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IntroductionVideolaryngoscopy (VL) is the recommended strategy for airway management in COVID-19 patients and guidelines recommends that all anesthesiologists should be trained to use and have immediate access to the device. However, the availability of VL in hospitals and its use may vary, as well as the choice of the device and necessary training. Our primary aim was to investigate data on availability of VL in Croatia, its use, the choice of the device and its implementation, with special consideration of COVID-19 management.Materials and methodsAn electronic survey was sent to all Croatian hospitals that have anesthesiology service available. The survey was designed to examine data on availability and use of VL with special consideration of COVID-19 wards. The survey was conducted between 1.03.2021 and 30.08.2021.ResultsResponse rate was 83%. VL was available in 86% of hospitals and the best supplied areas were intensive care units, general surgery and gynecology/obstetrics. The most common VL devices were Bonfils, C-MAC and C-MAC D-blade. The choice of VL was mainly based on centralized hospital procurement and informal introduction was found to be the most frequent training method. The VL was mainly used in Croatian hospitals in cases of difficult airway or as a backup method after failed intubation. Only 16% of hospitals reported regular use in everyday practice. Even though, VL was available in 64% of COVID-19 wards, only 21% of hospitals reported routine use.ConclusionAlthough VL is available in the majority of Croatian hospitals, its use is still mainly restricted to difficult airway scenarios. Use of VL in COVID-19 management is also low and education on the method is still mainly informal. Based upon our results better implementation in practice should be targeted, as well as formal skill trainings especially regarding COVID-19 care.

Copy number variants (CNVs) were the subject of extensive research in the past years. They are common features of the human genome that play an important role in evolution, contribute to population diversity, development of certain diseases, and influence host–microbiome interactions. CNVs have found application in the molecular diagnosis of many diseases and in non-invasive prenatal care, but their full potential is only emerging. CNVs are expected to have a tremendous impact on screening, diagnosis, prognosis, and monitoring of several disorders, including cancer and cardiovascular disease. Here, we comprehensively review basic definitions of the term CNV, outline mechanisms and factors involved in CNV formation, and discuss their evolutionary and pathological aspects. We suggest a need for better defined distinguishing criteria and boundaries between known types of CNVs.

Exosomes have the potential to be the future of personalized diagnostics and therapy. They are nano-sized particles between 30 and 100 nm flowing in the extracellular milieu, where they mediate cell–cell communication and participate in immune system regulation. Tumor-derived exosomes (TDEs) secreted from different types of cancer cells are the key regulators of the tumor microenvironment. With their immune suppressive cargo, TDEs prevent the antitumor immune response, leading to reduced effectiveness of cancer treatment by promoting a pro-tumorigenic microenvironment. Involved signaling pathways take part in the regulation of tumor proliferation, differentiation, apoptosis, and angiogenesis. Signal transducers and activators of transcription factors (STATs) and Janus kinase (JAK) signaling pathways are crucial in malignancies and autoimmune diseases alike, and their potential to be manipulated is currently the focus of interest. In this review, we aim to discuss exosomes, TDEs, and the JAK/STAT pathways, along with mediators like interleukins, tripartite motif proteins, and interferons.

Colorectal cancer (CRC) has one of the highest incidences among all types of malignant diseases, affecting millions of people worldwide. It shows slow progression, making it preventable. However, this is not the case due to shortcomings in its diagnostic and management procedure and a lack of effective non-invasive biomarkers for screening. Here, we discuss CRC-associated microRNAs (miRNAs) and gut microbial species with potential as CRC diagnostic and therapy biomarkers. We provide rich evidence of cross-kingdom miRNA-mediated interactions between the host and gut microbiome. miRNAs have emerged with the ability to shape the composition and dynamics of gut microbiota. Intestinal microbes can uptake miRNAs, which in turn influence microbial growth and provide the ability to regulate the abundance of various microbial species. In the context of CRC, targeting miRNAs could aid in manipulating the balance of the microbiota. Our findings suggest the need for correlation analysis between the composition of the gut microbiome and the miRNA expression profile.

