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The aim of this study was to quantify the physiological workload of manual laborers in industrial sugarcane and assess the effect of receiving a rest, shade, and hydration intervention to reduce heat stress exposure risk.In an observational study, physiological workload was evaluated for burned cane cutters (BCC), seed cutters (SC) and drip irrigation repair workers (DIRW) using heart rate (HR) recorded continuously (Polar®) across a work shift. Workers' percentage of maximal HR (%HRA total of 162 workers participated in this study [52 BCC (all male), 71 SC (13 female) and 39 DIRW (16 female)]. Average %HRmax across a work shift was similar between BCC and SC (BCC: 58%, SC: 59%), but lower in DIRW (51%). BCC and SC spent similar proportions of work shifts at hard/very hard intensities (BCC: 13%, SC: 15%), versus DIRW who worked mostly at light (46%) or light-moderate (39%) intensities. SC maximum ECTemp reached 38.2°C, BCC 38.1°C; while DIRW only reached 37.7°C. Females performed at a higher %HRIn this setting, BCC and SC both undertake very physiologically demanding work. Females maintained a higher workload than male co-workers. Regulated rest periods each hour, with water and shade access, appears to reduce physiological workload/strain.

Ornithine transcarbamylase deficiency (OTCD) is a monogenic disease of ammonia metabolism in hepatocytes. Severe disease is frequently treated by orthotopic liver transplantation. An attractive approach is the correction of a patient's own cells to regenerate the liver with gene-repaired hepatocytes. This study investigates the efficacy and safety of ex vivo correction of primary human hepatocytes. Hepatocytes isolated from an OTCD patient were genetically corrected ex vivo, through the deletion of a mutant intronic splicing site achieving editing efficiencies >60% and the restoration of the urea cycle in vitro. The corrected hepatocytes were transplanted into the liver of FRGN mice and repopulated to high levels (>80%). Animals transplanted and liver repopulated with genetically edited patient hepatocytes displayed normal ammonia, enhanced clearance of an ammonia challenge and OTC enzyme activity, as well as lower urinary orotic acid when compared to mice repopulated with unedited patient hepatocytes. Gene expression was shown to be similar between mice transplanted with unedited or edited patient hepatocytes. Finally, a genome-wide screening by performing CIRCLE-seq and deep sequencing of >70 potential off-targets revealed no unspecific editing. Overall analysis of disease phenotype, gene expression, and possible off-target editing indicated that the gene editing of a severe genetic liver disease was safe and effective.

