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Although the role of T lymphocytes in sarcoidosis (SA) and lung cancer (LC) is quite well reported, the occurrence of B cells in disease microenvironments may suggest their potential role as natural modifiers of the immune response. The aim of this study was to investigate the B-cell profile and lymphocyte-related hematological parameters between patients with SA, LC and healthy controls (HCs). The cells were assessed by flow cytometry and a hematological analyzer in peripheral blood (PB) and material from lymph nodes (LNs) obtained by the EBUS/TBNA method. We showed that in SA patients, there were higher percentages of naïve B and CD21low B cells and a lower percentage of class-switched memory B cells than LC patients in LNs. We observed a higher median proportion of non-switched memory and transitional B cells in the PB of SA patients than in LC patients. We noticed the lowest median proportion of class-switched memory B cells in the PB from SA patients. LC patients had a higher percentage of RE-LYMP and AS-LYMP than SA patients. Our study presented a different profile of B-cell subpopulations in SA and LC patients, distinguishing dominant subpopulations, and showed the relocation from distant compartments of the circulation to the disease microenvironment, thus emphasizing their role.

IntroductionAlthough thyroid abnormalities are observed less frequently in children than in adults, the increased incidence of thyroid cancer makes it mandatory for all pediatric surgeons to be knowledgeable about the disorders of this gland. Thyroid abnormalities can be associated with hyperthyroidism or hypothyroidism and euthyroidism and/or symmetric or asymmetric enlargement of the gland.AimThe present study was undertaken to retrospectively analyze the indications, surgical techniques used, results obtained, and complications found in the surgical treatment of thyroid diseases in children and adolescents in a surgical center for the macro-region of western Poland.MethodsThe data of 148 patients undergoing total or partial thyroidectomy between 2013 and 2022 were analyzed from the medical records of the Department of Pediatric Surgery, Traumatology, and Urology of the Medical University of Poznan, Poland.ResultsA total of 95 children underwent subtotal thyroidectomy and 64 underwent total thyroidectomy, of which the procedure was widened to include prophylactic removal of neck lymph nodes in 45 patients. There were 113 girls (76%) in the analyzed group, and the average age of the patients at the time of surgical treatment was 15 years. The average time from the diagnosis of thyroid disease to surgery was 4 months, ranging from 2 weeks to 3 years. Of the 64 patients undergoing total thyroid resection, 35 (54.69%) were diagnosed with thyroid cancer.ConclusionsCollaboration within a multidisciplinary team ensures optimal surgical outcomes in children and adolescents with thyroid disease. With extreme caution, thyroid removal is a safe procedure with few complications, but the experience of the surgeon performing thyroid surgery in children remains crucial. Despite the absence of such a diagnosis in the first fine-needle aspiration biopsy, the high percentage of thyroid carcinomas in the analyzed group may be because the initial biopsy was performed in a less experienced center, also in terms of histopathological laboratory. Hence, we point out the necessity of performing a repeat fine-needle aspiration biopsy (according to the Bethesda classification) in a more experienced center before the final decision of thyroidectomy.

The number of argyrophilic nucleolus organizer regions (AgNOR) is related to the proliferative activity of cells and the degree of neoplastic transformation. The surface area of AgNOR depending on nuclear structure may be a predictor of tumor recurrence, while research into acute leukemias is scarce. The aim of the study was to determine whether the assessment of AgNOR parameters is useful in the differentiation of acute leukemias and, together with cytogenetic changes, would allow for a quick evaluation of the risk group. The AgNOR structures were analyzed in terms of the shape, surface area and distribution in bone marrow blast cells in patients with acute leukemias. We observed significant differences in the AgNOR structures, simple, compound and complex patterns between acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Complex structures were more numerous in ALL than in AML patients. There were significant differences in the distribution of AgNOR configuration among various cytogenetic AML risk groups. We observed a significant difference in the mean number of AgNOR between ALL-T and ALL-B. We detected diversity in the AgNOR structures and pattern map in AML and ALL. Thus, presentation of a variety of AgNOR configurations is innovative and can be a useful method of differentiating patients with acute leukemia types and cytogenetic risk.

