Prognostic Value of the miR-17~92 Cluster in Chronic Lymphocytic Leukemia.

The aim of this study was to investigate the expression of miR-17∼92 cluster members in chronic lymphocytic leukemia (CLL) patients. Six microRNAs (miRNAs)-miR-17, miR-18a, miR-19a, miR-19b-1, miR-20a, and miR-92a-1-very poorly characterized in CLL patients, were chosen for the study to consider their possible role as cancer biomarkers. It is currently unclear to which extent miR-17~92 expression is related to other routinely measured CLL markers, and whether the findings can be of any clinical significance. To achieve this goal, we report the expression levels of these miRNAs detected by RT-qPCR in purified CD19+ B lymphocytes of 107 CLL patients and correlate them with existing clinical data. The study provides new evidence regarding the heterogeneity of miR-17~92 cluster members' expression in CLL patients. Higher miR-17-5p expression was associated with unfavorable prognostic factors (i.e., 17p and 11q deletions, CD38 and ZAP-70 expression). On the other hand, miR-19a, miR-20a, and miR-92a-1 negatively correlated with these adverse factors. The presence of del(13q) as a sole aberration was associated with a significantly lower miR-17-5p as well as higher miR-19a-3p and miR-92a-1-5p expression compared to patients carrying unfavorable genetic aberrations. Particularly, miR-20a could be considered an independent favorable prognostic factor. In a multivariate analysis, high miR-20a expression remained an independent marker predicting long TTT (time to treatment) for CLL patients.

Immunity in the ABM-DSGE Framework for Preventing and Controlling Epidemics-Validation of Results.

The COVID-19 pandemic has raised many questions on how to manage an epidemiological and economic crisis around the world. Since the beginning of the COVID-19 pandemic, scientists and policy makers have been asking how effective lockdowns are in preventing and controlling the spread of the virus. In the absence of vaccines, the regulators lacked any plausible alternatives. Nevertheless, after the introduction of vaccinations, to what extent the conclusions of these analyses are still valid should be considered. In this paper, we present a study on the effect of vaccinations within the dynamic stochastic general equilibrium model with an agent-based epidemic component. Thus, we validated the results regarding the need to use lockdowns as an efficient tool for preventing and controlling epidemics that were obtained in November 2020.

Temporal variability in the allergenicity of airborne Alternaria spores.

The concentration of fungal spores in the air is traditionally considered as a proxy of allergen exposure. However, in vitro experiments have shown that the allergenicity of Alternaria spores varies depending on ecophysiological and developmental factors. Despite the potential clinical significance of these findings, it has never been verified in outdoor environments. This study, therefore, aims to investigate variability in the amount of the major allergen (Alt a 1) released from Alternaria spores in outdoor air. During the 3-year monitoring study (2014-2016), the median seasonal allergenicity of Alternaria spores exceeded 8.6 × 10-3 pg Alt a 1/spore. The most allergenic spores were collected during the driest and the most polluted season (with respect to seasonal concentrations of ozone, sulphur dioxide, and particulate matter). Within the season, daily spore allergenicity ranged from 2.4 to 34.7 × 10-3 pg Alt a 1/spore (5th-95th percentile). No repeatable effects of weather and pollution on short-term variations in Alternaria spore allergenicity were found. However, during the episodes when high-potency spores were recorded, the air masses arrived from eastern directions. Contrary, the spores with the lowest allergenicity were related to western winds. This suggests that factors such as source area (habitat types) and species diversity could be responsible for the varying exposure to Alternaria allergens. Our findings show that high and low-potency spores are recorded in the air; therefore, the airborne concentrations of fungal spores alone may not be sufficient to provide allergy sufferers and healthcare professionals with information about allergen exposure.

Health hazards related to conidia of Cladosporium-biological air pollutants in Poland, central Europe.