Objective This study aimed to quantify the risk of COVID-19-related hospital admission in spouses living with partners in at-risk occupations in Denmark during 2020–21.Methods Within a registry-based cohort of all Danish employees (N=2 451 542), we identified cohabiting couples, in which at least one member (spouse) held a job that according to a job exposure matrix entailed low risk of occupational exposure to SARS-CoV-2 (N=192 807 employees, 316 COVID-19 hospital admissions). Risk of COVID-19-related hospital admission in such spouses was assessed according to whether their partners were in jobs with low, intermediate or high risk for infection. Overall and sex-specific incidence rate ratios (IRR) of COVID-19-related hospital admission were computed by Poisson regression with adjustment for relevant covariates.Results The risk of COVID-19-related hospital admission was increased among spouses with partners in high-risk occupations [adjusted IRR (IRRadj)1.59, 95% confidence interval (CI) 1.1–2.2], but not intermediate-risk occupations (IRRadj 0.97 95% 0.8–1.3). IRR for having a partner in a high-risk job was elevated during the first three pandemic waves but not in the fourth (IRRadj 0.48 95% CI 0.2–1.5). Sex did not modify the risk of hospital admission.Conclusions SARS-CoV-2 transmission at the workplace may pose an increased risk of severe COVID-19 among spouses in low-risk jobs living with partners in high-risk jobs, which emphasizes the need for preventive measures at the workplace in future outbreaks of epidemic contagious disease. When available, effective vaccines seem essential. OBJECTIVE: This study aimed to quantify the risk of COVID-19-related hospital admission in spouses living with partners in at-risk occupations in Denmark during 2020-21.METHODS: Within a registry-based cohort of all Danish employees (N=2 451 542), we identified cohabiting couples, in which at least one member (spouse) held a job that according to a job exposure matrix entailed low risk of occupational exposure to SARS-CoV-2 (N=192 807 employees, 316 COVID-19 hospital admissions). Risk of COVID-19-related hospital admission in such spouses was assessed according to whether their partners were in jobs with low, intermediate or high risk for infection. Overall and sex-specific incidence rate ratios (IRR) of COVID-19-related hospital admission were computed by Poisson regression with adjustment for relevant covariates.RESULTS: The risk of COVID-19-related hospital admission was increased among spouses with partners in high-risk occupations [adjusted IRR (IRRadj)1.59, 95% confidence interval (CI) 1.1-2.2], but not intermediate-risk occupations (IRRadj 0.97 95% 0.8-1.3). IRR for having a partner in a high-risk job was elevated during the first three pandemic waves but not in the fourth (IRRadj 0.48 95% CI 0.2-1.5). Sex did not modify the risk of hospital admission.CONCLUSIONS: SARS-CoV-2 transmission at the workplace may pose an increased risk of severe COVID-19 among spouses in low-risk jobs living with partners in high-risk jobs, which emphasizes the need for preventive measures at the workplace in future outbreaks of epidemic contagious disease. When available, effective vaccines seem essential.

Objective Long-term effects of ADHD medication on cognitive functions are not well known. This study investigates development of cognitive functions and ADHD symptoms on well-controlled medication for 1 year in children and adolescents. Study design This study is part of an ongoing open uncontrolled trial of long-term medication for ADHD in children and adolescents aged 6–18 years with any form of ADHD, and frequently comorbid autism spectrum disorder (ASD, 29%) or autistic traits (24%). Other comorbidities were oppositional defiant disorder, dyslexia/language disorder, borderline intellectual functioning, developmental coordination disorder. This analysis includes 87 participants (61 boys, 26 girls) who completed Wechsler tests at baseline and after 12 months. ADHD symptoms were investigator-rated on the ADHD Rating Scale-IV at the same time points. Results The whole group of children and adolescents showed significant improvements in Wechsler Full Scale IQ (FSIQ, mean at baseline 92.6, at 12 months 97.95), and on the Index Scales Verbal Comprehension, Working Memory and Processing Speed, after one year of well-controlled ADHD medication. Comorbid dyslexia/language impairment predicted a larger rise in FSIQ, but not gender, ADHD presentation or comorbid ASD. Robust improvements in ADHD symptoms were observed (mean ADHD-Rating Scale score at baseline 34.6, and at 12 months 18.3). Conclusions Cognitive test scores and ADHD symptoms were improved on well-controlled medication for 1 year in children and adolescents with ADHD, autism and other comorbidities. The main study limitation is the open uncontrolled trial design.

The aim of this study was to evaluate chronic pain 1 year after surgery, and risk factors for chronic pain after groin hernia repair in women.Groin hernia surgery in women is less frequently studied than in men. Chronic pain is common after groin hernia surgery and remains an important area with room for improvement. Previous studies are small or inconclusive. Guidelines recommend timely repair of all female groin hernias.From the Swedish Hernia Register 4021 female and 37,542 male patients operated between September 1, 2012 and August 30, 2017 responded to a patient-reported outcome questionnaire (response rate 70.0%) 1 year after primary groin hernia surgery. Multivariable analysis was performed to compare chronic postoperative pain in women with men as a control group, and to evaluate risk factors for chronic pain in women.Among women operated for groin hernia, 18% suffered chronic postoperative pain. The risk for chronic pain was significantly higher for women [odds ratio 1.3 (95% confidence interval 1.16-1.46). Three risk factors for chronic pain in women were found: high body mass index, high American Society of Anesthesiologists classification, and femoral hernia. No differences in chronic pain in women were seen when comparing surgical methods or emergency versus elective surgery.Almost one-fifth of women suffered of chronic pain affecting daily activity after groin hernia repair. Chronic pain was more common for women than men. In view of the high-rate chronic postoperative pain, further research on management strategies in female groin hernia is warranted.

