Childhood atopic dermatitis is associated with cardiovascular risk factors in young adulthood-A population-based cohort study.

BACKGROUND: Studies have indicated that atopic dermatitis (AD) is associated with an increased risk of cardiovascular disease (CVD). However, data are conflicting. Furthermore, the longitudinal effect of childhood AD on cardiovascular risk factors in young adulthood is less investigated. OBJECTIVES: To assess associations between AD in childhood and CVD risk factors in young adulthood. METHODS: The study encompasses longitudinal data from a population-based birth cohort. Participants with data up to age 24 years were included (n = 2270). The primary outcomes were body mass index (BMI), waist circumference (WC), body fat per cent (BF%) and blood pressure (BP) at 24 years. The secondary outcome was blood lipids. Severe AD was defined as AD in combination with sleep disturbance due to itching. RESULTS: In total, 18.6% (n = 420) had AD at 24 years. Males with AD had higher BMI (ßAdj. 0.81, 95% CI 0.15-1.47), BF% (ßAdj. 1.19, 95% CI 0.09-2.29), systolic BP (ßAdj. 1.92, 95% CI 0.02-3.82), total cholesterol (ßAdj. 0.14, 95% CI 0.00-0.28) and LDL cholesterol (ßAdj. 0.15, 95% CI 0.02-0.27) compared with males without AD. No associations were seen in females. Current AD with prepubertal onset was associated with increased BMI in both males (ßAdj. 0.89, 95% CI 0.11-1.67) and females (ßAdj. 0.72, 95% CI 0.11-1.33). At 24 years, 23.1% (n = 97) of all with AD, had severe disease, which was significantly associated with overweight in both sexes, with BMI (ßAdj. 1.83, 95% CI 0.72-2.94), WC (ßAdj. 4.03, 95% CI 1.54-6.52) and BF% (ßAdj. 2.49, 95% CI 0.60-4.39) in females and with BF% (ßAdj. 2.96, 95% CI 0.23-5.69) in males, compared with peers with mild to moderate AD. CONCLUSION: AD in males appears to be associated with CVD risk factors in young adulthood. The duration and severity of AD seem to be of importance in both sexes.

Prevalence and characteristics of atopic dermatitis among young adult females and males-report from the Swedish population-based study BAMSE.

BACKGROUND: There is limited knowledge regarding prevalence and characteristics of atopic dermatitis (AD) among young adults in the general population. OBJECTIVES: To study AD among young adults in a Swedish population-based birth cohort, with a particular focus on prevalence, sex differences including risk for AD at different ages, disease course and characteristics of AD at 24 years. METHODS: The BAMSE cohort includes 4089 individuals who have been followed regularly from birth to age 24 years regarding AD and atopic diseases. For this study 3055 individuals who answered questions regarding AD at the 24-year follow-up were included. All were invited to a clinical examination including skin examination, evaluation by William's criteria and collection of blood for analysis of specific IgE, and 2264 individuals chose to participate. RESULTS: At 24 years, the 12-month prevalence of AD was 17.8% and more females than males had AD (20.5% vs. 14.8%), P < 0.0001. The point prevalence of ongoing AD at clinical examination was 8.0%. AD severity as assessed by Patient-Oriented Eczema Measure (POEM) did not differ between sexes. The proportion of adult onset of AD was 16.9% (92 of 543), females 17.3% vs. males 16.4%. More females than males with AD at 24 years reported disturbed sleep due to itch (26.1% vs. 15.5%, P < 0.003). IgE sensitization was less common among females with AD than males with AD (61.3% vs. 79.6%, P < 0.0001). In addition, male sex (female sex being the reference) was associated with increased odds for AD the first year of life (OR: 1.31, 95% CI; 1.10-1.56), and decreased odds of AD in adolescence and young adulthood (OR: 0.66, 95% CI; 0.55-0.80). CONCLUSIONS: Atopic dermatitis is a common disease among young adults, and even though more females than males have AD at 24 years, adult onset of AD seems to be equally prevalent among both sexes in young adulthood.

Important research outcomes for treatment studies of perinatal depression: systematic overview and development of a core outcome set.

