SIMPLE: implementation of recommendations from international evidence-based guidelines on caesarean sections in the Netherlands. Protocol for a controlled before and after study

Background

Caesarean section (CS) rates are rising worldwide. In the Netherlands, the most significant rise is observed in healthy women with a singleton in vertex position between 37 and 42 weeks gestation, whereas it is doubtful whether an improved outcome for the mother or her child was obtained. It can be hypothesized that evidence-based guidelines on CS are not implemented sufficiently. Therefore, the present study has the following objectives: to develop quality indicators on the decision to perform a CS based on key recommendations from national and international guidelines; to use the quality indicators in order to gain insight into actual adherence of Dutch gynaecologists to guideline recommendations on the performance of a CS; to explore barriers and facilitators that have a direct effect on guideline application regarding CS; and to develop, execute, and evaluate a strategy in order to reduce the CS incidence for a similar neonatal outcome (based on the information gathered in the second and third objectives).

Methods

An independent expert panel of Dutch gynaecologists and midwives will develop a set of quality indicators on the decision to perform a CS. These indicators will be used to measure current care in 20 hospitals with a population of 1,000 women who delivered by CS, and a random selection of 1,000 women who delivered vaginally in the same period. Furthermore, by interviewing healthcare professionals and patients, the barriers and facilitators that may influence the decision to perform a CS will be measured. Based on the results, a tailor-made implementation strategy will be developed and tested in a controlled before-and-after study in 12 hospitals (six intervention, six control hospitals) with regard to effectiveness, experiences, and costs.

Discussion

This study will offer insight into the current CS care and into the hindering and facilitating factors influencing obstetrical policy on CS. Furthermore, it will allow definition of patient categories or situations in which a tailor-made implementation strategy will most likely be meaningful and cost effective, without negatively affecting the outcome for mother and child.

Trial registration

http://www.clinicaltrials.gov: NCT01261676     

Chemopreventive effects of Calluna vulgaris and Vitis vinifera extracts on UVB-induced skin damage in SKH-1 hairless mice

Solar ultraviolet radiation (UV) is a major cause of non-melanoma skin cancer in humans. Photochemoprevention with natural products represents a simple but very effective strategy in the management of cutaneous neoplasia. The study investigated the protective activity of Calluna vulgaris (Cv) and red grape seeds (Vitis vinifera L, Burgund Mare variety) (BM) extracts in vivo on UVB-induced deleterious effects in SKH-1 mice skin. Forty SKH-1 mice were randomly divided into 4 groups (n=10): control, UVB irradiated, Cv + UVB irradiated, BM+UVB irradiated. Both extracts were applied topically on the skin in a dose of 4 mg/40 μl/cm(2) before UVB exposure - single dose. The effects were evaluated in skin 24 hours after irradiation through the presence of cyclobutane pyrimidine dimers (CPDs) and sunburn cells, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6 levels. The antioxidant activity of BM extract was higher than those of Cv extract as determined using stable free radical DPPH assay and ABTS test. One single dose of UVB generated formation of CPDs (p<0.0001) and sunburn cells (p<0.0002) and increased the cytokine levels in skin (p<0.0001). Twenty hours following irradiation BM extract inhibited UVB-induced sunburn cells (p<0.02) and CPDs formation (p<0.0001). Pretreatment with Cv and BM extracts resulted in significantly reduced levels of IL-6 and TNF-α compared with UVB alone (p<0.0001). Our results suggest that BM extracts might be a potential candidate in preventing the damages induced by UV in skin.     

Number and mode of inheritance of QTL influencing backfat thickness on SSC2p in Sino-European pig pedigrees

Background

In the pig, multiple QTL associated with growth and fatness traits have been mapped to chromosome 2 (SSC2) and among these, at least one shows paternal expression due to the IGF2-intron3-G3072A substitution. Previously published results on the position and imprinting status of this QTL disagree between analyses from French and Dutch F2 crossbred pig populations obtained with the same breeds (Meishan crossed with Large White or Landrace).

Methods

To study the role of paternal and maternal alleles at the IGF2 locus and to test the hypothesis of a second QTL affecting backfat thickness on the short arm of SSC2 (SSC2p), a QTL mapping analysis was carried out on a combined pedigree including both the French and Dutch F2 populations, on the progeny of F1 males that were heterozygous (A/G) and homozygous (G/G) at the IGF2 locus. Simulations were performed to clarify the relations between the two QTL and to understand to what extent they can explain the discrepancies previously reported.

Results

The QTL analyses showed the segregation of at least two QTL on chromosome 2 in both pedigrees, i.e. the IGF2 locus and a second QTL segregating at least in the G/G F1 males and located between positions 30 and 51 cM. Statistical analyses highlighted that the maternally inherited allele at the IGF2 locus had a significant effect but simulation studies showed that this is probably a spurious effect due to the segregation of the second QTL.