Macrophages play an important role in the suppression and activation of immune anti-cancer response, but little is known about dominant macrophage phenotype in the lung cancer environment, evaluated by bronchoalveolar lavage fluid (BALF). The aim of this study was to characterize macrophages in BALF from a lung affected by cancer (cBALF) and a healthy lung (hBALF) of the same patient regarding their individual macrophage polarization and selected cytokines profile. A total of 36 patients with confirmed lung cancer were investigated. Macrophages markers: CD206 CD163 CD80 CD86 CD40 CD45, Arginase-1, and CD68 were evaluated by flow cytometry. Cytokines (IL-1 RA, IL-6, IL-10, TNF-α, IL-1β, IL-12, IL-23, and TGF-β) profile was analyzed. There was higher median proportion of macrophages in Cbalf than in Hbalf. The population of macrophages presented immunophenotype: Ccd68+bright CD206+bright CD163+bright CD80+ CD86+ CD40+bright CD45+ cArginase+. We observed some trends in the expression of the analyzed antigens in clBALF and hlBLAF. The highest concentrations of IL-1RA and IL-6 were in Cbalf and Hbalf supernatant. There were the correlations between pro- and anti-inflammatory cytokines. The findings showed that macrophages include a diverse and plastic group with the presence of different antigens and cytokines, and determining the target phenotype is a complex and variable process.

The mechanisms underlying the immune response to coronavirus disease 2019 (COVID-19) and the recovery process have not been fully elucidated. The aim of the study was to analyze leukocyte subpopulations in patients at significant time points (at diagnosis, and 3 and 6 months after infection) selected according to the analysis of changes in the lungs by the CT classification system, considering the severity of the disease. The study groups consisted of severe and non-severe COVID-19 patients. There was a significant decrease in CD8+ T cells, NK and eosinophils, with an increasing percentage of neutrophils during hospitalization. We noticed lower levels of CD4 and CD8 T lymphocytes, eosinophils, basophils, and CD16+ monocytes and elevated neutrophil levels in severe patients relative to non-severe patients. Three months after infection, we observed higher levels of basophils, and after 6 months, higher CD4/CD8 ratios and T cell levels in the severe compared to non-severe group. Non-severe patients showed significant changes in the leukocyte populations studied at time of hospitalization and both within 3 months and 6 months of onset. The CT CSS classification with parameters of the flow cytometry method used for COVID-19 patients determined changes that proved useful in the initial evaluation of patients.

Fragility scales are intended to help in therapeutic decisions. Here, we asked if the fragility assessment in MM patients ≥ 75 years old qualified for treatment by the local physician correlates with the choice of treatment: a two- or three-drug regimens. Between 7/2018 and 12/2019, we prospectively enrolled 197 MM patients at the start of treatment from the 13 Polish Myeloma Group centers. The data to assess fragility were prospectively collected, but centrally assessed fragility was not disclosed to the local center. The activity of daily living (ADL) could be assessed in 192 (97.5%) and was independent in 158 (80.2%), moderately impaired in 23 (11.7%), and 11 (5.6%) in completely dependent. Patients with more than three comorbidities made up 26.9% (53 patients). Thus, according to the Palumbo calculator, 43 patients were in the intermediate fitness group (21.8%), and the rest belonged to the frailty group (153, 77.7%). Overall, 79.7% of patients (157) received three-drug regimens and 20.3% (40) received two-drug regimens. In each ECOG group, more than three out of four patients received three-drug regimens. According to the ADL scale, 82.3% of the independent 65.2% of moderately impaired, and 81.8% of the dependent received three-drug regimens. Out of 53 patients with at least four comorbidities, 71.7% received three-drug regimens, and the rest received two-drug regimens. Thirty-four patients from the intermediate fit group (79.0%), and 123 (79.9%) from the frail group received three-drug regimens. Early mortality occurred in 25 patients (12.7%). No one discontinued treatment due to toxicity. To conclude, MM patients over 75 are mainly treated with triple-drug regimens, not only in reduced doses, regardless of their frailty scores. However, the absence of prospective fragility assessment did not negatively affect early mortality and the number of treatment discontinuations, which brings into question the clinical utility of current fragility scales in everyday practice.

