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Heart failure (HF) symptoms are related to reduced circulatory perfusion, peripheral congestion, also impaired peripheral muscle strength & oxygen utilization due to iron deficiency. Despite many premises, the correlation between myocardial iron load and failing heart function was not proved. The purpose of this study was to assess iron itself and iron-related proteins in human failing (FH) vs non-failing (NFH) myocardium. The study group consisted of 58 explanted FHs vs the control consisted of 31 NFHs unsuitable for transplantation. HF study group presented with LV dilatation (LVDD 67±8 mm; LVSD 59±13 mm), reduced contraction (LVEF 20±7.5%), RV enlargement (RVD 42±6.5 mm), pulmonary hypertension (2.21±0.93 Wu) and elevated NTproBNP (3955.5±2250.5pg/ml). We assessed iron serum markers: ferritin (FR), transferrin/saturation (TSAT), transferrin receptor (soluble sTfR), sTFR/log FR; myocardial iron homeostasis assessment: M-Iron (Instrumental Neutron Activation Analysis, μg/g) and iron gathering proteins (by ELISA): divalent metal transporter (DMT-1); L-type calcium channel (L-CH), TfR-1/TfR-2; ferritins: heavy (FT-H), light (FT-L) chain, mitochondrial (FT-MT); ferroportin (FPN) and oxidative stress marker: 4-hydroxynonenal (4-HNE). In FH vs NFH, M-Iron was reduced (164.6±25.2 vs 182.3±23.9; p=0.0358) however, did not apply to the entire group. Therefore we divvied the FH group into two subgroups (based on M-Iron concentration in NFH controls). Average iron concertation in non-iron-deficient (NIDM) subgroup was 172.5±19.1 (n=35) and in iron-deficient (IDM) subgroup wad 127.0±16.5; (n=23, p=0.0001). Regardless M-Iron load in FH vs NFH myocardial proteins expressions were reduced: L-CH (NIDM vs IDM vs NFH: 49.2±9.2; 42.5±4.2; 67.3±23.0, p=0.0022); FT-L (16.4±7.3; 11.6±4.8; 26.3±7.5, p= Interestingly, the iron load (NIDM-Iron vs IDM-Iron) did not modify the assessed clinical parameters. With regard to commonly used systemic iron markers only sTFR/log FR proved M-Iron load difference (NIDM-Iron vs IDM-Iron 0.6±0.2; 0.7±0.3; p=0.047910) In FH, we observed, the subgroup with the reduced M-Iron load. The observed reduction of iron gathering proteins were independent on M-Iron load, except DMT-1 the main iron transportation protein into the cell. The results showed that the HF degree and concertation of iron proteins are unlikely to be affected by the M-Iron load, except DMT-1 protein. The oxidative stress was also regardless from M-Iron load, and increased in the whole FH group. Commonly used systemic iron markers except sTFR/log FR did not define M-Iron load. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): The Cardinal Stefan Wyszyński National Institute of Cardiology

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired, immune-mediated, and clinically heterogeneous demyelinating disease affecting the nerve roots and peripheral nerves. We report a series of 4 patients who presented with early and progressive vision loss in the context of new-onset CIDP: 3 due to papilledema and 1 due to optic neuropathy without papilledema.This was a retrospective case series of 4 patients with vision loss as a presenting feature of CIDP evaluated at the Hospital of the University of Pennsylvania from January 2016 to August 2021. Demographic, clinical, diagnostic, and treatment data were collected via retrospective medical record review.Case 1 was a 51-year-old man with 2 months of progressive bilateral papilledema associated with reduced visual acuity (count fingers at 1 foot in each eye) and severely constricted visual fields. Case 2 was a 36-year-old man with 4 months of worsening headaches, reduced visual acuity (count fingers at 1 foot in each eye), severely constricted visual fields, and papilledema. Case 3 was a 39-year-old man with papilledema causing progressive vision loss (20/80 in both eyes), headaches, and relapsing limb sensorimotor deficits. Case 4 was a 19-year-old man with 3 months of progressive bilateral visual decline (20/400 in the right eye, 20/600 in the left eye), central scotoma, and optic disc pallor consistent with optic neuropathy without papilledema. All 4 patients met clinical and electrodiagnostic criteria of CIDP. Cases 3 and 4 each tested positive for serum neurofascin-155 IgG4 antibodies. All patients were managed with immunomodulatory therapy. Cases 1 and 2 also each required surgical intervention with bilateral optic nerve sheath fenestration and cerebrospinal fluid (CSF) shunting procedures.Vision loss from optic neuropathy with or without papilledema has rarely been reported in CIDP, and typically has been described in the context of longstanding disease. Our cases highlight how CIDP can present with early vision loss that may be profound and challenging to manage if diagnosis is delayed. CIDP should be considered in any patient with new progressive vision loss when associated with peripheral sensorimotor symptoms and elevated CSF protein. The small subgroup of CIDP patients with neurofascin-155 antibodies may be at particular risk of optic nerve involvement.

