Hydroxylation and self-assembly of colloidal hydrogenated nanodiamonds by aqueous oxygen radicals from atmospheric pressure plasma jet

Plasma chemical surface modification of nanoparticles in gas–liquid type reactors enables a controllable, specific, low-cost, and environmentally friendly alternative to wet chemistry methods or thermal and dry plasma treatments. Here the atmospheric pressure radio-frequency microplasma jet (µ-APPJ) operating with 0.6% O₂ in He is used to deliver aqueous oxygen radicals (AOR) to the surface of ∼3 nm hydrogenated detonation nanodiamonds (H-DNDs) suspended in water. The AOR-treated H-DND samples are characterized by FTIR and XPS spectroscopies and by AFM and SEM imaging. The main chemical reaction mechanism is identified as the abstraction of surface hydrogen atoms by O or OH radicals and a consequent attachment of the OH group, thereby increasing concentration of alcohols, carboxyls, and aldehydes on the DND''s surface. FTIR spectra reveal also a structural re-arrangement of the surface water on the AOR-treated H-DNDs. Yet zeta-potential of AOR-treated H-DNDs still remains positive (decreases from +45 mV to +30 mV). The chemical modification gives rise to formation of nanoscale chain-like aggregates when AOR-treated H-DNDs are deposited on Si substrate.

Colloidal nanodiamonds are hydroxylated by action of plasma-supplied O atoms and undergo self-assembly to chains.     

Sex and gender differences in Alzheimer’s disease: current challenges and implications for clinical practice

Alzheimer’s disease (AD) is characterized by high heterogeneity in disease manifestation, progression and risk factors. High phenotypic variability is currently regarded as one of the largest hurdles in early diagnosis and in the design of clinical trials; there is therefore great interest in identifying factors driving variability that can be used for patient stratification. In addition to genetic and lifestyle factors, the individual’s sex and gender are emerging as crucial drivers of phenotypic variability. Evidence exists on sex and gender differences in the rate of cognitive deterioration and brain atrophy, and in the effect of risk factors as well as in the patterns of diagnostic biomarkers. Such evidence might be of high relevance and requires attention in clinical practice and clinical trials. However, sex and gender differences are currently seldom appreciated; importantly, consideration of sex and gender differences is not currently a focus in the design and analysis of clinical trials for AD. The objective of this position paper is (i) to provide an overview of known sex and gender differences that might have implications for clinical practice, (ii) to identify the most important knowledge gaps in the field (with a special regard to clinical trials) and (iii) to provide conclusions for future studies. This scientific statement is endorsed by the European Academy of Neurology.     

Antibacterial C-geranylflavonoids from Paulownia tomentosa Fruits

Eight C-6-geranylflavonoids ( 1- 8) were isolated from an ethanol extract of Paulownia tomentosa fruits. Tomentodiplacone ( 1), 3'- O-methyl-5'-hydroxydiplacone ( 2), 3'- O-methyl-5'- O-methyldiplacone ( 3), and tomentodiplacone B ( 4) were obtained as new compounds, and 3'- O-methyldiplacol ( 5) was isolated for the first time from a natural source. The structures of these new compounds were determined by using mass spectrometry (including HRMS) and 1D and 2D NMR spectroscopy, and the absolute configurations of the compounds were determined by circular dichroism. The antibacterial activities of 1- 8 against seven bacteria and yeast were evaluated.     

The effect of outdoor air and indoor human activity on mass concentrations of PM(10), PM(2.5), and PM(1) in a classroom

