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This paper presents an investigation into the influence of repeating cycles of hydrothermal growth processes and rapid thermal annealing (HT+RTA) on the properties of CuO thin films. An innovative hydrothermal method ensures homogeneous single-phase films initially. However, their electrical instability and susceptibility to cracking under the influence of temperature have posed a challenge to their utilization in electronic devices. To address this limitation, the HT+RTA procedure has been developed, which effectively eliminated the issue. Comprehensive surface analysis confirmed the procedure’s ability to yield continuous films in which the content of organic compounds responsible for the formation of cracks significantly decreases. Structural analysis underscored the achieved improvements in the crystalline quality of the films. The implementation of the HT+RTA procedure significantly enhances the potential of CuO films for electronic applications. Key findings from Kelvin probe force microscopy analysis demonstrate the possibility of modulating the work function of the material. In addition, scanning capacitance microscopy measurements provided information on the changes in the local carrier concentration with each repetition. These studies indicate the increased usefulness of CuO thin films obtained from the HT+RTA procedure, which expands the possibilities of their applications in electronic devices.

BackgroundThe triglyceride (TG) content of low-density lipoprotein (LDL-TG) has been shown to be more predictive of atherosclerotic cardiovascular disease (ASCVD) events than the cholesterol content of LDL (LDL-C). The goal of our study was to develop an equation for estimating LDL-TG (eLDL-TG) based on the standard lipid panel and to compare it to estimated LDL-C as an ASCVD risk biomarker.MethodsUsing least-square regression analysis, the following eLDL-TG equation was developed: eLDL-TG=TG38.5+NonHDL-C5.75+9.75TGNonHDL-C+244HDL-C−2.95. LDL-TG was measured by the β-quantification (BQ) reference method (N = 40,202). LDL-C was calculated by the Sampson-NIH equation. The association of LDL-C and eLDL-TG with ASCVD risk markers was performed in the National Heart and Nutrition Examination Survey (NHANES) (N = 37,053) and with ASCVD events in a primary prevention cohort from the UK Biobank (UKB) (N = 429,367) and the Atherosclerosis Risk in Communities (ARIC) study (N = 14,632).ResultseLDL-TG showed better ASCVD risk stratification of UKB participants than LDL-C (Wilcoxon Chi-Square: 2,099.6 vs. 418.7, respectively). Receiving-operating characteristics analysis revealed that eLDL-TG had a stronger association with ASCVD events than LDL-C (AUC: 0.596 vs. 0.542, respectively) and other conventional lipid markers. Similar findings were found in ARIC. Discordance analysis in UKB showed that the group with low LDL-C/high eLDL-TG had a similar risk as the high LDL-C/high eLDL-TG group. Furthermore, these same two groups with the highest eLDL-TG levels and the highest ASCVD event rate also had higher mean levels of systolic blood pressure, Body Mass Index, hemoglobin A1C, and C-reactive protein than the two lower eLDL-TG groups. Using eLDL-TG > 44.6 mg/dl (80th percentile) as a cut-point leads to a hazard ratio of 1.32 (95% CI, 1.29–1.36) for ASCVD events, which remained significant after adjustment for LDL-C and apoB. Furthemore, using eLDL-TG as a risk-enhancer test leads to reclassification of 50% more high-risk individuals than current lipid-enhancer test rules.ConclusionsLike LDL-C, LDL-TG can also be calculated from the results of the standard lipid panel. Compared to estimated LDL-C, eLDL-TG was a better risk marker for primary prevention and hence could improve initial ASCVD risk stratification.

Lipid disorders are the most common (even 70%) and worst monitored cardiovascular risk factor (only 1/4 of patients in Poland and in CEE countries are on the low-density lipoprotein cholesterol (LDL-C) goal). To improve this, clear and simple diagnostic criteria should be introduced for all components of the lipid profile. These are the updated guidelines of the two main scientific societies in Poland in the area – the Polish Society of Laboratory Diagnostics (PSLD) and the Polish Lipid Association (PoLA), which, in comparison to those from 2020, introduce few important changes in recommendations (two main lipid targets, new recommendations on LDL-C measurements, calculations new goals for triglycerides, new recommendations on remnants and small dense LDL) that should help the practitioners to be early with the diagnosis of lipid disorders and in the effective monitoring (after therapy initiation), and in the consequence to avoid the first and recurrent cardiovascular events.

Abstract Background The accurate measurement of Low-density lipoprotein cholesterol (LDL-C) is critical in the decision to utilize the new lipid-lowering therapies like PCSK9-inhibitors (PCSK9i) for high-risk cardiovascular disease patients that do not achieve sufficiently low LDL-C on statin therapy. Objective To improve the estimation of low LDL-C by developing a new equation that includes apolipoprotein B (apoB) as an independent variable, along with the standard lipid panel test results. Methods Using β-quantification (BQ) as the reference method, which was performed on a large dyslipidemic population (N = 24,406), the following enhanced Sampson-NIH equation (eS LDL-C) was developed by least-square regression analysis: $$eS\,LDL-C= \frac{TC}{1.15}-\frac{HDL-C}{1.25}-\frac{TG}{6.99}-\frac{\left(TG\times NonHDL-C\right)}{1120}+\frac{{TG}^{2}}{8910}+\frac{\left(TG\times ApoB\right)}{1240}+\frac{ApoB}{4.54}-4.73$$ e S L D L - C = TC 1.15 - H D L - C 1.25 - TG 6.99 - T G × N o n H D L - C 1120 + TG 2 8910 + T G × A p o B 1240 + ApoB 4.54 - 4.73 Results The eS LDL-C equation was the most accurate equation for a broad range of LDL-C values based on regression related parameters and the mean absolute difference (mg/dL) from the BQ reference method (eS LDL-C: 4.51, Sampson-NIH equation [S LDL-C]: 6.07; extended Martin equation [eM LDL-C]: 6.64; Friedewald equation [F LDL-C]: 8.3). It also had the best area-under-the-curve accuracy score by Regression Error Characteristic plots for LDL-C