Pathogenic NR2F1 variants cause a rare autosomal dominant neurodevelopmental disorder referred to as the Bosch–Boonstra–Schaaf Optic Atrophy Syndrome. Although visual loss is a prominent feature seen in affected individuals, the molecular and cellular mechanisms contributing to visual impairment are still poorly characterized. We conducted a deep phenotyping study on a cohort of 22 individuals carrying pathogenic NR2F1 variants to document the neurodevelopmental and ophthalmological manifestations, in particular the structural and functional changes within the retina and the optic nerve, which have not been detailed previously. The visual impairment became apparent in early childhood with small and/or tilted hypoplastic optic nerves observed in 10 cases. High-resolution optical coherence tomography imaging confirmed significant loss of retinal ganglion cells with thinning of the ganglion cell layer, consistent with electrophysiological evidence of retinal ganglion cells dysfunction. Interestingly, for those individuals with available longitudinal ophthalmological data, there was no significant deterioration in visual function during the period of follow-up. Diffusion tensor imaging tractography studies showed defective connections and disorganization of the extracortical visual pathways. To further investigate how pathogenic NR2F1 variants impact on retinal and optic nerve development, we took advantage of an Nr2f1 mutant mouse disease model. Abnormal retinogenesis in early stages of development was observed in Nr2f1 mutant mice with decreased retinal ganglion cell density and disruption of retinal ganglion cell axonal guidance from the neural retina into the optic stalk, accounting for the development of optic nerve hypoplasia. The mutant mice showed significantly reduced visual acuity based on electrophysiological parameters with marked conduction delay and decreased amplitude of the recordings in the superficial layers of the visual cortex. The clinical observations in our study cohort, supported by the mouse data, suggest an early neurodevelopmental origin for the retinal and optic nerve head defects caused by NR2F1 pathogenic variants, resulting in congenital vision loss that seems to be non-progressive. We propose NR2F1 as a major gene that orchestrates early retinal and optic nerve head development, playing a key role in the maturation of the visual system., Jurkute et al. expands the phenotypic spectrum of pathogenic NR2F1 variants, providing a detailed characterization of the retinal and optic nerve changes with high-resolution optical coherence tomography imaging. Data from a mutant mouse model confirms the key role played by NR2F1 in directing retinogenesis and the development of the optic nerve head., Graphical Abstract Graphical Abstract

The aim of the paper is to present the procedure of non-standard road signs and markings implementation in Poland to improve road safety and traffic performance of road infrastructure. The authors investigated the following cases: road and its surroundings’ perception and understanding improvement; warning of increased risk of accidents; road works; speed management and ITS. The procedure was developed on the basis of interdisciplinary research, including: observation of drivers' behavior in real traffic; comparative crash analysis on sections with and without non-standard signs or markings; surveys on the understanding signs and marking; driving simulator experiments. As a result of the research, an implementation procedure for non-standard signs and markings, in the form of a flowchart, was developed. In the designed procedure the following study of non-standard signs can be distinguished: questionnaire studies, eye-tracking tests and driving simulator tests. The choice of the test method depends on the preliminary assessment of sign understanding, based on the results of the questionnaires. Moreover, thresholds for the declared understanding level, which determines the selection of additional tests to be done prior to the implementation of the sign, are given. The guidelines for conducting tests, analysis and monitoring of implementation were described as well.