The 12-h mass concentration of PM₁₀, PM_2.5, and PM₁ was measured in a lecturing room by means of three co-located Harvard impactors. The filters were changed at 8 AM and at 8 PM to cover the periods of presence and absence of students. Concentrations were assessed by gravimetry. Ambient PM₁₀ data were available for corresponding 12-h intervals from the nearest state air-quality-monitoring network station. The data were pooled into four periods according to the presence and absence of students—Monday-Thursday day (workday daytime), Monday-Thursday night (workday night), Friday-Sunday day (weekend daytime), and Friday-Sunday night (weekend night). Average indoor workday daytime concentrations were 42.3, 21.9 and 13.7 μg m⁻³, workday night were 20.9, 19.1 and 15.2 μg m⁻³, weekend daytime were 21.9, 18.1 and 11.4 μg m⁻³, and weekend night were 24.5, 21.3, and 15.6 μg m⁻³ for PM₁₀, PM_2.5, and PM₁, respectively. The highest 12-h mean, median, and maximum (42.3, 43.0, and 76.2 μg m⁻³, respectively) indoor concentrations were recorded on workdays during the daytime for PM₁₀. The statistically significant (r=0.68,P<0.0009) correlation between the number of students per hour per day and the indoor coarse fraction calculated as PM_10−2.5 during daytime on workdays indicates that the presence of people is an important source of coarse particles indoor. On workdays, the daytime PM₁₀ indoor/outdoor ratio was positively associated (r=0.93) with an increasing indoor coarse fraction (PM_10-2.5), also indicating that an important portion of indoor PM₁₀ had its source inside the classroom. With the exception of the calculated coarse fraction (PM_10-2.5), all of the measured indoor particulate matter fractions were significantly highly correlated with outdoor PM₁₀ and negatively correlated with wind velocity, showing that outdoor levels of particles influence their indoor concentrations.     

Polymers containing enzymatically degradable bonds, 7. Design of oligopeptide side-chains in poly[N-(2-hydroxypropyl)methacrylamide] copolymers to promote efficient degradation by lysosomal enzymes

N-(2-Hydroxypropyl)methacrylamide copolymers are considered to be a potential drug delivery system. To fulfil this role the drug-polymer linkage must be susceptible to intralysosomal hydrolysis. Taking p-nitroanilide as a drug analogue, copolymers were synthesized bearing oligopeptidyl-p-nitroanilide side-chains designed to match known specificities of the lysosomal enzymes cathepsin L or cathepsin D. Degradation of side-chains by rat liver lysosomal enzymes (measured by monitoring terminal p-nitroaniline release) occurred only in the presence of reduced glutathione (5 mmol/l) and was effectively inhibited by leupeptin, indicating the involvement of thiol-proteinases in every case. Depending on side-chain composition, between 20 and more than 50% of the terminal p-nitroaniline residues were liberated during a 5 h incubation. It has also been shown that 1) a polymer molecule may contain side-chains of a single type that are nevertheless differentially susceptible to lysosomal hydrolysis; 2) two of the side-chains studied liberate only a p-nitroaniline residue, whereas the others also release amino-acyl-p-nitroanilides; 3) the cleavage of all side-chains displays a broad pH optimum pH 5 to pH 7; 4) the Michaelis-Menten constant K_m for side-chain cleavage varied between 26,1 and 143,2 mg/ml, depending on the amino acid sequence of the side-chain.     

Juvenile polyarteritis: results of a multicenter survey of 110 children

OBJECTIVE: To characterize pediatric patients who had been diagnosed with polyarteritis nodosa (PAN) through necrotizing vasculitis of the small and mid-size arteries or those with characteristic findings on angiograms data were collected. STUDY DESIGN: Pediatricians were asked to classify their patients into one of the four suggested groups for juvenile PAN. Twenty-one pediatric centers worldwide participated with 110 patients. RESULTS: The girl:boy ratio was 56:54, with a mean age of 9.05 +/- 3.57 years. The cases were classified as: 33 (30%) cutaneous PAN; 5 (4.6%) classic PAN associated with hepatitis B surface antigen (HBs Ag); 9 (8.1%) microscopic polyarteritis of adults associated with antineutrophil cytoplasmic antibodies (ANCA); and 63 (57.2%) systemic PAN. Cutaneous PAN was disease confined to the skin and musculoskeletal system. All patients with HBs Ag-associated classic PAN were diagnosed with renal angiograms. Antiviral treatment was administered in most cases. Microscopic PAN patients had pulmonary-renal disease, in combination or separately. ANCA was present in 87%, and 2 patients progressed to end-stage renal failure. Patients classified with systemic PAN had multiple system involvement, almost all had constitutional symptoms, and all had elevated acute phase reactants. Corticosteroids and cyclophosphamide were the first choices of immunosuppressive treatment. The overall mortality was 1.1%. CONCLUSIONS: There were remarkable differences among pediatric patients with PAN, with different clinical manifestations and overall better survival and lower relapse rates when compared with adults.     

