Metatarsophalangeal joint pain in psoriatic arthritis: a cross-sectional study

Methods. Thirty-four consecutive patients with PsA (mean age 45.3 years, 65% female, mean disease duration 9.9 years) and 22 control participants (mean age 37.9 years, 64% female) underwent clinical and US examination to determine the presence of pain, swelling, synovitis, erosions, effusions and submetatarsal bursae at the MTP joints. Mean barefoot peak plantar pressures were determined at each MTP joint. Levels of pain, US-determined pathology and peak pressures were compared between groups. Binary logistic regression was used to identify demographic, clinical examination-derived, US-derived and plantar pressure predictors of pain at the MTP joints in the PsA group. Results. The presence of pain, deformity, synovitis, erosions (P < 0.001) and submetatarsal bursae and peak plantar pressure at MTP 3 (P < 0.05) were significantly higher in the PsA group. MTP joint pain in PsA was independently predicted by high BMI, female gender and the presence of joint subluxation, synovitis and erosion. Conclusion. These results suggest local inflammatory and structural factors, together with systemic factors (gender, BMI), are predominantly responsible for painful MTP joints in PsA, with no clear role for plantar pressure characteristics

Flavonoid-membrane Interactions: A Protective Role of Flavonoids at the Membrane Surface?

Flavonoids can exert beneficial health effects through multiple mechanisms. In this paper, we address the important, although not fully understood, capacity of flavonoids to interact with cell membranes. The interactions of polyphenols with bilayers include: (a) the partition of the more non-polar compounds in the hydrophobic interior of the membrane, and (b) the formation of hydrogen bonds between the polar head groups of lipids and the more hydrophilic flavonoids at the membrane interface. The consequences of these interactions are discussed. The induction of changes in membrane physical properties can affect the rates of membrane lipid and protein oxidation. The partition of certain flavonoids in the hydrophobic core can result in a chain breaking antioxidant activity. We suggest that interactions of polyphenols at the surface of bilayers through hydrogen bonding, can act to reduce the access of deleterious molecules (i.e. oxidants), thus protecting the structure and function of membranes

The metabolome of [2-(14)C](-)-epicatechin in humans: implications for the assessment of efficacy, safety, and mechanisms of action of polyphenolic bioactives

Diet is a major life style factor affecting human health, thus emphasizing the need for evidence-based dietary guidelines for primary disease prevention. While current recommendations promote intake of fruit and vegetables, we have limited understanding of plant-derived bioactive food constituents other than those representing the small number of essential nutrients and minerals. This limited understanding can be attributed to some extent to a lack of fundamental data describing the absorption, distribution, metabolism and excretion (ADME) of bioactive compounds. Consequently, we selected the flavanol (-)-epicatechin (EC) as an example of a widely studied bioactive food constituent and investigated the ADME of [2-(14)C](-)-epicatechin (300 μCi, 60 mg) in humans (n = 8). We demonstrated that 82 ± 5% of ingested EC was absorbed. We also established pharmacokinetic profiles and identified and quantified >20 different metabolites. The gut microbiome proved to be a key driver of EC metabolism. Furthermore, we noted striking species-dependent differences in the metabolism of EC, an insight with significant consequences for investigating the mechanisms of action underlying the beneficial effects of EC. These differences need to be considered when assessing the safety of EC intake in humans. We also identified a potential biomarker for the objective assessment of EC intake that could help to strengthen epidemiological investigations

Temporal trends of time to antiretroviral treatment initiation, interruption and modification: Examination of patients diagnosed with advanced HIV in Australia

INTRODUCTION: HIV prevention strategies are moving towards reducing plasma HIV RNA viral load in all HIV-positive persons, including those undiagnosed, treatment naïve, on or off antiretroviral therapy. A proxy population for those undiagnosed are patients that present late to care with advanced HIV. The objectives of this analysis are to examine factors associated with patients presenting with advanced HIV, and establish rates of treatment interruption and modification after initiating ART. METHODS: We deterministically linked records from the Australian HIV Observational Database to the Australian National HIV Registry to obtain information related to HIV diagnosis. Logistic regression was used to identify factors associated with advanced HIV diagnosis. We used survival methods to evaluate rates of ART initiation by diagnosis CD4 count strata and by calendar year of HIV diagnosis. Cox models were used to determine hazard of first ART treatment interruption (duration >30 days) and time to first major ART modification. RESULTS: Factors associated (p<0.05) with increased odds of advanced HIV diagnosis were sex, older age, heterosexual mode of HIV exposure, born overseas and rural-regional care setting. Earlier initiation of ART occurred at higher rates in later periods (2007-2012) in all diagnosis CD4 count groups. We found an 83% (69, 91%) reduction in the hazard of first treatment interruption comparing 2007-2012 versus 1996-2001 (p<0.001), and no difference in ART modification for patients diagnosed with advanced HIV. CONCLUSIONS: Recent HIV diagnoses are initiating therapy earlier in all diagnosis CD4 cell count groups, potentially lowering community viral load compared to earlier time periods. We found a marked reduction in the hazard of first treatment interruption, and found no difference in rates of major modification to ART by HIV presentation status in recent periods

