Please cite this paper as:Ørtoft G, Henriksen T, Hansen E, Petersen L. After conisation of the cervix, the perinatal mortality as a result of preterm delivery increases in subsequent pregnancy. BJOG ...2010;117:258–267.
Objective To determine the effects of one or two conisations on preterm delivery and perinatal mortality in subsequent pregnancies.
Design A population‐based cohort study.
Setting Aarhus University Hospital.
Population Preterm delivery and mortality rates were evaluated in 721 deliveries after one conisation, and in 37 deliveries after two conisations, and were compared with 390 deliveries after dysplasia and 74 552 deliveries that were not preceded by conisation or dysplasia.
Methods Cox regression was used to evaluate preterm delivery rates and perinatal mortality.
Main outcome measures Birthweight, gestational age (prior to 28, 32, and 37 weeks of gestation, respectively) and perinatal mortality.
Results The risk of preterm delivery was increased after one conisation adjusted hazard ratios (95% CI): <37 weeks, 2.8 (2.3–3.5); <28 weeks, 4.9 (2.5–9.7), and was further increased after two conisations adjusted hazard ratios (95% CI): <37 weeks, 9.9 (6–17); <28 weeks, 9.8 (1.4–70), compared with no conisation. One conisation was associated with an increased perinatal mortality <28 weeks, 9.9 (4.0–25). All three methods of conisation large loop excision of the transformation zone, electroknife and cold knife increased the risk of preterm delivery.
Conclusions A single conisation was associated with a 2.8‐fold increased risk of perinatal death, most likely because of a 4.9‐fold increase in extreme preterm delivery. Only 37 patients had two conisations, and the results showed a ten‐fold increase in the risk of preterm delivery.
Accumulating evidence support that mannan-binding lectin (MBL) is a promising prognostic biomarker for risk-stratification of diabetic micro- and macrovascular complications. Serum MBL levels are ...predominately genetically determined and depend on MBL genotype. However, Type 1 diabetes (T1D) is associated with higher MBL serum levels for a given MBL genotype, but it remains unknown if this is also the case for patients with T2D. In this study, we evaluated the impact of MBL genotypes on renal function trajectories serum MBL levels and compared MBL genotypes in newly diagnosed patients with T2D with age- and sex-matched healthy individuals. Furthermore, we evaluated differences in parameters of insulin resistance within MBL genotypes.
In a cross-sectional study, we included 100 patients who were recently diagnosed with T2D and 100 age- and sex-matched individuals. We measured serum MBL levels, MBL genotype, standard biochemistry, and DEXA, in all participants. A 5-year clinical follow-up study was conducted, followed by 12-year data on follow-up biochemistry and clinical status for the progression to micro- or macroalbuminuria for the patients with T2D.
We found similar serum MBL levels and distribution of MBL genotypes between T2D patients and healthy individuals. The serum MBL level for a given MBL genotype did not differ between the groups neither at study entry nor at 5-year follow-up. We found that plasma creatinine increased more rapidly in patients with T2D with the high MBL expression genotype than with the medium/low MBL expression genotype over the 12-year follow-up period (p = 0.029). Serum MBL levels did not correlate with diabetes duration nor with HbA1c. Interestingly, serum MBL was inversely correlated with body fat percentage in individuals with high MBL expression genotypes both at study entry (p=0.0005) and 5-years follow-up (p=0.002).
Contrary to T1D, T2D is not
associated with increased MBL serum level for a given MBL genotype or with diabetes duration. Serum MBL was inversely correlated with body fat percentage, and T2D patients with the high MBL expression genotype presented with deterioration of renal function.
The structure of GP-zones in an industrial, 7xxx-series Al–Zn–Mg alloy has been investigated by transmission electron microscopy methods: selected area diffraction, conventional and high-resolution ...imaging. Two types of GP-zones, GP(I) and (II) are characterized by their electron diffraction patterns. GP(I)-zones are formed over a wide temperature range, from room temperature to 140–150°C, independently of quenching temperature. The GP(I)-zones are coherent with the aluminum matrix, with internal ordering of Zn and Al/Mg on the matrix lattice, suggested to be based on AuCu(I)-type sub-unit, and anti-phase boundaries. GP(II) are formed after quenching from temperatures above 450°C, by aging at temperatures above 70°C. The GP(II)-zones are described as zinc-rich layers on {111}-planes, with internal order in the form of elongated domains. The structural relation to the η′-precipitate is discussed.
Gut microbial gene richness and specific bacterial species are associated with metabolic risk markers in humans, but the impact of host physiology and dietary habits on the link between the gut ...microbiota and metabolic markers remain unclear. The objective of this study was to identify gut metagenomic markers associated with estimates of insulin resistance, lipid metabolism and inflammation in obesity, and to explore whether the associations between metagenomic and metabolic markers persisted after adjustment for body fat, age and habitual dietary intake.
