Novel inflammatory markers in patients with severe COVID-19 and a pulmonary thrombotic event.

Venous thromboembolism (VTE), clinically manifested as deep vein thrombosis (DVT) or acute pulmonary embolism (PE), is the third most common acute cardiovascular syndrome following myocardial infarction and stroke. The annual incidence of PE is between 39 and 115 per 100,000 inhabitants. The incidence of VTE is almost eight times higher in people aged 80 and older than in the fifth decade of life. We performed a retrospective study of 226 COVID-19 patients and selected group of patients who experienced a pulmonary thrombotic event. The incidence of PE in hospitalized COVID-19 patients was approximately 1.9-8.9%. The retrospective nature of the analyzed cohorts and relatively short observation periods could have led to underestimation of the actual incidence of PE. This study underlines the role of novel inflammatory biomarkers such as neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in patients with a pulmonary thrombotic event in COVID-19. We suggest that these biomarkers may have high assessment value and complement routinely used biomarkers.

The analysis of Fe-dependent serum enzymes in severe COVID-19 with a pulmonary thrombotic event.

Introduction: COVID-19 patients in critical condition requiring ICU admission are more likely to experience thromboembolic complications, especially pulmonary embolism. Since the outbreak of coronavirus disease 2019 (COVID-19), clinicians have struggled with the attempt to diagnose and manage the severe and fatal complications of COVID-19 appropriately. Several reports have described significant procoagulatory events, including life-threatening pulmonary embolism, in these patients. The aim of the study was to analyze the results of selected serum enzymes in patients with a radiologically confirmed pulmonary thrombotic event based on the pulmonary tissue involvement assessed in a computed tomography (CT) scan. Material and methods: The retrospective study covered a group of 226 COVID-19 patients. Groups were divided based on the degree of lung tissue involvement in CT examinations, including patients with confirmed pulmonary embolism. The analyzed group consisted of 136 men and 90 women with mean age of 70 years. Results: The group consisted of patients with < 50% of lung volume changes who had higher parameter values in each analyzed parameter, except red blood cells (RBC) (p < 0.05). Especially, the level of ferritin was much higher in the first group (p = 0.000008). Elevated ferritin levels were observed in all patients with lung tissue involvement. Discussion: This line of research is critical in order to assess the predisposing conditions for pulmonary embolism occurrence in COVID-19, which can be used as a predictive factor for course of the disease. The conducted research will resolve whether there is a relationship between the selected laboratory parameters and the occurrence of pulmonary embolism in patients with COVID-19. Conclusions: The study demonstrated that elevated levels of several inflammatory and thrombotic parameters such as ferritin, D-dimer, C-reactive protein (CRP) as well as hemoglobin do not correlate with the degree of lung tissue involvement in the computed tomography image.

Brief Review of Endometriosis and the Role of Trace Elements.

Endometriosis is a chronic, estrogen-dependent, inflammatory condition that is defined as the presence of endometrial glands and stroma outside the uterine cavity. Despite the progress in research into the mechanisms leading to the development of endometriosis, its cause has not yet been established. It seems to be possible that the formation of oxidative stress may be one of the main causes of the development of endometriosis. There is much research that studies the potential role of trace elements in the appearance of endometrial-like lesions. Most studies focus on assessing the content of selected trace elements in the blood, urine, or peritoneal fluid in women with endometriosis. Meanwhile, little is known about the content of these elements in endometrial-like implants, which may be helpful in developing the theory of endometriosis. Investigations that are more comprehensive are needed to confirm a hypothesis that some trace elements play a role in the pathomechanism of endometriosis.

Recent Trends of microRNA Significance in Pediatric Population Glioblastoma and Current Knowledge of Micro RNA Function in Glioblastoma Multiforme.