Objective:Effective infection prevention and control (IPC) measures are key for protecting patients from nosocomial infections and require knowledge of transmission mechanisms in different settings. We performed a detailed outbreak analysis of the transmission and outcome of coronavirus disease 2019 (COVID-19) in a geriatric ward by combining whole-genome sequencing (WGS) with epidemiological data.Design:Retrospective cohort study.Setting:Tertiary-care hospital.Participants:Patients and healthcare workers (HCWs) from the ward with a nasopharyngeal sample (NPS) positive for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) RNA during the outbreak period.Methods:Patient data regarding clinical characteristics, exposure and outcome were collected retrospectively from medical records. Stored NPSs from 32 patients and 15 HCWs were selected for WGS and phylogenetic analysis.Results:The median patient age was 84 years and 17 (53%) of 32 were male. Also, 14 patients (44%) died within 30 days of sampling. Viral loads were significantly higher among the deceased. WGS was successful in 28 (88%) of 32 patient samples and 14 (93%) of 15 HCW samples. Moreover, 3 separate viral clades were identified: 1 clade and 2 subclades among both patient and HCW samples. Integrated epidemiological and genetic analyses revealed 6 probable transmission events between patients and supported hospital-acquired COVID-19 among 25 of 32 patients.Conclusions:WGS provided an insight into the outbreak dynamics and true extent of nosocomial COVID-19. The extensive transmission between patients and HCWs indicated that current IPC measures were insufficient. We recommend increased use of WGS in outbreak investigations to identify otherwise unknown transmission links and to evaluate IPC measures.

Aim To describe the structure and content of telephone support calls between mothers of preterm infants and support team members after hospital discharge. Design This is a qualitative study. Methods Data consisted of 19 recordings of telephone calls that occurred between March 2013 and December 2015. The calls were made by support team members to mothers within two weeks of discharge from the neonatal unit. Analyses were performed using content analysis. Results One category referred to what the support team members said that facilitated or did not facilitate the conversation. It was found that the support team members managed to have conversations that were tailored to the mother's current needs and conversations where the focus was on what the support team members thought was important. A second category referred to the topics the mothers talked about and that the mothers expressed both negative and positive feelings.

Long-term data on neurological and radiological outcome after aneurysmal subarachnoid hemorrhage (aSAH) are scarce. The aim of this study was to report neurological and radiological outcome15 years after aSAH.Patients with aSAH who were randomly assigned to endovascular treatment (EVT) or microsurgical treatment (MST) during 1997-2001 were included. Main end points were neurological outcome assessed by modified Rankin Scale, fatigue assessed by mental fatigue scale, and radiological outcome assessed by magnetic resonance angiography. Results for mental fatigue scale were compared with a control group.After 15-21 years, 46 (62.2%) of the 74 survivors replied to a questionnaire. Of these patients, 18 received MST, and 28 received EVT. Modified Rankin Scale score of 0-2 was found in 100% of patients in the EVT group and 88.8% of patients in the MST group. Moderate or severe mental fatigue was found in 7/28 patients (25%) in the EVT group and 7/18 patients (38.8%) in the MST group (P0.05), whereas moderate or severe mental fatigue was observed in 3/34 patients (8.9%) in the control group. Magnetic resonance angiography was performed in 29 patients. In the EVT group, new neck remnants were found in 2/16 patients (12.5%), and de novo aneurysm was found in 2/16 patients (12.5%). In the MST group, de novo aneurysm was found in 1/13 patients (7.7%).Neurological outcome at long-term follow-up after aSAH was good; however, mental fatigue was overrepresented in patients compared with healthy control subjects regardless of treatment modality. Residual or de novo aneurysm was found in 17% of patients warranting radiological long-term follow-up.