The spores of Cladosporium Link. are often present in the air in high quantities and produce many allergenic proteins, which may lead to asthma. An aerobiological spore monitoring program can inform patients about the current spore concentration in air and help their physicians determine the spore dose that is harmful for a given individual. This makes it possible to develop optimized responses and propose personalized therapy for a particular sensitive patient. The aim of this study was to assess the extent of the human health hazard posed by the fungal genus Cladosporium. For the first time, we have determined the number of days on which air samples in Poland exceeded the concentrations linked to allergic responses of sensitive patients, according to thresholds established by three different groups (2800/3000/4000 spores per 1m3 of the air). The survey was conducted over three consecutive growing seasons (April-September, 2010-2012) in three cities located in different climate zones of Poland (Poznan, Lublin and Rzeszow). The average number of days exceeding 2800 spores per cubic meter (the lowest threshold) ranged from 61 (2010) through 76 (2011) to 93 (2012), though there was significant variation between cities. In each year the highest concentration of spores in the air was detected in either Poznan or Lublin, both located on large plains with intensive agriculture. We have proposed that an effective, science-based software platform to support policy-making on air quality should incorporate biological air pollutant data, such as allergenic fungal spores and pollen grains.

Warm and dry weather accelerates and elongates Cladosporium spore seasons in Poland.

Temperature is the environmental factor that systematically changes for decades and, as in plants and animals, can significantly affect the growth and development of fungi, including the abundance of their sporulation. During the time of study (2010-2012), a rapid increase in air temperature was observed in Poland, which coincided with the substantial decrease in rainfall. The increase in annual mean temperatures at three monitoring sites of this study was 0.9 °C in Lublin and Rzeszow (east Poland) and 2.0 °C in Poznan (west Poland). Such warming of air masses was comparable to the average global air temperature rise in the period of 1880-2012 accounting for 0.85 °C, as reported by the Intergovernmental Panel on Climate Change. Moreover, there was a substantial decrease in rainfall, ranging from 32.7 % (Poznan) to 43.0 % (Rzeszow). We have demonstrated that under such conditions the mean and median values of total Cladosporium spore counts significantly increased and the spore seasons were greatly accelerated. Moreover, earlier start and later end of the season caused its extension, lasting from over 20 days in Rzeszow to around 60 days in Lublin and Poznan, when the cumulative amount of 5-95 % of spores was considered. The time of reaching the cumulative amount of 50 % of spores was up to 25 days earlier (difference in Poznan between 2010 and 2012). There was also a striking acceleration of the date of the maximal Cladosporium spore concentration per cubic metre of air (26 days for Lublin, 43 for Poznan and 56 for Rzeszow).

Determinants of Honey and Other Bee Products Use for Culinary, Cosmetic, and Medical Purposes.

Bee products have been used for centuries for culinary, medicinal, and cosmetic purposes, and their properties are still a subject of research, which provide new arguments in favour of their use. The research aimed to determine the current state of use of bee products by Polish consumers and determine the ways and conditions of their use, with particular reference to the level of nutritional knowledge and health status. The survey was conducted using the CAWI (Computer-Assisted Web Interview) method on 487 respondents. It was found that honey is used mainly for culinary purposes and, to a lesser extent, for medicinal and cosmetic purposes. Other bee products are much less commonly used than honey-mainly beeswax and royal jelly for cosmetic purposes and propolis and bee pollen for medicinal purposes. Segments distinguished by the frequency of use of honey for particular purposes were differentiated by gender, age, income level, use of other bee products, and motivation to use them. Their differences were also found in terms of the level of nutritional knowledge and self-assessed health status-the highest ratings in both categories were indicated by representatives of the Honey users' segment, which consisted of people who use honey most frequently for cooking, cosmetic and medicinal purposes. Regression analysis additionally showed that higher levels of nutritional knowledge and better health status were associated with the use of honey to treat gastrointestinal ailments and with the use of propolis for medicinal purposes.

Prognostic Potential of Galectin-9 mRNA Expression in Chronic Lymphocytic Leukemia.