Central nervous system tumors are a significant problem for modern medicine because of their location. The explanation of the importance of microRNA (miRNA) in the development of cancerous changes plays an important role in this respect. The first papers describing the presence of miRNA were published in the 1990s. The role of miRNA has been pointed out in many medical conditions such as kidney disease, diabetes, neurodegenerative disorder, arthritis and cancer. There are several miRNAs responsible for invasiveness, apoptosis, resistance to treatment, angiogenesis, proliferation and immunology, and many others. The research conducted in recent years analyzing this group of tumors has shown the important role of miRNA in the course of gliomagenesis. These particles seem to participate in many stages of the development of cancer processes, such as proliferation, angiogenesis, regulation of apoptosis or cell resistance to cytostatics.

TLR-4 Signaling vs. Immune Checkpoints, miRNAs Molecules, Cancer Stem Cells, and Wingless-Signaling Interplay in Glioblastoma Multiforme-Future Perspectives.

Toll-like-receptor (TLR) family members were detected in the central nervous system (CNS). TLR occurrence was noticed and widely described in glioblastomamultiforme (GBM) cells. After ligand attachment, TLR-4 reorients domains and dimerizes, activates an intracellular cascade, and promotes further cytoplasmatic signaling. There is evidence pointing at a strong relation between TLR-4 signaling and micro ribonucleic acid (miRNA) expression. The TLR-4/miRNA interplay changes typical signaling and encourages them to be a target for modern immunotherapy. TLR-4 agonists initiate signaling and promote programmed death ligand-1 (PD-1L) expression. Most of those molecules are intensively expressed in the GBM microenvironment, resulting in the autocrine induction of regional immunosuppression. Another potential target for immunotreatment is connected with limited TLR-4 signaling that promotes Wnt/DKK-3/claudine-5 signaling, resulting in a limitation of GBM invasiveness. Interestingly, TLR-4 expression results in bordering proliferative trends in cancer stem cells (CSC) and GBM. All of these potential targets could bring new hope for patients suffering from this incurable disease. Clinical trials concerning TLR-4 signaling inhibition/promotion in many cancers are recruiting patients. There is still a lot to do in the field of GBM immunotherapy.

Cerebral Small Vessel Disease.

Cerebral small vessel disease (CSVD) represents a cluster of various vascular disorders with different pathological backgrounds. The advanced vasculature net of cerebral vessels, including small arteries, capillaries, arterioles and venules, is usually affected. Processes of oxidation underlie the pathology of CSVD, promoting the degenerative status of the epithelial layer. There are several classifications of cerebral small vessel diseases; some of them include diseases such as Binswanger's disease, leukoaraiosis, cerebral microbleeds (CMBs) and lacunar strokes. This paper presents the characteristics of CSVD and the impact of the current knowledge of this topic on the diagnosis and treatment of patients.

Micro RNA Molecules as Modulators of Treatment Resistance, Immune Checkpoints Controllers and Sensitive Biomarkers in Glioblastoma Multiforme.

Based on genome sequencing, it is estimated that over 90% of genes stored in human genetic material are transcribed, but only 3% of them contain the information needed for the production of body proteins. This group also includes micro RNAs representing about 1%-3% of the human genome. Recent studies confirmed the hypothesis that targeting molecules called Immune Checkpoint (IC) open new opportunities to take control over glioblastoma multiforme (GBM). Detection of markers that indicate the presence of the cancer occupies a very important place in modern oncology. This function can be performed by both the cancer cells themselves as well as their components and other substances detected in the patients' bodies. Efforts have been made for many years to find a suitable marker useful in the diagnosis and monitoring of gliomas, including glioblastoma.

Beyond the Mind-Serum Trace Element Levels in Schizophrenic Patients: A Systematic Review.

The alterations in serum trace element levels are common phenomena observed in patients with different psychiatric conditions such as schizophrenia, autism spectrum disorder, or major depressive disorder. The fluctuations in the trace element concentrations might act as potential diagnostic and prognostic biomarkers of many psychiatric and neurological disorders. This paper aimed to assess the alterations in serum trace element concentrations in patients with a diagnosed schizophrenia. The authors made a systematic review, extracting papers from the PubMed, Web of Science, and Scopus databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Among 5009 articles identified through database searching, 59 of them were assessed for eligibility. Ultimately, 33 articles were included in the qualitative synthesis. This review includes the analysis of serum levels of the following trace elements: iron, nickel, molybdenum, phosphorus, lead, chromium, antimony, uranium, magnesium, aluminum, zinc, copper, selenium, calcium, and manganese. Currently, there is no consistency regarding serum trace element levels in schizophrenic patients. Thus, it cannot be considered as a reliable prognostic or diagnostic marker of schizophrenia. However, it can be assumed that altered concentrations of those elements are crucial regarding the onset and exaggeration of either psychotic or negative symptoms or cognitive dysfunctions.