Two new Ag(I) complexes with coumaric carboxylic acid derivatives have been synthesized. Structural studies of these noncrystalline complexes have been performed using a methodology that combines laboratory and synchrotron techniques, supported by density functional theory calculations. The arrangement of ligands around the Ag(I) cation has been refined using infrared, extended X-ray absorption fine structure, and X-ray absorption near edge structure spectroscopies. Different coordination modes of carboxylate ligands are observed for the studied compounds. Carboxylate bridges are characteristic for the Ag(I) complex with 4-oxo-4H-1-benzopyran-2-carboxylic acid (1), while a bidentate chelating motif was found for the complex with 2-oxo-2H-1-benzopyran-3-carboxylic acid (2). Additionally, the carbonyl oxygen atom of the coumarin ring coordinates to the silver cation in complex 2, while it is inactive in complex 1. Antimicrobial evaluation has been performed for both compounds. The complexes show activity against selected bacteria as well as Candida yeast. This activity is slightly lower for bacteria and the same or higher for Candida in relation to the reference substances: ciprofloxacin or fluconazole.

Our study reports the ultrasound-assisted synthesis of SnS and SnS2 in the form of nanoparticles using aqueous solutions of respective tin chloride and thioacetamide varying sonication time. The presence of both compounds is confirmed by powder X-ray diffraction, energy-dispersive X-ray spectroscopy, as well as Raman and FT-IR spectroscopic techniques. The existence of nanoparticles is proven by powder X-ray diffraction investigation and by high resolution transmission electron microscopy observations. The size of nanocrystallites are in the range of 3–8 nm and 30 50 nm for SnS, and 1.5–10 nm for SnS2. X-ray photoelectron spectroscopy measurements, used to investigate the chemical state of tin and sulphur atoms on the surface of nanoparticles, reveal that they are typically covered with tin on the same oxidation degree as respective bulk compound. Values of optical bandgaps of synthesized nanoparticles, according to the Tauc method, were 2.31, 1.47 and 1.05 eV for SnS (60, 90 and 120 min long synthesis, respectively), and 2.81, 2.78 and 2.70 eV for SnS2 (60, 90 and 120 min long synthesis, respectively). Obtained nanoparticles were utilized as photo- and sonocatalysts in the process of degradation of model azo-dye molecules by UV-C light or ultrasound. Quantum dots of SnS2 obtained under sonication lasting 120 min were the best photocatalyst (66.9 % color removal), while quantum dots of SnS obtained under similar sonication time were the best sonocatalyst (85.2 % color removal).

Background Frailty is common in heart failure (HF) and is associated with death but not routinely captured clinically. Frailty is linked with inflammation and malnutrition, which can be assessed by a novel plasma multimarker score: the metabolic vulnerability index (MVX). We sought to evaluate the associations between frailty and MVX and their prognostic impact. Methods and Results In an HF community cohort (2003–2012), we measured frailty as a proportion of deficits present out of 32 physical limitations and comorbidities, MVX by nuclear magnetic resonance spectroscopy, and collected extensive longitudinal clinical data. Patients were categorized by frailty score (≤0.14, >0.14 and ≤0.27, >0.27) and MVX score (≤50, >50 and ≤60, >60 and ≤70, >70). Cox models estimated associations of frailty and MVX with death, adjusted for Meta‐Analysis Global Group in Chronic Heart Failure (MAGGIC) score and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide). Uno's C‐statistic measured the incremental value of MVX beyond frailty and clinical factors. Weibull's accelerated failure time regression assessed whether MVX mediated the association between frailty and death. We studied 985 patients (median age, 77; 48% women). Frailty and MVX were weakly correlated (Spearman's ρ=0.21). The highest frailty group experienced an increased rate of death, independent of MVX, MAGGIC score, and NT‐proBNP (hazard ratio, 3.3 [95% CI, 2.5–4.2]). Frailty improved Uno's c‐statistic beyond MAGGIC score and NT‐proBNP (0.69–0.73). MVX only mediated 3.3% and 4.5% of the association between high and medium frailty groups and death, respectively. Conclusions In this HF cohort, frailty and MVX are weakly correlated. Both independently contribute to stratifying the risk of death, suggesting that they capture distinct domains of vulnerability in HF.

