydrolysis or inactivation by abundant nucleases in the systemic circulation. Therefore, the search for reliable miRNA delivery systems is crucial. Nanogels are one of the more effective nanocarriers because they are biocompatible and have a high drug-loading capacity. In this study, acrylamide-based nanogels containing cationic groups and redox-sensitive crosslinkers were developed for cellular delivery of anti-miR21 (a-miR21). To achieve this, post-polymerization loading of a-miR21 oligonucleotides into nanogels was performed by utilizing the electrostatic interaction between positively charged nanogels and negatively charged oligonucleotides. Different molar ratios of the amine groups (N) on the cationic nanogel and phosphate groups (P) on the miRNA were investigated. An N/P ratio of 2 allowed high miRNA loading capacity (MLC, 6.7% w/w) and miRNA loading efficiency (MLE, 99.7% w/w). Successful miRNA loading was confirmed by dynamic light scattering (DLS) and electrophoretic light scattering (ELS) measurements. miRNA-loaded nanogels (NG/miRNA) formed stable dispersions in biological media and showed an enhanced miRNA release profile in the presence of glutathione (GSH). Moreover, the addition of heparin to dissociate the miRNA from the cationic nanogels resulted in the complete release of miRNA. Lastly, a cell uptake study indicated that NG/miRNA could be easily taken up by cancer cells.

All for one: changes in mitochondrial morphology and activity during syncytial oogenesis†.

The syncytial groups of germ cells (germ-line cysts) forming in ovaries of clitellate annelids are an attractive model to study mitochondrial stage-specific changes. Using transmission electron microscopy, serial block-face scanning electron microscopy, and fluorescent microscopy, we analyzed the mitochondria distribution and morphology and the state of membrane potential in female cysts in Enchytraeus albidus. We visualized in 3D at the ultrastructural level mitochondria in cysts at successive stages: 2-celled, 4-celled, 16-celled cysts, and cyst in advanced oogenesis. We found that mitochondria form extensive aggregates-they are fused and connected into large and branched mitochondrial networks. The most extensive networks are formed with up to 10 000 fused mitochondria, whereas individual organelles represent up to 2% of the total mitochondrial volume. We classify such a morphology of mitochondria as a dynamic hyperfusion state and suggest that this can maintain their high activity and intensify the process of cellular respiration within the syncytial cysts. We found some individual mitochondria undergoing degradation, which implies that damaged mitochondria are removed from networks for their final elimination. As growing oocytes were shown to possess less active mitochondria than the nurse cells, the high activity of mitochondria in the nurse cells and their dynamic hyperfusion state are attributed to serve the needs of the growing oocyte. In addition, we measured by calorimetry the total antioxidant capacity of germ-line cysts in comparison with somatic tissue, and it suggests that antioxidative defense systems, together with mitochondrial networks, can effectively protect germ-line mitochondria from damage.

Data Integration-Possibilities of Molecular and Clinical Data Fusion on the Example of Thyroid Cancer Diagnostics.

(1) Background: The data from independent gene expression sources may be integrated for the purpose of molecular diagnostics of cancer. So far, multiple approaches were described. Here, we investigated the impacts of different data fusion strategies on classification accuracy and feature selection stability, which allow the costs of diagnostic tests to be reduced. (2) Methods: We used molecular features (gene expression) combined with a feature extracted from the independent clinical data describing a patient's sample. We considered the dependencies between selected features in two data fusion strategies (early fusion and late fusion) compared to classification models based on molecular features only. We compared the best accuracy classification models in terms of the number of features, which is connected to the potential cost reduction of the diagnostic classifier. (3) Results: We show that for thyroid cancer, the extracted clinical feature is correlated with (but not redundant to) the molecular data. The usage of data fusion allows a model to be obtained with similar or even higher classification quality (with a statistically significant accuracy improvement, a p-value below 0.05) and with a reduction in molecular dimensionality of the feature space from 15 to 3-8 (depending on the feature selection method). (4) Conclusions: Both strategies give comparable quality results, but the early fusion method provides better feature selection stability.