The aim of this study was to evaluate effects of person-centred inpatient care on care processes in terms of satisfaction with care and person-centred content in medical records, and to evaluate effects on self-reported health and self-efficacy.Internal medicine inpatient care is complex, covering patients varying in age, medical conditions, health status, and other aspects. There has been limited research on the impact of person-centred care (PCC) on satisfaction with care and health outcomes in internal medicine care environments regardless of diagnosis and care pathway.A quasi-experimental study with pre- and postmeasurements.Adult patients admitted to an internal medicine inpatient unit were consecutively included over 16 weeks in 2014 and 24 weeks in 2015-2016. Data were collected before a person-centred inpatient care intervention (N = 204) and 12 months after the intervention was implemented (N = 177). Data on satisfaction with care and self-reported health were collected at discharge and medical records were reviewed. The intervention included systematically applied person-centred assessment, health plans, and persistent PCC.After the intervention, patients rated higher satisfaction with care regarding essential components of PCC and more patients had received effective pain relief. There were no differences in information on self-care or medications, self-rated health, or self-efficacy.Care focused on the foundations of person-centredness seems to enhance both patients' perceptions of satisfaction and symptom management. Situational aspects such as care pathways should be considered when implementing person-centred inpatient care.CLINICALTRIALS.NCT03725813.目的;: 本研究在于从医疗记录中护理满意度和以人为本的内容方面评估以人为本的住院护理对护理过程的影响,并评估对自我报告式健康和自我效能的影响。 背景;: 内科医学住院护理是复杂的,涵盖不同年龄、医疗条件、健康状况等方面的患者。无论诊断和护理途径如何,关于以人为本型护理(简称为“PCC”)影响内科医学护理环境中护理满意度和健康结果的研究一直有限。 设计: 一项带有前后测量结果的准实验研究。 方法: 2014年和2015至2016年分别连续性16周和24周纳入了内科医学住院患者。在以人为本型住院护理干预前(204例)和干预实施后12个月(177例)收集了数据。出院时收集了关于护理满意度和自我报告式健康的数据,并审查了医疗记录。干预措施包括系统应用性以人为本型评估、健康计划和持续的以人为本型护理。 结果: 干预后,患者对以人为本型护理基本组成部分的护理满意度较高,更多患者获得了有效的疼痛缓解。关于自我护理或药物治疗、自测健康或自我效能的信息之间没有差异。 结论: 注重以人为本理论根据的护理似乎增强了患者对满意度和症状管理的认知。实施以人为本的住院护理时,应考虑护理路径等情境方面。 试验注册: ClinicalTrials.gov,注册号:NCT03725813.

This European consensus statement on essential colposcopy provides standards for the general colposcopist seeing women referred for colposcopy with an abnormal cervical screening test (including cytology and HPV tests) or with a clinically suspicious cervix. The article gives guidance regarding the aims and conduct of colposcopy. Recommendations are provided on colposcopy technique, the management of common colposcopy issues, treatment and follow-up of after treatment of CIN or early stage cervical. Colposcopists should make an informed decision on the management of each individual that is referred and organize appropriate follow-up. Cervical cancer is still a major health issue and the quality of care can only improve if there is a structured guidance for women with an abnormal smear or suspicious cervix. (C) 2020 Published by Elsevier B.V.