Purpose: Metabolic vulnerabilities can exacerbate inflammatory injury and inhibit repair in multiple sclerosis (MS). The purpose was to evaluate whether blood biomarkers of inflammatory and metabolic vulnerability are associated with MS disability and neurodegeneration. Methods: Proton nuclear magnetic resonance spectra were obtained from serum samples from 153 healthy controls, 187 relapsing–remitting, and 91 progressive MS patients. The spectra were analyzed to obtain concentrations of lipoprotein sub-classes, glycated acute-phase proteins, and small-molecule metabolites, including leucine, valine, isoleucine, alanine, and citrate. Composite indices for inflammatory vulnerability, metabolic malnutrition, and metabolic vulnerability were computed. MS disability was measured on the Expanded Disability Status Scale. MRI measures of lesions and whole-brain and tissue-specific volumes were acquired. Results: Valine, leucine, isoleucine, alanine, the Inflammatory Vulnerability Index, the Metabolic Malnutrition Index, and the Metabolic Vulnerability Index differed between healthy control and MS groups in regression analyses adjusted for age, sex, and body mass index. The Expanded Disability Status Scale was associated with small HDL particle levels, inflammatory vulnerability, and metabolic vulnerability. Timed ambulation was associated with inflammatory vulnerability and metabolic vulnerability. Greater metabolic vulnerability and inflammatory vulnerability were associated with lower gray matter, deep gray matter volumes, and greater lateral ventricle volume. Conclusions: Serum-biomarker-derived indices of inflammatory and metabolic vulnerability are associated with disability and neurodegeneration in MS.

BackgroundThe relationship between ketone bodies (KB) and mortality in patients with heart failure (HF) syndrome has not been well established.ObjectivesThe aim of this study is to assess the distribution of KB in HF, identify clinical correlates, and examine the associations between plasma KB and all-cause mortality in a population-based HF cohort.MethodsThe plasma KB levels were measured by nuclear magnetic resonance spectroscopy. Multivariable linear regression was used to examine associations between clinical correlates and KB levels. Proportional hazard regression was employed to examine associations between KB (represented as both continuous and categorical variables) and mortality, with adjustment for several clinical covariates.ResultsAmong the 1,382 HF patients with KB measurements, the median (IQR) age was 78 (68, 84) and 52% were men. The median (IQR) KB was found to be 180 (134, 308) μM. Higher KB levels were associated with advanced HF (NYHA class III–IV) and higher NT-proBNP levels (both P

IntroductionDefects in lipolysis can lead to hypertriglyceridemia, which can trigger acute pancreatitis and is also associated with cardiovascular disease. Decreasing plasma triglycerides (TGs) by activating lipoprotein lipase (LPL) with ApoC2 mimetic peptides is a new treatment strategy for hypertriglyceridemia. We recently described a dual ApoC2 mimetic/ApoC3 antagonist peptide called D6PV that effectively lowered TG in several mouse models but has limitations in terms of drug development. The aim of this study was to create the next generation of ApoC2 mimetic peptides.MethodsWe employed hydrocarbon staples, as well as select amino acid substitutions, to make short single helical mimetic peptides based on the last helix of ApoC2. Peptides were first tested for their ability to activate LPL and then in hypertriglyceridemia mouse models. All-atom simulations of peptides were performed in a lipid-trilayer model of TG-rich lipoproteins to discern their possible mechanism of action.ResultsWe designed a single stapled peptide called SP1 (21 residues), and a double stapled (stitched) peptide called SP2 (21 residues) and its N-terminal acylated analogue, SP2a. The hydrocarbon staples increased the amphipathicity of the peptides and their ability to bind lipids without interfering with LPL activation. Indeed, from all-atom simulations, the conformations of SP1 and SP2a are restrained by the staples and maintains the proper orientation of the LPL activation motif, while still allowing their deeper insertion into the lipid-trilayer model. Intraperitoneal injection of stapled peptides (1–5 umoles/kg) into ApoC2–hypomorphic mice or human ApoC3-transgenic resulted in an 80%–90% reduction in plasma TG within 3 h, similar to the much longer D6PV peptide (41 residues). Other modifications (replacement L-Glu20, L-Glu21 with their D-isomers, N-methylation of Gly19, Met2NorLeu and Ala1alpha-methylAla substitutions, N-terminal octanoylation) were introduced into the SP2a peptide. These changes made SP2a highly resistant to proteolysis against trypsin, pepsin, and Proteinase K, while maintaining similar efficacy in lowering plasma TG in mice.ConclusionWe describe a new generation of ApoC2 mimetic peptides based on hydron carbon stapling that are at least equally potent to earlier peptides but are much shorter and resistant to proteolysis and could be further developed into a new therapy for hypertriglyceridemia.