Seven antiphospholipid antibodies in HIV-positive patients: correlation with clinical course and laboratory findings

OBJECTIVE: To compare the clinical course of HIV-1-infected patients, their CD4+, CD8+ T lymphocytes, and viral loads (VL) with the levels of seven antiphospholipid antibodies (aPLs) before, during, and after the highly active antiretroviral therapy (HAART). PATIENTS AND METHODS: aPLs were examined in patients (20 men, 10 women, aged 12-64 years, median 33 years) from the AIDS center of Western Bohemia before the initiation of HAART, and two (23 patients), and five (20 patients) years later. Flow-cytometry was used for CD4+ and CD8+ T lymphocytes analysis, commercial kits were used for VL-measurements, and commercial enzyme-linked immunosorbent assay (ELISA) was used to determine serum levels of anti-beta2-glycoprotein I (GPI) of immunoglobulin G (IgG) and IgA isotypes, and anticardiolipin levels (ACA) of IgG and IgM isotypes. APLs screening also included L-alpha-phosphatidic (ph) acid, L-alpha-phosphatidylethanolamine, L-alpha-phosphatidyl-DL-glycerol, L-alpha-phosphatidylinositol, and L-alpha-phosphatidylserine of IgG and IgM autoantibodies. Statistical analysis was performed using cut-off levels for immunoglobulin-isotypes of aPLs using 3 S.D. or 95th percentile calculated using Statgraphics-software. RESULTS: In 14 of 21 patients treated by HAART an increased number of CD4+ T lymphocytes was detected, and in 14 of 21 patients VL decreased below detection threshold during the 5 years of observation. We did not observe correlations of aPLs with age, the initial low CD4+ and high number of CD8+ T lymphocytes, and the viremic levels over the entire observation period. We did not find the elevation of aPLs in 2 of 5 patients in stage C (AIDS). Ten of 11 HIV-positive homosexuals had positive aPLs, and the same result was seen in 7 of 10 patients infected through heterosexual intercourse. aPLs levels were significantly increased in 18 of 30 patients at the beginning of HAART. ACA IgG was elevated in 14 of 30 cases, IgG antibodies against L-alpha-ph-acid in 5 of 30, ph-ethanolamine in 10 of 30, ph-inositol in 9 of 30, and L-serine in 14 of 30, combined positivity of six aPLs together was detected in 10 HIV positive patients. Significantly decreased levels of aPLs because of HAART were found in eight patients. APLs were still present in only four patients after 5 years of the treatment. Abnormalities in blood clotting were not present in any of our patients. CONCLUSION: Results of screening for seven aPLs in HIV-positive patients suggest that HAART also positively influences the autoimmune response represented by aPLs levels, but individual differences in aPLs levels were observed.     

Mutual interactions of boar seminal plasma proteins studied by immunological and chromatographic methods

PROBLEM: Boar seminal plasma contains various types of proteins. Most of them belong to spermadhesins and some of them contain fibronectin type II domain. Almost all of these proteins are present under physiological conditions in aggregated forms differing in their relative molecular mass, composition, and binding properties. The study of mutual specific interactions between proteins of boar seminal plasma that could be involved in the formation of aggregated forms and most probably of sperm coating layers is the subject of our present communication. METHODS OF STUDY: Aggregated forms of boar seminal plasma proteins separated by size exclusion chromatography were analysed by Reversed-phase High-performance Liquid Chromatography (RP HPLC), SDS-PAGE and immunochemical methods (ELISA and immunoblotting). Mutual interactions between proteins were investigated by size exclusion chromatography of a mixture of separated monomer proteins and affinity chromatography of boar seminal plasma on immobilized spermadhesins. RESULTS: Composition of proteins that are adsorbed from boar seminal plasma to immobilized spermadhesins corresponds to that of aggregated forms found in seminal plasma. Mutual interactions between monomer forms observed by size exclusion chromatography are in good agreement with results of affinity chromatography. An existence of interactions between spermadhesins of the AQN and AWN families and the DQH sperm surface protein, as well as between proteins involved in the formation of heterodimer porcine seminal plasma I (PSP I)/PSP II was proved. CONCLUSION: Mutual specific interactions between protein components of boar seminal plasma were shown. These interactions participate in the formation of aggregated forms of proteins in seminal plasma and probably also in the arrangement and remodelling of protein coating layers of sperm. Aggregation of seminal plasma proteins is probably an important phenomenon in the fertilization process.