Xenoestrogens are natural or synthetic compounds that mimic the effect of endogenous estrogens and might cause cancer. We aimed to compare the global transcriptomic response to zearalenone (ZEA; mycotoxin) and bisphenol A (BPA; plastic additive) with the effect of physiological estradiol (E2) in the PEO1 human ovarian cell line by mRNA and microRNA sequencing. Estrogen exposure induced remarkable transcriptomic changes: 308, 288 and 63 genes were upregulated (log2FC > 1); 292, 260 and 45 genes were downregulated (log2FC < −1) in response to E2 (10 nM), ZEA (10 nM) and BPA (100 nM), respectively. Furthermore, the expression of 13, 11 and 10 miRNAs changed significantly (log2FC > 1, or log2FC < −1) after exposure to E2, ZEA and BPA, respectively. Functional enrichment analysis of the significantly differentially expressed genes and miRNAs revealed several pathways related to the regulation of cell proliferation and migration. The effect of E2 and ZEA was highly comparable: 407 genes were coregulated by these molecules. We could identify 83 genes that were regulated by all three treatments that might have a significant role in the estrogen response of ovarian cells. Furthermore, the downregulation of several miRNAs (miR-501-5p, let-7a-2-3p, miR-26a-2-3p, miR-197-5p and miR-582-3p) was confirmed by qPCR, which might support the proliferative effect of estrogens in ovarian cells.

MicroRNAs are short non-coding RNA molecules that are involved in tumor development and are considered to be promising candidates in cancer therapy. Here, we studied the role of miR-30s in the pathophysiology of ovarian cancer. According to our results miR-30a-5p, miR-30d-5p, and miR-30e-5p were overexpressed in the estrogen receptor α (ERα)-expressing PEO1 cell line compared to A2780 that lacks this receptor. Furthermore, the expression of miR-30a-5p, miR-30d-5p, and miR-30e-5p were induced in response to high-dose estrogen treatment in PEO1 where intensive cell death was observed according to the induction of apoptosis and autophagy. Lacking or blocking ERα function reduced tolerance to high-dose estrogen that suggests the importance of ERα-mediated estrogen response in the maintenance of proliferation. MiR-30d-5p mimic reduced cell proliferation in both A2780 and PEO1. Furthermore, it decreased the tolerance of PEO1 cells to high-dose estrogen by blocking the ERα-mediated estrogen response. This was accompanied by decreased SOX4 expression that is thought to be involved in the regulation of the PI3K/AKT pathway. Blocking this pathway by AZD8835 led to the same results. MiR-30d-5p or AZD8835 sensitized PEO1 cells to tamoxifen. We suggest that miR-30d-5p might be a promising candidate in the therapy of ovarian cancer.

Introduction Early endotracheal intubation improves neurological outcomes in cardiopulmonary resuscitation, although cardiopulmonary resuscitation is initially carried out by personnel with limited experience in a significant proportion of cases. Videolaryngoscopes might decrease the number of attempts and time needed, especially among novices. We sought to compare videolaryngoscopes with direct laryngoscopes in simulated cardiopulmonary resuscitation scenarios. Materials and methods Forty-four medical students were recruited to serve as novice users. Following brief, standardized training, students executed endotracheal intubation with the King Vision®, Macintosh and VividTrac® laryngoscopes, on a cardiopulmonary resuscitation trainer in normal and difficult airway scenarios. We evaluated the time to and proportion of successful intubation, the best view of the glottis, esophageal intubation, dental trauma and user satisfaction. Results In the normal airway scenario, significantly shorter intubation times were achieved using the King Vision® than the Macintosh laryngoscope. In the difficult airway scenario, we found that the VividTrac® was superior to the King Vision® and Macintosh laryngoscopes in the laryngoscopy time. In both scenarios, we noted no difference in the first-attempt success rate, but the best view of the glottis and dental trauma, esophageal intubation and bougie use were more frequent with the Macintosh laryngoscope than with the videolaryngoscopes. The shortest tube insertion times were achieved using the King Vision® in both scenarios. Conclusion All providers achieved successful intubation within three attempts, but we found no device superior in any of our scenarios regarding the first-attempt success rate. The King Vision® was superior to the Macintosh laryngoscope in the intubation time in the normal airway scenario and noninferior in the difficult airway scenario for novice users. We noted significantly less esophageal intubation using the videolaryngoscopes than using the Macintosh laryngoscope in both scenarios. Based on our results, the KingVision® might be recommended over the VividTrac® and Macintosh laryngoscopes for further evaluation.