Lipoprotein X (LP-X) is an abnormal cholesterol-rich lipoprotein particle that accumulates in patients with cholestatic liver disease and familial lecithin–cholesterol acyltransferase deficiency (FLD). Because there are no high-throughput diagnostic tests for its detection, a proton nuclear magnetic resonance (NMR) spectroscopy-based method was developed for use on a clinical NMR analyzer commonly used for the quantification of lipoproteins and other cardiovascular biomarkers. The LP-X assay was linear from 89 to 1615 mg/dL (cholesterol units) and had a functional sensitivity of 44 mg/dL. The intra-assay coefficient of variation (CV) varied between 1.8 and 11.8%, depending on the value of LP-X, whereas the inter-assay CV varied between 1.5 and 15.4%. The assay showed no interference with bilirubin levels up to 317 mg/dL and was also unaffected by hemolysis for hemoglobin values up to 216 mg/dL. Samples were stable when stored for up to 6 days at 4 °C but were not stable when frozen. In a large general population cohort (n = 277,000), LP-X was detected in only 50 subjects. The majority of LP-X positive cases had liver disease (64%), and in seven cases, had genetic FLD (14%). In summary, we describe a new NMR-based assay for LP-X, which can be readily implemented for routine clinical laboratory testing.

Zanubrutinib (BGB-3111, Brukinsa®, BeiGene) is a next-generation irreversible inhibitor of Bruton’s tyrosine kinase (BTK), developed by BeiGene in 2012 for the treatment of B-cell malignancies. It was designed to minimize off-target inhibition of TEC- and EGFR-family kinases. Zanubrutinib is more selective than ibrutinib for BTK versus EGFR, FGR, FRK, HER2, HER4, ITK, JAK3, LCK, BLK and TEC. In addition, compared to ibrutinib, zanubrutinib has improved oral absorption and better target occupancy. Zanubrutinib demonstrated a lower incidence of off-target toxicities and reduced severity than ibrutinib. Moreover, zanubrutinib is similar to acalabrutinib, with less activity against TEC and ITK. The preliminary phase 1 results suggest that zanubrutinib has clinical activity and the drug is well tolerated in patients with B-cell lymphoid malignancies. Recent clinical trials have found it to demonstrate excellent efficacy and good tolerability in patients with chronic lymphocytic leukemia (CLL), Waldenstrom macroglobulinemia (WM) and mantle cell lymphoma (MCL). In recent phase 3 studies, zanubrutinib was compared with ibrutinib in patients with relapsed/refractory (R/R) MW and RR CLL. In both trials, zanubrutinib was found to demonstrate clinically meaningful advantages in safety and tolerability over ibrutinib; in particular, it was associated with a lower risk of atrial fibrillation/flutter and major bleeding events. In the recent SEQUOIA study, comparing zanubrutinib with bendamustine and rituximab (BR) in patients with previously untreated CLL, zanubrutinib significantly improved progression-free survival versus BR, with an acceptable safety profile consistent with previous studies. Zanubrutinib also demonstrated good activity and tolerability in patients with R/R MCL, marginal zone lymphoma and follicular lymphoma. Trials examining the efficacy and safety of the combination of zanubrutinib with obinutuzumab venetoclax and other drugs are ongoing. This review summarizes the clinical efficacy and safety of zanubrutinib in lymphoid malignancies.

Sex chromosome aneuploidies (SCAs) are common chromosomal disorders characterised by an atypical number of sex chromosomes. Turner syndrome (TS), Klinefelter syndrome (KS), and Jacobs syndrome (JS) are associated with a wide spectrum of skeletal manifestations, including craniofacial and limb anomalies. This systematic review aimed to analyse the incidence of skeletal abnormalities in selected SCAs based on case reports. In this review, 55 articles were included from the MEDLINE/PubMed and Google Scholar databases, according to PRISMA guidelines. High-arched palate, skeletal class II, and cubitus valgus were most frequently demonstrated among TS patients. Patients with KS and JS most often presented micrognathia, hypertelorism, and flat nasal bridge in the craniofacial region. In contrast, radioulnar synostosis, clinodactyly, and pes planus could be observed in the limbs of KS patients. The presence of dysmorphic facial features and limb malformations may indicate SCAs, which are underdiagnosed in the general population due to a variety of phenotypes.

Highlights A new algorithm is described for categorizing dyslipidemic patients into Fredrickson-like lipoprotein phenotypes except for Type III. The new lipoprotein phenotypes were validated by NMR-lipoprotein analysis and by agarose gel electrophoresis/beta-quantification in a large number of subjects. The new lipoprotein phenotyping system identifies high-risk cardiovascular patients and helps direct clinical management. A major advance is that the new lipoprotein phenotypes are based on just the standard lipid panel, and thus can be automatically calculated by the clinical laboratory and widely implemented.

