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According to information over the world, production of high content paraffin oil is followed by a serious problem causing challenges in operation of wells. The problem is wax deposition on the inner surface of oil field equipment. The problem decreases system production and efficiency of operation of pumps, the failure of wells, control devices and oil collection and transportation systems. Wax deposition can lead to a complete closure of lifting pipes and annular channels in the interconnecting space, which causes the necessity of workovers to eliminate the wax deposition. This article describes the geophysical bases of the influence of high-frequency and ultra high-frequency electromagnetic fields for the heating and removal of wax from wells. Results of experimental studies of dielectric losses in wax samples of some oil fields are presented. Their dependence on frequency and temperature, as well as on the content of resins and asphaltenes in samples is established. The possibility of experimental determination of the melting point of wax by the data of dielectric studies is shown. Calculation studies of heating and melting the wax plugs in the oil pipeline were carried out under the influence of the type of electromagnetic waves capable of propagating in it as in a round waveguide. It is believed that the source of electromagnetic waves is moving. That allows overheating of the medium at some points and melts solid deposits along the entire length of a plug. Results of numerical studies allow monitoring the dynamics of heating and elimination of a wax plug by electromagnetic action.

Sustainable societies of the future should be designed on the basis of a green public budgeting, as green public 79 spending and investment are the key drivers of sustainable development. Studies on green budgeting have so far tended to focus on green taxes and favourable regulatory regimes for specific sectors, although 14 out of 38 OECD countries have introduced these in some form. Based on secondary research of Slovenian budget documentation for the period from 2018 to 2022, our research findings show that green and sustainable content is weak, both in terms of content and scope. Only 11 out of 24 policies and only 23 out of over 3000 projects have included some ideas of the green and sustainable concept. Due to the evolving methodology and framework of green budgeting, the research challenge could be identified in a repeated and deeper analysis, including the targets and indicators in the coming years.

A majority of modern war wounds are caused by blasts and high-energy ballistics. Extremity injuries predominate since modern body armor does not protect these areas due to mobility limitations. A less known and more insidious mechanism of enemy attack among our soldiers involves treachery by the local populace posing as noncombatants. One such recent event involved the contamination of tobacco with cyanide (CN). We describe a case of a soldier with CN intoxication due to ingestion of tobacco purchased from a local merchant. The soldier developed a complex neuropathic pain syndrome and was successfully treated with an inpatient high-dose intravenous ketamine infusion in combination with continuous peripheral nerve blockade. [ABSTRACT FROM AUTHOR]

Studying viral infections necessitates well-designed cell culture models to deepen our understanding of diseases and develop effective treatments. In this study, we present a readily available ex vivo 3D co-culture model replicating the human intestinal mucosa. The model combines fully differentiated human intestinal epithelium (HIE) with human monocyte-derived macrophages (hMDMs) and faithfully mirrors the in vivo structural and organizational properties of intestinal mucosal tissues. Specifically, it mimics the lamina propria, basement membrane, and the air-exposed epithelial layer, enabling the pioneering observation of macrophage migration through the tissue to the site of viral infection. In this study, we applied the HIE-hMDMs model for the first time in viral infection studies, infecting the model with two globally significant viruses: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human norovirus GII.4. The results demonstrate the model's capability to support the replication of both viruses and show the antiviral role of macrophages, determined by their migration to the infection site and subsequent direct contact with infected epithelial cells. In addition, we evaluated the production of cytokines and chemokines in the intestinal niche, observing an increased interleukin-8 production during infection. A parallel comparison using a classical in vitro cell line model comprising Caco-2 and THP-1 cells for SARS-CoV-2 experiments confirmed the utility of the HIE-hMDMs model in viral infection studies. Our data show that the ex vivo tissue models hold important implications for advances in virology research.IMPORTANCEThe fabrication of intricate ex vivo tissue models holds important implications for advances in virology research. The co-culture model presented here provides distinct spatial and functional attributes not found in simplified models, enabling the evaluation of macrophage dynamics under severe acute respiratory syndrome coronavirus 2 and human norovirus (HuNoV) infections in the intestine. Moreover, these models, comprised solely of primary cells, facilitate the study of difficult-to-replicate viruses such as HuNoV, which cannot be studied in cell line models, and offer the opportunity for personalized treatment evaluations using patient cells. Similar co-cultures have been established for the study of bacterial infections and different characteristics of the intestinal tissue. However, to the best of our knowledge, a similar intestinal model for the study of viral infections has not been published before.