OBJECTIVE: To develop a Core Outcome Set (COS) for treatment of perinatal depression. DESIGN: Systematic overview of outcomes reported in the literature and consensus development study. SETTING: International. POPULATION: Two hundred and twenty-two participants, mainly patients, healthcare professionals and researchers, representing 13 countries. METHODS: A systematic overview of outcomes reported in recently published research, a two-round Delphi survey and a consensus meeting at which the final COS was decided using modified nominal group technique. MAIN RESULTS: In the literature search, 1772 abstracts were identified and evaluated, and 165 studies were finally included in the review. In all, 106 outcomes were identified and included in the Delphi survey. In all, 222 participants registered for the first round of the Delphi survey and 151 (68%) responded. In the second round, 123 (55%) participants responded. Thirteen participants attended the consensus meeting, where the following nine outcomes were agreed upon for inclusion in the final COS: self-assessed symptoms of depression, diagnosis of depression by a clinician, parent to infant bonding, self-assessed symptoms of anxiety, quality of life, satisfaction with intervention, suicidal thoughts, attempted or committed suicide, thoughts of harming the baby, and adverse events. CONCLUSIONS: The relevant stakeholders prioritised outcomes and reached consensus on a COS comprising nine outcomes. We expect that this COS will contribute to the consistency and uniformity of outcome selection and reporting in future clinical trials involving treatment of perinatal depression. TWEETABLE ABSTRACT: Development of a core outcome set regarding treatment for perinatal depression by @SBU_en.

Polycystic ovary syndrome and risk of stillbirth: a nationwide register-based study.

OBJECTIVE: To investigate whether polycystic ovary syndrome (PCOS) is associated with increased risk of stillbirth and whether any such association is linked to PCOS with a severe hyperandrogenic profile. DESIGN: Nationwide register-based cohort study. SETTING: Sweden. POPULATION: The cohort consisted of women giving birth to singleton infants in 1997-2015. All women with a diagnosis of PCOS in the period 1997-2017 and a randomly selected reference group of women without PCOS diagnosis were included. PCOS with a severe hyperandrogenic profile was defined as a PCOS diagnosis with at least two dispensations of prescribed anti-androgens during 2005-2017. METHODS: The risk of stillbirth in women with PCOS was estimated through multiple logistic regression, using women without PCOS as a reference. Risks were expressed as adjusted odds ratios (aORs) with 95% confidence intervals (95% CIs), adjusted for maternal age, parity, body mass index, type-1 diabetes, educational level and country of birth. MAIN OUTCOME MEASURES: Stillbirth, at ≥22 weeks of gestation in 2008-2015 and at ≥28 weeks of gestation in 1997-2007. RESULTS: Compared with women without PCOS (n = 241 750), women with PCOS (n = 41 851) had a 50% increased risk of stillbirth (aOR 1.50, 95% CI 1.28-1.77). The incidence of stillbirth in women with PCOS was particularly increased at term. Women with PCOS and a severe hyperandrogenic profile (n = 13 713) did not have a stronger association with stillbirth than women with PCOS who did not have such a profile. CONCLUSIONS: PCOS is associated with stillbirth and should be considered as a possible risk factor in antenatal care. Further research is warranted to investigate possible causal mechanisms. TWEETABLE ABSTRACT: Women with PCOS have increased risk of stillbirth, and the incidence is particularly increased at term.

Weight of salivary gland ultrasonography compared to other items of the 2016 ACR/EULAR classification criteria for Primary Sjögren's syndrome.