Dysbetalipoproteinemia (hyperlipoproteinemia type III, HLP3) is a genetic disorder that results in the accumulation of cholesterol on highly atherogenic remnant particles. Traditionally, the diagnosis of HLP3 depended upon lipoprotein gel electrophoresis or density gradient ultracentrifugation. Because these two methods are not performed by most clinical laboratories, we describe here two new equations for estimating the cholesterol content of VLDL (VLDL-C), which can then be used for the diagnosis of HLP3. Using results from the beta-quantification (BQ) reference method on a large cohort of dyslipidemic patients (N = 24,713), we identified 115 patients with HLP3 based on having a VLDL-C to plasma TG ratio greater than 0.3 and plasma TG between 150 and 1,000 mg/dl. Next, we developed two new methods for identifying HLP3 and compared them to BQ and a previously described dual lipid apoB ratio method. The first method uses results from the standard lipid panel and the Sampson-NIH equation 1 for estimating VLDL-C (S-VLDL-C), which is then divided by plasma TG to calculate the VLDL-C/TG ratio. The second method is similar, but the Sampson-NIH equation 1 is modified or enhanced (eS-VLDL-C) by including apoB as an independent variable for predicting VLDL-C. At a cut-point of 0.194, the first method showed a modest ability for identifying HLP3 (sensitivity = 73.9%; specificity = 82.6%; and area under the curve (AUC) = 0.8685) but was comparable to the existing dual lipid apoB ratio method. The second method based on eS-VLDL-C showed much better sensitivity (96.5%) and specificity (94.5%) at a cut-point of 0.209. It also had an excellent AUC score of 0.9912 and was superior to the two other methods in test classification. In summary, we describe two new methods for the diagnosis of HLP3. The first one just utilizes the results of the standard lipid panel and the Sampson-NIH equation 1 for estimating (VLDL-C) (S-VLDL-C) and can potentially be used as a screening test. The second method (eS-VLDL-C), in which the Sampson-NIH equation 1 is modified to include apoB, is nearly as accurate as the BQ reference method. Because apoB is widely available at most clinical laboratories, the second method should improve both the accessibility and the accuracy of the HLP3 diagnosis.

Abstract Background Acute kidney injury (AKI) is common in hospitalized patients and is associated with poor patient outcomes and high costs of care. The implementation of clinical decision support tools within electronic medical record (EMR) could improve AKI care and outcomes. While clinical decision support tools have the potential to enhance recognition and management of AKI, there is limited description in the literature of how these tools were developed and whether they meet end-user expectations. Methods We developed and evaluated the content, acceptability, and usability of electronic clinical decision support tools for AKI care. Multi-component tools were developed within a hospital EMR (Sunrise Clinical Manager™, Allscripts Healthcare Solutions Inc.) currently deployed in Calgary, Alberta, and included: AKI stage alerts, AKI adverse medication warnings, AKI clinical summary dashboard, and an AKI order set. The clinical decision support was developed for use by multiple healthcare providers at the time and point of care on general medical and surgical units. Functional and usability testing for the alerts and clinical summary dashboard was conducted via in-person evaluation sessions, interviews, and surveys of care providers. Formal user acceptance testing with clinical end-users, including physicians and nursing staff, was conducted to evaluate the AKI order set. Results Considerations for appropriate deployment of both non-disruptive and interruptive functions was important to gain acceptability by clinicians. Functional testing and usability surveys for the alerts and clinical summary dashboard indicated that the tools were operating as desired and 74% (17/23) of surveyed healthcare providers reported that these tools were easy to use and could be learned quickly. Over three-quarters of providers (18/23) reported that they would utilize the tools in their practice. Three-quarters of the participants (13/17) in user acceptance testing agreed that recommendations within the order set were useful. Overall, 88% (15/17) believed that the order set would improve the care and management of AKI patients. Conclusions Development and testing of EMR-based decision support tools for AKI with clinicians led to high acceptance by clinical end-users. Subsequent implementation within clinical environments will require end-user education and engagement in system-level initiatives to use the tools to improve care.

Abstract We investigated clinical associations of ficolins and mannose-binding lectin (MBL) in 157 patients suffering from acute myeloid leukaemia (AML). Concentrations of ficolin-1, ficolin-2, ficolin-3 and MBL (before chemotherapy) in serum were determined as were selected polymorphisms of the corresponding genes (FCN1, FCN2, FCN3 and MBL2). The control group (C) consisted of 267 healthy unrelated individuals. Median level of ficolin-1 in patients was lower (p 7 days) fever (p = 0.026). Genotyping indicated an association of G/G homozygosity (corresponding to FCN1 gene − 542 G > A polymorphism) with malignancy [p = 0.004, OR = 2.95, 95% CI (1.41–6.16)]. Based on ROC analysis, ficolin-1, -2 and -3 may be considered candidate supplementary biomarkers of AML. Their high potential to differentiate between patients from non-malignant controls but also from persons suffering from other haematological cancers (multiple myeloma and lymphoma) was demonstrated.

New more effective lipid-lowering therapies have made it important to accurately determine Low-density lipoprotein-cholesterol (LDL-C) at both high and low levels. LDL-C was measured by the β-quantification reference method (BQ) (N = 40,346) and compared to Friedewald (F-LDL-C), Martin (M-LDL-C), extended Martin (eM-LDL-C) and Sampson (S-LDL-C) equations by regression analysis, error-grid analysis, and concordance with the BQ method for classification into different LDL-C treatment intervals. For triglycerides (TG) < 175 mg/dL, the four LDL-C equations yielded similarly accurate results, but for TG between 175 and 800 mg/dL, the S-LDL-C equation when compared to the BQ method had a lower mean absolute difference (mg/dL) (MAD = 10.66) than F-LDL-C (MAD = 13.09), M-LDL-C (MAD = 13.16) or eM-LDL-C (MAD = 12.70) equations. By error-grid analysis, the S-LDL-C equation for TG > 400 mg/dL not only had the least analytical errors but also the lowest frequency of clinically relevant errors at the low (190 mg/dL) LDL-C cut-points (S-LDL-C: 13.5%, F-LDL-C: 23.0%, M-LDL-C: 20.5%) and eM-LDL-C: 20.0%) equations. The S-LDL-C equation also had the best overall concordance to the BQ reference method for classifying patients into different LDL-C treatment intervals. The S-LDL-C equation is both more analytically accurate than alternative equations and results in less clinically relevant errors at high and low LDL-C levels.