Relevance of admission hyperglycaemia and diabetes mellitus to efficacy and safety of mechanical thrombectomy in stroke patients.

INTRODUCTION: The relevance of diabetes mellitus (DM) to the efficacy of mechanical thrombectomy (MT) has been the subject of few studies and with only inconclusive results. OBJECTIVES: This study aimed to evaluate the effect of DM and admission hyperglycaemia on the efficacy and safety of MT in stroke patients. MATERIAL AND METHODS: This retrospective study analysis focused on the relevance of admission hyperglyacemia and DM to the functional status of patients treated with MT at the Upper Silesian Medical Centre of the Silesian Medical University in Katowice, Poland. RESULTS: 417 stroke patients (median age 70 years) were qualified for the study. There were 103 patients (24.70%) with DM. Admission hyperglycaemia ≥ 140 mg% was found in 91 patients (21.82%), of whom 69 were diagnosed with DM before or during hospitalisation. The parameters with the strongest effect on the functional status on days 7, 90 and 365 were: age, and neurological status according to the National Institutes of Health Stroke Scale (NIHSS) on the first day of ischaemic stroke before MT. The angiographic effect indirect after MT and patient functional status on days 7, 90 and 365 were comparable between the groups, regardless of the DM burden. The frequency of symptomatic intracranial bleeding 24 hours after MT was comparable between patients with and patients without DM (p = 0.092). Model based on parameters were age, NIHSS on the first day of ischaemic stroke, an when score in Thrombolysis In Cerebral Infarct (TICI) showed good predictive attributes for the functional status of patients in the acute period (day 7). Age, a lack of admission hyperglycaemia, and the neurological state on day 1 of ischaemic stroke (before MT) were the key parameters for a favourable outcome (≤ 2 points on the modified Rankin Scale, mRS) on day 90. Admission hyperglycaemia ≥ 140 mg/dL, regardless of the presence or absence of DM, had a negative effect on achieving a good functional status one week after stroke onset. CONCLUSIONS: Diabetes mellitus has a neutral effect on the angiographic and clinical outcomes of mechanical thrombectomy in stroke patients. It does not increase the risk of intracranial haemorrhage after instrumental therapy. It is admission hyperglycaemia, rather than diabetes mellitus, that is a predictor of poor functional status in patients treated with thrombectomy. According to our results, the patient's neurological status, age, and the outcome of thrombectomy are relevant to the functional status in the acute ischaemic stroke period.

MCPIP1 expression positively correlates with melanoma-specific survival of patients, and its overexpression affects vital intracellular pathways of human melanoma cells.

The suppressive activity of monocyte chemoattractant protein 1-induced protein 1 (MCPIP1) an inflammation-related ribonuclease, has been described in a few cancer types but has yet to be assessed in the most common subtype of skin cancer: melanoma. Here, we have evaluated the MCPIP1 expression in melanoma tissues by reanalysis of publicly available transcriptome data from 89 melanoma samples, and immunohistochemical staining of 21 primary and 81 metastatic melanomas. Our data implicated decreased MCPIP1 expression in melanoma tumors compared to normal tissues, and positive correlation between high ribonuclease expression and melanoma-specific survival of patients. To investigate the ribonuclease activity in melanoma cells, MCPIP1 was ectopically expressed in the MV3 human melanoma cell line. Following the transcriptome, proteome, and intracellular signaling of MCPIP1-overexpressing MV3 cells was assessed via real-time quantitative polymerase chain reaction, Western blot analysis, and RNAseq. MV3 cells overexpressing MCPIP1 exhibited a broad range of alterations in the transcriptome and proteome, as well as in the phosphorylation status of a number of proteins, strongly indicating MCPIP1-dependent cell cycle arrest and inhibition of Akt/mTOR signaling in these cells. Moreover, we have shown, that MCPIP1 overexpression downregulates miRNA-193a-3p expression in MV3 cells. Furthermore, the majority of the described effects were dependent on the ribonucleolytic activity of the protein. The presented body of data strongly suggests a potential tumor suppressor role and possible future application as a positive prognostic marker of MCPIP1 protein in melanoma.

