48 research outputs found
Low gonorrhoea antimicrobial resistance and culture positivity rates in general practice: a pilot study
Objective In the Netherlands, the Gonococcal Resistance
to Antimicrobials Surveillance (GRAS) programme is carried
out at Centres for Sexual Health (CSH), which provide
care for sexual high-risk populations. However, half of
gonorrhoea infections are diagnosed in general practice
(GP). We performed a pilot study to explore expanding
GRAS to GPs using laboratory-based surveillance.
Additionally, antimicrobial resistance patterns of GP and
CSH patients were compared.
Methods Three laboratories from different regions were
included, which all perform gonorrhoea diagnostics for
GPs and used ESwab for patient sampling. Additional
culturing for all GP patients with gonorrhoea took place
from February to July 2018. After positive PCR-nucleic
acid amplification test, residual ESwab material was used
for culture. In positive cultures, susceptibility testing was
performed for azithromycin, ciprofloxacin, cefotaxime
and ceftriaxone using Etest.
Results During the study period, 484 samples were
put in culture. 16.5% of cultures were positive (n=80).
Antimicrobial resistance levels were low, with 2.6%
resistance to azithromycin, 21.5% to ciprofloxacin and
0.0% to cefotaxime and ceftriaxone. Resistance levels
in CSH GRAS data (first half of 2018) were 19.2%
for azithromycin, 31.5% for ciprofloxacin, 1.9% for
cefotaxime and 0.0% for ceftriaxone.
Conclusions Culture positivity rates for GP patients
were low, probably due to long transportation times
and awaiting PCR test results before attempting culture.
Positivity rates might be improved by making changes in
sampling and/or transportation methods, but that would
require involvement of GPs and patients instead of keeping
the surveillance lab based. Resistance levels appeared to
be lower at GPs than at the CSH, indicating that resistance
might emerge first in more high-risk populations. It is
important to consider all potentially relevant patient
populations when establishing a gonococcal antimicrobial
resistance surveillance programme. However, based on the
findings from this study the current GRAS programme will
not be extended to GPs
Direction of the oblique medial malleolar osteotomy for exposure of the talus
A medial malleolar osteotomy is often indicated for operative exposure of posteromedial osteochondral defects and fractures of the talus. To obtain a congruent joint surface after refixation, the oblique osteotomy should be directed perpendicularly to the articular surface of the tibia at the intersection between the tibial plafond and medial malleolus. The purpose of this study was to determine this perpendicular direction in relation to the longitudinal tibial axis for use during surgery. Using anteroposterior mortise radiographs and coronal computed tomography (CT) scans of 46 ankles (45 patients) with an osteochondral lesion of the talus, two observers independently measured the intersection angle between the tibial plafond and medial malleolus. The bisector of this angle indicated the osteotomy perpendicular to the tibial articular surface. This osteotomy was measured relative to the longitudinal tibial axis on radiographs. Intraclass correlation coefficients (ICC) were calculated to assess reliability. The mean osteotomy was 57.2 ± 3.2° relative to the tibial plafond on radiographs and 56.5 ± 2.8 on CT scans. This osteotomy corresponded to 30.4 ± 3.7° relative to the longitudinal tibial axis. The intraobserver (ICC, 0.90-0.93) and interobserver (ICC, 0.65-0.91) reliability of these measurements were good to excellent. A medial malleolar osteotomy directed at a mean 30° relative to the tibial axis enters the joint perpendicularly to the tibial cartilage, and will likely result in a congruent joint surface after reductio
Assessing the efficiency and significance of Methylated DNA Immunoprecipitation (MeDIP) assays in using in vitro methylated genomic DNA
<p>Abstract</p> <p>Background</p> <p>DNA methylation contributes to the regulation of gene expression during development and cellular differentiation. The recently developed Methylated DNA ImmunoPrecipitation (MeDIP) assay allows a comprehensive analysis of this epigenetic mark at the genomic level in normal and disease-derived cells. However, estimating the efficiency of the MeDIP technique is difficult without previous knowledge of the methylation status of a given cell population. Attempts to circumvent this problem have involved the use of <it>in vitro </it>methylated DNA in parallel to the investigated samples. Taking advantage of this stratagem, we sought to improve the sensitivity of the approach and to assess potential biases resulting from DNA amplification and hybridization procedures using MeDIP samples.</p> <p>Findings</p> <p>We performed MeDIP assays using <it>in vitro </it>methylated DNA, with or without previous DNA amplification, and hybridization to a human promoter array. We observed that CpG content at gene promoters indeed correlates strongly with the MeDIP signal obtained using <it>in vitro </it>methylated DNA, even when lowering significantly the amount of starting material. In analyzing MeDIP products that were subjected to whole genome amplification (WGA), we also revealed a strong bias against CpG-rich promoters during this amplification procedure, which may potentially affect the significance of the resulting data.</p> <p>Conclusion</p> <p>We illustrate the use of <it>in vitro </it>methylated DNA to assess the efficiency and accuracy of MeDIP procedures. We report that efficient and reproducible genome-wide data can be obtained via MeDIP experiments using relatively low amount of starting genomic DNA; and emphasize for the precaution that must be taken in data analysis when an additional DNA amplification step is required.</p
Pregnancies and Time to Pregnancy in Women With and Without a PreviousChlamydia trachomatisInfection
Background: A Chlamydia trachomatis infection (chlamydia) can result
in tubal factor infertility in women. To assess if this association results in
fewer pregnant women, we aimed to assess pregnancy incidences and time
to pregnancy among women with a previous chlamydia infection compared
with women without one and who were participating in the Netherlands
Chlamydia Cohort Study (NECCST).
