Drug–excipient interactions in ketoprofen: A vibrational spectroscopy study

Ketoprofen (3-benzoyl-alpha-methylbenzeneacetic acid) is a widely used nonsteroidal anti-inflammatory drug (NSAID), always administered in the form of drug-excipient physical mixtures (PMs). The occurrence of possible interactions between ketoprofen and two commonly used excipients-lactose (LAC) and polyvinylpyrrolidone (PVP)-was evaluated, through vibrational spectroscopy techniques [both Raman and Inelastic Neutron Scattering (INS)]. Spectral evidence of drug:excipient close contacts, which were enhanced by aging, was verified for the (1:1) (w:w) (ketoprofen:PVP) and (ketoprofen:LAC) PMs, both by Raman and INS. These interactions were found to involve mainly the central carbonyl and the terminal methyl-carboxylic moieties of the ketoprofen molecule, this being reflected in particular vibrational modes, such as the methyl torsion, the out-of-plane C-OH bending, and the inter-ring C=O stretching

Solution phase, solid state, and theoretical investigations on the MacMillan imidazolidinone

A combination of soln. phase NMR, X-ray crystallog. studies, and DFT calcns. provide a consistent structural conformation for iminium ions derived from the MacMillan imidazolidinone

Crystal structures and proton dynamics in potassium and cesium hydrogen bistrifluoroacetate salts with strong symmetric hydrogen bonds

The crystal structures of potassium and cesium bistrifluoroacetates were determined at room temperature and at 20 K and 14 K, respectively, with the single crystal neutron diffraction technique. The crystals belong to the I2/a and A2/a monoclinic space groups, respectively, and there is no visible phase transition. For both crystals, the trifluoroacetate entities form dimers linked by very short hydrogen bonds lying across a centre of inversion. Any proton disorder or double minimum potential can be rejected. The inelastic neutron scattering spectral profiles in the OH stretching region between 500 and 1000 cm^{-1} previously published [Fillaux and Tomkinson, Chem. Phys. 158 (1991) 113] are reanalyzed. The best fitting potential has the major characteristics already reported for potassium hydrogen maleate [Fillaux et al. Chem. Phys. 244 (1999) 387]. It is composed of a narrow well containing the ground state and a shallow upper part corresponding to dissociation of the hydrogen bond.Comment: 31 pages, 7 figure

Human DNA ligase III bridges two DNA ends to promote specific intermolecular DNA end joining

Mammalian DNA ligase III (LigIII) functions in both nuclear and mitochondrial DNA metabolism. In the nucleus, LigIII has functional redundancy with DNA ligase I whereas LigIII is the only mitochondrial DNA ligase and is essential for the survival of cells de-pendent upon oxidative respiration. The unique LigIII zinc finger (ZnF) domain is not required for catalytic activity but senses DNA strand breaks and stimulates intermolecular ligation of two DNAs by an unknown mechanism. Consistent with this activity, LigIII acts in an alternative pathway of DNA double strand break repair that buttresses canonical non-homologous end joining (NHEJ) and is manifest in NHEJ-defective cancer cells, but how LigIII acts in joining inter-molecular DNA ends versus nick ligation is unclear. To investigate how LigIII efficiently joins two DNAs, we developed a real-time, fluorescence-based as-say of DNA bridging suitable for high-throughput screening. On a nicked duplex DNA substrate, the results reveal binding competition between the ZnF and the oligonucleotide/oligosaccharide-binding do-main, one of three domains constituting the LigIII cat-alytic core. In contrast, these domains collaborate and are essential for formation of a DNA-bridging in-termediate by adenylated LigIII that positions a pair of blunt-ended duplex DNAs for efficient and specific intermolecular ligation

Some aspects of inelastic neutron scattering from inorganic compounds

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Improving catalyst activity in secondary amine catalysed transformations

The effect on catalyst performance of altering substituents at the 2-position of the Macmillan imidazolidinone has been examined. Condensation of L-phenylalanine N-methyl amide with acetophenone derivatives results in a series of imidazolidinones whose salts can be used to accelerate the Diels-Alder cycloaddition. Electron withdrawing groups significantly increases the overall rate of cycloaddition without compromise in selectivity. The most effective catalyst was shown to be efficient for a variety of substrates and the applicability of this catalyst to alternative secondary amine catalysed transformations is also discussed

The relationship between ventilatory threshold and repeated-sprint ability in competitive male ice hockey players