Natural killer (NK) cells play a crucial role in controlling viral infections. The ability to kill infected cells without prior immunization, yet being tolerant to self, healthy cells, depends on the balance of germ-line encoded surface receptors. NK-cell receptors are divided into either activating, leading to activation of NK cell and its cytotoxic and pro-inflammatory activity, or inhibitory, providing tolerance for a target cell. The signals from inhibitory receptors dominate and NK-cell activation requires stimulation of activating receptors. In viral infections, NK-cell interaction with infected cells can result in activation, memory-like NK-cell differentiation, or NK-cell exhaustion, which constitutes one of the viral immune evasion mechanisms. All of these states are associated with the modulation of NK-cell receptor expression. In this review, we summarize the current knowledge of NK-cell receptors and their role in viral infection control, as well as the alterations of their expression observed in acute or chronic infections. We present recently discovered SARS-CoV-2-mediated modulation of NK-cell receptor expression and compare them with other human viral infections. Finally, since modulation of NK-cell receptor activation gives a promising addition to currently used antiviral therapies, we briefly discuss the clinical significance and future perspective of the application of agonists or antagonists of activating and inhibitory receptors, respectively. In sum, our review shows that although much is known about NK-cell receptor biology, a deeper understanding of NK-cell receptors role in viral infections is still needed., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Immunology.)

Globally, an increasing prevalence of colorectal cancer (CRC) prompts a need for the development of new methods for early tumor detection. MicroRNAs (also referred to as miRNAs) are short non-coding RNA molecules that play a pivotal role in the regulation of gene expression. MiRNAs are effectively transferred to extracellular vesicle (EVs) membrane sacs commonly released by cells. Our study aimed to examine the expression of miRNAs in four CRC cell lines and EVs derived from them (tumor EVs) in comparison to the normal colon epithelium cell line and its EVs. EVs were isolated by ultracentrifugation from the culture supernatant of SW480, SW620, SW1116, HCT116 and normal CCD841CoN cell lines and characterized according to the MISEV2023 guidelines. MiRNAs were analyzed by small RNA sequencing and validated by quantitative PCR. The performed analysis revealed 22 common miRNAs highly expressed in CRC cell lines and effectively transferred to tumor EVs, including miR-9-5p, miR-182-5p, miR-196b-5p, miR-200b-5p, miR-200c-3p, miR-425-5p and miR-429, which are associated with development, proliferation, invasion and migration of colorectal cancer cells, as well as in vesicle maturation and transport-associated pathways. In parallel, normal cells expressed miRNAs, such as miR-369 and miR-143, which play a role in proinflammatory response and tumor suppression. The analysis of selected miRNAs in plasma-derived EVs and tumor samples from CRC patients showed the similarity of miRNA expression profile between the patients' samples and CRC cell lines. Moreover, miR-182-5p, miR-196-5p, miR-425-5p and miR-429 were detected in several EV samples isolated from patients' plasma. Our results suggest that miR-182-5p, miR-196b-5p and miR-429 are differentially expressed between EVs from CRC patients and healthy donors, which might have clinical implications.

Selective IgA deficiency (sIgAD), common variable immunodeficiency (CVID), and transient hypogammaglobulinemia of infancy (THI) are the most frequent forms of primary antibody deficiencies. Difficulties in initial diagnosis, especially in the early childhood, the familiar occurrence of these diseases, as well as the possibility of progression to each other suggest common cellular and molecular patomechanism and a similar genetic background. In this review, we discuss both similarities and differences of these three humoral immunodeficiencies, focusing on current and novel therapeutic approaches. We summarize immunoglobulin substitution, antibiotic prophylaxis, treatment of autoimmune diseases, and other common complications, i.e. cytopenias, gastrointestinal complications, and granulomatous disease. We discuss novel therapeutic approaches such as allogenic stem cell transplantation and therapies targeting-specific proteins, dependent on the patient's genetic defect. The diversity of possible therapeutics models results from a great heterogeneity of the disease variants, implying the need of personalized medicine approach as a future of primary humoral immunodeficiencies treatment., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Immunology.)