SIRT1, a NAD dependent histone and protein deacetylase, is a member of the histone deacetylase class III family. We previously showed that SIRT1 mRNA expression is significantly lower in peripheral blood mononuclear cells (PBMCs) of multiple sclerosis (MS) patients during relapses than in stable patients. We have now investigated SIRT1 as a possible biomarker to predict relapse as well as responsiveness to glatiramer acetate (GA) treatment in relapsing-remitting MS (RRMS) patients. Over the course of 2years, a cohort of 15 GA-treated RRMS patients were clinically monitored using the Expanded Disability Status Scale and assessed for MS relapses. Blood samples collected from MS patients were analyzed for levels of SIRT1 and histone H3 lysine 9 (H3K9) acetylation and dimethylation. During relapses, MS patients had a lower expression of SIRT1 mRNA than did stable MS patients. In addition, there was a significant decrease in H3K9 dimethylation (H3K9me2) during relapses in MS patients when compared to stable patients (p=0.01). Responders to GA treatment had significantly higher SIRT1 mRNA (p=0.01) and H3K9me2 levels than did non-responders (p=0.018). Receiver operating characteristic analysis was used to assess the predictive power of SIRT1 and H3K9me2 as putative biomarkers: for SIRT1 mRNA, the predictive value for responsiveness to GA treatment was 70% (p=0.04) and for H3K9me2 was 71% (p=0.03). Our data suggest that SIRT1 and H3K9me2 could serve as potential biomarkers for evaluating patients' responsiveness to GA therapy in order to help guide treatment decisions in MS.

Background/Introduction Obstructive sleep apnea (OSA) is one of the most common respiratory disease which is considered as a risk factor for cardiovascular disease and death. Although coexistence of OSA and arterial hypertension may be attributed to well-known common environmental risk factors for both diseases, a genetic background should be considered. LEPR rs1137101 polymorphism was reported to be associated with coronary artery disease and heart failure. Left ventricular hypertrophy is a part of hypertension-mediated organ damage assessment and an independent risk factor for adverse outcome in patients with hypertension. Purpose This study is aimed to establish the relationship between LEPR rs1137101 polymorphism and left ventricular hypertrophy in patients with OSA and arterial hypertension. Methods Consecutive patients with newly diagnosed OSA confirmed by polysomnography underwent genotyping for the single nucleotide polymorphisms of LEPR (rs1137101). LVH was diagnosed using standard 12-lead electrocardiogram according to the current European Society of Cardiology guidelines. Logistic regression was used to assess the relationship between LEPR rs1137101 polymorphisms and LVH. Results From 600 subjects diagnosed with OSA, 427 subjects with hypertension were included for further analysis (25.1% women, 74.9% men). In analyzed subpopulation mean age was 58.5±9.4 years, body mass index 33.7±6.6 kg/m2, apnea-hypopnea index 43.1±23.6/hour. In 34 (8.0%) subjects LVH was diagnosed. Genotyping revealed, that 123 (28.8%) subjects were LEPR rs1137101 AA homozygotes, 202 (47.3%) LEPR rs1137101 A/G heterozygotes and 102 (23.9) LEPR rs1137101 G/G homozygotes. Logistic regression showed, that LEPR rs1137101 A/A polymorphism vs A/G and G/G was associated with increased risk of LVH (odds ratio: 2.08, 95% confidence interval: 1.02–4.25, p=0.03). The relationship was significant also after adjustment for age, sex, apnea-hypopnea index and current smoking status (odds ratio: 2.28, 95% confidence interval: 1.08–4.83, p=0.03). Conclusions Our study shows a possible link between the polymorphism of the LEPR rs1137101 polymorphism and LVH in patients with OSA and arterial hypertension. Acknowledgement/Funding The study received financial support from the Polish National Science Centre (710/N-COST/2010/0)

Currently there is critical need for the identification of reliable biomarkers to help guide clinical management of multiple sclerosis (MS) patients. We investigated the combined roles of Response Gene to Complement 32 (RGC-32), FasL, CDC2, AKT, and IL-21 as possible biomarkers of relapse and response to glatiramer acetate (GA) treatment in relapsing-remitting MS (RRMS) patients. Over the course of 2 years, a cohort of 15 GA-treated RRMS patients was clinically monitored and peripheral blood mononuclear cells (PBMCs) were collected at 0, 3, 6, and 12 months. Target gene mRNA expression was measured in patients’ isolated PBMCs by real-time qRT-PCR. Compared to stable MS patients, those with acute relapses exhibited decreased expression of RGC-32 (p