Spruce is the most cultivated tree species in modern forestry in Central Europe, since it has the ability to grow on many soil types with profitable biomass accumulation. However, even-aged and uniform spruce forests are affected by recurring droughts and associated biotic stressors leading to large-scale diebacks across Central Europe causing controversies among foresters and nature conservationists. We investigate the role of spruce in historical woodlands by using 15666 spruce timbers from historical buildings and on the basis of pollen-based land cover estimates using the REVEALS model from 157 pollen sites in southern Central Europe. Start and end dates of the spruce timber samples and their dendrological characteristics (age, growth rates and stem diameters) were used to obtain information on past forest structures. Tree rings and REVEALS estimates are combined at a spatial scale of 1° × 1° resolution, grouped in four sub-regions, and a temporal resolution of 100-year time windows starting from 1150 to 1850 CE. We found that spruce dominates the species assemblage of construction timber with almost 41% and that the harvest age varies little through time, whereas a declining trend in growth rates and stem diameters are observed toward times before modern forestry. Temporal and regional differences in spruce abundance and building activity were found highlighting periods of (i) land abandonment and forest expansion in the 14th century, (ii) increased wood consumption during the 16th century due to population increase and beginning industrial developments, (iii) a forest recovery during and after the Thirty years' war, and (iv) afforestation efforts from the 1650s onwards. Furthermore, this study shows that spruce was constantly present in the study area in most studied sub-regions for the last 800 years. We demonstrate the need of combining tree-ring and pollen data to identify spatiotemporal patterns in spruce abundance and utilization.

Myelodysplastic syndromes (MDS) are common malignant disorders with a poor prognosis. It is necessary to search for new rapid diagnostic methods to detect MDS patients with cytogenetic changes. The aim of the study was to assess new hematological neutrophil- and monocyte- related parameters I then bone marrow of MDS patient with and without cytogenetic changes. A total of 45 patients with MDS, including 17 patients with cytogenetic changes, were examined. The study was conducted using the Sysmex XN-Series hematological analyzer. New neutrophil and monocyte parameters, such as immature granulocytes (IG), neutrophil reactivity intensity (NEUT-RI), neutrophil granularity intensity (NEUT-GI), neutrophil size (NE-FSC) and neutrophil/monocyte data relating to granularity, activity and volume (NE-WX/MO-WX, NE-WY/MO-WY, NE-WZ/MO-WZ, MO-X, MO-Y, MO-Z) were evaluated. We observed higher median proportions of NE-WX, NE-WY, NE-WZ, and IG counts in MDS patients with cytogenetic changes than in patients without cytogenetic changes. The NE-FSC parameter was lower in MDS patients with cytogenetic changes than in patients without cytogenetic changes. The combination of new neutrophil parameters was found to be a new successful approach in distinguishing MDS patients with cytogenetic changes from patients without cytogenetic changes. It appears that there may be unique neutrophil parameter signatures associated with an underlying mutation.

Lymphocytes play a leading role in regulation of the immune system in lung cancer patients. The recognition of T cells profile may help in prediction of effectiveness of anticancer immunotherapy. The aim of the study was to determine the dominant subpopulation of CD4+ and CD8+ lymphocytes in metastatic and non-metastatic lymph nodes (LNs) of lung cancer patients. LNs aspirates were obtained during EBUS/TBNA procedure and cells were analyzed by flow cytometry. We showed a higher percentage of CD4+ and CD8+ effector memory T cells in the metastatic than in the non-metastatic LNs (28.6 vs. 15.3% and 28.6 vs. 14.0%, p< 0.05). The proportion of CD45RO+ T regulatory cells (CD45RO+ Tregs) was higher in the metastatic LNs than in the non-metastatic ones (65.6 vs. 31%, p< 0.05). We reported the significant differences in T cell subsets depending on the lung cancer metastatic process. We observed that the effector memory T cells were predominant subpopulations in metastatic LNs. Lymphocyte profile in LNs is easy to evaluate by flow cytometry of EBUS/TBNA samples and may reflect the immune status in lung cancer.

