The Chitosan/Agarose/NanoHA Bone Scaffold-Induced M2 Macrophage Polarization and Its Effect on Osteogenic Differentiation In Vitro.

Chronic immune response to bone implant may lead to delayed healing and its failure. Thus, newly developed biomaterials should be characterized by high biocompatibility. Moreover, it is well known that macrophages play a crucial role in the controlling of biomaterial-induced inflammatory response. Immune cells synthesize also a great amount of signaling molecules that regulate cell differentiation and tissue remodeling. Non-activated macrophages (M0) may be activated (polarized) into two main types of macrophage phenotype: proinflammatory type 1 macrophages (M1) and anti-inflammatory type 2 macrophages (M2). The aim of the present study was to assess the influence of the newly developed chitosan/agarose/nanohydroxyapatite bone scaffold (Polish Patent) on the macrophage polarization and osteogenic differentiation. Obtained results showed that macrophages cultured on the surface of the biomaterial released an elevated level of anti-inflammatory cytokines (interleukin-4, -10, -13, transforming growth factor-beta), which is typical of the M2 phenotype. Moreover, an evaluation of cell morphology confirmed M2 polarization of the macrophages on the surface of the bone scaffold. Importantly, in this study, it was demonstrated that the co-culture of macrophages-seeded biomaterial with bone marrow-derived stem cells (BMDSCs) or human osteoblasts (hFOB 1.19) enhanced their osteogenic ability, confirming the immunomodulatory effect of the macrophages on the osteogenic differentiation process. Thus, it was proved that the developed biomaterial carries a low risk of inflammatory response and induces macrophage polarization into the M2 phenotype with osteopromotive properties, which makes it a promising bone scaffold for regenerative medicine applications.

Effect of Vitamin C/Hydrocortisone Immobilization within Curdlan-Based Wound Dressings on In Vitro Cellular Response in Context of the Management of Chronic and Burn Wounds.

Bioactive dressings are usually produced using natural or synthetic polymers. Recently, special attention has been paid to ß-glucans that act as immunomodulators and have pro-healing properties. The aim of this research was to use ß-1,3-glucan (curdlan) as a base for the production of bioactive dressing materials (curdlan/agarose and curdlan/chitosan) that were additionally enriched with vitamin C and/or hydrocortisone to improve healing of chronic and burn wounds. The secondary goal of the study was to compressively evaluate biological properties of the biomaterials. In this work, it was shown that vitamin C/hydrocortisone-enriched biomaterials exhibited faster vitamin C release profile than hydrocortisone. Consecutive release of the drugs is a desired phenomenon since it protects wounds against accumulation of high and toxic concentrations of the bioactive molecules. Moreover, biomaterials showed gradual release of low doses of the hydrocortisone, which is beneficial during management of burn wounds with hypergranulation tissue. Among all tested variants of biomaterials, dressing materials enriched with hydrocortisone and a mixture of vitamin C/hydrocortisone showed the best therapeutic potential since they had the ability to significantly reduce MMP-2 synthesis by macrophages and increase TGF-ß1 release by skin cells. Moreover, materials containing hydrocortisone and its blend with vitamin C stimulated type I collagen deposition by fibroblasts and positively affected their migration and proliferation. Results of the experiments clearly showed that the developed biomaterials enriched with bioactive agents may be promising dressings for the management of non-healing chronic and burn wounds.

[Sternal wound complications after cardiac surgery--a case report]. / Powiklania w gojeniu rany mostka po operacji kardiochirurgicznej--opis przypadku.

The authors presents case report of a 59-years-old man with triple vessel coronary artery disease, hypertension after myocardial infarction of the inferior wall with sternal wound complcations after coronary bypass grafting (CABG). On the fourth postoperative day the patient developed sternal dehiscence with wound infection. Infection was caused by Staphylococcus haemolyticus--coagulase-negative methicillin-resistant strain, MRCNS. An antimicrobial therapy and negative pressure wound therapy were used for complete wound healing.