Conclusions

Our results show that two QTL on SSC2p affect backfat thickness. Differences in the pedigree structures and in the number of heterozygous females at the IGF2 locus result in different imprinting statuses in the two pedigrees studied. The spurious effect observed when a maternally allele is present at the IGF2 locus, is in fact due to the presence of a second closely located QTL. This work confirms that pig chromosome 2 is a major region associated with fattening traits.     

A polycystin‐2 (TRPP2) dimerization domain essential for the function of heteromeric polycystin complexes

Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in two genes, PKD1 and PKD2, which encode polycystin‐1 (PC1) and polycystin‐2 (PC2), respectively. Earlier work has shown that PC1 and PC2 assemble into a polycystin complex implicated in kidney morphogenesis. PC2 also assembles into homomers of uncertain functional significance. However, little is known about the molecular mechanisms that direct polycystin complex assembly and specify its functions. We have identified a coiled coil in the C‐terminus of PC2 that functions as a homodimerization domain essential for PC1 binding but not for its self‐oligomerization. Dimerization‐defective PC2 mutants were unable to reconstitute PC1/PC2 complexes either at the plasma membrane (PM) or at PM‐endoplasmic reticulum (ER) junctions but could still function as ER Ca²⁺‐release channels. Expression of dimerization‐defective PC2 mutants in zebrafish resulted in a cystic phenotype but had lesser effects on organ laterality. We conclude that C‐terminal dimerization of PC2 specifies the formation of polycystin complexes but not formation of ER‐localized PC2 channels. Mutations that affect PC2 C‐terminal homo‐ and heteromerization are the likely molecular basis of cyst formation in ADPKD.     

Genome-wide association study of insect bite hypersensitivity in two horse populations in the Netherlands

Background

Insect bite hypersensitivity is a common allergic disease in horse populations worldwide. Insect bite hypersensitivity is affected by both environmental and genetic factors. However, little is known about genes contributing to the genetic variance associated with insect bite hypersensitivity. Therefore, the aim of our study was to identify and quantify genomic associations with insect bite hypersensitivity in Shetland pony mares and Icelandic horses in the Netherlands.

Methods

Data on 200 Shetland pony mares and 146 Icelandic horses were collected according to a matched case–control design. Cases and controls were matched on various factors (e.g. region, sire) to minimize effects of population stratification. Breed-specific genome-wide association studies were performed using 70 k single nucleotide polymorphisms genotypes. Bayesian variable selection method Bayes-C with a threshold model implemented in GenSel software was applied. A 1 Mb non-overlapping window approach that accumulated contributions of adjacent single nucleotide polymorphisms was used to identify associated genomic regions.

Results

The percentage of variance explained by all single nucleotide polymorphisms was 13% in Shetland pony mares and 28% in Icelandic horses. The 20 non-overlapping windows explaining the largest percentages of genetic variance were found on nine chromosomes in Shetland pony mares and on 14 chromosomes in Icelandic horses. Overlap in identified associated genomic regions between breeds would suggest interesting candidate regions to follow-up on. Such regions common to both breeds (within 15 Mb) were found on chromosomes 3, 7, 11, 20 and 23. Positional candidate genes within 2 Mb from the associated windows were identified on chromosome 20 in both breeds. Candidate genes are within the equine lymphocyte antigen class II region, which evokes an immune response by recognizing many foreign molecules.

Conclusions

The genome-wide association study identified several genomic regions associated with insect bite hypersensitivity in Shetland pony mares and Icelandic horses. On chromosome 20, associated genomic regions in both breeds were within 2 Mb from the equine lymphocyte antigen class II region. Increased knowledge on insect bite hypersensitivity associated genes will contribute to our understanding of its biology, enabling more efficient selection, therapy and prevention to decrease insect bite hypersensitivity prevalence.     

Synopsis of the hard ticks (Acari: Ixodidae) of Romania with update on host associations and geographical distribution

The current paper is a synoptic review of the distribution and host associations of the 25 species of hard tick fauna (family Ixodidae) in Romania. In addition to a full literature survey, original data is presented, based on eight years of occasional or targeted sample collection. The literature data on geographical distribution was transposed digitally to the decimal degree coordinate system. For each species, an updated distribution map is given together with all historical data and new host associations. Overall, our paper records 58 new tick-host associations for Romania: 20 for Ixodes ricinus, 1 for I. apronophorus, 6 for I. arboricola, 2 for I. hexagonus, 9 for I. redikorzevi, 1 for I. trianguliceps, 2 for I. vespertilionis, 2 for Haemaphysalis punctata, 1 for H. sulcata, 2 for H. concinna, 1 for D. marginatus, 4 for Rhipicephalus sanguineus sensu lato, 1 for R. bursa and 6 for Hyalomma marginatum.     