OBJECTIVE: Major salivary gland ultrasonography (SGUS) is widely used for the diagnosis of primary Sjögren's syndrome (pSS). Our objective was to assess the contribution of SGUS compared to other items of the 2016 ACR/EULAR pSS classification criteria, based on expert opinion. METHODS: A secure web-based relational database was used by 24 experts from 14 countries to assess 512 realistic vignettes developed from data of patients with suspected pSS. Each vignette provided classification criteria items and information on history, clinical symptoms and SGUS findings. Each expert assessed 64 vignettes, and each vignette was assessed by 3 experts. A diagnosis of pSS was defined according to at least 2 of 3 experts. Validation was performed in the independent French DiapSS cohort of patients with suspected pSS. RESULTS: A criteria-based pSS diagnosis and SGUS findings were independently associated with an expert diagnosis of pSS (P < 0.001). The derived diagnostic weights of individual items in the 2016 ACR/EULAR criteria including SGUS were as follows: anti-SSA, 3; focus score ≥ 1, 3; SGUS score ≥ 2, 1; positive Schirmer's test, 1; dry mouth, 1; and salivary flow rate < 0.1 mL/min, 1. The corrected C statistic area under the curve for the new weighted score was 0.96. Adding SGUS improves the sensitivity from 90.2 % to 95.6% with a quite similar specificity 84.1% versus 82.6%. Results were similar in the DiapSS cohort: adding SGUS improves the sensitivity from 87% to 93%. CONCLUSION: SGUS had similar weight compared to minor items, and its addition improves the performance of the 2016 ACR/EULAR classification criteria.

Peptidylarginine deiminase 4 (PAD4) activity in early rheumatoid arthritis.

Objectives: Peptidylarginine deiminases (PADs) are a family of calcium-dependent enzymes catalysing the conversion of arginine residues to citrulline, which may constitute a risk factor in rheumatoid arthritis (RA) pathogenesis. We investigated PAD activation by serum (PADAct) in early RA, and the associations between PAD activation and disease characteristics, treatment response, and progression of radiographic damage.Method: Sera from disease-modifying anti-rheumatic drug (DMARD)-naïve early RA patients (n = 225), classified according to the 2010 American College of Rheumatology/European League Against Rheumatism criteria, and healthy controls (n = 63) were analysed for PAD4 activating capacity at 0, 3, 12, and 24 months using a high-performance liquid chromatography fluorometric method. Associations for PADAct were evaluated by Mann-Whitney U and chi-squared tests. Changes in PADAct levels were compared using the Wilcoxon signed-rank test.Results: PADAct positivity occurred in 42% (n = 95) of the patients and was more prevalent in anti-citrullinated protein antibody (ACPA)-positive vs ACPA-negative patients (47% vs 20%, p = 0.002), but not in rheumatoid factor (RF)-positive vs RF-negative patients (44% vs 38%, p = 0.49). PADAct-positive were younger than PADAct-negative patients [mean ± sd 48.7 ± 13.5 vs 53.2 ± 13.7 years, p = 0.011]. Median [25th, 75th percentile] PADAct levels were higher in patients than in controls (8768 [7491, 11 393] vs 7046 [6347, 7906], p < 0.0001) and decreased after initiation of DMARD treatment, but were not associated with treatment response or progression of radiographic damage after 2 years of follow-up.Conclusion: Serum capacity to activate PAD4 was associated with ACPA and RF positivity and earlier disease onset in early RA patients, and decreased after initiation of DMARD treatment, indicating that anti-PAD treatment could potentially be beneficial in RA.

Abdominal adhesions in gynaecologic surgery after caesarean section: a longitudinal population-based register study.

OBJECTIVE: The aim of the study was to evaluate the association between abdominal adhesions at the time of gynaecologic surgery and a history of caesarean delivery, and to investigate obstetric factors contributing to adhesion formation after caesarean section (CS). DESIGN: Longitudinal population-based register study. SETTING: Sweden. POPULATION: Women undergoing benign hysterectomy and/or adnexal surgery in Sweden, 2000-2014, with a previous delivery during 1973-2013 (n = 15 479). METHODS: Information about abdominal adhesions during gynaecological surgery, prior medical history, pregnancies and deliveries were retrieved from Swedish National Health and Quality registers. MAIN OUTCOME MEASURES: Adhesions. RESULTS: In women with previous CS, adhesions were present in 37%, compared with 10% of women with no previous CS [odds ratio (OR): 5.18, 95% confidence interval (CI): 4.70-5.71]. Adhesions increased with the number of caesarean sections: 32% after one CS; 42% after two CS and 59% after three or more CS (P < 0.001). Regardless of the number of CS, factors at CS such as age ≥35 years (aOR: 1.28, 95% CI: 1.05-1.55), body mass index (BMI) ≥30 [adjusted OR (aOR): 1.91, 95% CI: 1.49-2.45] and postpartum infection (aOR: 1.55, 95% CI: 1.05-2.30) increased the risk of adhesions. CONCLUSIONS: Presence of adhesions in abdominal gynaecological surgery is associated with women's personal history of caesarean delivery. The number of caesarean sections was the important predictor of adhesions; advanced age, obesity and postpartum infection further increased the incidence. TWEETABLE ABSTRACT: Repeat caesarean, age, obesity and infection increased the risk of pelvic adhesions after caesarean section.