Obesity-associated deterioration of the hippocampus is partially restored after weight loss.

OBJECTIVE: Obesity is a multidimensional condition that is treatable by the restoration of a lean phenotype; however, some obesity-related outcomes may persist after weight normalization. Among the organs of the human body, the brain possesses a relatively low regenerative capacity and could retain perturbations established as a result of developmental obesity. Calorie restriction (CR) or a restricted ketogenic diet (KD) are successfully used as weight loss approaches, but their impact on obesity-related effects in the brain have not been previously evaluated. METHODS: We performed a series of experiments in a rat model of developmental obesity induced by a 12-week cafeteria diet, followed by CR to implement weight loss. First, we assessed the impact of obesity on neurogenesis (BrdU incorporation into the hippocampus), cognitive function (water maze), and concomitant changes in hippocampal protein expression (GC/MS-MS, western blot). Next, we repeated these experiments in a rat model of weight loss induced by CR. We also measured mitochondrial enzyme activity in rats after weight loss during the fed or fasting state. This study was extended by additional experiments with restricted KD used as a weight loss approach in order to compare the efficacy of two different nutritional interventions used in the treatment of obesity on hippocampal functions. By using a modified version of the water maze we evaluated cognitive abilities in rats subjected to weight loss by CR or a restricted KD. RESULTS: In this study, obesity affected metabolic processes, upregulated hippocampal NF-κB, and induced proteomic differences which were associated with impaired cognition and neurogenesis. Weight loss improved neurogenesis and enhanced cognition. While the expression pattern of some proteins persisted after weight loss, most of the changes appeared de novo revealing metabolic adjustment by overactivation of citrate synthase and downregulation of ATP synthase. As a consequence of fasting, the activity of these enzymes indicated hippocampal adaptation to negative energy balance during the weight loss phase of CR. Moreover, the effects on cognitive abilities measured after weight loss were negatively correlated with the animal weight measured at the final stage of weight gain. This was alleviated by KD, which improved cognition when used as a weight loss approach. CONCLUSIONS: The study shows that cognition and mitochondrial metabolism in the hippocampus are affected by CR- or KD-induced weight loss.

MCPIP1 ribonuclease can bind and cleave AURKA mRNA in MYCN-amplified neuroblastoma cells.

The role of the inflammation-silencing ribonuclease, MCPIP1 (monocyte chemoattractant protein-induced protein 1), in neoplasia continuous to emerge. The ribonuclease can cleave not only inflammation-related transcripts but also some microRNAs (miRNAs) and viral RNAs. The suppressive effect of the protein has been hitherto suggested in breast cancer, clear cell renal cell carcinoma, osteosarcoma, and neuroblastoma. Our previous results have demonstrated a reduced levels of several oncogenes, as well as inhibited growth of neuroblastoma cells upon MCPIP1 overexpression. Here, we investigate the mechanisms underlying the suppression of MYCN proto-oncogene, bHLH transcription factor (MYCN)-amplified neuroblastoma cells overexpressing the MCPIP1 protein. We showed that the levels of several transcripts involved in cell cycle progression decreased in BE(2)-C and KELLY cells overexpressing MCPIP1 in a ribonucleolytic activity-dependent manner. However, RNA immunoprecipitation indicated that only AURKA mRNA (encoding for Aurora A kinase) interacts with the ribonuclease. Furthermore, the application of a luciferase assay suggested MCPIP1-dependent destabilization of the transcript. Further analyses demonstrated that the entire conserved region of AURKA seems to be indispensable for the interaction with the MCPIP1 protein. Additionally, we examined the effect of the ribonuclease overexpression on the miRNA expression profile in MYCN-amplified neuroblastoma cells. However, no significant alterations were observed. Our data indicate a key role of the binding and cleavage of the AURKA transcript in an MCPIP1-dependent suppressive effect on neuroblastoma cells.