Galectin-9 (Gal-9), very poorly characterized in chronic lymphocytic leukemia (CLL), was chosen in our study to examine its potential role as a CLL biomarker. The relation of Gal-9 expression in malignant B-cells and other routinely measured CLL markers, as well as its clinical relevance are poorly understood. Gal-9 mRNA expression was quantified with RT-qPCR in purified CD19+ B-cells of 100 CLL patients and analyzed in the context of existing clinical data. Our results revealed the upregulation of Gal-9 mRNA in CLL cells. High Gal-9 mRNA expression was closely associated with unfavorable prognostic markers. In addition, Gal-9 expression in leukemic cells was significantly elevated in CLL patients who did not respond to the first-line therapy compared to those who did respond. This suggests its potential predictive value. Importantly, Gal-9 was an independent predictor for the time to treatment parameters. Thus, we can suggest an adverse role of Gal-9 expression in CLL. Interestingly, it is possible that Gal-9 expression is induced in B-cells by EBV infection, so we determined the patients' EBV status. Our suggestion is that EBV coinfection could worsen prognosis in CLL, partly due to Gal-9 expression upregulation caused by EBV.

Can Galectin-3 Be a Novel Biomarker in Chronic Lymphocytic Leukemia?

Galectin-3's (Gal-3) effect on the pathogenesis of chronic lymphocytic leukemia (CLL) has not yet been extensively studied. The present study aims to analyze the potential role of Gal-3 as a prognostic biomarker in CLL patients. The Gal-3 expression was evaluated in CLL cells with RT-qPCR and flow cytometry. Due to the unclear clinical significance of soluble Gal-3 in CLL, our goal was also to assess the prognostic value of Gal-3 plasma level. Because cell survival is significantly affected by the interaction between Gal-3 and proteins such as Bcl-2, the results of Gal-3 expression analysis were also compared with the expression of Bcl-2. The results were analyzed for known prognostic factors, clinical data, and endpoints such as time to first treatment and overall survival time. Our research confirmed that Gal-3 is detected in and on CLL cells. However, using Gal-3 as a potential biomarker in CLL is challenging due to the significant heterogeneity in its expression in CLL cells. Moreover, our results revealed that Gal-3 mRNA expression in leukemic B cells is associated with the expression of proliferation markers (Ki-67 and PCNA) as well as anti-apoptotic protein Bcl-2 and can play an important role in supporting CLL cells.

The Association between Postpartum Pelvic Girdle Pain and Pelvic Floor Muscle Function, Diastasis Recti and Psychological Factors-A Matched Case-Control Study.

There is uncertainty regarding the association between abdominal morphology, pelvic floor function, and psychological factors in women with postpartum pelvic girdle pain (PGP). The aim of this case-control study was to evaluate the differences between women with and without persistent PGP regarding pelvic floor function, diastasis recti, and psychological factors 6−24 weeks postpartum. Pelvic floor manometry, palpation examination of abdominal muscles, the International Consultation on Incontinence Questionnaire Short Form, The Depression, Anxiety and Stress Scale­21, and the Pain Catastrophizing Scale were used. The PGP group presented with lower vaginal resting pressure (p < 0.001), more tenderness (p = 0.018) and impaired voluntary activation of pelvic floor muscles (p ≤ 0.001). Women with pain also had more distortion on the level of the anterior abdominal wall (p = 0.001) and more severe diastasis recti (p = 0.046) when compared to pain-free controls. Lower vaginal resting pressure was the strongest factor explaining PGP (OR 0.702, 95%CI 0.502−0.981). There were no differences in terms of the pelvic floor strength, endurance, severity of urinary incontinence and reported distress between the groups. Women with PGP 6−24 weeks postpartum differ in pelvic floor and abdominal muscle function from the pain-free controls. Vaginal resting pressure may be an important factor in pelvic girdle pain shortly postpartum. Further studies are needed to see a trend in changes over time.