Accuracy of the Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity score and the Nottingham risk score in hip fracture patients in Sweden - A prospective observational study.

BACKGROUND: Little is known about accuracy of common risk prediction scores in elderly patients suffering from hip fractures. The objective of this study was to investigate accuracy of the Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) score, Portsmouth-POSSUM (P-POSSUM) score and the Nottingham Hip Fracture Score (NHFS) for prediction of mortality and morbidity in this patient group. METHODS: This was a prospective single centre observational study on 997 patients suffering out-of-hospital cervical, trochanteric or subtrochanteric fracture of the neck of the femur. Calibration and discrimination was assessed by calculating the ratio of observed to expected events (O:E) and areas under receiver operating characteristics curves (ROC). RESULTS: The 30-day mortality was 6.2% and complications, as defined by POSSUM, occurred in 41% of the patients. Overall O:E ratios for POSSUM, P-POSSUM and NHFS scores for 30-day mortality were 0.90, 0.98, and 0.79 respectively. The models underestimated mortality in the lower risk bands and overestimated mortality in the higher risk bands. In contrast, POSSUM predicted morbidity well with O:E ratios close to unity in most risk bands. The areas under the ROC curves for the scoring systems was 0.60-0.67. CONCLUSION: The POSSUM score and NHFS show moderate calibration and poor discrimination in this cohort. The results suggest that mortality and morbidity in hip fracture patients are largely dependent on factors that are not included in these scores.

Near Infrared Spectroscopy as a Predictor for Shunt Requirement During Carotid Endarterectomy.

OBJECTIVE/BACKGROUND: Near infrared spectroscopy (NIRS) continuously monitors regional cerebral oxygenation (rSO2) in the frontal lobes. This method may be used in patients during carotid endarterectomy to indicate the need for shunting. The aim of the study was to evaluate the value of NIRS in determining the need for selective shunting during CEA. A secondary aim was to compare NIRS with stump pressure. METHODS: Between January 2013 and October 2016, 185 patients from two vascular units, undergoing CEA under local anaesthesia were prospectively included. All patients gave informed consent to participate; there were no exclusion criteria. A Foresight® oximeter was used for rSO2 measurement, which was compared with stump pressure. Receiver operating characteristic curve analysis was used to identify optimal cutoff points, and sensitivity, specificity, and positive and negative predictive values were calculated. RESULTS: Twenty patients (10.8%) developed neurological symptoms during clamping. Mean stump pressure was lower in the group that developed neurological symptoms than in the group who did not (34 ± 19 mmHg vs. 55 ± 17 mmHg [p < . 01]). Corresponding NIRS results for the decrease in rSO2 on the ipsilateral side was 15 ± 7% versus 4 ± 6% (p < .01). Using stump pressure ≤50 mmHg as cutoff value for predicting symptoms, the sensitivity was 85% (95% confidence interval [CI] 64-95) and specificity 54% (95% CI 46-61). With a relative decrease in NIRS saturation (ΔrSO2) of 9%, sensitivity was 95% (95% CI 76-99), and specificity 81% (95% CI 74-86) to predict ischaemic symptoms during carotid clamping. Neurological deterioration during carotid clamping was detected in one patient with a relative decrease in rSO2 of <9% compared with three patients with a stump pressure >50 mmHg. CONCLUSION: NIRS allows continuous non-invasive monitoring of cerebral oxygenation during CEA, with high sensitivity and acceptable specificity in predicting cerebral ischaemia and the need for shunting, which makes it an attractive alternative to stump pressure.

Biochemical markers in vascular cognitive impairment associated with subcortical small vessel disease - A consensus report.