The Influence of Selected Meteorological Factors on the Prevalence and Course of Stroke.

Background: The objective of this study was to evaluate the impact of weather factors on stroke parameters. Methods: This retrospective study analyzed the records of stroke patients concerning the influence of meteorological conditions and moon phases on stroke parameters. Results: The study group consisted of 402 patients aged between 20 and 102; women constituted 49.8% of the subjects. Ischaemic stroke was diagnosed in 90.5% of patients and hemorrhagic stroke was diagnosed in 9.5% of patients. The highest number of hospitalizations due to stroke was observed in January (48 events); the lowest number was observed in July (23 events). There was no statistically significant correlation between the meteorological parameters on the day of onset and the preceding day of stroke and the neurological status (NIHSS) of patients. Mean air temperature on the day of stroke and the day preceding stroke was significantly lower in the group of patients discharged with a very good functional status (≤2 points in modified Rankin scale (mRS)) compared to the patients with a bad functional status (>2 points in mRS); respectively: 7.98 ± 8.01 vs. 9.63 ± 7.78; p = 0.041 and 8.13 ± 7.72 vs. 9.70 ± 7.50; p = 0.048). Humidity above 75% on the day of stroke was found to be a factor for excellent functional state (RR 1.61; p = 0.016). The total anterior circulation infarcts (in comparison with stroke in the other localization) were more frequent (70%) during a third quarter moon (p = 0.011). The following parameters had a significant influence on the number of stroke cases in relation to autumn having the lowest number of onsets: mean temperature (OR 1.019 95% CI 1.014-1.024, p < 0.000), humidity (OR 1.028, CI 1.023-1.034, p < 0.0001), wind speed (OR 0.923, 95% CI 0.909-0.937, p < 0.0001), insolation (OR 0.885, 95% CI 0.869-0.902, p < 0.0001), precipitation (OR 0.914, 95% CI 0.884-0.946, p < 0.0001). Conclusion: Air humidity and air temperature on the day of stroke onset as well as air temperature on the day preceding stroke are important for the functional status of patients in the acute disease period. A combination of the following meteorological parameters: lowered mean temperature and low sunshine, high humidity and high wind speed all increase the risk of stroke during the winter period. High humidity combined with high precipitation, low wind speed and low sunshine in the autumn period are associated with the lowest stroke incidence risk. A possible relationship between phases of the moon and the incidence requires further investigation.

A Possible Role for Arylsulfatase G in Dermatan Sulfate Metabolism.

Perturbations of glycosaminoglycan metabolism lead to mucopolysaccharidoses (MPS)-lysosomal storage diseases. One type of MPS (type VI) is associated with a deficiency of arylsulfatase B (ARSB), for which we previously established a cellular model using pulmonary artery endothelial cells with a silenced ARSB gene. Here, we explored the effects of silencing the ARSB gene on the growth of human pulmonary artery smooth muscle cells in the presence of different concentrations of dermatan sulfate (DS). The viability of pulmonary artery smooth muscle cells with a silenced ARSB gene was stimulated by the dermatan sulfate. In contrast, the growth of pulmonary artery endothelial cells was not affected. As shown by microarray analysis, the expression of the arylsulfatase G (ARSG) in pulmonary artery smooth muscle cells increased after silencing the arylsulfatase B gene, but the expression of genes encoding other enzymes involved in the degradation of dermatan sulfate did not. The active site of arylsulfatase G closely resembles that of arylsulfatase B, as shown by molecular modeling. Together, these results lead us to propose that arylsulfatase G can take part in DS degradation; therefore, it can affect the functioning of the cells with a silenced arylsulfatase B gene.

Differences in Gene Expression Profile of Primary Tumors in Metastatic and Non-Metastatic Papillary Thyroid Carcinoma-Do They Exist?