[Preliminary results of research on a new marker of idiopathic membranous nephropathy: anti-PLA2R]. / Wyniki wstepne badan nad nowym markerem idiopatycznej nefropatii bloniastej: anty-PLA2R).

UNLABELLED: Idiopathic membranous nephropathy (IMN) is a chronic glomerular disease. It is result of new discovery that the production of anti-PLA2R autoantibodies, reacting with phospholipase A2 receptor on the surface of podocytes. Specific antibodies occur in IMN patients blood in exacerbated of disease, and disappear during remission. It suggest that analyse of these parameter can prove quick diagnosis to recognize and monitoring treatment process. The aim of our work was to determine anti-PLA2R in patients with suspected IMN and persons during/after treatment in order to monitor the effectiveness of therapy. MATERIAL AND METHODS: The study group consisted of 22 patients. Patients were divided into two groups: Group A--patients with symptomatic nephrotic syndrome in the course of membranous nephropathy; Group B--patients diagnosed with IMN who monitored the effectiveness of therapy. We collected the serum samples for all patients and determined of anti-PLA2R autoantibodies by indirect immunofluorescence test. RESULTS: Antibodies were detected in 12 patients (54.54%): diagnosed (n = 5) and monitor (n = 7). All of patients with exacerbated disease process in monitored group had positive test results. CONCLUSIONS: Our data suggest that anti-PLA2R is a sensitive diagnostic method and good for monitoring of disease activity, but nevertheless a need for further research on a larger group of patients to confirm that the test is a reliable source of diagnostic information.

Premature rupture of membranes and changes in the vaginal microbiome - Probiotics.

Preterm birth affects approximately 15 million women worldwide, of which 30 % is due to preterm premature rupture of membranes (PPROM). The reasons for shortening the duration of pregnancy are seen in genetic, hormonal, immunological and socio-economic conditions. Recent years have provided a lot of evidence on the impact of the microbiota and whole microbiome on pregnant women, suggesting that the microorganisms inhabiting the vagina significantly affect the risk of preterm delivery. The aim of the study was to review studies evaluating the composition of the vaginal microflora and its role in the occurrence of preterm labor caused by PPROM, and to evaluate the potential beneficial effect of probiotics on preventing the development of preterm labor. Vaginal microbial dysbiosis is observed in PPROM, which, due to its association with a high risk of prematurity and infection, increases neonatal morbidity and mortality. Further research on biomarkers for screening, early prognosis and diagnosis of PPROM seems advisable. Probiotics as a potential intervention can prevent the development of pathological vaginal flora, reducing the risk of infection in women planning pregnancy and pregnant women.

Serologic Status of Borrelia burgdorferi sensu lato in Patients with Cardiovascular Changes.

Cardiovascular diseases, particularly coronary heart disease (CHD) caused by atherosclerosis, have the highest worldwide incidence and mortality rate of any type of disease. Aside from risk factors associated with lifestyle and comorbidities, infectious agents such as Borrelia burgdorferi sensu lato spirochetes, which cause Lyme disease, may also play a role in the development of cardiovascular disease. A growing number of scientific papers have mentioned Lyme carditis. The aim of this study was to find the level of anti-Borrelia IgG antibodies in the blood serum of patients with advanced coronary heart disease. Materials and methods: The study group included 70 patients undergoing coronary artery bypass grafting (CABG) and off-pump coronary artery bypass (OPCAB) surgery aged 50 to 82 (average 68.26). The ELISA test was used to detect anti-Borrelia/IgG antibodies in the blood serum. Serological testing revealed seropositivity in 34.29% of patients and 'borderline results' in 17.14% of patients. We found a link between antibody levels and tick bites but not with other risk factors for the development of CHD. Conclusions: These findings support the idea that, as one of many factors, the contact with spirochetal antigens may indicate a potential positive correlation with the formation of cardiovascular changes. More research, not only at the diagnostic level but also at the advanced research level, is needed.