Selective IgA deficiency (SIgAD) is the most common form and common variable immunodeficiency (CVID) is the most symptomatic form of predominant antibody deficiency. Despite differences in the clinical picture, a similar genetic background is suggested. A common feature of both disorders is the occurrence of autoimmune conditions. Regulatory T cells (T regs ) are the major immune cell type that maintains autoimmune tolerance. As the different types of abnormalities of T reg cells have been associated with autoimmune disorders in primary immunodeficiency (PID) patients, in our study we aimed to analyze the gene expression profiles of T reg cells in CVID and SIgAD patients compared to age-matched healthy controls. The transcriptome-wide gene profiling was performed by microarray technology. As a result, we analyzed and visualized gene expression patterns of isolated population of T reg cells. We showed the differences at the gene level between patients with and without autoimmunizations. Our findings suggest that the gene signatures of T reg cells isolated from SIgAD and CVID patients differ from age-matched healthy controls and from each other, presenting transcriptional profiles enriched in innate immune or Th response, respectively. The occurrence of autoimmunity in both types of PID is associated with down-regulation of class I IFNs signaling pathways. In summary, our findings improve our understanding of T reg dysfunctions in patients with common PIDs and associated autoimmunity.

Background: In the 21st century, endoscopic retrograde cholangiopancreatography (ERCP) has emerged as a diagnostic and therapeutic method for diseases of the pancreaticobiliary duct system. However, like any other diagnostic and therapeutic method, ERCP carries the risk of unwanted complications., Material and Methods: We retrospectively followed patients who underwent ERCP examinations from January 2013 to April 2023. We focused on early post-ERCP complications and their risk factors, prevention, treatment, and mortality., Results: A total of 4,814 patients were recorded, of which 175 patients had early post-ERCP complications, including acute pancreatitis, acute cholangitis, perforation, and bleeding. We focused on the statistical significance of risk factors such as BMI, repeated ERCP, bleeding disorders, and repeated pancreatitis or cholangitis., Conclusion: Ensuring proper preparation and appropriate indication for ERCP examination can significantly mitigate the risk of post-ERCP complications. Additionally, early diagnosis and prompt treatment of any post-ERCP complications are essential strategies for reducing mortality associated with these conditions (Tab. 3, Fig. 3, Ref. 32). Text in PDF www.elis.sk Keywords: post-ERCP complication, risk factor, BMI, prevention.

Transient hypogammaglobulinemia of infancy (THI) is one of the most common forms of hypogammaglobulinemia in the early childhood. THI is usually associated with chronic, recurrent bacterial and viral infections, life-threatening in some cases, yet its pathogenesis is still largely unknown. As our previous findings indicated the possible role of Treg cells in the pathomechanism of THI, the aim of the current study was to investigate gene expression profile of Treg cells isolated from THI patients. The transcriptome-wide gene profiling was performed using microarray technology on THI patients in two time-points: during (THI-1), and in resolution phase (THI-2) of hypogammaglobulinemia. As a result, a total of 1086 genes were differentially expressed in THI-1 patients, when compared to THI-2 as well as control group. Among them, 931 were up- and 155 downregulated, and part of them encodes genes important for Treg lymphocyte biology and function, i.e. transcription factors/cofactors that regulate FOXP3 expression. Thus, we postulate that Treg cells isolated from THI patients during hypogammaglobulinemia display enhanced suppressor transcriptome signature. Treg expression profile of THI children after normalization of Ig levels largely resembles the results obtained in healthy control group, suggesting THI Treg transcriptome seems to return to that observed in healthy children. Taken together, we suggest that THI pathomechanism is associated not only with transiently elevated Treg cell numbers, but also with their enhanced regulatory/inhibitory functions. These findings expand our knowledge of human Treg cells and may be useful for the future diagnosis or management of THI., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Immunology.)

The COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) heavily burdened the entire world socially and economically. Despite a generation of vaccines and therapeutics to confront infection, it remains a threat. Most available antivirals target viral proteins and block their activity or function. While such an approach is considered effective and safe, finding treatments for specific viruses of concern leaves us unprepared for developed resistance and future viral pandemics of unknown origin. Here, we propose ceragenins (CSAs), synthetic amphipathic molecules designed to mimic the properties of cationic antimicrobial peptides (cAMPs), as potential broad-spectrum antivirals. We show that selected CSAs exhibit antiviral activity against SARS-CoV-2 and low-pathogenic human coronaviruses 229E, OC43, and NL63. The mechanism of action of CSAs against coronaviruses is mainly attributed to the stimulation of antiviral cytokines, such as type I interferons or IL-6. Our study provides insight into a novel immunomodulatory strategy that might play an essential role during the current pandemic and future outbreaks., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Paul B. Savage and Robert Bucki are a paid consultants to N8 Medical, which focuses on commercialization of medical devices that incorporate ceragenins, and Robert Bucki received a travel funding from N8 Medical to attend TechnoSepsis meeting on Oct 5–7, 2022 in Spain., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Natural killer (NK) cells plays a pivotal role in the control of viral infections, and their function depend on the balance between their activating and inhibitory receptors. The immune dysregulation observed in COVID-19 patients was previously associated with downregulation of NK cell numbers and function, yet the mechanism of inhibition of NK cell functions and the interplay between infected cells and NK cells remain largely unknown., Methods: In this study we show that SARS-CoV-2 infection of airway epithelial cells can directly influence NK cell phenotype and functions in the infection microenvironment. NK cells were co-cultured with SARS-CoV-2 infected epithelial cells, in a direct contact with A549 ACE2/TMPRSS2 cell line or in a microenvironment of the infection in a 3D ex vivo human airway epithelium (HAE) model and NK cell surface expression of a set of most important receptors (CD16, NKG2D, NKp46, DNAM-1, NKG2C, CD161, NKG2A, TIM-3, TIGIT, and PD-1) was analyzed., Results: We observed a selective, in both utilized experimental models, significant downregulation the proportion of CD161 (NKR-P1A or KLRB1) expressing NK cells, and its expression level, which was followed by a significant impairment of NK cells cytotoxicity level against K562 cells. What is more, we confirmed that SARS-CoV-2 infection upregulates the expression of the ligand for CD161 receptor, lectin-like transcript 1 (LLT1, CLEC2D or OCIL), on infected epithelial cells. LLT1 protein can be also detected not only in supernatants of SARS-CoV-2 infected A549 ACE2/TMPRSS2 cells and HAE basolateral medium, but also in serum of COVID-19 patients. Finally, we proved that soluble LLT1 protein treatment of NK cells significantly reduces i) the proportion of CD161+ NK cells, ii) the ability of NK cells to control SARS-CoV-2 infection in A549 ACE2/TMPRSS2 cells and iii) the production of granzyme B by NK cells and their cytotoxicity capacity, yet not degranulation level., Conclusion: We propose a novel mechanism of SARS-CoV-2 inhibition of NK cell functions via activation of the LLT1-CD161 axis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lenart, Górecka, Bochenek, Barreto-Duran, Szczepański, Gałuszka-Bulaga, Mazur-Panasiuk, Węglarczyk, Siwiec-Koźlik, Korkosz, Łabaj, Baj-Krzyworzeka, Siedlar and Pyrc.)

