Lack of association between the chemokine receptor 5 polymorphism CCR5delta32 in rheumatoid arthritis and juvenile idiopathic arthritis

Background  

The chemokine receptor CCR5 has been detected at elevated levels on synovial T cells, and a 32 bp deletion in the CCR5 gene leads to a non-functional receptor. A negative association between the CCR5Δ32 and rheumatoid arthritis (RA) has been reported, although with conflicting results. In juvenile idiopathic arthritis (JIA), an association with CCR5 was recently reported. The purpose of this study was to investigate if the CCR5Δ32 polymorphism is associated with RA or JIA in Norwegian cohorts.     

European health inequality through the ‘Great Recession’: social policy matters

This paper investigates the association between the Great Recession and educational inequalities in self‐rated general health in 25 European countries. We investigate four different indicators related to economic recession: GDP; unemployment; austerity and a ‘crisis’ indicator signifying severe simultaneous drops in GDP and welfare generosity. We also assess the extent to which health inequality changes can be attributed to changes in the economic conditions and social capital in the European populations. The paper uses data from the European Social Survey (2002–2014). The analyses include both cross‐sectional and lagged associations using multilevel linear regression models with country fixed effects. This approach allows us to identify health inequality changes net of all time‐invariant differences between countries. GDP drops and increasing unemployment were associated with decreasing health inequalities. Austerity, however, was related to increasing health inequalities, an association that grew stronger with time. The strongest increase in health inequality was found for the more robust ‘crisis’ indicator. Changes in trust, social relationships and in the experience of economic hardship of the populations accounted for much of the increase in health inequality. The paper concludes that social policy has an important role in the development of health inequalities, particularly during times of economic crisis.     

Immunogenicity and safety of a combination of two serogroup B meningococcal outer membrane vesicle vaccines

MenBvac and MeNZB are safe and efficacious vaccines against serogroup B meningococcal disease. MenBvac is prepared from a B:15:P1.7,16 meningococcal strain (strain 44/76), and MeNZB is prepared from a B:4:P1.7-2,4 strain (strain NZ98/254). At 6-week intervals, healthy adults received three doses of MenBvac (25 microg), MeNZB (25 microg), or the MenBvac and MeNZB (doses of 12.5 microg of each vaccine) vaccines combined, followed by a booster 1 year later. Two-thirds of the subjects who received a monovalent vaccine in the primary schedule received the other monovalent vaccine as a booster dose. The immune responses to the combined vaccine were of the same magnitude as the homologous responses to each individual vaccine observed. At 6 weeks after the third dose, 77% and 87% of the subjects in the combined vaccine group achieved serum bactericidal titers of > or = 4 against strains 44/76 and NZ98/254, respectively, and 97% and 93% of the subjects achieved a fourfold or greater increase in opsonophagocytic activity against strains 44/76 and NZ98/254, respectively. For both strains, a trend of higher responses after the booster dose was observed in all groups receiving at least one dose of the respective strain-specific vaccine. Local and systemic reactions were common in all vaccine groups. Most reactions were mild or moderate in intensity, and there were no vaccine-related serious adverse events. The safety profile of the combined vaccine was not different from those of the separate monovalent vaccines. In conclusion, use of either of the single vaccines or the combination of MenBvac and MeNZB may have a considerable impact on the serogroup B meningococcal disease situation in many countries.     

A Polyprotein-Expressing Salmonid Alphavirus Replicon Induces Modest Protection in Atlantic Salmon (Salmo Salar) Against Infectious Pancreatic Necrosis

Vaccination is an important strategy for the control and prevention of infectious pancreatic necrosis (IPN) in farmed Atlantic salmon (Salmo salar) in the post-smolt stage in sea-water. In this study, a heterologous gene expression system, based on a replicon construct of salmonid alphavirus (SAV), was used for in vitro and in vivo expression of IPN virus proteins. The large open reading frame of segment A, encoding the polyprotein NH2-pVP2-VP4-VP3-COOH, as well as pVP2, were cloned and expressed by the SAV replicon in Chinook salmon embryo cells (CHSE-214) and epithelioma papulosum cyprini (EPC) cells. The replicon constructs pSAV/polyprotein (pSAV/PP) and pSAV/pVP2 were used to immunize Atlantic salmon (Salmo salar) by a single intramuscular injection and tested in a subsequent IPN virus (IPNV) challenge trial. A low to moderate protection against IPN was observed in fish immunized with the replicon vaccine that encoded the pSAV/PP, while the pSAV/pVP2 construct was not found to induce protection.     

The novel colorectal cancer biomarkers CDO1, ZSCAN18 and ZNF331 are frequently methylated across gastrointestinal cancers