Correlations Between Trace Elements in Selected Locations of the Human Brain in Individuals with Alcohol Use Disorder.

Trace element distribution varies in different locations of the human brain. Several elements were found to cause various negative effects, such as neurodegeneration. In this paper, we analyzed the interactions between seven trace elements: zinc (Zn), selenium (Se), manganese (Mg), iron (Fe), copper (Cu), chromium (Cr) and cobalt (Co) in individuals with alcohol use disorder (AUD) and individuals without (control group). Brain tissue samples from 31 individuals with AUD and 31 control subjects were harvested. Inductively coupled plasma optical emission spectrometry was used for trace element determination. In the control group, there were several positive correlations between Cr, Cu, Fe and Mn. In the AUD group, positive correlations between Co and Cr, Cu, Fe, Mn, Zn were found. The majority of correlations between Zn and other elements are positive. In the studied group, Mn had strong positive correlations with Co, Cr, Cu and Fe. The strongest positive correlation found between average element concentration was between Cu and Cr. The knowledge of kinetics and metabolism of trace elements as well as the impact of alcohol on these processes is essential for understanding the pathological processes and functioning of human brain tissue.

PD-L1/PD-1 Axis in Glioblastoma Multiforme.

Glioblastoma (GBM) is the most popular primary central nervous system cancer and has an extremely expansive course. Aggressive tumor growth correlates with short median overall survival (OS) oscillating between 14 and 17 months. The survival rate of patients in a three-year follow up oscillates around 10%. The interaction of the proteins programmed death-1 (PD-1) and programmed cell death ligand (PD-L1) creates an immunoregulatory axis promoting invasion of glioblastoma multiforme cells in the brain tissue. The PD-1 pathway maintains immunological homeostasis and protects against autoimmunity. PD-L1 expression on glioblastoma surface promotes PD-1 receptor activation in microglia, resulting in the negative regulation of T cell responses. Glioblastoma multiforme cells induce PD-L1 secretion by activation of various receptors such as toll like receptor (TLR), epidermal growth factor receptor (EGFR), interferon alpha receptor (IFNAR), interferon-gamma receptor (IFNGR). Binding of the PD-1 ligand to the PD-1 receptor activates the protein tyrosine phosphatase SHP-2, which dephosphorylates Zap 70, and this inhibits T cell proliferation and downregulates lymphocyte cytotoxic activity. Relevant studies demonstrated that the expression of PD-L1 in glioma correlates with WHO grading and could be considered as a tumor biomarker. Studies in preclinical GBM mouse models confirmed the safety and efficiency of monoclonal antibodies targeting the PD-1/PD-L1 axis. Satisfactory results such as significant regression of tumor mass and longer animal survival time were observed. Monoclonal antibodies inhibiting PD-1 and PD-L1 are being tested in clinical trials concerning patients with recurrent glioblastoma multiforme.

Serum iron, Magnesium, Copper, and Manganese Levels in Alcoholism: A Systematic Review.