Copper complexes with 1,3-disubstituted thiourea derivatives, all containing 3-(trifluoromethyl)phenyl tail and 1-alkyl/halogen-phenyl substituent, were synthesized. The experimental spectroscopic studies and theoretical calculation revealed that two ligands coordinate to Cu(II) in a bidentate fashion via thiocarbonyl S and deprotonated N atoms of thiourea moiety. Such monomers are characteristic of alkylphenylthiourea complexes, whereas the formation of a sandwich-type dimer is observed for halogeno derivatives. For the first time, the structural identifications of CuN2S2-based complexes using experimental and theoretical X-ray absorption near edge structure are demonstrated. The dimeric halogeno derivatives showed higher antimicrobial activity in comparison with alkylphenylthiourea complexes. The Cu(II) complex of 1-(4-chloro-3-nitrophenyl)-3-[3-(trifluoromethyl)phenyl]thiourea was active against 19 strains of methicillin-resistant Staphylococci (MIC = 2 µg/mL). This derivative acted as a dual inhibitor of DNA gyrase and topoisomerase IV isolated from Staphylococcus aureus. Additionally, complexes of halogenphenylthiourea strongly inhibited the growth of mycobacteria isolated from tuberculosis patients, even fourfold stronger than the reference isoniazid. The complexes exerted weak to moderate antitumor activity (towards SW480, SW620, and PC3) being non-toxic towards normal HaCaT cells.

The studied copper ore deposit is located in Miedzianka Mountain (Świętokrzyskie Mountains, central Poland). This deposit was exploited from the 13th century to the 1950s; therefore numerous historical adits are currently present. One of these is Teresa adit (established in 1805), consisting of underground mining corridors and natural cave developed in the Upper Devonian limestones, partially transformed by mining works. Samples of copper- and rock-forming minerals in limestones collected at seven sites within the richest copper-bearing mineralisation in this adit were studied with petrographic investigation of thin sections, micro-area chemical analysis (EDS), and XRD. This study shows the presence of various minerals: (a) Cu-Fe sulphides (relics of chalcopyrite) and Cu sulphides (covellite, chalcocite), (b) Cu-Fe oxides (cuprite and hematite), (c) Ca and Cu carbonates (calcite, azurite, and malachite), (d) clay minerals (Fe-Mg illite), and (e) micro-crystalline silica (quartz). For the first time in the studied deposit, we described chalcopyrite relics in cuprite pseudomorphosis, hematite with admixture of vanadium in pinkish-creme veins in limestones, and the presence of an admixture of Fe-Mg illite and microcystaline silica within cracks of limestones. In addition, for the first time, unit cell parameters of malachite and azurite from Miedzianka Mountain were determined, indicating very low substitutions of atoms other than Cu in their structures. We suppose that the minerals studied were formed during three types of copper mineralisation processes: (a) hydrothermal (relics of chalcopyrite), (b) secondary weathering (chalcocite, covellite, cuprite, hematite), and (c) adsorptive mineralisation (azurite, malachite). The latter stage is related to residuum, which consists of a mixture of Fe-Mg illite and micro-crystalline quartz, which was formed during the dissolution of limestones in karst processes in some crevices. We proposed a model of the formation of copper carbonates in the adsorption stage of the copper-bearing mineralisation in Miedzianka Mountain deposits. Two generations of calcite veins (older—red calcite and younger—crème-pinkish calcite) were also detected. Mineralogical–petrographical studies of samples revealed a high scientific and educational value. Due to the fact that the Teresa adit is planned to be made available to geotourists, this work is worth presenting to the public either in the adit and/or in a local museum in Miedzianka village.

Shift healthcare workers are a group particularly exposed to an increased risk of poor eating habits and are affected by many diseases. The aim of the study was to evaluate the dietary patterns (DPs), including the Polish-adapted Mediterranean Diet (Polish-aMED®) score, and dietary fat intake in association with the shift work of healthcare workers. This cross-sectional study involved 445 healthcare workers from the West Pomeranian in Poland. Dietary data were collected using an FFQ-6®. A posteriori DPs were derived with a Principal Component Analysis (PCA). The Polish-aMED® score and the individual’s percentage of energy from dietary fat (Pfat) were calculated. Healthcare shift work compared to the daily work was associated with approximately 2-times higher odds of adherence to the ‘Meat/fats/alcohol/fish’ DP in the upper tertile (OR: 2.38; 95% Cl: 1.27–4.47; p < 0.01) and higher Pfat >35% of total energy intake (OR: 1.73; 95% Cl: 1.06–2.83; p < 0.05). Healthcare shift work compared to the daily work was associated with approximately 50% lower odds of adherence to the ‘Pro-healthy’ DP in the middle tertile (OR: 0.48; 95% Cl: 0.26–0.89; p < 0.05) and a higher level of the Polish-aMED® score (OR: 0.57; 95% Cl: 0.33–0.98; p < 0.05), as well as lower odds of the constants of mealtime (OR: 0.54; 95% Cl: 0.33–0.89; p < 0.05). The obtained findings highlight the unhealthy food choices among shift healthcare workers. Thus, to avoid the negative health consequences, there is a need for nutritional education for healthcare workers, especially those working shifts.