Excavations at the Lower Palaeolithic Site at Elveden, Suffolk

The Lower Palaeolithic site at Elveden, Suffolk, was the subject of new excavations from 1995–1999. Excavations around the edge and in the centre of the former clay-pit revealed sediments infilling a lake basin that had formed in Lowestoft till, overlying Chalk, the till being attributed to the Anglian glaciation (MIS 12). The lake sediments contain pollen that can be assigned to pollen zones HoI and HoIIa of the early Hoxnian (MIS 11). Overlying grey clays contain ostracods, molluscs, vertebrates, and carbonate concretions. Together they are indicative of a fluvial environment in a temperate climate. AAR ratios (amino acid racemisation) on the molluscs also suggest correlation with MIS 11. Further indications of a fluvial context are indicated by thin spreads of lag gravel along opposite sides of the clay-pit, marking the edges of a channel. The gravel forms the raw material for the human industries which consist of handaxes, flake tools, flakes, and cores. Further artefacts are found in the overlying black clay, which is interpreted as a palaeosol that formed with the silting-up of the channel. The basin was further infilled with colluvial ‘brickearths’, which also contain artefacts that are probably derived from the underlying gravel. Further evidence of soil formation was identified in the ‘brickearth’. Coversands with periglacial involutions overlie the ‘brickearth’ at the top of the sequence. These probably formed in the last cold stage, the Devensian

Regular Consumption of a Flavanol-rich Chocolate can Improve Oxidant Stress in Young Soccer Players

The consumption of a diet rich in certain flavonoids, including the flavanol sub-class, has been associated with a reduced risk for vascular disease. We evaluated the effects of the regular consumption (14 d) of a flavanol-containing milk chocolate (FCMC) or cocoa butter chocolate (CBC) on variables related to vascular disease risk, oxidative stress and physical activity. Twenty-eight free-living, young (18–20 years old) male soccer players consumed daily 105 g of FCMC (168 mg of flavanols) or CBC (<5 mg of flavanols), as part of their normal diet. The consumption of FCMC was significantly associated with a decrease in diastolic blood pressure (-5 mm Hg), mean blood pressure (-5 mm Hg), plasma cholesterol (-11%), LDL-cholesterol (-15%), malondialdehyde (-12%), urate (-11%) and lactate dehydrogenase (LDH) activity (-11%), and an increase in vitamin E/cholesterol (+12%). No relevant changes in these variables were associated with CBC consumption. No changes in the plasma levels of (-)-epicatechin were observed following analysis of fasting blood samples. In conclusion, FCMC consumption was associated with changes in several variables often associated with cardiovascular health and oxidant stress. The presence of significant quantities of flavanols in FCMC is likely to have been one of the contributing factors to these results

Fermi Large Area Telescope Observations of the Cygnus Loop Supernova Remnant

We present an analysis of the gamma-ray measurements by the Large Area Telescope(LAT) onboard the \textit{Fermi Gamma-ray Space Telescope} in the region of the supernova remnant(SNR) Cygnus Loop(G74.0$-$8.5). We detect significant gamma-ray emission associated with the SNR in the energy band 0.2--100 GeV. The gamma-ray spectrum shows a break in the range 2--3 GeV. The gamma-ray luminosity is $\sim$ $1 \times 10^{33}$erg s$^{-1}$ between 1--100 GeV, much lower than those of other GeV-emitting SNRs. The morphology is best represented by a ring shape, with inner/outer radii 0$^\circ$.7 $\pm$ 0$^\circ$.1 and 1$^\circ$.6 $\pm$ 0$^\circ$.1. Given the association among X-ray rims, \halpha filaments and gamma-ray emission, we argue that gamma rays originate in interactions between particles accelerated in the SNR and interstellar gas or radiation fields adjacent to the shock regions. The decay of neutral pions produced in nucleon-nucleon interactions between accelerated hadrons and interstellar gas provides a reasonable explanation for the gamma-ray spectrum.Comment: accepted by ApJ, 34 pages, 6 figure