Spondyloarthropathies (SpA) are a family of rheumatic disorders that could be divided into axial (axSpA) and peripheral (perSpA) sub-forms depending on the disease clinical presentation. The chronic inflammation is believed to be driven by innate immune cells such as monocytes, rather than self-reactive cells of adaptive immune system. The aim of the study was to investigate the micro-RNA (miRNA) profiles in monocyte subpopulations (classical, intermediate and non-classical subpopulations) acquired from SpA patients or healthy individuals in search for prospective disease specific and/or disease subtype differentiating miRNA markers. Several SpA-specific and axSpA/perSpA differentiating miRNAs have been identified that appear to be characteristic for specific monocyte subpopulation. For classical monocytes, upregulation of miR-567 and miR-943 was found to be SpA-specific, whereas downregulation of miR-1262 could serve as axSpA-differentiating, and the expression pattern of miR-23a, miR-34c, mi-591 and miR-630 as perSpA-differentiating markers. For intermediate monocytes, expression levels of miR-103, miR-125b, miR-140, miR-374, miR-376c and miR-1249 could be used to distinguish SpA patients from healthy donors, whereas the expression pattern of miR-155 was identified as characteristic for perSpA. For non-classical monocytes, differential expression of miR-195 was recognized as general SpA indicator, while upregulation of miR-454 and miR-487b could serve as axSpA-differentiating, and miR-1291 as perSpA-differentiating markers. Our data indicate for the first time that in different SpA subtypes, monocyte subpopulations bear disease-specific miRNA signatures that could be relevant for SpA diagnosis/differentiation process and may help to understand SpA etiopathology in the context of already known functions of monocyte subpopulations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Stec, Czepiel, Lenart, Piestrzyńska-Kajtoch, Plewka, Bieniek, Węglarczyk, Szatanek, Rutkowska-Zapała, Guła, Kluczewska, Baran, Korkosz and Siedlar.)

The first line of antiviral immune response in the lungs is secured by the innate immunity. Several cell types take part in this process, but airway macrophages (AMs) are among the most relevant ones. The AMs can phagocyte infected cells and activate the immune response through antigen presentation and cytokine release. However, the precise role of macrophages in the course of SARS-CoV-2 infection is still largely unknown. In this study, we aimed to evaluate the role of AMs during the SARS-CoV-2 infection using a co-culture of fully differentiated primary human airway epithelium (HAE) and human monocyte-derived macrophages (hMDMs). Our results confirmed abortive SARS-CoV-2 infection in hMDMs, and their inability to transfer the virus to epithelial cells. However, we demonstrated a striking delay in viral replication in the HAEs when hMDMs were added apically after the epithelial infection, but not when added before the inoculation or on the basolateral side of the culture. Moreover, SARS-CoV-2 inhibition by hMDMs seems to be driven by cell-to-cell contact and not by cytokine production. Together, our results show, for the first time, that the recruitment of macrophages may play an important role during the SARS-CoV-2 infection, limiting the virus replication and its spread., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Barreto-Duran, Szczepański, Gałuszka-Bulaga, Surmiak, Siedlar, Sanak, Rajfur, Milewska, Lenart and Pyrć.)

The types of injuries seen in combat action on a naval surface ship may be similar in many respects to the injuries seen in ground combat, and the principles of care for those injuries remain in large part the same. However, some contradistinctions in the care of combat casualties on a ship at sea must be highlighted, since this care may entail a number of unique challenges and different wounding patterns. This paper presents a scenario in which a guided missile destroyer is struck by a missile fired from an unmanned aerial vehicle operated by an undetermined hostile entity. Despite the presence of casualties who require care, the primary focus of a naval vessel that has just been damaged by hostile action is to prevent the ship from sinking and to conserve the fighting force on board the ship to the greatest extent possible. The casualties in this scenario include sailors injured by both blast and burns, as well as a casualty with a non-fatal drowning episode. Several of the casualties have also suffered the effects of a nearby underwater explosion while immersed. Challenges in the care of these casualties include delays in evacuation, the logistics of obtaining whole blood for transfusion while at sea, and transporting the casualties to the next higher level of care aboard a Casualty Receiving and Treatment Ship. As the National Defense Strategy pivots to a focus on the potential for maritime combat, the medical community must continue to maintain readiness by preparing fo., (2022.)