IntroductionA major complication of sepsis is the development of acute kidney injury (AKI). Recently, it was shown that intracellular actin released from damaged tissues appears in the urine of patients with multiple organ dysfunction syndrome. Our aims were to measure urinary actin (u-actin) concentrations of septic and control patients and to test if u-actin levels could predict AKI and mortality.MethodsBlood and urine samples were collected from septic and sepsis-related AKI patients at three time points (T1-3): T1: within 24 hours after admission; T2: second day morning; T3: third day morning of follow-up. Patients with malignancies needing palliative care, end-stage renal disease or kidney transplantation were excluded. Serum and u-actin levels were determined by quantitative Western blot. Patients were categorized by the Sepsis-3 and KDIGO AKI classifications.ResultsIn our study, 17 septic, 43 sepsis-induced AKI and 24 control patients were enrolled. U-actin levels were higher in septic patients compared with controls during follow-up (pConclusionU-actin may be a complementary diagnostic biomarker to se-creatinine in sepsis-related AKI while higher u-actin levels also seem to reflect the severity of AKI. Further investigations may elucidate the importance of u-actin release in sepsis-related AKI.

Lynch syndrome (LS) is an autosomal dominant inherited cancer predisposition disorder, which may manifest as colorectal cancer (CRC), endometrial cancer (EC) or other malignancies of the gastrointestinal and genitourinary tract as well as the skin and brain. Its genetic cause is a defect in one of the four key DNA mismatch repair (MMR) loci. Testing of patients at risk is currently based on the absence of MMR protein staining and detection of mutations in cancer tissue and the germline, microsatellite instability (MSI) and the hypermethylated state of the MLH1 promoter. If LS is shown to have caused CRC, lifetime follow-up with regular screening (most importantly, colonoscopy) is required. In recent years, DNA and RNA markers extracted from liquid biopsies have found some use in the clinical diagnosis of LS. They have the potential to greatly enhance the efficiency of the follow-up process by making it minimally invasive, reproducible, and time effective. Here, we review markers reported in the literature and their current clinical applications, and we comment on possible future directions.

Abstract Background Our aim was to compare the perioperative time courses of matrix metalloproteinase-9 (MMP-9) and its inhibitor (TIMP-1) in during carotid endarterectomy (CEA) and carotid artery stenting (CAS). Methods In our prospective study, twenty-five patients who were scheduled to undergo CAS were enrolled. We used a matched, historical CEA group as controls. Blood samples were collected at four time points: T1: preoperative; T2: 60 min after stent insertion; T3: first postoperative morning; and T4: third postoperative morning. Plasma MMP-9 and TIMP-1 levels were measured by ELISA. Results In the CEA group, the plasma levels of MMP-9 were significantly elevated at T3 compared to T1. In the CAS group, there was no significant difference in MMP-9 levels in the perioperative period. MMP-9 levels were significantly higher in the T3 samples of the CEA group compared to the CAS group. Significantly lower TIMP-1 levels were measured in both groups at T2 than at T1 in both groups. MMP-9/TIMP-1 at T3 was significantly higher than that at T1 in the CEA group compared to both T1 and the CAS group. Conclusions CAS triggers smaller changes in the MMP-9-TIMP-1 system during the perioperative period, which may correlate with a lower incidence of central nervous system complications. Additional studies as well as cognitive and functional surveys are warranted to determine the clinical relevance of our findings. Trial registration NIH U.S. National Library of Medicine, Clinicaltrials.gov,NCT03410576, 24.01.2018, Retrospectively registered

Early detection, characterization and monitoring of cancer are possible by using extracellular vesicles (EVs) isolated from non-invasively obtained liquid biopsy samples. They play a role in intercellular communication contributing to cell growth, differentiation and survival, thereby affecting the formation of tumor microenvironments and causing metastases. EVs were discovered more than seventy years ago. They have been tested recently as tools of drug delivery to treat cancer. Here we give a brief review on extracellular vesicles, exosomes, microvesicles and apoptotic bodies. Exosomes play an important role by carrying extracellular nucleic acids (DNA, RNA) in cell-to-cell communication causing tumor and metastasis development. We discuss the role of extracellular vesicles in the pathogenesis of cancer and their practical application in the early diagnosis, follow up, and next-generation treatment of cancer patients.