Faecal DNA from 53 women with obesity was analysed through quantitative metagenomic sequencing and analysis, and a systematic search was performed for bacterial genes associated with estimates of insulin resistance, inflammation and lipid metabolism. Subsequently, the correlations between metagenomic species and metabolic markers were tested by linear regression models, with and without covariate adjustment.
One hundred and fourteen metagenomic species correlated with metabolic markers (P<0.001) including Akkermansia muciniphila, Bilophila wadsworthia, Bifidobacterium longum and Faecalibacterium prausnitzii, but also species not previously associated with metabolic markers including Bacteroides faecis and Dorea longicatena. The majority of the identified correlations between bacterial species and metabolic markers persisted after adjustment for differences in body fat, age and dietary macronutrient composition; however, the negative correlation with insulin resistance observed for B. longum and F. prausnitzii appeared to be modified by the intake of dietary fibre and fat, respectively.
This study shows that several gut bacterial species are linked to metabolic risk markers in obesity, also after adjustment for potential confounders, such as long-term diet composition. The study supports the use of gut metagenomic markers for metabolic disease prediction and warrants further investigation of causality.
Summary
Background
Chronic oro‐facial pain patients often perceive the painful face area as “swollen” without clinical signs, that is a perceptual distortion (PD). Local anaesthetic (LA) injections ...in healthy participants are also associated with PD.
Objective
The aim was to explore whether PD evoked by LA into the infraorbital region could be modulated by adding mechanical stimulation (MS) to the affected area.
Methods
Mechanical stimulation was given with a brush and a 128‐mN von Frey filament. Firstly, sixty healthy participants were randomly divided into three groups: (i) LA control, (ii) LA with MS, (iii) isotonic solution (ISO) with MS as an additional control condition. To further examine the role of a multisensory modulation, an additional experiment was conducted. Twenty participants received LA with MS (filament) in addition to visual feedback of their distorted face. The results of the two experiments are presented together.
Results
All three LA groups experienced PD; per contra, PD was not reported in the ISO group. MS alone did not change the magnitude of PD: brush (P = .089), filament (P = .203). However, when the filament stimulation was combined with additional visual information of a distorted face, there was observable decrease in PD (P = .002).
Conclusion
The findings indicate the importance of multisensory integration for PD and represent a significant step forward in the understanding of the factors that may influence this common condition. Future studies are encouraged to investigate further the cortical processing for possible implications for PD in pain management.
A highly specific and potent (7 nM cellular IC 50 ) inhibitor of p38α kinase was identified directly from a 12.6 million membered DNA-encoded small molecule library. This was achieved using the high ...fidelity yoctoReactor technology (yR) for preparing the DNA-encoded library, and a homogeneous screening technique – the binder trap enrichment technology (BTE). Although structurally atypical to other kinase blockers, this inhibitor was found by X-ray crystallography to interact with the ATP binding site and provide strong distortion of the P-loop. Remarkably, it assumed an alternative binding mode as it lacks key features of known kinase inhibitors such as typical hinge binding motifs. Interestingly, the inhibitor bound assuming a canonical type-II (‘DFG-out’) binding mode by forming hinge hydrogen bonds with the backbone, showed excellent shape complementarity, and formed a number of specific polar interactions. Moreover, the crystal structure showed, that although buried in the p38α active site, the original DNA attachment point of the compound was accessible through a channel created by the distorted P-loop conformation. This study demonstrates the usability of DNA-encoded library technologies for identifying novel chemical matter with alternative binding modes to provide a good starting point for drug development.
•Full genome characterization of a PRRSV-2 strain causing significant clinical disease in the field.•Examination of the field isolate in an experimental infection study in growing pigs.•Investigation ...of the prophylactic effect of a current MLV PRRS-2 vaccine against the field isolate.
Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is the cause of severe reproductive and respiratory disease in swine worldwide. In Denmark, both PRRSV-1 and PRRSV-2 are circulating and approximately 35% of pig herds are seropositive for PRRSV.
In November 2010, a pig herd in the Northern part of Denmark experienced an infection with PRRSV-2 with clinical signs that were much more severe than normally reported from current Danish PRRSV-2 affected herds. Due to the clinical observations of reproductive failure in sows and high mortality in piglets, it was speculated that a new, more pathogenic or vaccine evading PRRSV strain had emerged in Denmark. The overall aim of the present study was to perform a genetic and biological characterization of the virus isolated from the diseased herd. Complete genome sequencing of isolates from this herd revealed that although the case strain had some unique genetic features including a deduced 3 amino acid deletion, it was in overall very similar to the other PRRS-2 viruses circulating in Denmark. In an experimental trial in growing pigs, no overt clinical signs or pathology were observed following intranasal inoculation with the new virus isolate. Virus shedding, acute phase protein responses and serological responses were comparable to those seen after experimental challenge with a Danish PRRSV-2 reference strain isolated in 1997. Vaccination with a commercial modified live PRRSV-2 vaccine had a clear reducing effect on virus shedding, magnitude, and duration of viremia and viral load in the lungs. Overall, the results indicate that the severe disease observed in the field was contributed by additional factors in combination with the PRRS virus infection.