Abstract Background Sarcoidosis is a multisystemic granulomatous disease with still unknown etiology. Our previous studies showed a significantly higher percentage of CD34 + cells in the peripheral blood in patients with sarcoidosis (SA) compared to the control group. The objective of the present study was to characterized of the CD34 + cell population in peripheral blood in patients with SA with reference to the control group. Moreover in patients with SA, fibrocytes and endothelial cells were analysed and their relationship to the fibrosis process based on assessment of diffusing capacity for carbon monoxide (DLCO). Methods Data from patients diagnosed with SA at Military Institute of Medicine (Warsaw, Poland) between January 2018 and December 2019 were collected and analysed ongoing basis. Peripheral blood was collected from 26 patients with newly diagnosed pulmonary SA and 16 healthy subjects. The immunomagnetic method and flow cytometry were used. Among the CD34+ progenitor cells were assessed: low-differentiated cells, hematopoietic progenitor cells and endothelial progenitor cells. The Statistica 12.0 software was used for a statistical analysis. Results We observed a significantly higher percentage of low-differentiated cells (13.8 vs. 2.3, P = 0.001) and endothelial cells (0.3 vs. 0.0, P = 0.001) in patients with SA compared to the control group. In the study group the median proportion of fibrocytes was 1.877% (0.983–2.340) in patients with DLCO 80% was 0.795% (0.139–1.951) (P = 0.72). The median proportion of endothelial progenitor cells was higher in patients with DLCO 80%: 0.451% (0.177–0.857) (P = 0.44). Conclusions In conclusion we demonstrated for the first time the immunophenotype of peripheral CD34 + cells with the degree of their differentiation. The study confirmed the involvement of low differentiated cells and endothelial cells in patients with SA.

Although variations in building activity are a useful indicator of societal well-being and demographic development, historical datasets for larger regions and longer periods are still rare. Here, we present 54,045 annually precise dendrochronological felling dates from historical construction timber from across most of Europe between 1250 and 1699 CE to infer variations in building activity. We use geostatistical techniques to compare spatiotemporal dynamics in past European building activity against independent demographic, economic, social and climatic data. We show that the felling dates capture major geographical patterns of demographic trends, especially in regions with dense data coverage. A particularly strong negative association is found between grain prices and the number of felling dates. In addition, a significant positive association is found between the number of felling dates and mining activity. These strong associations, with well-known macro-economic indicators from pre-industrial Europe, corroborate the use of felling dates as an independent source for exploring large-scale fluctuations of societal well-being and demographic development. Three prominent examples are the building boom in the Hanseatic League region of northeastern Germany during the 13th century, the onset of the Late Medieval Crisis in much of Europe c. 1300, and the cessation of building activity in large parts of central Europe during armed conflicts such as the Thirty Years’ War (1618–1648 CE). Despite new insights gained from our European-wide felling date inventory, further studies are needed to investigate changes in construction activity of high versus low status buildings, and of urban versus rural buildings, and to compare those results with a variety of historical documentary sources and natural proxy archives.

Gene therapy is a promising strategy to cure rare diseases. The lack of regulatory sequences ensuring specific and robust expression in skeletal and cardiac muscle is a substantial limitation of gene therapy efficiency targeting the muscle tissue. Here we describe a novel muscle hybrid (MH) promoter that is highly active in both skeletal and cardiac muscle cells. It has an easily exchangeable modular structure, including an intronic module that highly enhances the expression of the gene driven by it. In cultured myoblasts, myotubes, and cardiomyocytes, the MH promoter gives relatively stable expression as well as higher activity and protein levels than the standard CMV and desmin gene promoters or the previously developed synthetic or CKM-based promoters. Combined with AAV2/9, the MH promoter also provides a high in vivo expression level in skeletal muscle and the heart after both intramuscular and systemic delivery. It is much more efficient than the desmin-encoding gene promoter, and it maintains the same specificity. This novel promoter has potential for gene therapy in muscle cells. It can provide stable transgene expression, ensuring high levels of therapeutic protein, and limited side effects because of its specificity. This constitutes an improvement in the efficiency of genetic disease therapy. Keywords: muscle promoter, expression cassette, AAV, vector, skeletal muscles, heart, C2C12, myotubes