The Role of Anti-PLA2R and Anti-THSD7A Antibodies in the Pathogenesis and Diagnostics of Primary Membranous Nephropathy: A Review of Current Knowledge for Clinical Practice.

Primary membranous nephropathy (PMN) is considered a major cause of nephrotic syndrome. The discovery of circulating autoantibodies directed against glomerular podocytes helped to classify them as autoimmune diseases. Over the past years, there has been an increasing significance of anti-Phospholipase A2 Receptor (anti-PLA2R), which has been detected in 70-80% of PMN cases, and relevance of anti-Thrombospondin type I domain-containing 7A (anti-THSD7A) even though they are present in 2-5% of patients. The results of clinical and experimental studies indicate that these antibodies are pathogenic. It radically changed the diagnostic and therapeutic approach. Measurement of antibody titers in the serum seems to be a valuable tool for identifying PMN and for the assessment of disease activity. By monitoring pathogenic antibodies levels rather than proteinuria or reduced glomerular filtration rate (GFR) as an indicator of glomerular disease, physicians would easier divide patients into those with active and inactive PMN disease and decide about their therapy. The aim of this review is to evaluate scientific evidence about the role of autoantibodies, namely anti-PLA2R and anti-THSD7A, as PMN biomarkers. The present manuscript focuses on PMN pathogenesis and key data of diagnosis, monitoring of the disease, and treatment strategies that are currently being used in clinical practice.

Burn Wound Healing: Clinical Complications, Medical Care, Treatment, and Dressing Types: The Current State of Knowledge for Clinical Practice.

According to the World Health Organization (WHO), it is estimated that each year approximately 11 million people suffer from burn wounds, 180,000 of whom die because of such injuries. Regardless of the factors causing burns, these are complicated wounds that are difficult to heal and are associated with high mortality rates. Medical care of a burn patient requires a lot of commitment, experience, and multidirectional management, including surgical activities and widely understood pharmacological approaches. This paper aims to comprehensively review the current literature concerning burn wounds, including classification of burns, complications, medical care, and pharmacological treatment. We also overviewed the dressings (with an emphasis on the newest innovations in this field) that are currently used in medical practice to heal wounds.

Atypical Hemolytic Uremic Syndrome after SARS-CoV-2 Infection: Report of Two Cases.

Atypical hemolytic uremic syndrome (aHUS) is a life-threatening disease causing systemic thrombotic microangiopathy (TMA) due to the fact of complement dysregulation. Immune activation by viruses, including SARS-CoV-2, can lead to the development of an episode of aHUS against a background of genetic dysregulation in the complement pathway. This paper presents an analysis of two cases of aHUS-siblings diagnosed with familial disease, with a genetic predisposition to aHUS, in whom infection with SARS-CoV-2 was a strong trigger of disease recurrence. The quick recognition and treatment with eculizumab in the early stage of the disease resulted in a rapid improvement in clinical conditions and laboratory parameters.

Citrobacter freundii and Acinetobacter baumanii infection in a patient with neoplastic lung disease - Case report.

An 85-year-old male with a tumour in his right lung was admitted to Internal Diseases Ward to continue treatment after suffering a sudden cardiac arrest. An empiric antibiotic therapy with amoxycillin was introduced due to increased inflammation markers. Blood and sputum were collected. An abundant growth of AmpC ß-lactamase-producing Citrobacter freundii was observed in culture grown from the sputum. The antibiogram showed retained sensitivity to fluoroquinolones. The therapy was modified by replacing ß-lactam with ciprofloxacin. Neither clinical nor laboratory improvement were observed. Blood culture indicated sepsis of Acinetobacter baumannii etiology. The strain was suspected of producing OXA carbapenemase (CARBA test positive), KPC (-), MBL (-). Antibiogram illustrated retained sensitivity to gentamicin and colistin with complete resistance to ciprofloxacin. Another modification in treatment was implemented and ciprofloxacin was replaced with colistin.

Association of uromodulin with acute kidney injury in patients undergoing cardiac surgery.