LPL is a secreted enzyme that hydrolyzes triglycerides from circulating lipoproteins. Individuals lacking LPL suffer from severe hypertriglyceridemia, a risk factor for acute pancreatitis. One potential treatment is to administer recombinant LPL as a protein therapeutic. However, use of LPL as a protein therapeutic is limited because it is an unstable enzyme that is difficult to produce in large quantities. Furthermore, these considerations also limit structural and biochemical studies that are needed for large-scale drug discovery efforts. We demonstrate that the yield of purified LPL can be dramatically enhanced by coexpressing its maturation factor, LMF1, and by introducing novel mutations into the LPL sequence to render it resistant to proteolytic cleavage by furin. One of these mutations introduces a motif for addition of an N-linked glycan to the furin-recognition site. Furin-resistant LPL has previously been reported, but is not commonly used. We show that our modifications do not adversely alter LPL's enzymatic activity, stability, or in vivo function. Together, these data show that furin-resistant LPL is a useful reagent for both biochemical and biomedical studies.

Background. Among many causes of hypertriglyceridemia (HTG), familial chylomicronemia syndrome (FCS) is a rare monogenic disorder that manifests as severe HTG and acute pancreatitis. Among the known causal genes for FCS, mutations in APOC2 only account for 90% post-sessions and appeared to reduce pancreatitis episodes. Experimental ANGPTL3 and APOC3 inhibitors each lowered TG by >50%. Conclusions. Our case demonstrates the importance of delineating and defining the underlying etiology of a rare disorder to optimize therapy and to minimize unfavorable outcomes.

There are numerous traces of mining activity in the Miedzianka Mountain (Świętokrzyskie Mountains, Poland), because copper and silver ores have been mined in this region since at least the 13th century. The history of scientific research on the Miedzianka Mountain ore deposit spans almost 200 years. Almost 40 minerals have been found: ore minerals of Cu and Fe, and also secondary minerals, including carbonates, sulphates and even very rare arsenates, phosphates and vanadates. Three new minerals have been found, staszicite, lubeckite and miedziankite, but their chemical composition has not been precisely determined and therefore their names have not been approved by the International Mineralogical Association (IMA). The Miedzianka Mountain deposit is an important area on the map of educational activities. It is included in the “Świętokrzyskie Archaeological and Geological Trail” as a site of historical (mining and metallurgy) and natural (geological sciences) heritage. Despite the large potential, none of the underground workings (adits and shafts) are currently available to the public. Our research and exploration of the Teresa adit, which is one of the historical underground complexes of the Miedzianka Mountain, show that this adit displays a wide spectrum of topics in the field of mineralogy, geology and mining history. The Teresa adit, which is a 523 m system of underground corridors, contains 270 m of natural karst caves altered by mining works and is constituted of Upper Devonian limestones, locally cut by cherry shales. In several sites of the adit unique features can be observed, such as: (1) old mining works—galleries carved in the rock back in the 19th century; (2) interesting vein mineralization with secondary-colored copper carbonates and multi-colored calcite veins; (3) mineralization with azurite domination; and (4) karst phenomena (coatings, flowstone, dripstones and stalactites) in a cave part of the adit. The sites with unique features suggest that the Teresa adit is highly suitable to be presented to tourists. That is why we propose seven sites on the underground route that could be the basis for further projects to create a “geotouristic trail” in the Teresa adit. The proposal to make the Teresa adit available to tourists is in line with the tendency to protect the post-industrial landscape associated with former mining activities.

In this work, we present the results of valorisation of geosites for the geotourist path in the lower part of the Chochołowska Valley, with particular emphasis on tourist activity of people using wheelchairs and elderly people with motor disabilities. Five geosites were valorized: (1) Siwiańskie Turnie Outcrop, (2) Wielkie Koryciska Rock Gate, (3) Chochołowski Stream Riverbed, (4) Niżna Chochołowska Gate, (5) Chochołowskie Karst Spring. Selected geosites are easily accessible by people with limited mobility, including wheelchairs. They are located along a wide, flat asphalt road on the distance of 3.5 km and the altitude difference of 100 metres. Various sedimentary rocks, such as limestones, marls, and dolomites can be seen in geosites. These rocks represent two geological-tectonic structures, the so-called: Choč Nappe (geosies: Siwiańskie Turnie Outcrop, Wielkie Koryciska Rock Gate) and Krížna Nappe (geosite Niżna Chochołowska Gate). Two more characteristic phenomena can be observed: hydrogeological phenomena related to the karst processes seen in Chochołowskie Karst Spring, and geomorphological phenomena observed in Chochołowski stream riverbed. The results of valorisation showed that the evaluated geosites of the geoturistic path have very high geotouristic values. This indicates that the lower part of the Chochołowska Valley has a high geotouristic potential for people using wheelchairs and elderly people with motor disabilities who already are, or want to become active geoturists. Benefit of creating of this type of geotourist paths is the expansion of the tourist offer and the development of services in the Podhale region, with particular emphasis on the people with physical disabilities.

