Acidophytic, oligotrophic lichens on tree trunks are widely considered to be the most sensitive biota to elevated concentrations of atmospheric ammonia (NH3). We studied the relationships between ...measured NH3 concentrations and the composition of macrolichen communities on the acidic bark of Pinus sylvestris and Quercus robur and the base-rich bark of Acer platanoides and Ulmus glabra at ten roadside and ten non-roadside sites in Helsinki, Finland. NH3 and nitrogen dioxide (NO2) concentrations were higher at the roadside than non-roadside sites indicating traffic as the main source of NH3 and nitrogen oxides (NOx). The diversity of oligotrophs on Quercus was lower at the roadside than non-roadside sites, while that of eutrophs was higher. The abundance and presence of oligotrophic acidophytes (e.g., Hypogymnia physodes) decreased with increasing NH3 concentration (2-year means = 0.15–1.03 μg m−3) especially on Q. robur, while those of eutrophic/nitrophilous species (e.g., Melanohalea exasperatula, Physcia tenella) increased. The abundance of some nitrophytes seemed to depend only on bark pH, i.e., their abundances were highest on Ulmus, which had the highest average bark pH. Overall, the results of lichen bioindicator studies may depend on tree species (bark pH) and lichen species used in calculating indices describing the air quality impact. Nevertheless, Quercus is recommended to be used to study the impact of NH3 alone and in combination with NOx on lichen communities, because the responses of both oligotrophic acidophytes and eutrophic species can already be observed at NH3 concentrations below the current critical level.
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•NH3 was measured at roadside and non-roadside sites using passive samplers.•Changes in epiphytic lichen communities were found at <1 μg NH3 m−3.•NH3 decreased the diversity of oligotrophs on Quercus at roadsides.•NH3 increased the diversity of eutrophs on Quercus at roadsides.•The ratio of acidophytes to nitrophytes on Quercus depended on both NH3 and bark pH.
Acidophytic, oligotrophic lichens on tree trunks are widely considered to be the most sensitive biota to elevated concentrations of atmospheric ammonia (NH
). We studied the relationships between ...measured NH
concentrations and the composition of macrolichen communities on the acidic bark of Pinus sylvestris and Quercus robur and the base-rich bark of Acer platanoides and Ulmus glabra at ten roadside and ten non-roadside sites in Helsinki, Finland. NH
and nitrogen dioxide (NO
) concentrations were higher at the roadside than non-roadside sites indicating traffic as the main source of NH
and nitrogen oxides (NO
). The diversity of oligotrophs on Quercus was lower at the roadside than non-roadside sites, while that of eutrophs was higher. The abundance and presence of oligotrophic acidophytes (e.g., Hypogymnia physodes) decreased with increasing NH
concentration (2-year means = 0.15-1.03 μg m
) especially on Q. robur, while those of eutrophic/nitrophilous species (e.g., Melanohalea exasperatula, Physcia tenella) increased. The abundance of some nitrophytes seemed to depend only on bark pH, i.e., their abundances were highest on Ulmus, which had the highest average bark pH. Overall, the results of lichen bioindicator studies may depend on tree species (bark pH) and lichen species used in calculating indices describing the air quality impact. Nevertheless, Quercus is recommended to be used to study the impact of NH
alone and in combination with NO
on lichen communities, because the responses of both oligotrophic acidophytes and eutrophic species can already be observed at NH
concentrations below the current critical level.