Abstract Background Direct laryngoscopy remains the gold standard for endotracheal intubation and is preferred by experienced operators. However, an increasing number of reports currently support videolaryngoscopy, particularly for novice users. The widespread use of videolaryngoscopy may be limited due to financial limitations, especially in low-income countries. Therefore, affordable single-use scopes are now becoming increasingly popular. We sought to compare these new scopes with direct laryngoscopes and the previously tested videolaryngoscopes in mannequins by novices. Methods Fifty medical students were recruited to serve as novice users. Following brief, standardized training, students were asked to execute endotracheal intubation with each of the devices, including the Airtraq®, a custom-made videolaryngoscope, the King Vision®, the Macintosh laryngoscope and the VividTrac®, on an airway trainer (Laerdal Airway Management Trainer®) in normal and difficult airway scenarios. We evaluated the time to and the proportion of successful intubation, the best view of the glottis, esophageal intubation, dental trauma and user satisfaction. Results We observed no differences in esophageal intubation. However, intubation-related times, the view of the glottis and operator satisfaction were significantly better throughout the study with the commercial videolaryngoscopes. In comparison, the custom-made videolaryngoscope performance proved to be similar to that of the Macintosh laryngoscope. The VividTrac® performance was similar (P > 0.05) or significantly better than that of the King Vision® in both scenarios. Conclusions Based upon our results, the Airtraq®, King Vision® and VividTrac® were superior to the Macintosh laryngscope in both normal and difficult airway scencarios for novice users. In particular, our study is the first to report that the VividTrac® shows promise for further clinical evaluation.

Background: Preeclampsia (PE) is the major cause of maternal and fetal morbidity and mortality, affecting 3–8% of all pregnancies around the globe. miRNAs are small, noncoding RNA molecules, which negatively regulate gene expression. Abnormally expressed miRNAs contribute to pregnancy complications such as PE. The aim of our study was to find possible regulatory mechanisms by system biology approaches, which are connected to the pathogenesis of PE. Methods: We integrated publicly available miRNA and gene expression profiles and created a network from the significant miRNA–mRNA pairs with the help of MAGIA and Cytoscape softwares. Two subnetworks were expanded by adding protein–protein interactions. Differentially expressed miRNAs were identified for the evaluation of their regulatory effect. We analyzed the miRNAs and their targets using different bioinformatics tools and through literature research. Results: Altogether, 52,603 miRNA–mRNA interactions were generated by the MAGIA web tool. The top 250 interactions were visualized and pairs with q < 0.0001 were analyzed, which included 85 nodes and 80 edges signalizing the connections between 52 regulated genes and 33 miRNAs. A total of 11 of the regulated genes are PE related and 9 of them were targeted by multiple miRNAs. A total of 8 miRNAs were associated with PE before, and 13 miRNAs regulated more than 1 mRNA. Hsa-mir-210 was the highest degree node in the network and its role in PE is well established. Conclusions: We identified several miRNA–mRNA regulatory mechanisms which may contribute to the pathogenesis of PE. Further investigations are needed to validate these miRNA–mRNA interactions and to enlighten the possibilities of developing potential therapeutic targets.