We have previously shown that RGC-32 is involved in cell cycle regulation in vitro. To define the in vivo role of RGC-32, we generated RGC-32 knockout mice. These mice developed normally and did not spontaneously develop overt tumors. To assess the effect of RGC-32 deficiency on cell cycle activation in T cells, we determined the proliferative rates of CD4(+) and CD8(+) T cells from the spleens of RGC-32(-/-) mice, as compared to wild-type (WT, RGC-32(+/+)) control mice. After stimulation with anti-CD3/anti-CD28, CD4(+) T cells from RGC-32(-/-) mice displayed a significant increase in [(3)H]-thymidine incorporation when compared to WT mice. In addition, both CD4(+) and CD8(+) T cells from RGC-32(-/-) mice displayed a significant increase in the proportion of proliferating Ki67(+) cells, indicating that in T cells, RGC-32 has an inhibitory effect on cell cycle activation induced by T-cell receptor/CD28 engagement. Furthermore, Akt and FOXO1 phosphorylation induced in stimulated CD4(+) T-cells from RGC-32(-/-) mice were significantly higher, indicating that RGC-32 inhibits cell cycle activation by suppressing FOXO1 activation. We also found that IL-2 mRNA and protein expression were significantly increased in RGC-32(-/-) CD4(+) T cells when compared to RGC-32(+/+) CD4(+) T cells. In addition, the effect of RGC-32 on the cell cycle and IL-2 expression was inhibited by pretreatment of the samples with LY294002, indicating a role for phosphatidylinositol 3-kinase (PI3K). Thus, RGC-32 is involved in controlling the cell cycle of T cells in vivo, and this effect is mediated by IL-2 in a PI3K-dependent fashion.

Multiple sclerosis (MS) is an inflammatory, demyelinating, and neurodegenerative disease of the central nervous system. The complement system has an established role in the pathogenesis of MS, and evidence suggests that its components can be used as biomarkers of disease-state activity and response to treatment in MS. Plasma C4a levels have been found to be significantly elevated in patients with active relapsing-remitting MS (RRMS), as compared to both controls and patients with stable RRMS. C3 levels are also significantly elevated in the cerebrospinal fluid (CSF) of patients with RRMS, and C3 levels are correlated with clinical disability. Furthermore, increased levels of factor H can predict the transition from relapsing to progressive disease, since factor H levels have been found to increase progressively with disease progression over a 2-year period in patients transitioning from RRMS to secondary progressive (SP) MS. In addition, elevations in C3 are seen in primary progressive (PP) MS. Complement components can also differentiate RRMS from neuromyelitis optica. Response gene to complement (RGC)-32, a novel molecule induced by complement activation, is a possible biomarker of relapse and response to glatiramer acetate (GA) therapy, since RGC-32 mRNA expression is significantly decreased during relapse and increased in responders to GA treatment. The predictive accuracy of RGC-32 as a potential biomarker (by ROC analysis) is 90% for detecting relapses and 85% for detecting a response to GA treatment. Thus, complement components can serve as biomarkers of disease activity to differentiate MS subtypes and to measure response to therapy.

Stainless steel 316L (SS316L) is a common material used in orthopedic implants. Bacterial colonization of the surface and subsequent biofilm development can lead to refractory infection of the implant. Since the greatest risk of infection occurs perioperatively, strategies that reduce bacterial adhesion during this time are important. As a strategy to limit bacterial adhesion and biofilm formation on SS316L, self-assembled monolayers (SAMs) were used to modify the SS316L surface. SAMs with long alkyl chains terminated with hydrophobic (-CH3) or hydrophilic (oligoethylene glycol) tail groups were used to form coatings and in an orthogonal approach, SAMs were used to immobilize gentamicin or vancomycin on SS316L for the first time to form an “active” antimicrobial coating to inhibit early biofilm development. Modified SS316L surfaces were characterized using surface infrared spectroscopy, contact angles, MALDI-TOF mass spectrometry and atomic force microscopy. The ability of SAM-modified SS316L to retard biofilm development by Staphylococcus aureus was functionally tested using confocal scanning laser microscopy with COMSTAT image analysis, scanning electron microscopy and colony forming unit analysis. Neither hydrophobic nor hydrophilic SAMs reduced biofilm development. However, gentamicin-linked and vancomycin-linked SAMs significantly reduced S. aureus biofilm formation for up to 24 and 48 hours, respectively.