BACKGROUND: Vascular cognitive impairment (VCI) is a heterogeneous entity with multiple aetiologies, all linked to underlying vascular disease. Among these, VCI related to subcortical small vessel disease (SSVD) is emerging as a major homogeneous subtype. Its progressive course raises the need for biomarker identification and/or development for adequate therapeutic interventions to be tested. In order to shed light in the current status on biochemical markers for VCI-SSVD, experts in field reviewed the recent evidence and literature data. METHOD: The group conducted a comprehensive search on Medline, PubMed and Embase databases for studies published until 15.01.2017. The proposal on current status of biochemical markers in VCI-SSVD was reviewed by all co-authors and the draft was repeatedly circulated and discussed before it was finalized. RESULTS: This review identifies a large number of biochemical markers derived from CSF and blood. There is a considerable overlap of VCI-SSVD clinical symptoms with those of Alzheimer's disease (AD). Although most of the published studies are small and their findings remain to be replicated in larger cohorts, several biomarkers have shown promise in separating VCI-SSVD from AD. These promising biomarkers are closely linked to underlying SSVD pathophysiology, namely disruption of blood-CSF and blood-brain barriers (BCB-BBB) and breakdown of white matter myelinated fibres and extracellular matrix, as well as blood and brain inflammation. The leading biomarker candidates are: elevated CSF/blood albumin ratio, which reflects BCB/BBB disruption; altered CSF matrix metalloproteinases, reflecting extracellular matrix breakdown; CSF neurofilment as a marker of axonal damage, and possibly blood inflammatory cytokines and adhesion molecules. The suggested SSVD biomarker deviations contrasts the characteristic CSF profile in AD, i.e. depletion of amyloid beta peptide and increased phosphorylated and total tau. CONCLUSIONS: Combining SSVD and AD biomarkers may provide a powerful tool to identify with greater precision appropriate patients for clinical trials of more homogeneous dementia populations. Thereby, biomarkers might promote therapeutic progress not only in VCI-SSVD, but also in AD.

Post-traumatic stress symptoms in Swedish obstetricians and midwives after severe obstetric events: a cross-sectional retrospective survey.

OBJECTIVE: To examine post-traumatic stress reactions among obstetricians and midwives, experiences of support and professional consequences after severe events in the labour ward. DESIGN: Cross-sectional online survey from January 7 to March 10, 2014. POPULATION: Members of the Swedish Society of Obstetrics and Gynaecology and the Swedish Association of Midwives. METHODS: Potentially traumatic events were defined as: the child died or was severely injured during delivery; maternal near-miss; maternal mortality; and other events such as violence or threat. The validated Screen Questionnaire Posttraumatic Stress Disorder (SQ-PTSD), based on DSM-IV (1994) 4th edition, was used to assess partial post-traumatic stress disorder (PTSD) and probable PTSD. MAIN OUTCOME MEASURES: Partial or probable PTSD. RESULTS: The response rate was 47% for obstetricians (n = 706) and 40% (n = 1459) for midwives. Eighty-four percent of the obstetricians and 71% of the midwives reported experiencing at least one severe event on the delivery ward. Fifteen percent of both professions reported symptoms indicative of partial PTSD, whereas 7% of the obstetricians and 5% of the midwives indicated symptoms fulfilling PTSD criteria. Having experienced emotions of guilt or perceived insufficient support from friends predicted a higher risk of suffering from partial or probable PTSD. Obstetricians and midwives with partial PTSD symptoms chose to change their work to outpatient care significantly more often than colleagues without these symptoms. CONCLUSIONS: A substantial proportion of obstetricians and midwives reported symptoms of partial or probable PTSD after severe traumatic events experienced on the labour ward. Support and resilience training could avoid suffering and consequences for professional carers. TWEETABLE ABSTRACT: In a survey 15% of Swedish obstetricians and midwives reported PTSD symptoms after their worst obstetric event.

Low Protein A20 in Minor Salivary Glands is Associated with Lymphoma in Primary Sjögren's Syndrome.