Uromodulin (Umod) is a protein produced exclusively in the kidneys, and it is the most abundant protein in human urine. Scientific studies show that it can be a valuable diagnostic tool in monitoring kidney function. Clinical applications of Umod are probably wider. One of them is the role of a biomarker in cardiac surgery-associated acute kidney injury (CSA-AKI). Data from scientific studies indicate that a lower level of Umod in urine prior to surgery is associated with a higher risk of developing CSA-AKI after the procedure. A higher serum Umod level is suspected to be a good prognostic factor in the context of renal healing. It seems that the current state of knowledge supports the protective role of Umod in the course of AKI. Large, multi-center clinical trials would allow for the consolidation of preliminary scientific data and a more accurate understanding of the role of Umod as a CSA-AKI biomarker.

The Role of GPR120 Receptor in Essential Fatty Acids Metabolism in Schizophrenia.

A growing body of evidence confirms abnormal fatty acid (FAs) metabolism in the pathophysiology of schizophrenia. Omega-3 polyunsaturated fatty acids (PUFAs) are endogenous ligands of the G protein-coupled receptors, which have anti-inflammatory properties and are a therapeutic target in many diseases. No clinical studies are concerned with the role of the GPR120 signaling pathway in schizophrenia. The aim of the study was to determine the differences in PUFA nutritional status and metabolism between patients with schizophrenia (SZ group) and healthy individuals (HC group). The study included 80 participants (40 in the SZ group, 40 in the HC group). There were no differences in serum GPR120 and PUFA concentrations and PUFA intake between the examined groups. In the HC group, there was a relationship between FAs in serum and GPR120 concentration (p < 0.05): α-linolenic acid (ALA) (R = -0.46), docosahexaenoic acid (DHA) (R = -0.54), omega-3 PUFAs (R = -0.41), arachidonic acid (AA) (R = -0.44). In the SZ group, FA serum concentration was not related to GPR120 (p > 0.05). In the HC group, ALA and DHA serum concentrations were independently associated with GPR120 (p < 0.05) in the model adjusted for eicosapentaenoic acid (EPA) and accounted for 38.59% of GPR120 variability (p < 0.05). Our results indicate different metabolisms of FAs in schizophrenia. It is possible that the diminished anti-inflammatory response could be a component connecting GPR120 insensitivity with schizophrenia.

The Differences between Gluten Sensitivity, Intestinal Biomarkers and Immune Biomarkers in Patients with First-Episode and Chronic Schizophrenia.

Schizophrenia is a heterogeneous disorder without a fully elucidated etiology and mechanisms. One likely explanation for the development of schizophrenia is low-grade inflammation, possibly caused by processes in the gastrointestinal tract related to gluten sensitivity. The aims of this study were to: (1) compare levels of markers of gluten sensitivity, inflammation and gut permeability, and (2) determine associations between gluten sensitivity, inflammation, and intestinal permeability in patients with first-episode/chronic (FS/CS) schizophrenia and healthy individuals (HC). The total sample comprised 162 individuals (52 FS; 50 CS, and 60 HC). The examination included clinical variables, nutritional assessment, and serum concentrations of: high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), soluble CD14 (sCD14), anti-Saccharomyces cerevisiae antibody (ASCA), antigliadin antibodies (AGA) IgA/IgG, antibodies against tissue transglutaminase 2 (anti-tTG) IgA, anti-deamidated gliadin peptides (anti-DGP) IgG. A significant difference between groups was found in sCD14, ASCA, hs-CRP, IL-6 and AGA IgA levels. AGA IgG/IgA levels were higher in the FS (11.54%; 30.77%) and CS (26%; 20%) groups compared to HC. The association between intestinal permeability and inflammation in the schizophrenic patients only was noted. The risk for developing schizophrenia was odds ratio (OR) = 4.35 (95% confidence interval (CI 1.23-15.39) for AGA IgA and 3.08 (95% CI 1.19-7.99) for positive AGA IgG. Inflammation and food hypersensitivity reactions initiated by increased intestinal permeability may contribute to the pathophysiology of schizophrenia. The immune response to gluten in FS differs from that found in CS.