Background and Purpose— Atrial fibrillation (AF) is increasingly recognized as the single most important cause of disabling ischemic stroke in the elderly. We undertook an international survey to characterize the frequency of AF-associated stroke, methods of AF detection, and patient features. Methods— Consecutive patients hospitalized for ischemic stroke in 2013 to 2014 were surveyed from 19 stroke research centers in 19 different countries. Data were analyzed by global regions and World Bank income levels. Results— Of 2144 patients with ischemic stroke, 590 (28%; 95% confidence interval, 25.6–29.5) had AF-associated stroke, with highest frequencies in North America (35%) and Europe (33%) and lowest in Latin America (17%). Most had a history of AF before stroke (15%) or newly detected AF on electrocardiography (10%); only 2% of patients with ischemic stroke had unsuspected AF detected by poststroke cardiac rhythm monitoring. The mean age and 30-day mortality rate of patients with AF-associated stroke (75 years; SD, 11.5 years; 10%; 95% confidence interval, 7.6–12.6, respectively) were substantially higher than those of patients without AF (64 years; SD, 15.58 years; 4%; 95% confidence interval, 3.3–5.4; P r =0.76; P =0.0002). Conclusions— This cross-sectional global sample of patients with recent ischemic stroke shows a substantial frequency of AF-associated stroke throughout the world in proportion to the mean age of the stroke population. Most AF is identified by history or electrocardiography; the yield of conventional short-duration cardiac rhythm monitoring is relatively low. Patients with AF-associated stroke were typically elderly (>75 years old) and more often women.

Corrosion of the metal oxide surface of cupronickel (CuNi) alloys is a problem in applications such as household water pipes, industrial pipelines, and marine vessels. On other substrates, thin films have been used as barriers to corrosion. Here, the formation of self-assembled monolayers (SAMs) on the CuNi metal oxide surface has been investigated. Stable, well-ordered SAMs of octadecylphosphonic acid (ODPA) and 16-phosphonohexadecanoic acid (COOH-PA) were formed on the metal oxide surface of CuNi foils (55% Cu/45% Ni) using a solution deposition method. The ODPA modified surfaces could be used to provide a non-reactive barrier that inhibits corrosion of the CuNi metal oxide surface. Meanwhile, COOH-PA films could be used for further surface reactions such as surface initiated polymerization, in which polymer coatings are grown directly from a well-ordered film. Film-modified surfaces were characterized using diffuse reflectance infrared Fourier transform spectroscopy, contact angle analysis, and matrix assisted laser desorption ionization time of flight mass spectrometry. The ability of the films to inhibit corrosion by limiting oxidation of the CuNi surface was assessed using cyclic voltammetry.

Perfluorocarbon thin films and polymer brushes were formed on stainless steel 316 L (SS316L) to control the surface properties of the metal oxide. Substrates modified with the films were characterized using diffuse reflectance infrared Fourier transform spectroscopy (DRIFT), contact angle analysis, atomic force microscopy (AFM), and cyclic voltammetry (CV). Perfluorooctadecanoic acid (PFOA) was used to form thin films by self-assembly on the surface of SS316L. Polypentafluorostyrene (PFS) polymer brushes were formed by surface-initiated polymerization using SAMs of 16-phosphonohexadecanoic acid (COOH-PA) as the base. PFOA and PFS were effective in significantly reducing the surface energy and thus the interfacial wetting properties of SS316L. The SS316L control exhibited a surface energy of 38 mN/m compared to PFOA and PFS modifications, which had surface energies of 22 and 24 mN/m, respectively. PFOA thin films were more effective in reducing the surface energy of the SS316L compared to PFS polymer brushes. This is attributed to the ordered PFOA film presenting aligned CF(3) terminal groups. However, PFS polymer brushes were more effective in providing corrosion protection. These low-energy surfaces could be used to provide a hydrophobic barrier that inhibits the corrosion of the SS316L metal oxide surface.

The aim of the present study was to assess the effects of bodybuilding training combined with administration of L-carnitine, weightlifting training combined with administration of creatine, and isometric training combined with administration of β-hydroxy-β-methylbutyrate (HMB) on maximal strength and body composition of athletes. The studies were conducted on groups of beginners practising bodybuilding training (n=63) and isometric training (n=69) as well as on a group of advanced powerlifters (n=50) practising weightlifting training. The obtained results indicate that the most desirable and beneficial supportive effect in strength sports was exhibited by HMB. No significant differences in body composition of subjects practising bodybuilding training were detected between those who were given L-carnitine and those who received placebo, an observation confirming controversies over the capacity of the former to reduce fat content. However, significant differences in maximal strength were demonstrated between the examined groups of athletes. Significant differences in the examined parameters were also detected within the group of advanced powerlifters practising weightlifting between those who were supplemented with creatine and those who were given placebo. Thus, the use of creatine in the development of physical capacity in advanced athletes may be advisable.