Background/objective The relationship between ventilatory threshold (VT1, VT2) and repeated-sprint ability (RSA) in competitive male ice hockey players was investigated. Methods Forty-three male ice hockey players aged 18–23 years competing in NCAA Division I, NCAA Division III, and Junior A level participated. Participants performed an incremental graded exercise test on a skate treadmill to determine V˙ role= presentation style= box-sizing: border-box; margin: 0px; padding: 0px; display: inline-block; line-height: normal; font-size: 14.4px; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; position: relative; \u3eV˙O2peak, VT1, and VT2 using MedGraphics Breezesuit™ software (v-slope). Participants performed an on-ice repeated shift (RSA) test consisting of 8-maximal skating bouts, lasting approximately 25 s and interspersed with 90 s of passive recovery, to determine first gate, second gate, and total sprint decrement (%dec). Pearson product-moment correlations and multiple regressions were used to assess relationships between ventilatory threshold variables (VT1, VT2, Stage at VT1, and Stage at VT2) and RSA (first gate, second gate, and total course decrement). Results Stage at VT2 was the only variable substantially correlated with first gate (r = −0.35; P \u3c 0.05), second gate (r = −0.58; P \u3c 0.001) and total course decrement (r = −0.42; P \u3c 0.05). Conclusion The results of this study demonstrated that VT is substantially associated with RSA, and VT2 is more strongly correlated with RSA than V˙ role= presentation style= box-sizing: border-box; margin: 0px; padding: 0px; display: inline-block; line-height: normal; font-size: 14.4px; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; position: relative; \u3eV˙O2peak. This study suggests that longer duration high-intensity interval training at intensities that increase workrate at VT2 may lead to possible improvements in RSA

Relationships between digit ratio (2D:4D) and basketball performance in Australian men

Objective To investigate relationships between the digit ratio (2D:4D) and competitive basketball performance in Australian men. Methods Using an observational cross‐sectional design a total of 221 Australian basketball players who competed in the Olympic Games, International Basketball Federation World Championships/Cup, Australian National Basketball League, Central Australian Basketball League or socially had their 2D:4Ds measured. Analysis of variance was used to assess differences in mean 2D:4Ds between men playing at different competitive standards, with relationships between 2D:4Ds and basketball game‐related statistics assessed using Pearson\u27s product moment correlations in men playing at a single competitive standard. Results There were significant differences between competitive standards for the left 2D:4D following Bonferroni correction, but not for the right 2D:4D, with basketballers who achieved higher competitive standards tending to have lower left 2D:4Ds. No important correlations between 2D:4D and basketball game‐related statistics were found, with correlations typically negligible. Conclusions This study indicated that the 2D:4D can discriminate between basketballers competing at different standards, but not between basketballers within a single competitive standard using objective game‐related statistics

Temporal trends in the handgrip strength of 2,592,714 adults from 14 countries between 1960 and 2017: A systematic analysis

Background: Handgrip strength (HGS) is an excellent marker of functional capability and health in adults, although little is known about temporal trends in adult HGS. Objectives: The aim of this study was to systematically analyze national (country-level) temporal trends in adult HGS, and to examine relationships between national trends in adult HGS and national trends in health-related and socioeconomic/demographic indicators. Methods: Data were obtained from a systematic search of studies reporting temporal trends in HGS for adults (aged ≥20 years) and by examining national fitness datasets. Trends in mean HGS were estimated at the country-sex-age group level by best-fitting sample-weighted linear/polynomial regression models, with national and sub-regional (pooled data across geographically similar countries) trends estimated by a post-stratified population-weighting procedure. Pearson’s correlations quantified relationships between national trends in adult HGS and national trends in health-related and socioeconomic/demographic indicators. Results: Data from 10 studies/datasets were extracted to estimate trends in mean HGS for 2,592,714 adults from 12 high- and 2 upper-middle-income countries (from Asia, Europe and North America) between 1960 and 2017. National trends were few, mixed and generally negligible pre-2000, whereas most countries (75% or 9/12) experienced negligible-to-small declines ranging from an effect size of 0.05 to 0.27, or 0.6 to 6.3%, per decade post-2000. Sex- and age-related temporal differences were negligible. National trends in adult HGS were not significantly related to national trends in health and socioeconomic/demographic indicators. Conclusions: While trends in adult HGS are currently limited to 14 high- and upper-middle-income countries from 3 continents, adult HGS appears to have declined since 2000 (at least among most of the countries in this analysis), which is suggestive of corresponding declines in functional capability and health. PROSPERO registration number: CRD42013003678. KEY POINTS National (country-level) trends in adult handgrip strength (HGS) were few, mixed and generally negligible pre-2000, and generally negligible and indicated declines post-2000 Sex- and age-related temporal differences in adult HGS were negligible-to-small at the country level and negligible at the regional level National trends in adult HGS were not significantly related to national trends in health and socioeconomic/demographic indicator