Patients with primary Sjögren's syndrome (pSS) have an increased risk of developing lymphomas, particularly the subtype mucosa-associated lymphoid tissue (MALT) lymphoma. Chronic antigen stimulation and increased activation of nuclear factor-κB (NF-κB) are important factors for the pathogenesis of MALT lymphomas. Protein A20 is an inhibitor of NF-κB. A recent study of pSS-associated MALT lymphomas identified potential functional abnormalities in the TNFAIP3 gene, which encodes protein A20. The present study aimed to assess protein A20 by immunohistochemistry (IHC) in minor salivary glands (MSGs) and lymphoma tissue sections of patients with pSS and investigate a potential association with lymphoma development. Protein A20 staining in lymphocytes was scored in four categories (0 = negative, 1 = weak, 2 = moderate and 3 = strong). For statistical purposes, these scores were simplified into negative (scores 0-1) and positive (scores 2-3). We investigated associations between protein A20-staining, focus scores, germinal centre (GC)-like structures and monoclonal B-cell infiltration in MSGs. MSG protein A20 staining was weaker in pSS patients with lymphomas than in those without lymphomas (P = 0.01). Weak protein A20 staining was also highly associated with a lack of GC formation (P < 0.01). Finally, weaker A20 staining was observed in the majority of pSS-associated MALT lymphoma tissues. In conclusion, we found absent or weak protein A20 immunoreactivity in MSGs of patients with pSS with lymphomas. This finding indicates that protein A20 downregulation in lymphocytes might be a mechanism underlying lymphoma genesis in patients with pSS.

Discrepancy in compliance between the clinical and genetic diagnosis of choroidal hypoplasia in Danish Rough Collies and Shetland Sheepdogs.

Collie eye anomaly (CEA) is a congenital, inherited ocular disorder which is widespread in herding breeds. Clinically, the two major lesions associated with CEA are choroidal hypoplasia (CH) and coloboma, and both lesions are diagnosed based on ophthalmological examination. A 7.8-kb intronic deletion in the gene encoding non-homologous end-joining factor 1 (NHEJ1) has been reported to be the causative mutation underlying CH when present in the homozygous state. In this study, we have investigated the compliance between the clinical and genetic diagnosis of CH in the Danish Rough Collie and Shetland Sheepdog populations. Our results show that the deletion in NHEJ1 is not predictive for CH in the Danish Rough Collie population, whereas the clinical and genetic diagnosis is in accordance with each other in the Shetland Sheepdog population. Based on these results, it can be concluded that the intronic deletion in NHEJ1 is not the causative mutation but, rather, a marker linked to the locus underlying the trait in some populations but linked to both the wild-type and CH-causing locus in most dogs in the Danish Rough Collie population.

Peri-procedural Risk with Urgent Carotid Artery Stenting: A Population based Swedvasc Study.

OBJECTIVES: Current European Society for Vascular Surgery guidelines recommend that patients with a symptomatic carotid stenosis should be operated on within 14 days of onset of symptoms. Recent reports indicate that carotid endarterectomy (CEA) within 2 days of a neurological event may be associated with a higher peri-procedural risk of stroke. Whether urgent carotid artery stenting (CAS) carries a similar high risk is unclear. The aim of this study was to analyze if urgent CAS increases the peri-procedural risks. METHODS: Retrospective analysis of all CAS registered in Swedvasc, a validated nationwide registry, between January 1, 2005, and March 20, 2014. Only symptomatic patients treated for a stenosis of the internal carotid artery were included. Patients were categorized according to time from index event to surgery; 0-2 days, 3-7 days, 8-14 days, and 15-180 days. Primary outcome was 30 day combined stroke and death rate. RESULTS: 323 patients underwent CAS for symptomatic carotid artery stenosis. The demographic and clinical data were similar in the groups. No procedure related complications or deaths were observed in the urgent CAS group. The 30 day combined stroke and death rate did not differ significantly between the groups; zero of 13 (0%; 95% CI 0-26.6) in the group treated 0-2 days versus four of 85 (4.7%; 95% CI 1.5-11.9), at 3-7 days, five of 80 (6.3%; 95% CI 2.4-14.1) at 8-14 days, and six of 145 (4.1%; 95% CI 1.7-8.9) for the patients treated at 15-180 days (p = .757). Stroke and death were not more frequent for patients treated within 1 week compared with after 1 week: 4 out of 98 (4.1%; 95% CI 1.3-9.0) versus 11/225 (4.9%; 95% CI 2.7-8.6) (p = .751). CONCLUSIONS: In this national registry study, CAS performed within 1 week of the onset of a neurologic event was not associated with an additional risk of a peri-operative complication compared with those treated subsequently.