Preliminary measurements were carried out of the solubility of the O 2- buffering assemblage bismuth + bismite (Bi 2 O 3 ) in aqueous liquid–vapor and vapor-only systems at temperatures of 220, 250 and 300 °C. All experiments were carried out in Ti reaction vessels and were designed such that the Bi solids were contained in a silica tube that prevented contact with liquid water at any time during the experiment. Two blank (no Bi solids present) liquid–vapor experiments at 220 °C yielded Bi concentrations (±1 σ ) in the condensed liquid of 0.22 ± 0.02 mg/L, whereas the solubility measurements at this temperature yielded an average value of approximately 6 ± 9 mg/L, with replicate experiments ranging from 0.3 to 26 mg/L. Although the 6 mg/L value is associated with a considerable degree of uncertainty, the experiments do indicate transport of Bi through the vapor phase. Measured Bi concentrations in the condensed liquid at 250 °C were in the same range as those at 220 °C, whereas those at 300 °C were significantly lower (i.e., all below the blank value). Vapor-only experiments necessarily contained much smaller initial volumes of water, thereby making the results more susceptible to contamination. Single blank runs at 220 and 300 °C yielded Bi concentrations of 82 and 16 mg/L, respectively. Measured concentrations (±1 σ ) of Bi in the vapor-only solubility experiments at 220 °C were 235 ± 78 mg/L for an initial water volume of 0.5 mL, and at 300 °C were 56 ± 30 mg/L and 33 ± 21 for initial water volumes of 1 and 2 mL, respectively, suggesting strong preferential partitioning of Bi into the vapor. The results indicate a negative dependence of Bi solubility on temperature, but are inconclusive with respect to the dependence of Bi solubility on water density or fugacity. The experiments reported here suggest that significant Bi transport is possible in the vapor phase. Comparison of the liquid–vapor and vapor-only experiments further suggests that, at the conditions studied, the solubility of Bi in the vapor is significantly higher than that in the liquid phase (calculated distribution coefficients, i.e., C Vapor / C Liquid at 220 °C ranged from 81 to 168, where C is concentration in mg/L). The concentrations measured in the vapor-only experiments at 220 °C are approximately 11 orders of magnitude higher than those calculated from available thermodynamic data assuming no interaction between volatile Bi species and water molecules. This finding indicates that hydration of volatile Bi species probably occurs to a significant extent; similar to behavior observed previously in published vapor phase solubility studies of other metals. However, the interpretation of the results was complicated by the formation of Bi silicate phases and the lack of certainty that O 2 fugacity buffering was effective throughout the experiments.

Data on the solubility of Re metal in subcritical hydrothermal solutions presented in Xiong and Wood (2001) have been reinterpreted assuming that the following reaction controlled dissolved Re concentrations: ReO2( s ) + 2H2O( l ) ↔ Re(OH)4( aq ). The formation of ReO2( s ) on the surface of Re metal at the conditions of the previous experiments was demonstrated conclusively in a new experiment using X-ray photoelectron spectroscopy (XPS). The temperature dependence (200°–25°C) of the equilibrium constant for the above reaction at − 4700 ± 760 infinite dilution can be expressed as \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathit{K}\ =\ \frac{{-}4700\ {\pm}\ 760}{\mathit{T}}\ +\ 6.2\ {\pm}\ 2.0(2{\sigma})\) \end{document}. These new equilibrium constants predict that metallic rhenium, ReO2( s ), and ReS2( s ) have much lower solubilities than those implied in Xiong and Wood (2001). Based upon the new equilibrium constants, the free energy of formation, the enthalpy of formation, and entropy at the reference state (298.15 K and 1 bar) for the neutral rhenium species, Re(OH)4( aq ) (also alternatively formulated as ReO(OH)2( aq )), are derived in this study. Based on derived equilibrium constants at 25°C for dissolution of ReS2( s ) as Re(OH)4( aq ), we predict that rhenium can be enriched in the reduced zone in supergene environments in porphyry copper-molybdenum deposits.