A three-month laboratory-based prospective survey was conducted at four major university hospitals covering one-third of the Danish population in order to determine the prevalence, significance, and ...susceptibility pattern of aspergilli in airway samples. Samples received in January–March 2007 for routine microbiologic investigation were examined for
Aspergillus
following routine procedures and with extended incubation (5 days). Identification was done by morphologic criteria and susceptibility testing using EUCAST method for azoles and amphotericin B E-test. Invasive aspergillosis (IA) was evaluated using modified EORTC/MSG criteria. A total of 11,368 airway samples were received. Growth of
Aspergillus
spp. was found in 129 and 151 patients using routine and extended incubation, respectively. Three patients had proven IA (2%), 11 probable (7%), four had allergic bronchopulmonary aspergillosis (ABPA) (3%), but the majority was colonised (88%). Underlying conditions were cystic fibrosis in 82 patients (55%), chronic obstructive pulmonary disease in 19 (13%) and haematological disorder in 11 (7%). Twenty-six patients (18%) were at intensive care unit and 69 (47%) received steroid treatment. Azole MICs were elevated for five isolates as follows (itraconazole, posaconazole, voriconazole MICs mg/L): two
A. fumigatus
isolates (>4; >4; 2 and >4; 0.125; 1), one
A. lentulus
isolate (2; 2; 0.5) and two
A. terreus
isolates (2; 2; 2 and 2; 0.125; 1). For four isolates the amphotericin B MIC was >1 μg/ml (3/112
A. fumigatus
, 1/2
A. terreus
). In conclusion,
Aspergillus
appears to be an important pathogen in Denmark. Elevated itraconazole MICs were detected in 4% of the isolates including a multi-azole resistant isolate.
Needle-related distress is a common yet poorly recognised and managed problem among haemodialysis (HD) patients. The aim of this pilot study is to test the feasibility and acceptability of the INJECT ...Intervention-an innovative psychology-based intervention to empower patients to self-manage needle distress with the support of dialysis nurses.
This investigator-initiated, single-arm, non-randomised feasibility study will take place in a large dialysis service in Adelaide, Australia. Participants will include patients aged ≥ 18 years, commencing or already receiving maintenance HD, recruited through dialysis physicians and nursing staff as individuals believed to be at risk of needle distress. They will be screened for inclusion using the Dialysis Fear of Injection Questionnaire (DFIQ) and enrolled into the study if the score is ≥ 2. The multi-pronged intervention encompasses (i) psychologist review, (ii) patient self-management program and (iii) nursing education program. The primary aim is to evaluate feasibility and acceptability of the intervention from patient and dialysis nurse perspectives, including recruitment, retention, engagement with the intervention and completion. Secondary exploratory outcomes will assess suitability of various tools for measuring needle distress, evaluate acceptability of the nursing education program and measure cannulation-related trauma and vascular access outcomes.
The results will inform the protocol for larger trials addressing needle distress in HD patients.
Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12621000229875, approved 4 April 2021, https://www.anzctr.org.au/ .
Summary
Anecdotally, chronic oro‐facial pain patients may perceive the painful face area as ‘swollen’. Because there are no clinical signs, these self‐reported ‘illusions’ may represent perceptual ...distortions and can be speculated to contribute to the maintenance of oro‐facial pain. This descriptive study investigated whether chronic oro‐facial pain patients experience perceptual distortions – a kind of body image disruption. Sixty patients were consecutively recruited to fill in questionnaires regarding i) pain experience, ii) self‐reports of perceptual distortion and iii) psychological condition. Perceptual distortions were examined in the total group and in three diagnostic subgroups: i) painful post‐traumatic trigeminal neuropathy (PPTN), ii) painful temporomandibular disorder (TMD) or iii) persistent idiopathic facial pain (PIFP). A large proportion of oro‐facial pain patients reported perceptual distortions of the face (55·0%). In the diagnostic subgroups, perceptual distortions were most pronounced in PPTN patients (81·5%) but with no significant group differences. In the total group of chronic oro‐facial pain patients, the present pain intensity explained 16·9% of the variance in magnitude of the perceptual distortions (R2 = 16·9, F(31) = 6·3, P = 0·017). This study demonstrates that many chronic oro‐facial pain patients may experience perceptual distortions. Future studies may clarify the mechanisms underlying perceptual distortions, which may point towards new complementary strategies for the management of chronic oro‐facial pain.