Long-Term Persistence of an Anxiolytic Drug (Oxazepam) in a Large Freshwater Lake.

Production and human consumption of pharmaceuticals result in contamination of surface waters worldwide. Little is known about the long-term (i.e., over decades) fate of pharmaceuticals in aquatic systems. Here, we show that the most prescribed anxiolytic in Sweden (oxazepam) persists in its therapeutic form for several decades after being deposited in a large freshwater lake. By comparing sediment cores collected in 1995 and 2013, we demonstrate that oxazepam inputs from the early 1970s remained in the sediments until sampling in 2013, despite in situ degradation processes and sediment diagenesis. In laboratory and pond experiments, we further reveal that therapeutic forms of oxazepam can persist over several months in cold (5 °C) lake water free from UV light. We conclude that oxazepam can persist in lakes over a time scale much longer than previously realized and that levels can build up in lakes due to both a legacy of past inputs and a growing urban population.

The risk of uterine rupture is not increased with single- compared with double-layer closure: a Swedish cohort study.

OBJECTIVE: To compare single- with double-layer closure of the uterus for the risk of uterine rupture in women attempting vaginal birth after one prior caesarean delivery. DESIGN: Cohort study. SETTING: Sweden. POPULATION: From a total of 19 604 nulliparous women delivered by caesarean section in the years 2001-2007, 7683 women attempting vaginal birth in their second delivery were analysed. METHODS: Data from population-based registers were linked to hospital-based registers that held data from maternity and delivery records. Logistic regression was used to estimate the risk of uterine rupture after single- or double-layer closure of the uterus. Results are presented as odds ratios (ORs) with 95% confidence intervals (95% CIs). MAIN OUTCOME MEASURE: Uterine rupture. RESULTS: Uterine rupture during labour occurred in 103 (1.3%) women. There was no increased risk of uterine rupture when single- was compared with double-layer closure of the uterus (OR 1.17; 95% CI 0.78-1.76). Maternal factors associated with uterine rupture were: age ≥35 years and height ≤160 cm. Factors from the first delivery associated with uterine rupture in a subsequent delivery were: infection and giving birth to an infant large for gestational age. Risk factors from the second delivery were induction of labour, use of epidural analgesia, and a birthweight of ≥4500 g. CONCLUSIONS: There was no significant difference in the rate of uterine rupture when single-layer closure was compared with double -layer closure of the uterus.

Key roles for MYC, KIT and RET signaling in secondary angiosarcomas.

BACKGROUND: Angiosarcomas may develop as primary tumours of unknown cause or as secondary tumours, most commonly following radiotherapy to the involved field. The different causative agents may be linked to alternate tumorigenesis, which led us to investigate the genetic profiles of morphologically indistinguishable primary and secondary angiosarcomas. METHODS: Whole-genome (18k) c-DNA-mediated annealing, selection, extension and ligation analysis was used to genetically profile 26 primary and 29 secondary angiosarcomas. Key findings were thereafter validated using RT-qPCR, immunohistochemistry and validation of the gene signature to an external data set. RESULTS: In total, 103 genes were significantly deregulated between primary and secondary angiosarcomas. Secondary angiosarcomas showed upregulation of MYC, KIT and RET and downregulation of CDKN2C. Functional annotation analysis identified multiple target genes in the receptor protein tyrosine kinase pathway. The results were validated using RT-qPCR and immunohistochemistry. Further, the gene signature was applied to an external data set and, herein, distinguished primary from secondary angiosarcomas. CONCLUSIONS: Upregulation of MYC, KIT and RET and downregulation of CDKN2C characterise secondary angiosarcoma, which implies possibilities for diagnostic application and a mechanistic basis for therapeutic evaluation of RET-kinase-inhibitors in these highly aggressive tumours.