Multiple sclerosis (MS) is a demyelinating disease characterized by chronic inflammation of the central nervous system, in which many factors can act together to influence disease susceptibility and progression. SIRT1 is a member of the histone deacetylase class III family of proteins and is an NAD(+)-dependent histone and protein deacetylase. SIRT1 can induce chromatin silencing through the deacetylation of histones and plays an important role as a key regulator of a wide variety of cellular and physiological processes including DNA damage, cell survival, metabolism, aging, and neurodegeneration. It has gained a lot of attention recently because many studies in animal models of demyelinating and neurodegenerative diseases have shown that SIRT1 induction can ameliorate the course of the disease. SIRT1 expression was found to be decreased in the peripheral blood mononuclear cells of MS patients during relapses. SIRT1 represents a possible biomarker of relapses and a potential new target for therapeutic intervention in MS. Modulation of SIRT1 may be a valuable strategy for treating or preventing MS and neurodegenerative central nervous system disorders.

Background Environment pesticide effects principally depend on their niche distribution and chemical stability/decomposition, according to seasonal variations. In areas of intensive pesticide use, populations are therefore more vulnerable to any detrimental effects, eg increased hypersensitivity, and may become conditioned to their short/long term actions depending on the patterns of use. Of particular concern are developmental …

The performance of an in situ-forming injectable membrane designed to retain antibody molecules in vivo is described. The system entails an aqueous mixture of peptide amphiphiles (referred to as"EAK16-II" and "EAKH6") and intermediate proteins (anti-H6 antibody and protein A/G) through which therapeutic IgG molecules are colocalized and oriented. Scanning electron micrographs show IgG molecules localized on the EAK16-II/EAKH6 membrane. IgG were captured via specific interactions and remained biologically active in vitro. Upon administration into mice subcutaneously, the amphiphilic peptides coassembled into stable His-tags displaying materials locally. The system was shown to retain in vivo a fluorescent dye-labeled IgG in two epithelial tumor lines. IgG coadministered with the system were found to remain in 4T1 mouse mammary tumors for up to 120 h, while free antibody was cleared within the first 24 h. Decreased clearance was also found in B16 melanoma established in mouse footpads. These studies demonstrated that the immobilizing mechanism was effective in enhancing the retention of IgG locally in vivo. The injectable system may be used to enhance the delivery of immune modulatory antibodies in tumors.

The paper was created within statute studies at the Faculty of Drilling, Oil and Gas at AGH University of Science and Technology in Krakow, Poland. Grant No. 11.11.190.555

Silver nanoparticles (AgNPs) are the most commonly used nanoparticles owing to their antimicrobial properties. The motivation of the present study was (1) to analyze the effect of silver particle size on rat tissue distribution at different time points, (2) to determine the accumulation of AgNPs in potential rat target organs, (3) to analyze the intracellular distribution of AgNPs and (4) to examine the excretion of AgNPs by urine and feces. AgNPs were characterized by dynamic light scattering (DLS), zeta potential measurements, BET surface area measurements, transmission and scanning electron microscopy. AgNPs (20 and 200 nm) were administered intravenously (i.v.) to male Wistar rats at a dose of 5 mg kg(-1) of body weight. Biological material was sampled 24 h, 7 and 28 days after injection. Using inductively coupled plasma-mass spectrometry (ICP-MS) and transmission electron microscopy (TEM) it was observed that AgNPs translocated from the blood to the main organs and the concentration of silver in tissues was significantly higher in rats treated with 20 nm AgNPs as compared with 200 nm AgNPs. The highest concentration of silver was found in the liver after 24 h. After 7 days, a high level of silver was observed in the lungs and spleen. The silver concentration in the kidneys and brain increased during the experiment and reached the highest concentration after 28 days. Moreover, the highest concentration of AgNPs was observed in the urine 1 day after the injection, maintained high for 14 days and then decreased. The fecal level of silver in rats was the highest within 2 days after AgNPs administration and then decreased.

We examined a group of people professionally at risk of exposure to low doses of ionizing radiation (altogether 49 individuals). Age, use of therapeutic drugs, work-related exposure to hazardous agents, previous exposures to diagnostic X-rays, such as patient and nuclear medical examination, were registered. For each individual, the occupational radiation burden received over the past period of 5 years was taken from the official personal records based on film dosimetry controlled every month. A matched group of controls was chosen among the administrative employees (40 individuals). The mean age of the studied population at the time of blood sampling was 49 years (range 24-69). The individuals were divided into groups according to risk of exposure and sex. The alkaline comet assay was used to measure DNA breaks and alkali-labile sites. We compared the mean tail moments, tail length and percentage of DNA in the tail. There was a significant difference between the control and hazard groups in DNA damage. Higher DNA damage was also found for men than for women in the control group. There was no relation of DNA damage to age either in control or hazard group. Additionally, analysis of distributions of tail moment values pointed to a considerable individual diversity even in the control group. Therefore, further investigations were necessary into the suitability of the comet assay as a biological dosimetry method; the results obtained so far warrant such investigations.