The aim of this paper was to review recent literature (from 2000 onwards) and summarize the newest findings on fluctuations in the concentration of some essential macro- and microelements in those patients with a history of chronic alcohol abuse. The focus was mainly on four elements which the authors found of particular interest: Iron, magnesium, copper, and manganese. After independently reviewing over 50 articles, the results were consistent with regard to iron and magnesium. On the other hand, data were limited, and in some cases contradictory, as far as copper and manganese were concerned. Iron overload and magnesium deficiency are two common results of an excessive and prolonged consumption of alcohol. An increase in the levels of iron can be seen both in the serum and within the cells, hepatocytes in particular. This is due to a number of factors: Increased ferritin levels, lower hepcidin levels, as well as some fluctuations in the concentration of the TfR receptor for transferrin, among others. Hypomagnesemia is universally observed among those suffering from alcoholism. Again, the causes for this are numerous and include malnutrition, drug abuse, respiratory alkalosis, and gastrointestinal problems, apart from the direct influence of excessive alcohol intake. Unfortunately, studies regarding the levels of both copper and manganese in the case of (alcoholic) liver disease are scarce and often contradictory. Still, the authors have attempted to summarize and give a thorough insight into the literature available, bearing in mind the difficulties involved in the studies. Frequent comorbidities and mutual relationships between the elements in question are just some of the complications in the study of this topic.

Increased Aluminum Content in Certain Brain Structures is Correlated with Higher Silicon Concentration in Alcoholic Use Disorder.

INTRODUCTION: Alcohol overuse may be related to increased aluminum (Al) exposure, the brain accumulation of which contributes to dementia. However, some reports indicate that silicon (Si) may have a protective role over Al-induced toxicity. Still, no study has ever explored the brain content of Al and Si in alcoholic use disorder (AUD). MATERIALS AND METHODS: To fill this gap, the present study employed inductively coupled plasma optical emission spectrometry to investigate levels of Al and Si in 10 brain regions and in the liver of AUD patients (n = 31) and control (n = 32) post-mortem. RESULTS: Al content was detected only in AUD patients at mean ± SD total brain content of 1.59 ± 1.19 mg/kg, with the highest levels in the thalamus (4.05 ± 12.7 mg/kg, FTH), inferior longitudinal fasciculus (3.48 ± 9.67 mg/kg, ILF), insula (2.41 ± 4.10 mg/kg) and superior longitudinal fasciculus (1.08 ± 2.30 mg/kg). Si content displayed no difference between AUD and control, except for FTH. Positive inter-region correlations between the content of both elements were identified in the cingulate cortex, hippocampus, and ILF. CONCLUSIONS: The findings of this study suggest that AUD patients may potentially be prone to Al-induced neurodegeneration in their brain-although this hypothesis requires further exploration.

Ultra high field TOF-MRA: A method to visualize small cerebral vessels. 7T TOF-MRA sequence parameters on different MRI scanners - Literature review.

INTRODUCTION: Time-of-flight (TOF) angiography is a technique allowing to visualize the blood flow in vessels. 7T ToF-MRA is able to visualize the whole Circle of Willis including small perforating branches without any known side effects as opposed to usually used DSA and CTA with high exposition to the radiation and high doses of contrast as far as CTA is concerned. AIM: The aim of this review is to describe ultra-high field ToF-MRA and present different protocol data depending on the scanner used in the study. MATERIALS AND METHODS: PubMed, Embase, Ovid, Google Scholar databases were searched. Selection of studies for this systematic review included 7T magnetic resonance angiography studies. We searched for type of head coil used in various studies, flip angle, echo time, repetition time, field-of-view (FOV), number of slices per slab, matrix, voxel size and acquisition time. DISCUSSION: Visualization for the small perforating vessels of the Circle of Willis, that are not fully visualized using low-field-strength MRA is improving with increasing magnetic field strength, which has been proved by several studies. CONCLUSION: Ultra-high filed ToF-MRA has found to be a superior method in depicting cerebral microvasculature. 7T ToF-MRA seems to be a reliable method for visualization of arteries up to the second order cerebral arteries and has a potential to replace DSA.

New Horizons for Hydroxyapatite Supported by DXA Assessment-A Preliminary Study.