Even cyanobacteria from ecosystems of low biodiversity, such as the Baltic Sea, can constitute a rich source of bioactive metabolites. Potent toxins, enzyme inhibitors, and anticancer and antifungal agents were detected in both bloom-forming species and less commonly occurring cyanobacteria. In previous work on the Baltic Pseudanabaena galeata CCNP1313, the induction of apoptosis in the breast cancer cell line MCF-7 was documented. Here, the activity of the strain was further explored using human dermal fibroblasts, African green monkey kidney, cancer cell lines (T47D, HCT-8, and A549 ACE2/TMPRSS2 ) and viruses (SARS-CoV-2, HCoV-OC43, and WNV). In the tests, extracts, chromatographic fractions, and the main components of the P. galeata CCNP1313 fractions were used. The LC-MS/MS analyses of the tested samples led to the detection of forty-five peptides. For fourteen of the new peptides, putative structures were proposed based on MS/MS spectra. Although the complex samples (i.e., extracts and chromatographic fractions) showed potent cytotoxic and antiviral activities, the effects of the isolated compounds were minor. The study confirmed the significance of P. galeata CCNP1313 as a source of metabolites with potent activity. It also illustrated the difficulties in assigning the observed biological effects to specific metabolites, especially when they are produced in minute amounts.

Background: Immature immune systems predispose very low birth weight (VLBW) neonates to systemic infections in early life. Defective inflammasome function may increase a neonate's susceptibility to late-onset sepsis (LOS)., Methods: Blood samples were taken on the 5 th day of life (DOL) for all VLBW neonates (non-LOS and before-LOS groups; N.=76), and within 24 hours of sepsis onset (LOS group; N.=39). Monocyte (MO) subsets and intracellular interleukin-1β (IL-1β) expression were analyzed using flow cytometry. Inflammasome function, defined as level of IL-1β and interleukin-18 (IL-18) was measured with enzyme-linked immunosorbent assay. IRA B cells were reported as a fraction of all B cells., Results: Stimulation of classical MO in non-LOS cells demonstrated a higher expression of intracellular IL-1β in comparison to MO from before LOS group. Serum from the LOS group revealed a higher level of IL-18. Stimulation of mononuclear cultures from samples taken during LOS resulted in significantly increased supernatant level of IL-1β and IL-18 in comparison to samples taken on 5 th DOL. No changes in the levels of IRA B cells were detected with the onset of sepsis., Conclusions: We did not observe a difference in the functioning of the inflammasome within monocytes taken on 5 th DOL from premature VLBW neonates. Furthermore, there was no observable change in the IRA B cells of the septic and non-septic groups. The decreased expression of intracellular IL-1β within classical MO of the before-LOS group may be an independent risk factor for LOS development.

There is evidence that a lack of appropriate knowledge regarding global changes might be associated with various psychopathological responses. In this study, we tested the hypothesis that knowledge about COVID-19 correlates with the severity of psychopathological symptoms as measured by standardized questionnaires. The questionnaires were obtained using the Computer Assisted Web Interviews (CAWI) method during the second wave of the COVID-19 pandemic in Poland using the original COVID-19 knowledge questionnaire and the General Health Questionnaire-28 (GHQ-28). A series of bivariate tests and linear regression analyses were performed with a p < 0.05. All analyses were performed in Statistica 13.3. We enrolled 1,002 respondents. The rate of correct answers in the original questionnaire ranged from 44.6 to 84.1%, and the average was 60.1%. Four hundred and twenty participants (42%) met the criterion for the presence of relevant psychopathological symptoms. A significant negative correlation was found between the number of points obtained in the COVID-19 knowledge questionnaire and the GHQ-28 scores, both in relation to the total score and all its subscales. The following factors in the linear regression model were correlated with severity of somatic symptoms: knowledge about the COVID-19 pandemic ( B = -0.12, P = 0.000), sex ( B = 0.12, P = 0.000), use of psychiatric or psychological care ( B = 0.20, P < 0.000) and chronic diseases ( B = 0.09, P = 0.002). In this study, we observed a negative correlation between the knowledge about the COVID-19 pandemic and the severity of psychopathological symptoms. The results clearly indicate that the complexity of the global problem of the current pandemic is related to the development of psychopathological symptoms. However, longitudinal studies are needed to identify the direction of causality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Maciaszek, Lenart, Misiak, Grzebieluch, Gawłowski, Ciułkowicz, Łuc, Szcześniak and Rymaszewska.)

