AbstractBackgroundMonitoring changes in the epidemiology of cystic fibrosis (CF) pathogens is essential for clinical research, quality improvement, and clinical management. MethodsWe analyzed data ...reported to the European Cystic Fibrosis Society Patient Registry (ECFSPR) from 2011 to 2016 to determine the overall and the age-specific annual prevalence and incidence of selected CF pathogens and their trends during these years. The ECFSPR collects data on three chronic infections: Pseudomonas aeruginosa (PsA), Burkholderia cepacia complex Species (BCC) and Staphylococcus aureus (SA), as well as on the occurrence of non-tuberculous mycobacteria (NTM) and Stenotrophomonas maltophilia (SM). The same analyses were performed for different country groups, according to their gross national income (GNI). ResultsThe pathogens with the highest prevalence were SA and PsA, with prevalence, in 2016, equal to 38.3% and 29.8% respectively, followed by SM (8.1%). The pathogens with the lowest prevalence were NTM (3.3%) and BCC (3.1%). The overall prevalence and incidence significantly decreased for PsA; they also decreased for BCC, while they increased significantly for SA. The overall prevalence of NTM and SM increased significantly. The most considerable prevalence changes were observed for PsA, which decreased across all income country groups and all age strata (with the exception of 0–1 years) The prevalence and incidence of pathogens differed significantly according to GNI. ConclusionsThe epidemiology of CF pathogens in Europe has changed; epidemiologic data differ significantly among countries with different socio-economic status. The causes of these observations are multifactorial and include improvements in clinical care and infection control.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in people with cystic fibrosis (pwCF) can lead to severe outcomes.
In this observational study, the European Cystic Fibrosis ...Society Patient Registry collected data on pwCF and SARS-CoV-2 infection to estimate incidence, describe clinical presentation and investigate factors associated with severe outcomes using multivariable analysis.
Up to December 31, 2020, 26 countries reported information on 828 pwCF and SARS-CoV-2 infection. Incidence was 17.2 per 1000 pwCF (95% CI: 16.0-18.4). Median age was 24 years, 48.4% were male and 9.4% had lung transplants. SARS-CoV-2 incidence was higher in lung-transplanted (28.6; 95% CI: 22.7-35.5)
non-lung-transplanted pwCF (16.6; 95% CI: 15.4-17.8) (p≤0.001).SARS-CoV-2 infection caused symptomatic illness in 75.7%. Factors associated with symptomatic SARS-CoV-2 infection were age >40 years, at least one F508del mutation and pancreatic insufficiency.Overall, 23.7% of pwCF were admitted to hospital, 2.5% of those to intensive care, and regretfully 11 (1.4%) died. Hospitalisation, oxygen therapy, intensive care, respiratory support and death were 2- to 6-fold more frequent in lung-transplanted
non-lung-transplanted pwCF.Factors associated with hospitalisation and oxygen therapy were lung transplantation, cystic fibrosis-related diabetes (CFRD), moderate or severe lung disease and azithromycin use (often considered a surrogate marker for
infection and poorer lung function).
SARS-CoV-2 infection yielded high morbidity and hospitalisation in pwCF. PwCF with forced expiratory volume in 1 s <70% predicted, CFRD and those with lung transplants are at particular risk of more severe outcomes.
This paper focuses on turning a commonly used industrial plastic, unreinforced polyoxymethylene copolymer (POM-C), using a cutting tool made of polycrystalline diamond (PCD). Conducted experimental ...investigation was the basis for the analysis of the influence of cutting parameters on cutting energy, determination of specific cutting energy and construction of specific cutting energy consumption maps, the analysis of the relationship between the specific cutting energy and the un-deformed chip thickness, the evaluation of the machinability, and the analysis of cutting energy considering machinability. A multi-objective optimization problem with cutting energy and MRR as conflicting objective functions was also studied and solved using two optimization approaches. Observed correlations between cutting parameters and cutting energy or specific cutting energy are different compared to other studies that analysed different standard engineering materials. The depth of cut turned out to be the key cutting parameter for the achievement of a trade-off between the cutting energy and MRR. Variable influences of the feed rate and the cutting speed on cutting energy and specific cutting energy, depending on the depth of cut value, are also observed. Chip form turned out to be the prevalent criteria for the evaluation of unreinforced POM-C machinability. There is a combination of cutting parameter ranges and the range of cross sectional ratio (ratio of the depth of cut and feed rate) which ensure formation of favourable chip forms. Optimization of cutting parameter values can lead to substantial energy savings in removing a unit volume of unreinforced POM-C, either by observing only the cutting energy or by including the consideration of the machinability.