Molecular mechanisms of distant metastases (M1) in papillary thyroid cancer (PTC) are poorly understood. We attempted to analyze the gene expression profile in PTC primary tumors to seek the genes associated with M1 status and characterize their molecular function. One hundred and twenty-three patients, including 36 M1 cases, were subjected to transcriptome oligonucleotide microarray analyses: (set A-U133, set B-HG 1.0 ST) at transcript and gene group level (limma, gene set enrichment analysis (GSEA)). An additional independent set of 63 PTCs, including 9 M1 cases, was used to validate results by qPCR. The analysis on dataset A detected eleven transcripts showing significant differences in expression between metastatic and non-metastatic PTC. These genes were validated on microarray dataset B. The differential expression was positively confirmed for only two genes: IGFBP3, (most significant) and ECM1. However, when analyzed on an independent dataset by qPCR, the IGFBP3 gene showed no differences in expression. Gene group analysis showed differences mainly among immune-related transcripts, indicating the potential influence of tumor immune infiltration or signal within the primary tumor. The differences in gene expression profile between metastatic and non-metastatic PTC, if they exist, are subtle and potentially detectable only in large datasets.

Bis-anthracycline WP760 abrogates melanoma cell growth by transcription inhibition, p53 activation and IGF1R downregulation.

Anthracycline chemotherapeutics, e.g. doxorubicin and daunorubicin, are active against a broad spectrum of cancers. Their cytotoxicity is mainly attributed to DNA intercalation, interference with topoisomerase activity, and induction of double-stranded DNA breaks. Since modification of anthracyclines can profoundly affect their pharmacological properties we attempted to elucidate the mechanism of action, and identify possible molecular targets, of bis-anthracycline WP760 which previously demonstrated anti-melanoma activity at low nanomolar concentrations. We studied the effect of WP760 on several human melanoma cell lines derived from tumors in various development stages and having different genetic backgrounds. WP760 inhibited cell proliferation (IC50 = 1-99 nM), impaired clonogenic cell survival (100 nM), and inhibited spheroid growth (≥300 nM). WP760 did not induce double-stranded DNA breaks but strongly inhibited global transcription. Moreover, WP760 caused nucleolar stress and led to activation of the p53 pathway. PCR array analysis showed that WP760 suppressed transcription of ten genes (ABCC1, MTOR, IGF1R, EGFR, GRB2, PRKCA, PRKCE, HDAC4, TXNRD1, AKT1) associated with, inter alia, cytoprotective mechanisms initiated in cancer cells during chemotherapy. Furthermore, WP760 downregulated IGF1R and upregulated PLK2 expression in most of the tested melanoma cell lines. These results suggest that WP760 exerts anti-melanoma activity by targeting global transcription and activation of the p53 pathway and could become suitable as an effective therapeutic agent.

Initial stage of the biofilm formation on the NiTi and Ti6Al4V surface by the sulphur-oxidizing bacteria and sulphate-reducing bacteria.

The susceptibility to the fouling of the NiTi and Ti6Al4V alloys due to the adhesion of microorganisms and the biofilm formation is very significant, especially in the context of an inflammatory state induced by implants contaminated by bacteria, and the implants corrosion stimulated by bacteria. The aim of this work was to examine the differences between the sulphur-oxidizing bacteria (SOB) and sulphate-reducing bacteria (SRB) strains in their affinity for NiTi and Ti6Al4V alloys. The biofilms formed on alloy surfaces by the cells of five bacterial strains (aerobic SOB Acidithiobacillus thiooxidans and Acidithiobacillus ferrooxidans, and anaerobic SRB Desulfovibrio desulfuricans-3 strains) were studied using scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). The protein concentrations in liquid media have also been analyzed. The results indicate that both alloys tested may be colonized by SOB and SRB strains. In the initial stage of the biofilm formation, the higher affinity of SRB to both the alloys has been documented. However, the SOB strains have indicated the higher (although differentiated) adaptability to changing environment as compared with SRB. Stimulation of the SRB growth on the alloys surface was observed during incubation in the liquid culture media supplemented with artificial saliva, especially of lower pH (imitated conditions under the inflammatory state, for example in the periodontitis course). The results point to the possible threat to the human health resulting from the contamination of the titanium implant alloys surface by the SOB (A. thiooxidans and A. ferrooxidans) and SRB (D. desulfuricans).