Development trends regarding the business-related urban complexes seem to evolve from the “big-box” towards the more “multi-use” types of structures. Within it, the special role is reserved for places, which—due to economic, political, and geographical reasons—have not been previously considered as major business hubs. Only recently, places like cities in Central and Eastern Europe have become attractive locations for business complexes. These could offer centrally located and attractive locations for new structures, which resulted in the development of the new type of commercial centers—in the form of multi-use districts, walkable, and complemented by other uses. Therefore, to some extent, these cities “surpassed the development line” of the commercial and business complexes, and have become home to something much more advanced. Within the article, the cases from Poland, including Gdańsk, Warsaw, Cracow, and Wroclaw, are discussed. Not only is the urban arrangement of selected complexes presented, but the planning and socio-economic, legal, and infrastructural aspects of these developments are also discussed.

Emery-Dreifuss muscular dystrophy type 1 (EDMD1) is a rare genetic disease caused by mutations in the EMD gene coding for a nuclear envelope protein emerin. We generated and characterized induced pluripotent stem cells (iPSCs) from two EDMD1 patients bearing a mutation c.del153C and from one healthy donor. That mutation leads to generation of premature STOP codon. Established iPSCs are very valuable tool for disease pathogenesis investigation and for the development of new therapeutic methods after differentiation to cardiac or muscle cells. Obtained iPSCs show the proper morphology, pluripotency markers expression, normal karyotype and potential to differentiate into three germ layers.

This paper presents the energy potential of biogas obtained from the anaerobic digestion (AD) of sewage sludge (SS) preceded by thermal hydrolysis (THP) using Cambi THP® technology. The presented data are for the Tarnów (Poland) wastewater treatment plant for the year 2020. A detailed energy balance of biogas and its use in the cogeneration process and in the production of heat in the water boiler and the steam boiler is presented. The article contains data on the amount of processed SS and the content of dry matter and dry organic matter at different stages of the technological process. The annual plant operation resulted in the production of 3,276,497 Nm3 of biogas as a result of processing 8684 tonnes of dry solids (tDS) of municipal SS from the Tarnów wastewater treatment plant (WWTP) and regional WWTPs. The energy potential of the produced biogas was 75,347.06 GJ. The average calorific value of biogas was 23,021 kJ/Nm3.. The obtained biogas production allowed us to cover the thermal energy demand of the THP 100%. The annual average specific biogas conversion rate during the study period was 0.761 Nm3/kg of dry organic matter reduced and the average organic matter content reduction in the sludge was 64.60%.

Repetition of the same processes on different objects or units of a construction project and their concurrent execution makes it necessary to use the same limited resources at the same time. Managers prefer simple heuristic priority rules to scheduling construction activities, but there is not one the best for all projects. In addition that the experience from deterministic scheduling problems and priority-rule methods cannot always be directly transferred to stochastic environment.

Menopause is a major turning point in a woman’s life that is characterized by declining ovarian function and decreased serum estrogen levels. The resulting hormonal changes particularly affect the skin, with postmenopausal symptoms such as loss of structural architecture and increased propensity to damage becoming rapidly noticeable. Interestingly, studies have shown that estrogen deprivation in postmenopausal conditions accelerates many skin changes, including dryness, atrophy, fine wrinkling, and poor wound healing. Thus, the effects of low estrogen on the skin are an important endogenous cause of aging skin in women, yet topical treatment strategies that target cutaneous symptoms are limited. The goal of this article is to provide an overview of the role of estrogen in the skin and changes associated with estrogen deficiency, as well as review alternatives to systemic estrogen therapy and describe the effects of these interventions on cutaneous aging in postmenopausal skin. Specifically, clinical studies that utilize topical estrogens and topical isoflavones, which are soy-derived compounds that interact with estrogen receptors, are discussed. Keywords: Topical estrogen, topical isoflavone, genistein, menopause, post-menopause, skin