Methods: The NECCST is a cohort of women of reproductive age tested
for chlamydia in a chlamydia screening trial between 2008 and 2011 and
reinvited for NECCST in 2015 to 2016. Chlamydia status (positive/negative)
was defined using chlamydia screening trial–nucleic acid amplification test
results, chlamydia immunoglobulin G presence in serum, or self-reported
chlamydia infections. Data on pregnancies were collected via questionnaires in 2015–2016 and 2017–2018. Overall p
Genome-wide Association Study of Borderline Personality Disorder Reveals Genetic Overlap with Bipolar Disorder, Major Depression and Schizophrenia
Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of bipolar disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case–control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was (i) to detect genes and gene sets involved in BOR and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic overlap between BIP, major depression (MDD) and schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests and gene-set analyses were performed in 998 BOR patients and 1545 controls. Linkage disequilibrium score regression was used to detect the genetic overlap between BOR and these disorders. Single marker analysis revealed no significant association after correction for multiple testing. Gene-based analysis yielded two significant genes: DPYD (P=4.42 × 10−7) and PKP4 (P=8.67 × 10−7); and gene-set analysis yielded a significant finding for exocytosis (GO:0006887, PFDR=0.019; FDR, false discovery rate). Prior studies have implicated DPYD, PKP4 and exocytosis in BIP and SCZ. The most notable finding of the present study was the genetic overlap of BOR with BIP (rg=0.28 [P=2.99 × 10−3]), SCZ (rg=0.34 [P=4.37 × 10−5]) and MDD (rg=0.57 [P=1.04 × 10−3]). We believe our study is the first to demonstrate that BOR overlaps with BIP, MDD and SCZ on the genetic level. Whether this is confined to transdiagnostic clinical symptoms should be examined in future studies
Sheep Lung Segmental Delivery Strategy Demonstrates Adenovirus Priming of Local Lung Responses to Bacterial LPS and the Role of Elafin as a Response Modulator
Viral lung infections increase susceptibility to subsequent bacterial infection. We questioned whether local lung administration of recombinant adenoviral vectors in the sheep would alter the susceptibility of the lung to subsequent challenge with bacterial lipopolysaccharide (LPS). We further questioned whether local lung expression of elafin, a locally produced alarm anti-LPS/anti-bacterial molecule, would modulate the challenge response. We established that adenoviral vector treatment primed the lung for an enhanced response to bacterial LPS. Whereas this local effect appeared to be independent of the transgene used (Ad-o-elafin or Ad-GFP), Ad-o-elafin treated sheep demonstrated a more profound lymphopenia in response to local lung administration of LPS. The local influence of elafin in modulating the response to LPS was restricted to maintaining neutrophil myeloperoxidase activity, and levels of alveolar macrophage and neutrophil phagocytosis at higher levels post-LPS. Adenoviral vector-bacterial synergism exists in the ovine lung and elafin expression modulates such synergism both locally and systemically
Integrating Academic and Everyday Learning Through Technology: Issues and Challenges for Researchers, Policy Makers and Practitioners
This paper builds on work undertaken over a number of years by a group of international researchers with an interest in the potential of connecting academic and everyday practices and knowledge. Drawing extensively on literature and our own work, we first discuss the challenges around defining informal learning, concluding that learning is multidimensional and has varying combinations of formal and informal attributes. We then highlight the potential of technology for integrating formal and informal learning attributes and briefly provide some exemplars of good practice. We then discuss in depth the challenges and issues of this approach to supporting learning from the perspective of pedagogy, research, policy and technology. We also provide some recommendations of how these issues may be addressed. We argue that for the learner, integration of formal and informal learning attributes should be an empowering process, enabling the learner to be self-directed, creative and innovative, taking learning to a deeper level. Given the complexity of the learning ecosystem, this demands support from the teacher but also awareness and understanding from others such as parents, family, friends and community members. We present a conceptual model of such an ecosystem to help develop further discussions within and between communities of researchers, policy makers and practitioners