Dual Energy X-ray Absorptiometry (DXA) is a tool that allows the assessment of bone density. It was first presented by Cameron and Sorenson in 1963 and was approved by the Food and Drug Administration. Misplacing the femoral neck box, placing a trochanteric line below the midland and improper placement of boundary lines are the most common errors made during a DXA diagnostic test made by auto analysis. Hydroxyapatite is the most important inorganic component of teeth and bone tissue. It is estimated to constitute up to 70% of human bone weight and up to 50% of its volume. Calcium phosphate comes in many forms; however, studies have shown that only tricalcium phosphate and hydroxyapatite have the characteristics that allow their use as bone-substituted materials. The purpose of this study is aimed at analyzing the results of hip densitometry and hydorxyapatite distribution in order to better assess the structure and mineral density of the femoral neck. However, a detailed analysis of the individual density curves shows some qualitative differences that may be important in assessing bone strength in the area under study. To draw more specific conclusions on the therapy applied for individual patients, we need to determine the correct orientation of the bone from the resulting density and document the trends in the density distribution change. The average results presented with the DXA method are insufficient.

Hydroxyapatite Use in Spine Surgery-Molecular and Clinical Aspect.

Hydroxyapatite possesses desirable properties as a scaffold in tissue engineering: it is biocompatible at a site of implantation, and it is degradable to non-toxic products. Moreover, its porosity enables infiltration of cells, nutrients and waste products. The outcome of hydroxyapatite implantation highly depends on the extent of the host immune response. Authors emphasise major roles of the chemical, morphological and physical properties of the surface of biomaterial used. A number of techniques have been applied to transform the theoretical osteoconductive features of HAp into spinal fusion systems-from integration of HAp with autograft to synthetic intervertebral implants. The most popular uses of HAp in spine surgery include implants (ACDF), bone grafts in posterolateral lumbar fusion and transpedicular screws coating. In the past, autologous bone graft has been used as an intervertebral cage in ACDF. Due to the morbidity related to autograft harvesting from the iliac bone, a synthetic cage with osteoconductive material such as hydroxyapatite seems to be a good alternative. Regarding posterolateral lumbar fusion, it requires the graft to induce new bone growth and reinforce fusion between the vertebrae. Hydroxyapatite formulations have shown good results in that field. Moreover, the HAp coating has proven to be an efficient method of increasing screw fixation strength. It can decrease the risk of complications such as screw loosening after pedicle screw fixation in osteoporotic patients. The purpose of this literature review is to describe in vivo reaction to HAp implants and to summarise its current application in spine surgery.

PD-L1/miR-155 Interplay in Pediatric High-Grade Glioma.

High-grade pediatric glioma (p-HGG-WHO 2021, formerly GBM-WHO 2016), as a common, aggressive, and highly lethal primary brain malignancy in adults, accounts for only 3-15% of primary brain tumors in pediatric patients. After leukemia, brain malignancies are the second most common in the pediatric population and first in incidences concerning solid tumors. This study was designed on the basis of 14 pediatric patients hospitalized at Children's Memorial Health Institute in Warsaw, Poland, due to p-HGG treatment. All the patients had a histopathological diagnosis performed by an experienced neuropathologist according to WHO guidelines (WHO 2016 Grade IV Glioblastoma). A significant correlation was found between the miR-155 concentration and the level of PD-L1 expression in p-HGG tumor tissue. Very few reports have indicated PD-L1 expression in pediatric patients.

Chronic Alcohol Abuse Alters Hepatic Trace Element Concentrations-Metallomic Study of Hepatic Elemental Composition by Means of ICP-OES.

Trace element accumulation varies in different human tissues. Distribution of several elements was found to be disrupted in the case of excessive alcohol consumption, causing negative effects and exacerbation of pathological processes in the liver. In this study, we analyzed the levels and interactions between seven trace elements including calcium (Ca), cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), potassium (K), and magnesium (Mg), manganese (Mn), sodium (Na), zinc (Zn), and selenium (Se) in individuals with alcohol-use disorder (AUD) and patients without AUD (control group). The liver samples were collected during autopsy from 39 individuals with AUD and 45 control subjects. Elemental composition inductively coupled plasma optical emission spectrometry (ICP-OES) after wet mineralization by nitric acid was applied for the evaluation of the samples. Positive correlations dominated in the AUD group, mainly in relation to Mg, which strongly positively correlated with Ca, Mn, Fe; K correlated with Mn and Zn, and Cu positively correlated with K and Zn. The strongest positive correlation in the AUD group was observed for the Mg-Mn pair (r = 0.87). Significant statistical differences (p < 0.05) between the groups concerned the average concentration of Co, Cu, Mn, and Mg, which were lower in the AUD group, and Fe, the level of which was significantly higher in the AUD group compared to the control group. Evaluation of the chronic alcohol consumption effect on the accumulation of trace elements in the liver allows a better understanding of the pathological processes taking place in this organ.