Summary
R‐CVP (cyclophosphamide, vincristine, prednisone) and R‐CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone + rituximab) are immunochemotherapy regimens frequently used for remission ...induction of indolent non‐Hodgkin lymphomas (iNHLs). Rituximab maintenance (RM) significantly improves progression‐free survival (PFS) in patients with complete/partial remission (CR/PR). Here we report the final results of a randomized study comparing R‐CVP to R‐CHOP both followed by RM. Untreated patients in need of systemic therapy with symptomatic and progressive iNHLs including follicular (FL) and marginal zone lymphoma (MZL), mucosa‐associated lymphoid tissue (MALT), small lymphocytic (SLL), and lymphoplasmacytic (LPL) lymphoma were eligible. Patients were randomized to receive R‐CVP or R‐CHOP for eight cycles or until complete response (CR). All patients with CR/PR (partial response) received RM 375 mg/m2 q 2 months for 12 cycles. Primary endpoint was event‐free survival (EFS). Two‐hundred and fifty patients FL 42%, MZL/MALT 38%, LPL/ Waldenström Macroglobulinaemia (WM) 11%, SLL 9% were enrolled and randomized (R‐CHOP: 127, R‐CVP: 123). Median age was 56 years (21–85), 44% were male, 90% were in stage III–IV, 43% of FL patients had a Follicular Lymphoma International Prognostic Index (FLIPI) score ≥3, and 33·4% of all patients had an IPI score ≥3. At the end of induction treatment, the CR/PR rate was 43·6/50·9% and 36·3/60·8% in the R‐CHOP and R‐CVP groups (P = 0·218) respectively. After a median follow‐up of 67, 66, and 70 months, five‐year EFS was 61% vs. 56% (not significant), progression‐free survival (PFS) was 71% vs. 69% (not significant) and overall survival (OS) was 84% vs. 89% in the R‐CHOP vs. the R‐CVP arm respectively. Grade III/IV adverse events (65 vs. 22) occurred in 40 (33·1%) and 18 (15·3%) patients, P = 0·001; neutropenia in 16 (11·6%) and 4 (3·4%) patients, P = 0·017; infection in 14 (10·7%) and 3 (2·5%) patients,; P = 0·011; and a second neoplasm in three versus seven patients., in the R‐CHOP and the R‐CVP groups respectively. This multicentre randomized study with >five‐year follow‐up shows similar outcome in patients with indolent lymphoma in need of systemic therapy treated with R‐CVP or R‐CHOP immunochemotherapy and rituximab maintenance in both arms. The minor toxicity of the R‐CVP regimen makes it a reasonable choice for induction treatment, leaving other active agents like doxorubicin or bendamustin for second‐line therapy.
The aim was to describe the spectrum of inner ear malformations in CHARGE syndrome and propose a Computed Tomography (CT) detailed scan evaluation methodology. The secondary aim was to correlate the ...CT findings with hearing thresholds.
Twenty ears of ten patients diagnosed with CHARGE syndrome were subjected to CT analysis focusing on the inner ear and internal acoustic canal. The protocol used is presented in detail. ASSR results were analyzed and correlated with inner ear malformations.
Cochlear hypoplasia type III was the most common malformation found in 12 ears (60%). Cochlear hypoplasia type II, aplasia with a dilated vestibule, and rudimentary otocyst were also identified. In 20%, no cochlear anomaly was found. The lateral Semicircular Canal (SCC) absence affected 100% of ears, the absence of the posterior SCC 95%, and the superior SCC 65%. Better development of cochlea structures and IAC correlated significantly with the lower hearing thresholds.
This study demonstrated that rudimentary SCC or a complete absence of these SCCs was universally observed in all patients diagnosed with CHARGE syndrome. This finding supports the idea that inner ear anomalies are a hallmark feature of the CHARGE, contributing to its distinct clinical profile. The presence of inner ear malformations has substantial clinical implications. Audiological assessments are crucial for CHARGE syndrome, as hearing loss is common. Early detection of these malformations can guide appropriate interventions, such as hearing aids or cochlear implants, which may significantly improve developmental outcomes and communication for affected individuals. Recognizing inner ear malformations as a diagnostic criterion presents implications beyond clinical diagnosis. A better understanding of these malformations can advance the knowledge of CHARGE pathophysiology. It may also help guide future research into targeted therapies to mitigate the impact of inner ear anomalies on hearing and balance function.
4.
Hypochlorite (HOCl), a strong oxidant and antimicrobial agent, has been proposed to be associated with hemostatic abnormalities during inflammatory response. However, its complex impact on hemostasis ...is not completely understood. In this report we studied the effect of clinically relevant (micromolar) HOCl concentrations on thrombus formation under flow, kinetics of platelet-fibrin clot formation, its architecture, retraction, and lysis. We found that HOCl (up to 500 µM) did not affect kinetics of coagulation measured in whole blood. HOCl (500-1000 µM) markedly diminished thrombus formation under flow. Clot retraction rate was reduced by HOCl dose-dependently (50-500 µM). HOCl (125-500 µM) inhibited fibrinolysis in whole blood and in platelet-depleted plasma, dose-dependently. Activity of plasmin was reduced by HOCl at concentrations started from 500 µM. HOCl (up to 500 µM) did not reduce plasminogen binding to fibrin under flow. HOCl (125-500 µM) modulated architecture of fibrin- and platelet-fibrin clots towards structures made of thin and densely packed fibers. Exposure of pure fibrinogen to HOCl (10-1000 µM) resulted in formation of dityrosine and was associated with altered fibrin structure derived from such modified fibrinogen. HOCl-altered fibrin net structure was not related with modulation of platelet procoagulant response, thrombin generation, and factor XIII activity. We conclude that, in human blood, clinically relevant HOCl concentrations may inhibit thrombus formation under flow, clot retraction and fibrinolysis. Fibrinolysis and clot retraction seem to be the most sensitive to HOCl-evoked inhibition. HOCl-modified fibrinogen and altered clot structure associated with it are likely to be primary sources of attenuated fibrinolysis.