Ixodes ricinus is the dominant questing tick in forest habitats in Romania: the results from a countrywide dragging campaign

In 2010 and 2011, questing ticks were collected from 188 forested locations in all the 41 counties of Romania using the dragging method. The total of 13,771 ticks collected belonged to eleven species: Ixodes ricinus (86.9?%), Dermacentor marginatus (9.5?%), Haemaphysalis punctata (2.6?%), H. concinna (0.6?%), H. sulcata (0.3?%), H. parva (0.1?%), Hyalomma marginatum (0.02?%), D. reticulatus (0.02?%), I. crenulatus (0.007?%), I. hexagonus (0.007?%) and I. laguri (0.007?%). Ixodes ricinus was present in 97.7?% (n?=?180) of locations, occurring exclusively in 41.7?% of the locations, whereas it was the dominant species in 38.8 % of the other locations, accounting for over 70?% of the total tick community. The following most common questing ticks were D. marginatus, H. punctata and H. concinna. Ixodes ricinus co-occurred with one, two or three sympatric species. The occurrence of D. reticulatus in forested habitats from Romania was found to be accidental.     

Low sclerostin levels: a predictive marker of persistent inflammation in ankylosing spondylitis during anti-tumor necrosis factor therapy?

Introduction

Sclerostin levels have been reported to be low in ankylosing spondylitis (AS), but there is no data regarding the possible role of this Wnt inhibitor during anti-tumor necrosis factor (TNF) therapy. The present study longitudinally evaluated sclerostin levels, inflammatory markers and bone mineral density (BMD) in AS patients under anti-TNF therapy.

Methods

Thirty active AS patients were assessed at baseline, 6 and 12 months after anti-TNF therapy regarding clinical parameters, inflammatory markers, BMD and baseline radiographic damage (mSASSS). Thirty age- and sex-matched healthy individuals comprised the control group. Patients'' sclerostin levels, sclerostin binding low-density lipoprotein receptor-related protein 6 (LRP6) and BMD were evaluated at the same time points and compared to controls.

Results

At baseline, AS patients had lower sclerostin levels (60.5 ± 32.7 vs. 96.7 ± 52.9 pmol/L, P = 0.002) and comparable sclerostin binding to LRP6 (P = 0.387) than controls. Improvement of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Ankylosing Spondylitis quality of life (ASQoL) was observed at baseline vs. 6 vs. 12 months (P < 0.01). Concomitantly, a gradual increase in spine BMD (P < 0.001) and a positive correlation between baseline mSASSS and spine BMD was found (r = 0.468, P < 0.01). Inflammatory parameters reduction was observed comparing baseline vs. 6 vs. 12 months (P <0.01). Sclerostin levels progressively increased [baseline (60.5 ± 32.7) vs. 6 months (67.1 ± 31.9) vs. 12 months (72.7 ± 32.3) pmol/L, P <0.001]. At 12 months, the sclerostin levels remained significantly lower in patients compared to controls (72.7 ± 32.3 vs. 96.70 ± 52.85 pmol/L, P = 0.038). Moreover, sclerostin serum levels at 12 months were lower in the 10 patients with high C reactive protein (CRP) (≥ 5 mg/l) compared to the other 20 patients with normal CRP (P = 0.004). Of note, these 10 patients with persistent inflammation also had lower sclerostin serum levels at baseline compared to the other patients (P = 0.023). Univariate logistic regression analysis demonstrated that AS patients with lower sclerostin serum levels had an increased risk to have high CRP at 12 months (odds ratio = 7.43, 95% CI 1.23 to 45.01, P = 0.020) than those with higher sclerostin values.

Conclusions

Persistent low sclerostin levels may underlie continuous inflammation in AS patients under anti-TNF therapy.     

Regulation of human natural cytotoxicity by IgG. III. Interaction between negative regulation by monomeric IgG and positive regulation by interferons of different types

Our prior reported results have demonstrated the dose-dependent inhibition of human natural killer (NK) cell activity upon treatment of peripheral blood mononuclear cells (PBMC) with monomeric IgG (mIgG) prior to the cytotoxic assay. In the present study, the combined effects on NK activity of human interferon (IFN) of each of the three types and mIgG, respectively, were determined. NK cells incubated with IFN alpha or IFN beta had augmented cytotoxicity against K562 target cells but remained responsive to negative regulation by mIgG. PBMC treated with human recombinant IFN gamma had unchanged cytotoxic activity but became partially resistant to suppression by mIgG. This ability of IFN gamma to interfere with the negative regulation of NK activity by cytophilic mIgG was seen when the cytokine was preincubated with effector cells prior to, simultaneously with, or after their exposure to inhibitor protein. These data provide some clues regarding the possible biological significance of the mIgG-induced down-regulation of NK cells which, when required for host protection, might be appreciably reversed or blocked by IFN gamma produced by NK cells or T cells in response to various agents.