Effects of grazer presence on genetic structure of a phenotypically diverse diatom population.

Studies of predator-prey systems in both aquatic and terrestrial environments have shown that grazers structure the intraspecific diversity of prey species, given that the prey populations are phenotypically variable. Populations of phytoplankton have traditionally considered comprising only low intraspecific variation, hence selective grazing as a potentially structuring factor of both genetic and phenotypic diversity has not been comprehensively studied. In this study, we compared strain specific growth rates, production of polyunsaturated aldehydes, and chain length of the marine diatom Skeletonema marinoi in both grazer and non-grazer conditions by conducting monoclonal experiments. Additionally, a mesocosm experiment was performed with multiclonal experimental S. marinoi populations exposed to grazers at different levels of copepod concentration to test effects of grazer presence on diatom diversity in close to natural conditions. Our results show that distinct genotypes of a geographically restricted population exhibit variable phenotypic traits relevant to grazing interactions such as chain length and growth rates. Grazer presence affected clonal richness and evenness of multiclonal Skeletonema populations in the mesocosms, likely in conjunction with intrinsic interactions among the diatom strains. Only the production of polyunsaturated aldehydes was not affected by grazer presence. Our findings suggest that grazing can be an important factor structuring diatom population diversity in the sea and emphasize the importance of considering clonal differences when characterizing species and their role in nature.

Experiences of living with asthma - a focus group study with adolescents and parents of children with asthma.

OBJECTIVE: The goal for asthma treatment is that every individual, so far as possible, shall live without symptoms and exacerbations. Patients and health care professionals sometimes have different perceptions of what is important for achieving good quality of life. This work aims to describe the experiences among adolescents as well as those of parents with young children living with asthma. METHODS: Four focus group interviews were performed, two with parents of young children and two with adolescents. The data were qualitatively analyzed, using Systematic Text Condensation. RESULT: Three themes relevant to the participants' experiences of living with asthma were presented; strategies, frustrations and expectations. The adolescents wanted to be like their peers and developed their own strategies for self-management of asthma, which included not always taking medication as prescribed. The parents emphasized frustration regarding not being believed, lack of understanding feelings of loneliness, or anxiety. One identified expectation was that the participants wanted to be met with competence and understanding in asthma care from health care professionals. Another expectation expressed among parents was that teachers in nursery and primary schools should have more knowledge and understanding on how to care for children with asthma. CONCLUSION: Living with asthma leads to developing personal strategies in self-management of asthma. Moreover both parents and adolescents had expectations of being met by competent and understanding health care professionals. Developing a partnership between patients and health care professionals could be a successful way to improve the care of patients with asthma.

Ecotoxicological evaluation of poly(epsilon-caprolactone) nanocapsules containing triazine herbicides.

The triazine class of herbicides includes the compounds ametryn, atrazine, and simazine, which are used to control weeds in plantations of crops such as maize, sorghum, and sugar cane. Despite their acceptance in agriculture, these herbicides can be dangerous to the environment, depending on their toxicity, the degree of contamination, and the duration of exposure. Controlled release systems are increasingly used to mitigate problems of toxicity and minimize environmental impacts, and can also increase herbicide efficiency. The objective of this work was to prepare poly(epsilon-caprolactone) nanocapsules containing ametryn and atrazine, and evaluate their toxicity to aquatic organisms as well as in cytogenetic tests employing human lymphocyte cultures. The PCL nanocapsules were prepared according to the interfacial deposition of pre-formed polymer method. Ecotoxicological assays were performed with the alga Pseudokirchneriella subcapitata and the microcrustacean Daphnia similis. The cytogenetic tests consisted of observing mitotic index alterations after exposing lymphocyte cell cultures to different formulations. Encapsulation of the herbicides in the nanocapsules resulted in lower toxicity to the alga and higher toxicity to the microcrustacean, compared to the herbicides alone. The cytogenetic tests showed that formulations of nanocapsules containing the herbicides were less toxic than the herbicides alone. The findings indicate the potential of the nanocapsule formulations in agricultural applications, where they could help to reduce the quantities of herbicides used as well as impacts on the environment and human health.