We have previously shown that gastrointestinal cancers display similar epigenetic aberrations. In a recent study, we identified frequently methylated genes for cholangiocarcinoma (CDO1, DCLK1, SFRP1 and ZSCAN18), where one of these genes, DCLK1, was also confirmed to be highly methylated in colorectal cancer. The aim of the present study was to determine whether these four genes, in addition to one gene found to be methylated in colon cancer cell lines (ZNF331), are commonly methylated across gastrointestinal malignancies, as well as explore their role as potential biomarkers. Quantitative methylation specific PCR (qMSP) of colorectal cancer (n = 164) and normal colorectal mucosa (n = 106) samples showed that all genes were frequently methylated in colorectal cancer (71–92%) with little or no methylation in normal mucosa (0–3%). Methylation of minimum two of these five genes identified 95% of the tumors with a specificity of 98%, and an area under the receiver operating characteristics curve (AUC) of 0.98. For gastric (n = 25) and pancreatic (n = 20) cancer, the same panel detected 92% and 90% of the tumors, respectively. Seventy‐four cancer cell lines were further analyzed by qMSP and real time RT‐PCR. In addition to the previously reported DCLK1, a high negative correlation between promoter DNA methylation and gene expression was observed for CDO1, ZNF331 and ZSCAN18. In conclusion, the high methylation frequency of these genes in colorectal‐ as well as in gastric‐, pancreatic‐ and bile duct cancer confirmed an epigenetic similarity between gastrointestinal cancer types, and simultaneously demonstrated their potential as biomarkers, particularly for colorectal cancer detection.     

Social inequalities in "sickness": does welfare state regime type make a difference? A multilevel analysis of men and women in 26 European countries

In comparative studies of health inequalities, public health researchers have usually studied only disease and illness. Recent studies have also examined the sickness dimension of health, that is, the extent to which ill health is accompanied by joblessness, and how this association varies by education within different welfare contexts. This research has used either a limited number of countries or quantitative welfare state measures in studies of many countries. In this study, the authors expand on this knowledge by investigating whether a regime approach to the welfare state produces consistent results. They analyze data from the European Union Statistics on Income and Living Conditions (EU-SILC); health was measured by limiting longstanding illness (LLSI). Results show that for both men and women reporting LLSI in combination with low educational level, the probabilities of non-employment were particularly high in the Anglo-Saxon and Eastern welfare regimes, and lowest in the Scandinavian regime. For men, absolute and relative social inequalities in sickness were lowest in the Southern regime; for women, inequalities were lowest in the Scandinavian regime. The authors conclude that the Scandinavian welfare regime is more able than other regimes to protect against non-employment in the face of illness, especially for individuals with low educational level.     

Bovine lactoferrin digested with human gastrointestinal enzymes inhibits replication of human echovirus 5 in cell culture

Many infant formulas are enriched with lactoferrin (Lf) because of its claimed beneficial effects on health. Native bovine Lf (bLf) is known to inhibit in vitro replication of human enteroviruses, a group of pathogenic viruses that replicate in the gut as their primary infection site. On the basis of a model digestion and human gastrointestinal enzymes, we hypothesized that bLf could retain its antiviral properties against enterovirus in the gastrointestinal tract, either as an intact protein or through bioactive peptide fragments released by digestive enzymes. To test our hypothesis, bLf was digested with human gastric juice and duodenal juice in a 2-step in vitro digestion model. Two gastric pH levels and reduction conditions were used to simulate physiological conditions in adults and infants. The antiviral activity of native bLf and of the digested fractions was studied on echovirus 5 in vitro, using various assay conditions, addressing several mechanisms for replication inhibition. Both native and digested bLf fractions revealed a significant inhibitory effect, when added before or simultaneously with the virus onto the cells. Furthermore, a significant stronger sustained antiviral effect was observed when bLf was fully digested in the gastric phase with fast pH reduction to 2.5, compared with native bLf, suggesting the release of antiviral peptides from bLf during the human digestion process. In conclusion, this study demonstrates that bLf may have a role in the prevention of human gastrointestinal virus infection under physiological conditions and that food containing bLf may protect against infection in vivo.     

Effects of Two vs. Four Weekly Campus Board Training Sessions on Bouldering Performance and Climbing-Specific Tests in Advanced and Elite Climbers

This study examined the effects of two or four weekly campus board training sessions among highly accomplished lead climbers. Sixteen advanced-to-elite climbers were randomly allocated to two (TG2), or four weekly campus board training sessions (TG4), or a control group (CG). All groups continued their normal climbing routines. Pre- and post-intervention measures included bouldering performance, maximal isometric pull-up strength using a shallow rung and a large hold (jug), and maximal reach and moves to failure. Rate of force development (RFD; absolute and 100ms) was calculated in the rung condition. TG4 improved maximal force in the jug condition (effect size (ES) = 0.40, p = 0.043), and absolute RFD more than CG (ES = 2.92, p = 0.025), whereas TG2 improved bouldering performance (ES = 2.59, p = 0.016) and maximal moves to failure on the campus board more than CG (ES = 1.65, p = 0.008). No differences between the training groups were found (p = 0.107–1.000). When merging the training groups, the training improved strength in the rung condition (ES = 0.87, p = 0.002), bouldering performance (ES = 2.37, p = 0.006), maximal reach (ES = 1.66, p = 0.006) and moves to failure (ES = 1.43, p = 0.040) more than CG. In conclusion, a five-week campus board training-block is sufficient for improving climbing-specific attributes among advanced-to-elite climbers. Sessions should be divided over four days to improve RFD or divided over two days to improve bouldering performance, compared to regular climbing training.Key points

• Five weeks of volume equated campus board training may similarly improve finger strength, maximal reach and number of campus moves to failure regardless of training frequency.
• Four weekly sessions may be more effective than two weekly sessions for improving rate of force development in an isometric pull-up using a climbing-specific hold
• Two weekly sessions could be more effective than four weekly sessions for improving bouldering performance when volume is equated.

Key words: Isometric, pull-up, rate of force development, strength