Innate Immunity Derived Factors as External Modulators of the CXCL12 - CXCR4 Axis and Their Role in Stem Cell Homing and Mobilization

<p>The &#945;-chemokine CXCL12 (stromal derived factor-1; SDF-1) and its corresponding G_&#945;I protein-coupled CXCR4 receptor axis play an important role in retention of hematopoietic stem progenitor cells (HSPCs) in bone marrow (BM) stem cell niches. CXCL12 has also been identified as a strong chemoattractant for HSPCs and implicated both in homing of HSPCs to BM after transplantation and in egress of these cells from BM into peripheral blood (PB). However, since CXCL12, as a peptide, is highly susceptible to degradation by proteolytic enzymes, its real biological availability in biological fluids may be somewhat limited. In this review, we will present data demonstrating that the CXCL12-CXCR4 axis is positively modulated by innate immunity-derived several external factors, ensuring that even low (near threshold) doses of CXCL12 still exert a robust chemotactic influence on HSPCs.</p

Phylodynamic Dispersal of SARS-CoV-2 Lineages Circulating across Polish–German Border Provinces

Introduction: The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has evolved into a worldwide outbreak, with significant molecular evolution over time. Large-scale phylodynamic studies allow to map the virus spread and inform preventive strategies. Aim: This study investigates the extent of binational dispersal and dynamics of SARS-CoV-2 lineages between seven border provinces of the adjacent countries of Poland and Germany to reconstruct SARS-CoV-2 transmission networks. Methods: Following three pandemic waves from March 2020 to the end of May 2021, we analysed a dataset of 19,994 sequences divided into B.1.1.7|Alpha and non-Alpha lineage groups. We performed phylogeographic analyses using the discrete diffusion models to identify the pathways of virus spread. Results: Based on population dynamics inferences, in total, 673 lineage introductions (95% HPD interval 641–712) for non-Alpha and 618 (95% HPD interval 599–639) for B.1.1.7|Alpha were identified in the area. For non-Alpha lineages, 5.05% binational, 86.63% exclusively German, and 8.32% Polish clusters were found, with a higher frequency of international clustering observed for B.1.1.7|Alpha (13.11% for binational, 68.44% German and 18.45% Polish, p < 0.001). We identified key transmission hubs for the analysed lineages, namely Saxony, West Pomerania and Lower Silesia. Conclusions: Clustering patterns between Poland and Germany reflect the viral variant transmission dynamics at the international level in the borderline area. Tracing the spread of the virus between two adjacent large European countries may provide a basis for future intervention policies in cross-border cooperation efforts against the spread of the pandemics

Prostate Cancer Eligible for Radical Prostatectomy: Self-Esteem of Patients and Forms of Coping with Stress

The purpose of this study was to analyze the strategies and styles of coping with stress and self-esteem in patients diagnosed with prostate cancer. One hundred and five patients with prostate cancer participated in the study. Coping strategies were assessed with the Mini-Cope questionnaire, coping styles were assessed with the Coping Inventory for Stressful Situations, and self-esteem was assessed with the Rosenberg Self-Esteem Scale. Patients&rsquo; self-esteem and stress coping styles and strategies were analyzed using a Pearson correlation analysis. A stepwise linear regression analysis was performed to determine the predictors of self-esteem. The self-esteem level was positively related to the task-focused style (r = 0.228) and negatively related to the emotion-focused style (r = &minus;0.329). The self-esteem level was significantly positively related to the strategies of active coping (r = 0.358), planning (r = 0.355), and seeking emotional support (r = 0.319) and was negatively related to self-blaming (r = &minus;0.448) and to substance use (r = &minus;0.301). The predictors of self-esteem level were: the strategies of self-blaming, planning, and the support-seeking dimension (F(3, 95) = 17.65; p &lt; 0.001), explaining 33.8% of the variability in subjects&rsquo; self-esteem level. The moderating effect of age occurred in patients up to 65 years; it was statistically insignificant in patients older than 65 years. Replacement of the self-blame strategy and the emotion-focused style may lead to higher self-esteem of patients. The level of self-esteem can predict the strategies of self-blaming, planning, and the dimension of seeking support. For patients up to 65 years, psychological support should include reinforcement of adaptive forms of coping

Transmitted HIV drug resistance and subtype patterns among blood donors in Poland