In the preceding paper [M. Wojewodzka, M. Kruszewski, T. Iwanenko, A.R. Collins, I. Szumiel, Application of the comet assay for monitoring DNA damage in workers exposed to chronic low dose irradiation. I. Strand breakage., Mutat. Res. 416 (1998) 21-35], we reported the results of DNA damage examination carried out for a group of people (49 individuals) professionally at risk of exposure to low doses of ionizing radiation as measured by the alkaline comet assay. Here, we used the method in combination with oxidative base damage-specific endonucleases to estimate base damage in the same individuals. These were endonuclease III (endoIII) and formamidopyrimidine glycosylase (FPG). In contrast to the previous investigations, we found no statistically significant difference in base damage between the control and hazard groups. Interestingly, the hazard group exhibited lower level of enzyme-sensitive sites than the control; however, this different was not significant. No correlation of base damage with age was found, similarly as in the case of DNA damage measured by the alkaline comet assay. Interindividual variability of base damage precluded exposure estimation for single individuals, since several members of the control group exhibited high comet parameters.

A relatively high number of bovine cryopreserved oocytes analyzed by the comet assay (Men et al. 2003 Mol. Reprod. Dev. 64, 245) showed compromised DNA integrity. The DNA fragmentation (comet tails) was found in 29% of slow cooled oocytes, in 20% of oocytes vitrified in straws and in 24% of oocytes vitrified in open pulled straws (OPS). Present study used the comet assay to compare the DNA status of 151 in vitro matured bovine oocytes vitrified in straws, in OPS or in droplets. It was assumed that the droplet method (Papis et al. 2000 Theriogenology 54, 651), which has gentle pre-equilibration prior to vitrification, would offer better protection of DNA. OPS vitrification was performed using a solution consisting of 20% DMSO, 20% ethylene glycol (EG), and 0.5 M sucrose. For in-straw and in-droplet vitrification, VS14 (5.5 M EG and 1.0 M sucrose) solution was used. In these two methods pre-equilibration in 3% EG solution for 15 min was applied. Fresh oocytes exposed to 0.5 mM of hydrogen peroxide for 5 min served as the positive control. Fresh M II oocytes served as the negative control. The comet assay was performed according to the procedure of Men et al. (2003) with some modifications aimed at enhancing the sensitivity of the method. The zona pellucida was removed using 0.5% pronase solution, followed by placing of the oocytes in droplets of low-melting agarose on slides. These were subjected to overnight treatment in lysis buffer, followed by 40 min of DNA unfolding and 30 min electrophoresis. Following air drying, the slides were stained with DAPI fluorochrome and photographed. The pictures were saved as anonymous consecutive files to enable objective assessment. Of 119 vitrified oocytes, 112 (94%) were evaluated. The remainder were lost or displayed atypical pictures. The comets could not be analyzed with the Comet v.3.0 software, possibly due to the large size of each oocyte. Six main classes of comet tails were distinguished ranging from no tail (class 0) to heavy and long tail (class 5). Positive control oocytes displayed class 4 (36%) or 5 (64%) tails. Negative control oocytes formed class 0 (18%) to class 3 (47%) comet tails. The oocytes vitrified using minimum volume methods fell within the same range, with 80% and 76% of oocytes vitrified in droplets and OPS, respectively, forming class 1 or 2 tails. One OPS vitrified oocyte (2.2%) expressed a class 5 tail. A small but significant proportion of oocytes vitrified in straws (15.4%, P d 0.05, ANOVA) formed class 4 tails typical of positive control oocytes. In conclusion, in spite of pre-equilibration, a significant proportion of oocytes vitrified in straws contained detectable levels of DNA fragmentation, due probably to the lower cooling rate. The minimum volume protocols (the droplet and OPS methods) caused virtually no damage as assessed by the DNA comet assay. Results presented here differ from those reported previously. Reasons for differences remain to be established.