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•Inflammation is associated with formation of large quantities of HOCl.•We tested the hypothesis that HOCl may affect hemostasis in humans.•HOCl inhibited thrombus formation under flow, clot retraction, and fibrinolysis.•Inhibition of fibrinolysis was associated with the formation of denser fibrin net.•HOCl-evoked fibrinogen modifications are likely cause of altered fibrin structure.
Summary
The efficacy of salvage treatment of diffuse large B‐cell lymphoma (DLBCL) patients who relapse or progress (rrDLBCL) after initial therapy is limited. Efficacy and safety of ofatumumab with ...iphosphamide, etoposide and cytarabine (O‐IVAC) was evaluated in a single‐arm study. Dosing was modified for elderly patients. Patients received up to six cycles of treatment. The primary end‐point was the overall response rate (ORR). Patients were evaluated every two cycles and then six and 12 months after treatment. Other end‐points included progression‐free survival (PFS), event‐free survival (EFS), overall survival (OS) and safety. Seventy‐seven patients received salvage treatment with O‐IVAC. The average age was 56.8 years; 39% had an Eastern Cooperative Oncology Group (ECOG) performance status of at least 3; 78% had disease of Ann Arbor stage 3 or 4; 58% received one or more prior salvage therapies. The ORR for O‐IVAC was 54.5%. The median duration of study follow‐up was 70 months. The median PFS and EFS were 16.3 months each. The median OS was 22.7 months. Age, ECOG performance status and the number of prior therapy lines were independent predictors of survival. Treatment‐related mortality was 15.5%. O‐IVAC showed a high response rate in a difficult‐to‐treat population and is an attractive treatment to bridge to potentially curative therapies.
Air pollution in the vicinity of roads is a complex and growing problem. In urbanised areas, there are many sources of dust emissions, but one of the main ones is road traffic. Investigating and ...assessing the physical and chemical properties of road dust and, more specifically, dust collected from surface courses is one way of providing an opportunity not only to identify the contribution of the emitters concerned to the formation of dust air pollution in the vicinity of roads but above all the environmental risks associated with traffic emissions. The study aimed to analyse the elemental composition of dust with a fraction <0.1 mm, collected from asphalt and concrete roads characterised by the highest technical and service parameters in Poland. The samples were analysed using a Shimadzu EDX 7000 energy-dispersive X-ray fluorescence spectrometer, then the results were statistically analysed using the t-Welch test, and the enrichment factors EF were determined. It was shown that road dust with a grain size of less than 0.1 mm collected from asphalt surface course was extremely highly enriched in Cu, Cr, Pb and S, while that from the concrete surface course was enriched in Zn and Zr, indicating a strong anthropogenic origin of these elements; exhaust gases were identified as their source. Irrespective of the type of surface course, very high dust enrichment occurs for Ca, Mn, Ni, S, Ti and Y. These elements may originate from the abrasion process of vehicle tyres. For road dust collected from both road types, the most similar EF values were found for Fe, K, Mn, Si, Sr and Ti. The source of these elements is most likely the roadside soil. It follows that the type of road surface is not the main determinant of the composition of road dust with a fraction <0.1 mm.
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•Increased capacity of anti-ROS mechanisms in PDT-resistant cells.•Higher activity of DNA repair and ATM kinase in PDT resistant glioblastoma cells.•Inhibition of APE1 and ATM leads ...to increased sensitivity to PDT.
Photodynamic therapy (PDT) is a clinically approved cancer therapy of low invasiveness. The therapeutic procedure involves administering a photosensitizing drug (PS), which is then activated with monochromatic light of a specific wavelength. The photochemical reaction produces highly toxic oxygen species. The development of resistance to PDT in some cancer cells is its main limitation. Several mechanisms are known to be involved in the development of cellular defense against cytotoxic effects of PDT, including activation of antioxidant enzymes, drug efflux pumps, degradation of PS, and overexpression of protein chaperons. Another putative factor that plays an important role in the development of resistance of cancer cells to PDT seems to be DNA repair; however, it has not been well studied so far. To explore the role of DNA repair and other potential novel mechanisms associated with the resistance to PDT in the glioblastoma cells, cells stably resistant to PDT were isolated from PDT sensitive cells following repetitive PDT cycles. Duly characterization of isolated PDT-resistant glioblastoma revealed that the resistance to PDT might be a consequence of several mechanisms, including higher repair efficiency of oxidative DNA damage and repair of DNA breaks. Higher activity of APE1 endonuclease and increased expression and activation of DNA damage kinase ATM was demonstrated in the U-87 MGR cell line, suggesting and proving that they are good targets for sensitization of resistant cells to PDT.