Association Among Pelvic Girdle Pain, Diastasis Recti Abdominis, Pubic Symphysis Width, and Pain Catastrophizing: A Matched Case-Control Study.

OBJECTIVE: Pregnancy-related pelvic girdle pain (PGP) may persist or occur postpartum and negatively affects women's lives. There is uncertainty regarding the association between the structures of the bony pelvis, diastasis recti abdominis (DRA), pain processing, and PGP and to what extent these factors should be considered during physical therapy. This study aimed to evaluate the differences between women with and without PGP shortly after delivery regarding the separation of a pubic symphysis, DRA, and pain catastrophizing. METHODS: Women diagnosed with PGP 24 to 72 hours after vaginal delivery were matched to pain-free controls according to age and parity. Ultrasound evaluations of diastasis recti (interrecti distance [IRD]) during rest and curl-up task and pubic symphysis (interpubic width) were performed. The Pain Catastrophizing Scale was used to assess the level of catastrophizing. A special Cox regression model was used to fit a conditional logistic regression for a 1:2 matched case-control study. RESULTS: Thirty-five women with clinically diagnosed PGP and 70 matched controls were included in the study. The PGP group had a significantly higher pre-pregnancy body mass index than the control group. After adjusting for body mass index in multiple conditional logistic regression, the interpubic distance (odds ratio = 1.64; 95% CI = 1.22 to 2.20) and IRD during curl-up (odds ratio = 2.01; 95% CI = 1.08 to 3.74) were significantly associated with PGP. Pain catastrophizing and IRD at rest were not associated with PGP in univariable or multivariable analysis. CONCLUSIONS: Pain catastrophizing is similar for women with and without PGP early postpartum. However, the degree of the pubic symphysis and rectus abdominis separation during the curl-up task are positively associated with PGP shortly after delivery. IMPACT: This study indicates that a reconsideration of the way we look at DRA is warranted. The development of a more comprehensive assessment including objective measurements and a biopsychosocial understanding is needed to inform directions for further postpartum physical therapy.

Prognostic Value of Tie2-Expressing Monocytes in Chronic Lymphocytic Leukemia Patients.

Tie2-expressing monocytes (TEMs) are associated with tumor progression and metastasis. This unique subset of monocytes has been identified as a potential prognostic marker in several solid tumors. However, TEMs remain poorly characterized in hematological cancers, including chronic lymphocytic leukemia (CLL). This study analyzed, for the first time, the clinical significance of TEM population in CLL patients. Flow cytometry analysis of TEMs (defined as CD14+CD16+Tie2+ cells) was performed at the time of diagnosis on peripheral blood mononuclear cells from 104 untreated CLL patients. Our results revealed an expansion of circulating TEM in CLL patients. These monocytes express high levels of VEGF and suppressive IL-10. A high percentage of TEM was associated closely with unfavorable prognostic markers (ZAP-70, CD38, 17p and 11q deletion, and IGHV mutational status). Moreover, increased percentages of circulating TEMs were significantly higher in patients not responding to the first-line therapy as compared to responding patients, suggesting its potential predictive value. High TEM percentage was also correlated with shorter overall survival (OS) and shorter time to treatment (TTT). Importantly, based on multivariate Cox regression analysis, TEM percentage was an independent predictor for TTT. Thus, we can suggest the adverse role of TEMs in CLL.

Particle size distribution of the major Alternaria alternata allergen, Alt a 1, derived from airborne spores and subspore fragments.