Development of a population of cancer cells: Observation and modeling by a Mixed Spatial Evolutionary Games approach.

Living cells, like whole living organisms during evolution, communicate with their neighbors, interact with the environment, divide, change their phenotypes, and eventually die. The development of specific ways of communication (through signaling molecules and receptors) allows some cellular subpopulations to survive better, to coordinate their physiological status, and during embryonal development to create tissues and organs or in some conditions to become tumors. Populations of cells cultured in vitro interact similarly, also competing for space and nutrients and stimulating each other to better survive or to die. The results of these intercellular interactions of different types seem to be good examples of biological evolutionary games, and have been the subjects of simulations by the methods of evolutionary game theory where individual cells are treated as players. Here we present examples of intercellular contacts in a population of living human cancer HeLa cells cultured in vitro and propose an evolutionary game theory approach to model the development of such populations. We propose a new technique termed Mixed Spatial Evolutionary Games (MSEG) which are played on multiple lattices corresponding to the possible cellular phenotypes which gives the possibility of simulating and investigating the effects of heterogeneity at the cellular level in addition to the population level. Analyses performed with MSEG suggested different ways in which cellular populations develop in the case of cells communicating directly and through factors released to the environment.

Direct Exposure to Outdoor Air Pollution Worsens the Functional Status of Stroke Patients Treated with Mechanical Thrombectomy.

Background The effect of air pollutants on the functional status of stroke patients in short-term follow-up is unknown. The aim of this study was to evaluate the effect of air pollution occurring in the stroke period and during hospitalization on the functional status of patients undergoing mechanical thrombectomy (MT). Methods Our study included stroke patients for which the individual-level exposure to ambient levels of O3, CO, SO2, NO2, PM2.5, and PM10 during the acute stroke period was assessed. The correlations between the air pollutants' concentration and the patients' functional state were analyzed. A total of 499 stroke patients (mean age: 70) were qualified. Results The CO concentration at day of stroke onset was found to be significant regarding the functional state of patients on the 10th day (OR 0.014 95% CI 0-0.908, p = 0.048). The parameters which increased the risk of death in the first 10 days were as follows: NIHSS (OR 1.27; 95% CI 1.15-1.42; p < 0.001), intracranial bleeding (OR 4.08; 95% CI 1.75-9.76; p = 0.001), and SO2 concentration on day 2 (OR 1.21; 95% CI 1.02-1.47; p = 0.03). The parameters which increased the mortality rate within 90 days include age (OR 1.07; 95% CI 1.02-1.13; p = 0.005) and NIHSS (OR 1.37; 95% CI 1.19-1.63; p < 0.001). Conclusions Exposure to air pollution with CO and SO2 during the acute stroke phase has adverse effects on the patients' functional status. A combination of parameters, such as neurological state, hemorrhagic transformation, and SO2 exposure, is unfavorable in terms of the risk of death during a hospitalization due to stroke. The risk of a worsened functional status of patients in the first month of stroke rises along with the increase in particulate matter concentrations within the first days of stroke.

The Usefulness of Outpatient Cardiac Telemetry in Patients with Cryptogenic Stroke.