Evaluation of the effectiveness of rehabilitation of people diagnosed with schizophrenia using clinical tools, psychological tests, QEEG, and the brain-derived neurotrophic factor (BDNF). / Ocena skutecznosci rehabilitacji osób z rozpoznaniem schizofrenii z wykorzystaniem narzedzi klinicznych, testów psychologicznych, QEEG i neurotropowego czynnika BDNF.

OBJECTIVES: The aim of the study was to evaluate the level of cognitive and social functioning in two groups of schizophrenia patients using clinical tools, psychological tests, QEEG, and changes in the brain-derived neurotrophic factor (BDNF) activity in subjects' serum. METHODS: Randomly selected men diagnosed with schizophrenia were enrolled in the study and divided into two groups. Gr. 1 was formed by patients who did not undergo a structured rehabilitation program, while Gr. 2 was formed by patients undergoing standard rehabilitation, as provided in theprogramof the Psychiatric Rehabilitation Unit. Both groups underwent a comparative analysis of demographic parameters and based on: PANSS, AIS, GSES, and BCIS, psychological tests CTT-1, CTT-2, d2, QEEG, and changes in blood BDNF levels. To assess the effect of rehabilitation, the results obtained in both groups were compared after 12 weeks and their analysis was performed in accordance with assumptions for the experimental project. The study presents research hypotheses and pre-test and post-test comparisons of the groups, on the basis of selected research tools. RESULTS: The data obtained in measurement 1 indicate that both groups did not differ significantly in terms of: age, education, place of residence, treatment at outpatient facilities, medicines taken, and suicide attempts. Differences concerned: marital status, children, number of hospitalizations, and employment status. Furthermore, no significant differences were found for the studied groups concerning: serum levels of the brain-derived neurotrophic factor, values obtained on the PANSS, AIS, and GSES, and alpha/theta, theta/beta and theta/SMR ratios. The analyses performed in measurement 2 indicate that structured rehabilitation influences reduce negative symptoms, cause an increase in BDNF levels, cause an improvement in cognitive and social functioning and positively influence the perception speed and accuracy. CONCLUSIONS: The positive effect of structured rehabilitation influences allows to say that rehabilitation represents a necessary part of the comprehensive psychiatric treatment and should already be implemented during the first episode of the illness.

Can brain-derived neurotrophic factor (BDNF) be an indicator of effective rehabilitation interventions in schizophrenia? / Czy czynnik neurotropowy BDNF moze byc wskaznikiem skutecznych oddzialywan rehabilitacyjnych w schizofrenii?

The increasing body of evidence implies that brain-derived neurotrophic factor (BDNF) is the most common neurotrophin in the nervous system, playing an important role as an effectiveness indicator for rehabilitation interventions in schizophrenia patients. Currently, with the modern laboratory and instrumental diagnostic methods it is possible to diagnose deficits influencing the level of patient's functioning and use them as a basis for establishing individual re-adaptation programs for schizophrenia patients considering various forms of the therapy in different environments. Based on the PubMed and Scopus search tools a review of the available literature was performed and the paper presents current results of studies analyzing a relationship between selected rehabilitation interventions used in schizophrenia patients and changes in BDNF levels (a correlation between BDNF levels and physical activity and EEG Biofeedback therapy). Out of 240 records identified in total, the ones concerning the subject matter of the paper were taken into account. Studies concerning use of the presented method appear to indicate usefulness of BDNF factor in evaluation of effectiveness of implemented rehabilitation interventions in this group of patients. Changes in neurotrophin levels may indicate a synergy of the central and the peripheral nervous system, and high BDNF levels depending on physical activity and a neuromodulating effect of the EEG Biofeedback therapy may indicate their effectiveness. Use of various neurorehabilitation methods may improve the social functioning in schizophrenia patients. Treating BDNF as a biological indicator of those processes may represent an interesting hypothesis.