PD-L1 Expression Correlated with p53 Expression in Pediatric Glioblastoma Multiforme.

High-grade gliomas are infrequent in the pediatric population compared to adults, nevertheless, mortality and morbidity caused by malignant gliomas in this group of patients remain significant. PD-L1 and PD-1 Immune checkpoints (IC) molecules maintain immunological balance between activation and suppression. Eighteen patients with a histopathological diagnosis of pediatric glioblastoma multiforme (GBM, WHO IV) were studied. In total, PD-L1 expression was detected in 8 patients (44%). The molecular aspect of IC and immunotherapy targeted on PD-1/PD-L1 axis in pediatric population may be a promising adjuvant therapy in pediatric glioblastoma multiform treatment, however, this subject requires further investigation.

Autism spectrum disorder: Trace elements imbalances and the pathogenesis and severity of autistic symptoms.

The identification of biomarkers as diagnostic tools and predictors of response to treatment of neurological developmental disorders (NDD) such as schizophrenia (SZ), attention deficit hyperactivity disorder (ADHD), or autism spectrum disorder (ASD), still remains an important challenge for clinical medicine. Metallomic profiles of ASD patients cover, besides essential elements such as cobalt, chromium, copper, iron, manganese, molybdenum, zinc, selenium, also toxic metals burden of: aluminum, arsenic, mercury, lead, beryllium, nickel, cadmium. Performed studies indicate that children with ASD present a reduced ability of eliminating toxic metals, which leads to these metals' accumulation and aggravation of autistic symptoms. Extensive metallomic studies allow a better understanding of the importance of trace elements as environmental factors in the pathogenesis of ASD. Even though a mineral imbalance is a fact in ASD, we are still expecting relevant tests and the elaboration of reference levels of trace elements as potential biomarkers useful in diagnosis, prevention, and treatment of ASD.

Aberrant Structural Network Architecture in Leber's Hereditary Optic Neuropathy. Minimum Spanning Tree Graph Analysis Application into Diffusion 7T MRI.

Examining individuals with Leber's hereditary optic neuropathy (LHON) provides a rare opportunity to understand how changes in mitochondrial DNA and loss of vision can be related to changes in organization of the whole-brain structural network architecture. In comparison with the previous neuroimaging studies with LHON participants, which were focused mainly on analyzing changes which occur in different areas of the patient's brain, network analysis not only makes it possible to observe single white matter fibers' aberrations but also the whole-brain nature of these changes. The purpose of our study was to better understand whole-brain neural network changes in LHON participants and see the correlation between the clinical data and the changes. To achieve this, we examined fifteen LHON patients and seventeen age-matched healthy subjects with the usage of ultra-high filed 7T magnetic resonance imaging (MRI). Basing on the analysis on MRI diffusion tensor imaging (DTI) data, whole-brain structural neural networks were reconstructed with the use of the minimum spanning tree algorithm (MST) for every participant. Our results revealed that the structural network in LHON participants was altered at both the local and the global level. The global network structures of LHON subjects were less centralized with path-like organization and there was an imbalance in the main hub centrality. Moreover, the inspection of nodes and hubs in terms of their anatomical placement revealed that in the LHON participants the prominent hubs were located within the basal ganglia (i.e. bilateral caudate, left pallidum), which differed them from healthy controls. An analysis of the relationships between the global MST metrics and LHON participants' clinical characteristics revealed significant correlations between the global network metrics and the duration of illness. Furthermore, the nodal parameters of the optic chiasm were significantly correlated with the duration of illness and the averaged thickness of the right retinal nerve fiber layer (RNFL). These findings clearly showed that the progression of the disease is accompanied by alterations within the brain network structure and its efficiency.