Background: Candidatus Neoehrlichia mikurensis (CNM) is an emerging tick-born pathogen and usually causes symptomatic infection only in immunocompromised patients. Apart from one described case found in the literature where cultivation was successful, all cases so far were diagnosed by using broad-range 16S rDNA PCR., Case Presentation: Our patient presented with a prolonged febrile state of unknown origin. Clinical presentation, extensive medical workup and classic microbiologic testing were non-conclusive. Several infectious agents and other causes for the febrile state were excluded. In the end, a broad-range 16S rDNA PCR was to be performed to confirm the diagnosis of CNM infection. Treatment was successful with doxycycline., Conclusions: Due to the obscurity of the pathogen, diagnostic workup in CNM is prolonged and challenging. More awareness is need about this emerging infectious disease in countries with high prevalence of tick-borne diseases as standard microbiological methods are not successful in confirming the diagnosis.

Spondyloarthritis (SpA) is characterized by chronic inflammation and structural damage involving spine and peripheral joints. Monocytes, as part of innate immune system, following migration into affected tissue, may play a role in the pathogenesis of SpA. Here, potential associations between osteogenesis-linked gene expression profile in particular monocyte subpopulations and clinical signs of SpA were investigated. The 20 patients with axial and 16 with peripheral SpA were enrolled in the study. Monocyte subpopulations (classical-CD14 ++ CD16 - , intermediate-CD14 ++ CD16 +  and non-classical-CD14 + CD16 ++ ) were isolated from blood using flow cytometry and gene expression analysis was performed using real-time PCR method and TaqMan Array, Human Osteogenesis, Fast 96-well plates. Next, the characteristic clinical features shared by axial and peripheral SpA were analyzed in the context of the expression of selected genes in the three subpopulations of monocytes. We demonstrated that expression of VEGFA in classical and MSX2 in non-classical monocytes were associated with the number of swollen and painful peripheral joints of SpA patients. We conclude that monocytes may contribute to the development of peripheral arthritis in SpA patients. This might be possible through subpopulation specific effects, linking number of inflamed joints with expression of VEGFA in classical monocytes and MSX2 in non-classical monocytes.

Severe, recurrent or atypical Herpes simplex virus (HSV) infections are still posing clinical and diagnostic problem in clinical immunology facilities. However, the molecular background of this disorder is still unclear. The aim of this study was to investigate the expression of activating receptors on NK cells (CD16, NKp46, NKG2D, NKp80, 2B4, CD48 and NTB-A) and checkpoint molecule PD-1 on T lymphocytes and NK cells, in patients with severe and/or recurrent infections with HSV and age-matched healthy control subjects. As a result, we noticed that patients with severe and/or recurrent infection with HSV had significantly lower percentage of CD16 bright CD56 dim and higher percentage of CD16 dim CD56 bright NK cell subsets, when compared to control subjects, which may be associated with abnormal NK cell maturation during chronic HSV infection. Patients had also significantly downregulated expression of CD16 receptor on CD16 bright NK cells. The expression of activating receptors was significantly reduced on patients' NK cells - either both the percentage of NK cells expressing the receptor and MFI of its expression (NKp46, NKp80 and 2B4 on CD16 bright CD56 dim cells and NKp46 on CD16 dim CD56 bright cells) or only MFI (NKG2D on both NK cell subsets). It should be noted that the reduction of receptor expression was limited to NK cells, since there was no differences in the percentage of receptor-positive cells or MFI on T cells. However, NTB-A receptor was the only one which expression was not only simultaneously changed in patients' NK and T cells, but also significantly upregulated on CD16 dim CD56 bright NK cell and CD8 + cell subsets. Patients had also upregulated proportion of CD4 + T cells expressing PD-1. Thus, we suggest that an increased percentage of PD-1 + cells may represent an independent indirect mechanism of downregulation of antiviral response, separate from the reduction of NK cell activating receptors expression. Altogether, our studies indicate two possible mechanisms which may promote perpetuation of HSV infection: 1) selective inhibition of activating receptors on NK cells, but not on T cells, and 2) upregulation of checkpoint molecule PD-1 on CD4 + T cells., (Copyright © 2021 Elsevier GmbH. All rights reserved.)