Monocytes play a role in viral biology, but little is known about the monocyte subpopulation in the course of COVID-19 disease. The aim of the study was the analysis of classical, intermediate and non-classical monocytes with expression of PD-L1 and CD62L, TIM-3 and CD86 molecules in peripheral blood (PB) to distinguish patients with SARS-CoV-2 infection from convalescent patients. The study group consisted of 55 patients with SARS-CoV-2 infection and 51 convalescent patients. The cells were analyzed by flow cytometry. The number and proportion of monocytes were lower in patients with COVID-19 than convalescent patients. We observed a lower proportion of non-classical monocytes in COVID-19 patients than convalescent ones. There was a higher proportion of PDL-1-positive intermediate monocytes in COVID-19 patients than convalescent ones. We noticed a higher geometric mean fluorescence intensity (GeoMean) of PD-L1 on intermediate monocytes in COVID-19 patients than convalescent patients, and a higher proportion of CD62L-positive monocytes in COVID-19 patients in comparison with convalescent ones. We found a higher GeoMean of CD62L on monocytes in COVID-19 patients than convalescent ones. Assessment of PD-L1- and CD62L-positive monocyte subsets may identify patients with a possible predisposition for rapid recovery. The monitoring of monocyte subsets in PB might be a useful test in COVID-19 patients.

Abstract The aim of the study: The aim of the work was to determine the level of knowledge of the rural population on the subject of prevention and risk factors for hypertension. Material and method: The research covered a group of 200 people living in rural areas. The research was carried out from May to June 2017. A questionnaire of one's own authorship was used in the work, consisting of 19 closed one-choice questions. Results: The research shows that people living in rural areas have a high level of knowledge regarding the norms of normal blood pressure. 92% of the respondents correctly indicated the upper values of systolic pressure, and 98% of the respondents were able to determine the correct values of diastolic pressure. The knowledge of the subjects regarding dietary recommendations, physical activity and stimulants such as coffee and cigarettes was at low and medium Conclusions: : The low level of knowledge about risk factors and prophylaxis of hypertension was possessed by 48.5% of respondents, the remaining 51.5% of respondents had knowledge at the secondary level Key words: hypertension, risk factors, prophylaxis

The evaluation of argyrophilic nucleolar organizer regions (AgNORs) uses a simple method used in research into neoplasm. Bone marrow aspirates from 70 patients with acute leukemia underwent morphological, immunophenotypic, and genetic assessment and were stained with silver nitrate. In leukemic cells, the mean AgNORs number, mean AgNORs area, and mean AgNOR-area-to-nucleus-area ratio were calculated in patients with acute myeloid leukemia (AML), patients with acute lymphoblastic leukemia (ALL), and selected risk groups. A higher value of all measured AgNOR parameters was observed in patients with AML compared to the ALL group. In AML patients, a higher mean AgNOR area was found in the ELN3 cytogenetic group compared to the ELN2 cytogenetic group. A higher value of the mean AgNOR count was observed in patients with white blood cells (WBCs) > 12 × 109/L than in the group with WBCs ≤ 12 × 109/L, as well as in patients with >20% blasts in peripheral blood (PB) than in patients with ≤20% blasts in PB. In the ALL group, a higher mean AgNOR-area-to-nucleus-area ratio was found in group with the presence of Philadelphia chromosome Ph(+) than without the Philadelphia chromosome Ph(−). AgNOR parameter analysis is a valuable method for differentiation of AML and ALL in adults.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) with cerebral venous sinus thrombosis (CVST) has been recently reported after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We present a case of a patient with fulminant CVST and thrombocytopenia after receiving the ChAdOx1 nCoV-19 vaccine. Although the patient received immediate anticoagulant and intravenous immune globulin treatment, he died within 24 h after hospital admission. VITT and CVST are rare conditions; however, the course may be fatal. Therefore, clinicians should be familiarized with the clinical and laboratory features of VITT.