The occurrence of antibodies against Legionella pneumophila in patients with autoimmune rheumatic diseases.

INTRODUCTION: Patients with autoimmune rheumatic diseases are more susceptible to infection, owing to the underlying disease itself or to its treatment. Most commonly, infections affect the respiratory and urinary tracts. One of the etiological factors of infections in these patients is the bacteria of the genus Legionella. OBJECTIVES: The aim of the study was to assess the prevalence of anti-Legionella pneumophila (L. pneumophila) antibodies in patients with autoimmune rheumatic diseases and to analyze individual and environmental risk factors for the development of Legionella infection in patients with positive antibody results. PATIENTS AND METHODS: The study group consisted of 165 patients with autoimmune rheumatic diseases and 100 healthy subjects. Serum samples were tested for the presence of specific antibodies in the immunoglobulin (Ig) M and IgG classes against L. pneumophila serogroups 1 to 7 (SG 1-7) and the IgG class for serogroup 1 (SG 1). RESULTS: Antibodies against L. pneumophila were found in 7 patients (4%): 5 cases with antibody positivity only in the IgG class and 2 cases with antibody positivity in both classes. In patients with positive IgG antibodies for SG 1-7, specific antibodies for L. pneumophila SG 1 were not detected. In the control group, positive results were obtained in 9 cases (9%): IgM positivity in 6 (6%) and IgG positivity in 3 (3%). CONCLUSIONS: The frequency of antibodies to L. pneumophila in our patients is comparable to that in healthy individuals. L. pneumophila should be recognized as a potential pathogen in patients with autoimmune rheumatic diseases. Primary disease condition, immunosuppressive therapy, and other risk factors should not be ignored in these patients.

Gentamicin-impregnated collagen sponge for preventing sternal wound infection after cardiac surgery.

The frequency of sternal wound infection (SWI) after cardiac surgery ranges from 0.5% to 8% and is associated with significant morbidity, mortality, and treatment cost. Perioperative antibiotic prophylaxis is not sufficient to fully prevent the contamination of the surgical access site. One of the most effective methods for the prevention of wound infection seems to be the use of gentamicin-impregnated collagen sponge, which is successfully used in abdominal and orthopedic surgery. Surgically implantable topical antibiotics can reduce wound infection in cardiac patients as well, but the efficacy of SWI prevention in cardiac surgery still raises many questions.

Borrelia burgdorferi sensu lato as activators of the complement system in in vitro model.

INTRODUCTION: The following parameters were analyzed: C5a, which is significant in classical and alternative pathways of the complement system activation, and factor H, the major function of which is to regulate the alternative pathway. Factor H, in the case of Borrelia infection, is combined by CRASPs proteins of spirochetes, and thus prevents C3b molecules from contact with the pathogen, opsonisation and lysis of bacteria. MATERIAL AND METHODS: The experimental material in the model for the presented work consisted of whole blood of healthy persons (without the presence of antibodies anti-Borrelia) and persons with clinical symptoms of Lyme disease, which was stimulated with three genospecies of spirochetes recognized as pathogenic in Poland and Europe: B. afzelii, B. burgdorferi s.s. and B. garinii. RESULTS: The increase in the level of C5a in the experimental model after in vitro stimulation of whole blood with three genospecies Borrelia can be treated as an indicator of an effective activation of the complement's cascade. The increase in level C5a in the plasma relies on the genospecies and the strongest is for B. garinii. The decrease in the level of factor H, observed after the incubation of whole blood with three genospecies Borrelia, shows that this parameter was included in the spirochetes' mechanisms acting against factors of the innate immunity system of a host, which prevents lysis of bacteria via the alternative pathway. CONCLUSIONS: The results obtained on the basis of the in vitro model can be analysed from the aspect of spirochetes' real contact with a host's organism during the bite of infected ticks. Despite blocking of the alternative pathway, Borrelia initiate the activation cascade regardless of antibodies via the first contact of a host's organism with spirochetes, or in accordance with antibodies during the infection or subsequent contact with bacteria.