•Depth of cut enables trade-off between cutting energy and material removal rate.•The developed specific cutting energy maps could serve process planners.•Referential specific cutting energy for turning of POM-C using PCD tool determined.•Cross sectional ratio range ensuring formation of favourable chip forms determined.•Chip form is the prevalent criteria for the evaluation of POM-C machinability.
Three novel copper complexes with tridentate N2O ligand di(2-pyridil) ketone 1-adamantoyl hydrazone (Addpy) of the formula CuII2CuI2(Addpy)2Br2(μ-Br4) (1), catena-polyCuCl(μ-Addpy)(μ-Cl)CuCl2n (2) ...and Cu(Addpy)(NCS)2 (3) were synthesized. Complexes are characterized by X-ray crystallography, spectral (UV–Vis, FTIR), electrochemical (CV) analyses, and magnetochemical measurements. Investigation of anticancer potential of Cu(II) complexes, mode of cell death, apoptosis, and inhibition of angiogenesis were performed. All tested malignant cell lines (HeLa, LS174, A549, K562, and MDA-MB-231) showed high sensitivity to the examined Cu(II) complexes. It has been shown that the complexes induce apoptosis in the caspase 3-dependent manner, whereas the anti-angiogenic effects of 1, 2, and 3 have been confirmed in EA.hy926 cells using a tube formation assay.
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•Three novel copper(II) complexes with hydrazine ligand were synthesized.•The complexes have good cytotoxic effect.•The cytotoxic complexes induce apoptosis in the caspase 3-dependent manner.•All three complexes exhibit moderate antiangiogenic activity.
Biotransformation of toxic selenium ions to non-toxic species has been mainly focused on biofortification of microorganisms and production of selenium nanoparticles (SeNPs), while far less attention ...is paid to the mechanisms of transformation. In this study, we applied a combination of analytical techniques with the aim of characterizing the SeNPs themselves as well as monitoring the course of selenium transformation in the mycelium of the fungus
Phycomyces blakesleeanus
. Red coloration and pungent odor that appeared after only a few hours of incubation with 10 mM Se
+4
indicate the formation of SeNPs and volatile methylated selenium compounds. SEM–EDS confirmed pure selenium NPs with an average diameter of 57 nm, which indicates potentially very good medical, optical, and photoelectric characteristics. XANES of mycelium revealed concentration-dependent mechanisms of reduction, where 0.5 mM Se
+4
led to the predominant formation of Se–S-containing organic molecules, while 10 mM Se
+4
induced production of biomethylated selenide (Se
−2
) in the form of volatile dimethylselenide (DMSe) and selenium nanoparticles (SeNPs), with the SeNPs/DMSe ratio rising with incubation time. Several structural forms of elemental selenium, predominantly monoclinic Se
8
chains, together with trigonal Se polymer chain, Se
8
and Se
6
ring structures, were detected by Raman spectroscopy.