IntroductionVideolaryngoscopy (VL) as a new airway management technique has evolved in recent decades, and a large number of videolaryngoscopes are now available on the market. Most recent major guidelines already recommend the immediate availability and use of VL in difficult airway management scenarios. However, national data on the availability of VL, introduction into practice and patterns of use are rarely published. Therefore, the current study aimed to provide data on VL in Hungary.Materials and methodsAn electronic survey was designed and popularized with the help of the Hungarian Society of Anaesthesiology and Intensive Therapy to explore the availability, use, and practice of and attitudes toward VL among Hungarian anesthesiologists. The survey was conducted between 01.01.2018 and 31.12.2018.ResultsIn total, 324 duly completed forms were returned and analyzed. Responders were mainly males (58%), specialists (80%) and those involved mainly in anesthesia practice (68%) in the public sector. Two hundred and ten (65%) responders had access to various videolaryngoscopes and were mainly from surgery, intensive care and traumatology units. No responders reported the availability of eight videolaryngoscopes out of the eighteen listed devices, and 32% of the responders had never used any videolaryngoscope in clinical settings. The most commonly available devices were KingVision, MacGrath Mac and Airtraq. Most of the responders reported using videolaryngoscopes mainly for difficult airway management and reported using a fiberscope as the first alternative device. Popular methods for selecting videolaryngoscopes included the following: short clinical trial (n = 67/324), decision of the departmental lead (n = 65/324) and price (n = 54/324). The majority of responders had some training prior to clinical application, but training was mainly voluntary. Overall, 98% of the responders considered videolaryngoscopes beneficial.ConclusionsApproximately two-thirds of Hungarian anesthesiologists have immediate access to videolaryngoscopes, which are used mainly for difficult airway management. The overall attitude towards VL is positive, and many videolaryngoscopes are known and have been used by Hungarian anesthesiologists. However, only a few devices on the market are used commonly. Based on the results, further improvement might be recommended regarding VL training and availability.

(1) Background: Glioblastoma multiforme (GBM) is among the most aggressive cancers with a poor prognosis. Treatment options are limited, clinicians lack efficient prognostic and predictive markers. Circulating miRNAs—besides being important regulators of cancer development—may have potential as diagnostic biomarkers of GBM. (2) Methods: In this study, profiling of 798 human miRNAs was performed on blood plasma samples from 6 healthy individuals and 6 patients with GBM, using a NanoString nCounter Analysis System. To validate our results, five miRNAs (hsa-miR-433-3p, hsa-miR-362-3p, hsa-miR-195-5p, hsa-miR-133a-3p, and hsa-miR-29a-3p) were randomly chosen for RT-qPCR detection. (3) Results: In all, 53 miRNAs were significantly differentially expressed in plasma samples of GBM patients when data were filtered for FC 1 and FDR 0.1. Target genes of the top 39 differentially expressed miRNAs were identified, and we carried out functional annotation and pathway enrichment analysis of target genes via GO and KEGG-based tools. General and cortex-specific protein–protein interaction networks were constructed from the target genes of top miRNAs to assess their functional connections. (4) Conclusions: We demonstrated that plasma microRNA profiles are promising diagnostic and prognostic molecular biomarkers that may find an actual application in the clinical practice of GBM, although more studies are needed to validate our results.

The term liquid biopsy reveals a non-invasive diagnostic method that might be based on the quantification of cell-free microRNAs in body fluids. However, the identification of candidates for liquid biopsy is challenging. Our aim was to compare the cell-free expression of miR-483-5p, miR-205-5p, and let-7f-5p in ovarian cell cultures and plasma samples of patients with ovarian cancer. Both the intracellular and cell-free expression of miR-205-5p and let-7f-5p proved to be higher in the Estrogen Receptor α (ERα) expressing PEO1 cell-line than in the estrogen non-sensitive A2780. Moreover, the expression of let-7f-5p was up-regulated in response to estradiol exposure that was diminished after the addition of an ERα selective antagonist. MiR-483-5p had lower intracellular and cell-free expression in PEO1. All these miRNAs had detectable expression level in plasma samples, among which miR-205-5p proved to be overexpressed in the plasma samples of patients with ovarian tumors compared to healthy controls and possessed an acceptable diagnostic potential with ROC-AUC 0.683 (95% CI 0.57–0.795). Functional annotation clustering of the target genes of miR-205-5p revealed several clusters involved in cancer development. We suggest that miR-205-5p might be a promising biomarker candidate in ovarian cancer that should be further analyzed in larger sample size.