Fungal fragments are abundant immunoreactive bioaerosols that may outnumber the concentrations of intact spores in the air. To investigate the importance of Alternaria fragments as sources of allergens compared to Alternaria spores, we determined the levels of Alternaria spores and Alt a 1 (the major allergen in Alternaria alternata spores) collected on filters within three fractions of particulate matter (PM) of different aerodynamic diameter: (1) PM>10, (diameter>10 µm); (2) PM2.5-10 (2.5-10µm); (3) PM2.5 (0.12-2.5 µm). The airborne particles were collected using a three stage high-volume ChemVol cascade impactor during the Alternaria sporulation season in Poznan, Poland (30 d between 6 July and 22 September 2016). The quantification of Alt a 1 was performed using the enzyme-linked immunosorbent assay. High concentrations of Alt a 1 were recorded during warm and dry d characterized by high sunshine duration, lack of clouds and high dew point values. Atmospheric concentrations of Alternaria spores correlated significantly (r = 0.930, p < 0.001) with Alt a 1 levels. The highest Alt a 1 was recorded in PM2.5-10 (66.8 % of total Alt a 1), while the lowest in PM2.5 (<1.0 %). Significantly more Alt a 1 per spore (>30 %) was observed in PM2.5-10 than in PM>10. This Alt a 1 excess may be derived from sources other than spores, e.g. hyphal fragments. Overall, in outdoor air the major source of Alt a 1 are intact Alternaria spores, but the impact of other fungal fragments (hyphal parts, broken spores, conidiophores) cannot be neglected, as they may increase the total atmospheric Alt a 1 concentration.

Atmospheric exposure to the major Artemisia pollen allergen (Art v 1): Seasonality, impact of weather, and clinical implications.

Artemisia pollen grains are important aeroallergens worldwide. The amount of allergenic proteins produced by pollen, or pollen allergenicity, is regulated by both genes and the environment. As a result, even closely related plant taxa may release pollen with distinctly different allergen contents. Here, we determined the variability in atmospheric exposure to the major Artemisia pollen allergen, Art v 1, during the pollination seasons of two common species, i.e., A. vulgaris (early flowering species) and A. campestris (late flowering species), in Poznan, Poland (2013-2015). Artemisia pollen grains were collected using Hirst-type volumetric trap, while Art v 1 was collected by a two-stage cascade impactor (PM10 and PM>10 air fractions) and quantified by immunoenzymatic analysis. The results showed that daily Art v 1 levels correlated significantly with mean daily concentrations of Artemisia pollen (from r = 0.426 to r = 0.949, depending on air fraction and peak of the season). Significant differences were observed between 1) the median pollen allergenicity in different seasons (from 2.5 to 4.7 pg Art v 1/pollen) and 2) the median pollen allergenicity in different peak periods of the season (from 1.8 to 6.7 pg Art v 1/pollen). During the late peak (flowering of A. campestris), the median pollen allergenicity was significantly higher (on average by 63%, p < 0.05) than that during A. vulgaris flowering. The highest mean seasonal pollen allergenicity was observed during the wettest season, while the lowest was observed during the driest season (from July-August). In summary, our study showed distinct differences in Artemisia pollen allergenicity, that were not only related to daily and seasonal variability, which may exceed 800% and 80%, respectively but also noticeable when two common Artemisia species were compared. Therefore, we argue that variability in pollen allergenicity (both seasonal and species-specific) should be considered in future studies assessing pollen exposure.

High M-MDSC Percentage as a Negative Prognostic Factor in Chronic Lymphocytic Leukaemia.

In the current study, we analysed the role and prognostic value of myeloid-derived suppressor cells (MDSC) in chronic lymphocytic leukaemia (CLL). The frequency of circulating monocytic MDSC (M-MDSC; defined as CD14+CD11b+CD15-HLA-DR-/low cells) was assessed in correlation with clinical and laboratory parameters characterising the disease activity and patient immune status. Samples of peripheral blood from untreated CLL patients and healthy volunteers were stained with monoclonal antibodies for flow cytometry analysis. CLL patients with M-MDSC percentages above 9.35% (according to the receiver operating characteristic (ROC) analysis) had a shorter time-to-treatment and shorter survival time than the group with a lower percentage of M-MDSC. The M-MDSC percentage was higher in patients with adverse prognostic factors (i.e., 17p and 11q deletion and CD38 and ZAP-70 expression). A high M-MDSC percentage was linked to significantly lower expression of the CD3ζ in T cells. Furthermore, an analysis of immune regulatory molecules (arginase 1 (ARG1), nitric oxide synthase (NOS2), indoleamine 2,3-dioxygenase (IDO), transforming growth factor beta (TGF-ß), and interleukin (IL)-10) was performed. By the means of flow cytometry and RT-qPCR, we showed an overexpression of three of them in M-MDSC of CLL patients. M-MDSC cells seem to be an important factor in the immunosuppressive microenvironment of CLL and seem to be a good and novel prognostic factor.