Introduction: Anti-CD20 antibody plus chemotherapy is one of the standard treatments for follicular lymphoma (FL) patients in need of therapy. Obinutuzumab-based regimens demonstrated improved ...progression- free survival (PFS) compared to rituximab plus chemotherapy (NCT01332968). Recently, the course of treatment of FL patients was disrupted by the COVID-19 pandemic due to immunosuppressive nature of therapy, in particular, of the maintenance treatment with the anti-CD20 antibody. Patients and Methods: We report on the results of obinutuzumab combined with different chemotherapy induction regimens in consecutive FL patients who started treatment at hemato-oncology centers in Poland between August 2018 and December 2022. The choice of chemotherapy (CVP, CHOP or bendamustine) was left to the discretion of the centre providing the treatment. Obinutuzumab maintenance was given to patients who achieved at least partial response (PR) after induction immunochemotherapy. Patients, who developed signs or symptoms suggesting acute COVID-19 infection were tested for the presence of SARS-COV 2. In other cases tests were performed according to local policy. The response was evaluated with computed tomography or positron emission tomography according to Lugano 2014 Criteria. Chi-square test was used to compare percentages. Survival analyses were based on the Kaplan-Meier method. Results: The study group included 257 treatment-naive FL patients. The median age (range) was 55 (27-89) years, 42.4% of patients were males. 65.0% (n=167) of patients had comorbidities. According to FLIPI 47.1% of patients were classified as high risk, 33.9% as intermediate and 19.1% as low risk, whereas 39.5%, 23.2% and 37.3% of patients were in PRIMA PI high, intermediate and low risk groups, respectively. Median number of GELF criteria was 3 (range 0-9). Induction chemotherapy included: CVP in 52.1% (n=134), CHOP in 33.1% (n=85) and bendamustine in 14.8% (n=38) of patients. Median number of cycles was 6 (range 1 - 8). After induction immunochemotherapy complete response (CR), PR, stable disease (SD) and progression disease (PD) rates were: 66.0%, 29.6%, 0.4% and 4.0%, respectively. Maintenance treatment was given to 217 patients (85.1%). Progression within 2 years of the start of treatment (POD24) occurred in 5.8% (n=15) of patients. With a median follow up of 23.7 months, 7.4% patients (n=19) relapsed, 13.2% of patients died (n=34). Death was caused by COVID-19 in 20, and by other infection in 2 cases. Three patients died from FL, 2 patients - due to other malignancy, and one each from myocardial infarction and treatment toxicity. Cause of death was unknown in five cases. The SARS-CoV-2 infection was detected in 125 patients with no apparent relation to the type of chemotherapy regimen (p=0.762). COVID-19 severity was unknown in 8.1% (n=9) and defined by investigators as asymptomatic in 23.4% (n=26), mild in 44.1% (n=49), severe 19.8% (n=22) and critical in 4.5% (n=5). The highest increase in the number of COVID-19 occurred in the first six months of 2022. 13.8% of patients (n=17) had SARS-COV-2 infection prior to immunochemotherapy, 28.5% (n=35) during induction immunochemotherapy, 53.7% (n=66) during maintenance, and 4.1% (n=5) after completion of the treatment. 3-year OS and PFS was 84% (95%CI: 78%-90%) and 74% (95%CI: 66% - 82%), respectively (Figure 1AB). 3-year OS of patients without COVID-19 was 92% (95%CI: 87% - 98%), while 3-year OS of patients with COVID-19 was 78% (95%CI: 69% - 88%) (p = 0.007), (Figure 1C). Conclusions: The survival of our real-world series of patients treated with obinutuzumab-based regimens was apparently worse than in the original study. These results may have been influenced by more prevalent high and intermediate risk factors, high tumor burden, as well as high frequency of SARS-COV 2 infection in our group of patients. OS was particularly lower among patients who had symptomatic COVID disease . These results seem to support a recommendation to initiate treatment in strictly symptomatic FL patients only, even if they formally meet GELF criteria. In the context of COVID-19 pandemic, CVP or CHOP might be preferred over more immunosuppressive bendamustine, and obinutuzumab maintenance treatment should be considered with caution as appropriate.
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