Gains and losses of large segments of genomic DNA, known as copy number variants (CNVs) gained considerable interest in clinical diagnostics lately, as particular forms may lead to inherited genetic diseases. In recent decades, researchers developed a wide variety of cytogenetic and molecular methods with different detection capabilities to detect clinically relevant CNVs. In this review, we summarize methodological progress from conventional approaches to current state of the art techniques capable of detecting CNVs from a few bases up to several megabases. Although the recent rapid progress of sequencing methods has enabled precise detection of CNVs, determining their functional effect on cellular and whole-body physiology remains a challenge. Here, we provide a comprehensive list of databases and bioinformatics tools that may serve as useful assets for researchers, laboratory diagnosticians, and clinical geneticists facing the challenge of CNV detection and interpretation.

Exposure to physiological estrogens or xenoestrogens (e.g., zearalenone or bisphenol A) increases the risk for cancer. However, little information is available on their significance in ovarian cancer. We present a comprehensive study on the effect of estradiol, zearalenone and bisphenol A on the phenotype, mRNA, intracellular and cell-free miRNA expression of human epithelial ovarian cell lines. Estrogens induced a comparable effect on the rate of cell proliferation and migration as well as on the expression of estrogen-responsive genes (GREB1, CA12, DEPTOR, RBBP8) in the estrogen receptor α (ERα)-expressing PEO1 cell line, which was not observable in the absence of this receptor (in A2780 cells). The basal intracellular and cell-free expression of miR200s and miR203a was higher in PEO1, which was accompanied with low ZEB1 and high E-cadherin expression. These miRNAs showed a rapid but intermittent upregulation in response to estrogens that was diminished by an ERα-specific antagonist. The role of ERα in the regulation of the MIR200B-MIR200A-MIR429 locus was further supported by publicly available ChIP-seq data. MiRNA expression of cell lysates correlated well with cell-free miRNA expression. We conclude that cell-free miR200s might be promising biomarkers to assess estrogen sensitivity of ovarian cells.

Glioblastoma is a primary Central Nervous System (CNS) malignancy with poor survival. Treatment options are scarce and despite the extremely heterogeneous nature of the disease, clinicians lack prognostic and predictive markers to characterize patients with different outcomes. Certain immunohistochemistry, FISH, or PCR-based molecular markers, including isocitrate dehydrogenase1/2 (IDH1/2) mutations, epidermal growth factor receptor variant III (EGFRvIII) mutation, vascular endothelial growth factor overexpression (VEGF) overexpression, or (O6-Methylguanine-DNA methyltransferase promoter) MGMT promoter methylation status, are well-described; however, their clinical usefulness and accuracy is limited, and tumor tissue samples are always necessary. Liquid biopsy is a developing field of diagnostics and patient follow up in multiple types of cancer. Fragments of circulating nucleic acids are collected in various forms from different bodily fluids, including serum, urine, or cerebrospinal fluid in order to measure the quality and quantity of these markers. Multiple types of nucleic acids can be analyzed using liquid biopsy. Circulating cell-free DNA, mitochondrial DNA, or the more stable long and small non-coding RNAs, circular RNAs, or microRNAs can be identified and measured by novel PCR and next-generation sequencing-based methods. These markers can be used to detect the previously described alterations in a minimally invasive method. These markers can be used to differentiate patients with poor or better prognosis, or to identify patients who do not respond to therapy. Liquid biopsy can be used to detect recurrent disease, often earlier than using imaging modalities. Liquid biopsy is a rapidly developing field, and similarly to other types of cancer, measuring circulating tumor-derived nucleic acids from biological fluid samples could be the future of differential diagnostics, patient stratification, and follow up in the future in glioblastoma as well.