TLR2 Expression on Leukemic B Cells from Patients with Chronic Lymphocytic Leukemia.

Antigenic stimulation is considered as a possible trigger of neoplastic transformation in chronic lymphocytic leukemia (CLL). B-cell receptor plays a key role in the interactions between the microenvironment and leukemic cells; however, an important role has also been attributed to Toll-like receptors (TLRs). It is believed that disorders of TLR expression may play a part in the pathogenesis of CLL. In this study, we investigated the potential role of TLR2 in CLL by analyzing its expression on leukemic B cells in correlation with clinical and laboratory parameters characterizing disease activity and patients' immune status. We assessed the frequencies of TLR2+/CD19+ cells by the flow cytometry method in peripheral blood of 119 patients with CLL. The percentage of TLR2+/CD19+ cells was significantly lower in patients with CLL as compared to the healthy volunteers. There was also a lower percentage of TLR2+/CD19+ cells in CLL patients with poor prognostic factors, such as ZAP70 and/or CD38 expression, 17p and/or 11q deletion. On the other hand, among patients with del(13q14) associated with favorable prognosis, the percentage of TLR2+/CD19+ cells was higher than among those with del(11q22) and/or del(17p13) as well as in the control group. We found an association between low percentage of CD19+/CD5+/TLR2+ cells and shorter time to treatment. We also demonstrated the relationship between low percentage of CD19+/CD5+ TLR2-positive and overall survival (OS) of CLL patients. CLL patients with a proportion of 1.6% TLR2-positive B CD5+ cells (according to the receiver operating characteristic curve analysis) or more had a longer time to treatment and longer OS than the group with a lower percentage of TLR2 positive cells. To sum up, the results of the study suggest that low TLR2 expression is associated with poor prognosis in CLL patients. The monitoring of CD19+/CD5+/TLR2+ cells number may provide useful information on disease activity. Level of TLR2 expression on leukemic B cells may be an important factor of immunological dysfunction for patients with CLL. Our study suggests that TLR2 could becomes potential biological markers for the clinical outcome in patients with CLL.

Determination of factors responsible for the bioweathering of copper minerals from organic-rich copper-bearing Kupferschiefer black shale.

The aim of this study was to investigate the bioweathering of copper minerals present in the alkaline, copper-bearing and organic-rich Kupferschiefer black shale through the action of a consortium of indigenous lithobiontic, heterotrophic, neutrophilic bacteria isolated from this sedimentary rock. The involvement of microorganisms in the direct/enzymatic bioweathering of fossil organic matter of the rock was confirmed. As a result of bacterial activity, a spectrum of various organic compounds such as urea and phosphoric acid tributyl ester were released from the rock. These compounds indirectly act on the copper minerals occurring in the rock and cause them to weather. This process was reflected in the mobilization of copper, iron and sulfur and in changes in the appearance of copper minerals observed under reflected light. The potential role of identified enzymes in biodegradation of fossil organic matter and role of organic compounds released from black shale as a result of this process in copper minerals weathering was discussed. The presented results provide a new insight into the role of chemical compounds released by bacteria during fossil organic matter bioweathering potentially important in the cycling of copper and iron deposited in the sedimentary rock. The originality of the described phenomenon lies in the fact that the bioweathering of fossil organic matter and, consequently, of copper minerals occur simultaneously in the same environment, without any additional sources of energy, electrons and carbon.