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Numerous studies have shown that the choice of measurement strategy (number and position of measurement points) when measuring form error on a coordinate-measuring machine (CMM) depends on the ...characteristics of the machining process which was used to machine the examined surface. The accuracy of form error assessment is the primary goal of verification procedures and accuracy is considered perfect only in the case of the ideal verification operator. Since the ideal verification operator in the “point-by-point” measuring mode is almost never used in practice, the aim of this study was to examine a relationship which had not been examined in earlier studies, namely how the machining process, surface roughness and a reduced number of points in the measurement strategy affect the accuracy of flatness error assessment. The research included four most common cutting processes applied to flat surfaces divided into nine different classes of roughness. In order to determine functional dependency between the observed input variables and the output, statistical regression models and neuro-fuzzy logic (artificial intelligence tool) were used. The analyses confirmed the significance of all three input parameters, with surface roughness being the most significant one. Both the statistical regression models and neuro-fuzzy models proved to be adequate, matching the experimental results. The use of these models makes it possible to determine flatness error measured on a CMM if input variables considered in the paper are known.
•Pyridine-based hydrazonyl-selenazoles and their sulfur isosteres were investigated•In-silico calculations were used to check pharmacokinetic profiles•Compounds showed low micromolar GI50 values on ...six solid cancer cell lines•Se-isosteres have better antioxidant capacity than standards in the tested assays
To evaluate the impact of chalcogen atom type, we performed a comparative study of antioxidant capacity and antiproliferative activity of a focused library of three pyridine-based hydrazonyl-1,3-selenazoles and their sulfur isosteres in five antioxidant assays and in six human solid tumor cell lines, respectively. In-silico calculations were further used to check pharmacokinetic profiles of investigated compounds such as drug-likeness parameters and interaction with water. Generally, selenium compounds appear to be more potent in comparison to sulfur isosteres in the performed essays.
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Several studies support the evidence of increased incidence of hematological complications in Gaucher disease including monoclonal and polyclonal gammopathies and blood malignancies, especially ...multiple myeloma. Serum concentrations of immunoglobulins and PCR analysis of the IGH gene rearrangements were performed. The clonal PCR products were directly sequenced and analyzed with the appropriate database and tools. Serum monoclonal proteins were detected and identified by electrophoresis. Among 27 Gaucher patients, clonal IGH rearrangement was discovered in eight, with 5/8 having also serum monoclonal protein. Elevated immunoglobulins were detected in 9/27 patients. Follow-up data for 17 patients showed that the clonal rearrangement remained the same in four of them, however, in one patient it disappeared after the follow-up period. The remaining 12/17 patients were without previous IGH clonal rearrangement and remained so after the follow-up. Although clonal expansion may occur relatively early in the disease course, at least judging by the IGH gene rearrangements in Gaucher patients, the detected clones may be transient. A careful clinical follow-up in these patients is mandatory, including monitoring for lymphoid neoplasms, especially multiple myeloma.
Five pentacoordinate copper(II) complexes with 2‐acetylpyridine or di(2‐pyridyl) ketone 1‐adamantoyl hydrazone ligands (Adpy and Addpy, respectively) of the formulae CuCl2(Adpy) (1), ...Cu2(μ‐Cl)2(Adpy‐H)2 (2), Cu(NCS)2(Adpy) (3), Cu2(μ‐Cl)2(Addpy‐H)2 (4), and Cu2(NCS)2(μ‐Addpy‐H)2 (5) were synthesized and characterized by spectral, electrochemical, and X‐ray structural analysis. Flow cytometry and morphological analysis confirmed that the copper(II) complexes 2 and 5 induced accumulation of a sub‐G1 phase population, and fluorescence microscopy indicated the presence of large cells in apoptosis. The interaction of the copper(II) complexes with calf thymus DNA (CT‐DNA) was monitored by changes in their UV/Vis spectra. The observed intrinsic binding constants for 2 and 5 (Kb = 1.77 × 106 and 3.58 × 106 M–1, respectively) together with ethidium displacement fluorescence experiments indicate intercalative binding. Complexes 2 and 5 showed nuclease activity against pUC19 plasmid DNA.
Five CuII complexes with 2‐acetylpyridine or di(2‐pyridyl) ketone 1‐adamantoyl hydrazones have been prepared and physicochemically characterized. All of the tested complexes exhibit strong cytotoxic activity and induce apoptosis as the primary method of cell death. An intercalative mode of interaction with DNA was determined, and pronounced double‐strand cleavage of supercoiled DNA was observed.
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