Liquid biopsy recently became a very promising diagnostic method that has several advantages over conventional invasive methods. Liquid biopsy may serve as a source of several important biomarkers including cell-free nucleic acids (cf-NAs). Cf-DNA is widely used in prenatal testing in order to characterize fetal genetic disorders. Analysis of cf-DNA may provide information about the mutation profile of tumor cells, while cell-free non-coding RNAs are promising biomarker candidates in the diagnosis and prognosis of cancer. Many of these markers have the potential to help clinicians in therapy selection and in the follow-up of patients. Thus, cf-NA-based diagnostics represent a new path in personalized medicine. Although several reviews are available in the field, most of them focus on a limited number of cf-NA types. In this review, we give an overview about all known cf-NAs including cf-DNA, cf-mtDNA and cell-free non-coding RNA (miRNA, lncRNA, circRNA, piRNA, YRNA, and vtRNA) by discussing their biogenesis, biological function and potential as biomarker candidates in liquid biopsy. We also outline possible future directions in the field.

Summary: The functional role of AMPA receptor (AMPAR)-mediated synaptic signaling between neurons and oligodendrocyte precursor cells (OPCs) remains enigmatic. We modified the properties of AMPARs at axon-OPC synapses in the mouse corpus callosum in vivo during the peak of myelination by targeting the GluA2 subunit. Expression of the unedited (Ca2+ permeable) or the pore-dead GluA2 subunit of AMPARs triggered proliferation of OPCs and reduced their differentiation into oligodendrocytes. Expression of the cytoplasmic C-terminal (GluA2(813-862)) of the GluA2 subunit (C-tail), a modification designed to affect the interaction between GluA2 and AMPAR-binding proteins and to perturb trafficking of GluA2-containing AMPARs, decreased the differentiation of OPCs without affecting their proliferation. These findings suggest that ionotropic and non-ionotropic properties of AMPARs in OPCs, as well as specific aspects of AMPAR-mediated signaling at axon-OPC synapses in the mouse corpus callosum, are important for balancing the response of OPCs to proliferation and differentiation cues. : In the brain, oligodendrocyte precursor cells (OPCs) receive glutamatergic AMPA-receptor-mediated synaptic input from neurons. Chen et al. show that modifying AMPA-receptor properties at axon-OPC synapses alters proliferation and differentiation of OPCs. This expands the traditional view of synaptic transmission by suggesting neurons also use synapses to modulate behavior of glia. Keywords: NG2, OPC, oligodendrocytes, myelination, white matter, synaptic, AMPA receptors, glutamate, proliferation, differentiation

Ovarian cancer is one of the most common cancer types in women characterized by a high mortality rate due to lack of early diagnosis. Circulating miRNAs besides being important regulators of cancer development could be potential biomarkers to aid diagnosis. We performed the circulating miRNA expression analysis in plasma samples obtained from ovarian cancer patients stratified into FIGO I, FIGO III, and FIGO IV stages and from healthy females using the NanoString quantitative assay. Forty-five miRNAs were differentially expressed, out of these 17 miRNAs showed significantly different expression between controls and patients, 28 were expressed only in patients, among them 19 were expressed only in FIGO I patients. Differentially expressed miRNAs were ranked by the network-based analysis to assess their importance. Target genes of the differentially expressed miRNAs were identified then functional annotation of the target genes by the GO and KEGG-based enrichment analysis was carried out. A general and an ovary-specific protein−protein interaction network was constructed from target genes. Results of our network and the functional enrichment analysis suggest that besides HSP90AA1, MYC, SP1, BRCA1, RB1, CFTR, STAT3, E2F1, ERBB2, EZH2, and MET genes, additional genes which are enriched in cell cycle regulation, FOXO, TP53, PI-3AKT, AMPK, TGFβ, ERBB signaling pathways and in the regulation of gene expression, proliferation, cellular response to hypoxia, and negative regulation of the apoptotic process, the GO terms have central importance in ovarian cancer development. The aberrantly expressed miRNAs might be considered as potential biomarkers for the diagnosis of ovarian cancer after validation of these results in a larger cohort of ovarian cancer patients.