Abstract Surveillance on the HIV molecular variability, risk of drug resistance transmission and evolution of novel viral variants among blood donors remains an understudied aspect of hemovigilance. This nationwide study analyses patterns of HIV diversity and transmitted resistance mutations. Study included 185 samples from the first time and repeat blood donors with HIV infection identified by molecular assay. HIV protease, reverse transcriptase and integrase were sequenced using population methods. Drug resistance mutation (DRM) patterns were analyzed based on the Stanford Interpretation Algorithm and standardized lists of transmitted mutations. Phylogeny was used to investigate subtyping, clustering and recombination patterns. HIV-1 subtype B (89.2%) followed by subtype A6 (7.6%) were predominant, while in three (1.6%) cases, novel recombinant B/A6 variants were identified. Non-B variants were more common among repeat donors (14.5%) compared to the first time ones (1.8%), p = 0.011, with higher frequency (9.9%) of A6 variant in the repeat donor group, p = 0.04. Major NRTI DRMs were observed in 3.8%, NNRTI and PI in 0.6% and INSTI 1.1% of cases. Additionally, E157Q polymorphism was observed in 9.8% and L74I in 11.5% of integrase sequences. Transmission of drug resistance among blood donors remains infrequent. Subtype patters increase in complexity with emergence of novel intersubtype A6B recombinants

SARS-CoV-2 Whole-Genome Sequencing by Ion S5 Technology&mdash;Challenges, Protocol Optimization and Success Rates for Different Strains

The COVID-19 pandemic demonstrated how rapidly various molecular methods can be adapted for a Public Health Emergency. Whether a need arises for whole-genome studies (next-generation sequencing), fast and high-throughput diagnostics (reverse-transcription real-time PCR) or global immunization (construction of mRNA or viral vector vaccines), the scientific community has been able to answer all these calls. In this study, we aimed at the assessment of effectiveness of the commercially available solution for full-genome SARS-CoV-2 sequencing (AmpliSeq&trade; SARS-CoV-2 Research Panel and Ion AmpliSeq&trade; Library Kit Plus, Thermo Fisher Scientific). The study is based on 634 samples obtained from patients from Poland, with varying viral load, assigned to a number of lineages. Here, we also present the results of protocol modifications implemented to obtain high-quality genomic data. We found that a modified library preparation protocol required less viral RNA input in order to obtain the optimal library quantity. Concurrently, neither concentration of cDNA nor reamplification of libraries from low-template samples improved the results of sequencing. On the basis of the amplicon success rates, we propose one amplicon to be redesigned, namely, the r1_1.15.1421280, for which less than 50 reads were produced by 44% of samples. Additionally, we found several mutations within different SARS-CoV-2 lineages that cause the neighboring amplicons to underperform. Therefore, due to constant SARS-CoV-2 evolution, we support the idea of conducting ongoing sequence-based surveillance studies to continuously validate commercially available RT-PCR and whole-genome sequencing solutions

Renal and Inflammation Markers&mdash;Renalase, Cystatin C, and NGAL Levels in Asymptomatic and Symptomatic SARS-CoV-2 Infection in a One-Month Follow-Up Study

The aim of our study was to evaluate the influence of asymptomatic infection and the occurrence of symptomatic COVID-19 on specific biochemical, renal, and immune parameters&mdash;renalase, neutrophil gelatinase-associated lipocalin (NGAL) cystatin C (CysC), and creatinine&mdash;and their weekly fluctuations during a one-month observation period in COVID-19 patients admitted to hospital. The study involved 86 individuals: 30 patients with diagnosed COVID-19, 28 people with asymptomatic infection confirmed with IgG antibodies&mdash;the IG(+) group&mdash;and 28 individuals without any (IgG, IgE) anti-SARS-CoV-2 antibodies&mdash;the IG(&minus;) group. In the COVID-19 group, blood was drawn four times: (1) on day 0/1 after admission to hospital (C1 group), (2) 7 days later (C7 group), (3) 14 days later (C14 group), and (4) 28 days later (C28 group). In the IG(&minus;) and IG(+) groups, blood was drawn once. There were no significant differences in creatinine, Cys C, and uric acid between any of the analyzed groups. NGAL levels were significantly higher in IG(+) and at all time-points in the COVID-19 groups than in controls. A similar observation was made for renalase at the C7, C14, and C28 time-points. Plasma renalase, NGAL, and CysC are unrelated to kidney function in non-critically ill COVID-19 patients and those with asymptomatic infection. Renalase and NGAL are most likely related to the activation of the immune system rather than kidney function. Asymptomatic SARS-CoV-2 infection causes a rise in plasma NGAL levels similar to those observed in symptomatic COVID-19 patients. Therefore, more attention should be paid to tracking and monitoring the health of these people