Introduction: Atrial fibrillation (AF), apart from non-stenotic supracardiac atherosclerosis and neoplastic disease, is the leading cause of cryptogenic stroke, including embolic stroke of un-determined source (ESUS). The aim of our study was to determine the prevalence of AF in ESUS patients based on 30-day telemetric heart rate monitoring initiated within three months after stroke onset. Another aim was to identify factors that increase the likelihood of detecting subsequent AF among ESUS patients. Material and Methods: patients with first-ever stroke classified as per the ESUS definition were eligible for this study. All patients underwent outpatient 30-day telemetric heart rate monitoring. Results: In the period between 2020 and 2022, 145 patients were included. The mean age of all qualified patients was 54; 40% of eligible patients were female. Six patients (4.14%), mostly male patients (4 vs. 2), were diagnosed with AF within the study period. In each case, the diagnosis related to a patient whose stroke occurred in the course of large vessel occlusion. Episodes of AF were detected between day 1 and 25 after starting ECG monitoring. Out of the analyzed parameters that increase the probability of, A.F.; only supraventricular extrasystoles proved to be an independent factor regarding an increased risk of AF [OR 1.046, CI 95% 1.016-1.071, p-value < 0.01]. Conclusions: The use of telemetry heart rhythm monitoring in an outpatient setting can detect AF in 4% of ESUS patients who have undergone prior diagnostic procedures for cardiogenic embolism. Supraventricular extrasystoles significantly increases the likelihood of AF detection in patients with ESUS within three months following stroke. Comorbid coronary artery disease, diabetes and hypertension, rather than a single-factor clinical burden, increase the likelihood of AF detection in older ESUS patients. ESUS in the course of large vessel occlusion is probably associated with an increased likelihood of cardiogenic embolism.

Effect of gluten on the digestive tract and fat body of Telodeinopus aoutii (Diplopoda).

Adult specimens or larvae of invertebrates used as food for vertebrates are often maintained close to gluten so they might become vectors for cereal proteins. However, the tissues and internal organs can respond differently in animals with different feeding habits. The midgut epithelium might be a first and sufficient barrier preventing uptake and effects of gluten on the whole body, while the fat body is the main organ that accumulates different xenobiotics. Good models for such research are animals that do not feed on gluten-rich products in their natural environment. The project's goal was to investigate alterations in the midgut epithelium and fat body of the herbivorous millipede Telodeinopus aoutii (Diplopoda) and analyze cell death processes activated by gluten. It enabled us to determine whether changes were intensified or reversed by adaptive mechanisms. Adult specimens were divided into control and experimental animals fed with mushrooms supplemented with gluten and analyzed using transmission electron microscopy, flow cytometry, and confocal microscopy. Two organs were isolated for the qualitative and quantitative analysis: the midgut and the fat body. Our study of the herbivorous T. aoutii which does not naturally feed on gluten containing diet showed that continuous and prolonged gluten feeding activates repair processes that inhibit the processes of cell death (apoptosis and necrosis) and induce an increase in cell viability.

Epileptiform activity in the acute phase of stroke predicts the outcomes in patients without seizures.

Background and purpose: The abnormalities in EEG of stroke-patients increase the risk of epilepsy but their significancy for poststroke outcome is unclear. This presented study was aimed at determining the prevalence and nature of changes in EEG recordings from the stroke hemisphere and from the contralateral hemisphere. Another objective was to determine the significance of abnormalities in EEG in the first days of stroke for the post-stroke functional status on the acute and chronic phase of disease. Methods: In all qualified stroke-patients, EEG was performed during the first 3 days of hospitalization and at discharge. The correlation between EEG abnormalities both in the stroke hemisphere and in the collateral hemisphere with the neurological and functional state in various time points was performed. Results: One hundred thirty-one patients were enrolled to this study. Fifty-eight patients (44.27%) had abnormal EEG. The sporadic discharges and generalized rhythmic delta activity were the most common abnormalities in the EEG. The neurological status on the first day and the absence of changes in the EEG in the hemisphere without stroke were the independent factors for good neurological state (0-2 mRS) at discharge. The age-based analysis model (OR 0.981 CI 95% 0.959-1.001, p = 0.047), neurological status on day 1 (OR 0.884 CI 95% 0.82-0.942, p < 0.0001) and EEG recording above the healthy hemisphere (OR 0.607 CI 95% 0.37-0.917, p = 0.028) had the highest prognostic value in terms of achieving good status 90 days after stroke. Conclusions: Abnormalities in EEG without clinical manifestation are present in 40% of patients with acute stroke. Changes in EEG in acute stroke are associated with a poor neurological status in the first days and poor functional status in the chronic period of stroke.