Ovarian cancer is a highly heterogeneous disease and its formation is affected by many epidemiological factors. It has typical lack of early signs and symptoms, and almost 70% of ovarian cancers are diagnosed in advanced stages. Robust, early and non-invasive ovarian cancer diagnosis will certainly be beneficial. Herein we analysed the regulatory sequence methylation profiles of the RASSF1, PTEN, CDH1 and PAX1 tumour suppressor genes by pyrosequencing in healthy, benign and malignant ovarian tissues, and corresponding plasma samples. We recorded statistically significant higher methylation levels (p < 0.05) in the CDH1 and PAX1 genes in malignant tissues than in controls (39.06 ± 18.78 versus 24.22 ± 6.93; 13.55 ± 10.65 versus 5.73 ± 2.19). Higher values in the CDH1 gene were also found in plasma samples (22.25 ± 14.13 versus 46.42 ± 20.91). A similar methylation pattern with positive correlation between plasma and benign lesions was noted in the CDH1 gene (r = 0.886, p = 0.019) and malignant lesions in the PAX1 gene (r = 0.771, p < 0.001). The random forest algorithm combining methylation indices of all four genes and age determined 0.932 AUC (area under the receiver operating characteristic (ROC) curve) prediction power in the model classifying malignant lesions and controls. Our study results indicate the effects of methylation changes in ovarian cancer development and suggest that the CDH1 gene is a potential candidate for non-invasive diagnosis of ovarian cancer.

Both preeclampsia and the HELLP syndrome have their origin in the placenta. The aim of this study is to review genetic factors involved in development of preeclampsia and the HELLP syndrome using literature search in PubMed. A familial cohort links chromosomes 2q, 5q, and 13q to preeclampsia. The chromosome 12q is coupled with the HELLP syndrome. The STOX1 gene, the ERAP1 and 2 genes, the syncytin envelope gene, and the −670 Fas receptor polymorphisms are involved in the development of preeclampsia. The ACVR2A gene on chromosome 2q22 is also implicated. The toll-like receptor-4 (TLR-4) and factor V Leiden mutation participate both in development of preeclampsia and the HELLP syndrome. Carriers of the TT and the CC genotype of the MTHFR C677T polymorphism seem to have an increased risk of the HELLP syndrome. The placental levels of VEGF mRNA are reduced both in women with preeclampsia and in women with the HELLP syndrome. The BclI polymorphism is engaged in development of the HELLP syndrome but not in development of severe preeclampsia. The ACE I/D polymorphism affects uteroplacental and umbilical artery blood flows in women with preeclampsia. In women with preeclampsia and the HELLP syndrome several genes in the placenta are deregulated. Preeclampsia and the HELLP syndrome are multiplex genetic diseases.

Abstract Simulators are widely used in medical education, but objective and automatic assessment is not feasible with low-fidelity simulators, which can be solved with artificial intelligence (AI) and virtual reality (VR) solutions. The effectiveness of a custom-made VR simulator and an AI-based evaluator of a laparoscopic peg transfer exercise was investigated. Sixty medical students were involved in a single-blinded randomised controlled study to compare the VR simulator with the traditional box trainer. A total of 240 peg transfer exercises from the Fundamentals of Laparoscopic Surgery programme were analysed. The experts and AI-based software used the same criteria for evaluation. The algorithm detected pitfalls and measured exercise duration. Skill improvement showed no significant difference between the VR and control groups. The AI-based evaluator exhibited 95% agreement with the manual assessment. The average difference between the exercise durations measured by the two evaluation methods was 2.61 s. The duration of the algorithmic assessment was 59.47 s faster than the manual assessment. The VR simulator was an effective alternative practice compared with the training box simulator. The AI-based evaluation produced similar results compared with the manual assessment, and it could significantly reduce the evaluation time. AI and VR could improve the effectiveness of basic laparoscopic training.

In our research, we investigated the surface cover of the Karcsa Lake, a relic of the former Tisza riverbed, by digitising and evaluating images from several dates (1966, 2000, 2005, 2007, 2011, 2020) over the past 50 years. In addition to monitoring the changes in land cover over the past decades, our results have been used to draw conclusions about the extent to which the lake environment may be pressuring the lake and the proportion of ecologically valuable areas. By evaluating the above, we can draw conclusions about the future of a valuable lake. [ABSTRACT FROM AUTHOR]