Aim. Plasma apolipoprotein C-II (apoC-II) activates lipoprotein lipase (LPL) and thus lowers plasma triglycerides (TG). We previously reported that a human apoC-II mimetic peptide (C-II-a) decreased plasma TG in apoC-II mutant mice, as well as in apoE-knockout mice. Because it is unknown what tissues take up free fatty acids (FFAs) released from TG after C-II-a peptide administration, we investigated in mice TG plasma clearance and tissue incorporation, using 3H-triolein as a tracer, with and without C-II-a treatment. Methods and Results. Intralipid® fat emulsion was labeled with 3H-triolein and then mixed with or without C-II-a. Addition of the peptide did not alter mean particle size of the lipid emulsion particles (298 nm) but accelerated their plasma clearance. After intravenous injection into C57BL/6N mice, the plasma half-life of the 3H-triolein for control and C-II-a treated emulsions was 18.3 ± 2.2 min and 14.8 ± 0.1 min, respectively. In apoC-II mutant mice, the plasma half-life of 3H-triolein for injected control and C-II-a treated emulsions was 30.1 ± 0.1 min and 14.8 ± 0.1 min, respectively. C57BL/6N and apoC-II mutant mice at 120 minutes after the injection showed increased tissue incorporation of radioactivity in white adipose tissue when C-II-a treated emulsion was used. Higher radiolabeled uptake of lipids from C-II-a treated emulsion was also observed in the skeletal muscle of C57BL/6N mice only. In case of apoC-II mutant mice, decreased uptake of radioactive lipids was observed in the liver and kidney after addition of C-II-a to the lipid emulsion. Conclusions. C-II-a peptide promotes the plasma clearance of TG-rich lipid emulsions in wild type and apoC-II mutant mice and promotes the incorporation of fatty acids from TG in the lipid emulsions into specific peripheral tissues.

Since the seminal breakthrough of treating diabetic patients with insulin in the 1920s, there has been great interest in developing other proteins and their peptide mimetics as therapies for a wide variety of other medical disorders. Currently, there are at least 60 different peptides that have been approved for human use and over 150 peptides that are in various stages of clinical development. Peptides mimetic of the major proteins on lipoproteins, namely apolipoproteins, have also been developed first as tools for understanding apolipoprotein structure and more recently as potential therapeutics. In this review, we discuss the biochemistry, peptide mimetics design and clinical trials for peptides based on apoA-I, apoE and apoC-II. We primarily focus on applications of peptide mimetics related to cardiovascular diseases. We conclude with a discussion on the limitations of peptides as therapeutic agents and the challenges that need to be overcome before apolipoprotein mimetic peptides can be developed into new drugs.

Zinc oxide nanopowders doped with 1–15 mol % cobalt were produced by the microwave solvothermal synthesis (MSS) technique. The obtained nanoparticles were annealed at 800 °C in nitrogen (99.999%) and in synthetic air. The material nanostructure was investigated by means of the following techniques: X-ray diffraction (XRD), helium pycnometry density, specific surface area (SSA), inductively coupled plasma optical emission spectrometry (ICP-OES), extended X-ray absorption fine structure (EXAFS) spectroscopy, scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS) and with magnetometry using superconducting quantum interference device (SQUID). Irrespective of the Co content, nanoparticles in their initial state present a similar morphology. They are composed of loosely agglomerated spherical particles with wurtzite-type crystal structure with crystallites of a mean size of 30 nm. Annealing to temperatures of up to 800 °C induced the growth of crystallites up to a maximum of 2 μm in diameter. For samples annealed in high purity nitrogen, the precipitation of metallic α-Co was detected for a Co content of 5 mol % or more. For samples annealed in synthetic air, no change of phase structure was detected, except for precipitation of Co3O4 for a Co content of 15 mol %. The results of the magentometry investigation indicated that all as-synthesized samples displayed paramagnetic properties with a contribution of anti-ferromagnetic coupling of Co–Co pairs. After annealing in synthetic air, the samples remained paramagnetic and samples annealed under nitrogen flow showed a magnetic response under the influences of a magnetic field, likely related to the precipitation of metallic Co in nanoparticles.

The article presents the originality and the timeless meaning of the 1959 Eugène Ionesco play, Rhinoceros which is situated, despite its unambiguous ‘animal’ parable, within the Theatre of the Absurd. In the perspective of the author of the article it is not only Ionesco’s protest against fascism conditioned by the political circumstances which is significant in particular time but the work portraying mechanisms of influence on society, which appears as ‘the masses’, the whole of the society, devoid of any deeper connection with ethical and moral values of humanistic culture, common to all authoritarian ideologies. Among others, the article refers to opinions of scholars of drama and theatre critics on the evolution of Ionesco’s dramatic works and such sociological‑cultural and literary contexts as: 1) José Ortega y Gasset’s thoughts on brutal ‘direct action’ applied to the masses by force factors and on ‘fear of touch’ felt by an individual defending the values of humanistic culture, included in The Revolt of the Masses; 2) plays by Ionesco in which the theme of metamorphosis is important; 3) other works of the Theatre of the Absurd of similar meaning but using different artistic means, Samuel Beckett’s Catastrophe in particular.