Highlights • Male predominance and obesity is commonly found in hospitalized COVID-19 patients. • Chronic kidney disease and previous stroke are independent risk factors for death. • Clinical frailty scale level is the strongest predictor for mortality among older patients., Objectives This study investigated demographics, comorbidities, and death rate in hospitalized patients with confirmed COVID-19. In addition, we hypothesized that functional status, according to the Clinical Frailty Scale (CFS), in patients aged 65 years or older is a better predictor of poor outcome than age and comorbidities. Methods A total of 255 randomly selected COVID-19 patients admitted to a university hospital were included and followed up for 60 days. Patient data were extracted manually from the electronic health records with use of a standardized protocol. Results The age of the study population ranged between 20 and 103 years (mean age 66 years ± 17 years). Hypertension, diabetes mellitus, and obesity were the three most prevalent comorbidities. At the 60-day follow-up, 70 patients (27%) had died. In multivariate analyses, age, chronic kidney disease, and previous stroke were associated with death. Most fatal cases (90%) occurred in patients aged 65 years or older. Among such patients, CFS level was the only predictor of death in multivariate analyses. Conclusions This study shows that increasing age, chronic kidney disease, and previous stroke significantly contribute to a fatal outcome in hospitalized patients with COVID-19. In patients aged 65 years or older, CFS level was the strongest prognostic factor for death.

Background The incidence of cutaneous malignant melanoma (CMM) is increasing worldwide. In Sweden, over 4600 cases were diagnosed in 2018. The prognosis after radical surgery varies considerably with tumor stage. In recent years, new treatment options have become available for metastatic CMM. Early onset of treatment seems to improve outcome, which suggests that early detection of recurrent disease should be beneficial. Consequently, in several countries imaging is a part of the routine follow-up program after surgery of high risk CMM. However, imaging has drawbacks, including resources required (costs, personnel, equipment) and the radiation exposure. Furthermore, many patients experience anxiety in waiting for the imaging results and investigations of irrelevant findings is another factor that also could cause worry and lead to decreased quality of life. Hence, the impact of imaging in this setting is important to address and no randomized study has previously been conducted. The Swedish national guidelines stipulate follow-up for 3 years by clinical examinations only. Methods The TRIM study is a prospective randomized multicenter trial evaluating the potential benefit of imaging and blood tests during follow-up after radical surgery for high-risk CMM, compared to clinical examinations only. Primary endpoint is overall survival (OS) at 5 years. Secondary endpoints are survival from diagnosis of relapse and health-related quality of life (HRQoL). Eligible for inclusion are patients radically operated for CMM stage IIB-C or III with sufficient renal function for iv contrast-enhanced CT and who are expected to be fit for treatment in case of recurrence. The planned number of patients is > 1300. Patients are randomized to clinical examinations for 3 years +/− whole-body imaging with CT or FDG-PET/CT and laboratory tests including S100B protein and LDH. This academic study is supported by the Swedish Melanoma Study Group. Discussion This is the first randomized prospective trial on the potential benefit of imaging as a part of the follow-up scheme after radical surgery for high-risk CMM. Results The first patient was recruited in June 2017 and as of April 2020, almost 500 patients had been included at 19 centers in Sweden. Trial registration ClinicalTrials.gov, NCT 03116412. Registered 17 April 2017, https://clinicaltrials.gov/ct2/show/study/NCT03116412

The majority of anti-cancer therapies target the proliferating tumor cells, while the tumor stroma, principally unaffected, survives, and provide a niche for surviving tumor cells. Combining tumor cell and stroma-targeting therapies thus have a potential to improve patient outcome. The neuroblastoma stroma contains cancer-associated fibroblasts expressing microsomal prostaglandin E synthase-1 (mPGES-1). mPGES-1-derived prostaglandin E2 (PGE2 ) is known to promote tumor growth through increased proliferation and survival of tumor cells, immune suppression, angiogenesis, and therapy resistance, and we, therefore, hypothesize that mPGES-1 constitutes an interesting stromal target. Here, we aimed to develop a relevant in vitro model to study combination therapies. Co-culturing of neuroblastoma and fibroblast cells in 3D tumor spheroids mimic neuroblastoma tumors with regard to the cyclooxygenase/mPGES-1/PGE2 pathway. Using the spheroid model, we show that the inhibition of fibroblast-derived mPGES-1 enhanced the cytotoxic effect of doxorubicin and vincristine and significantly reduced tumor cell viability and spheroid growth. Cyclic treatment with vincristine in combination with an mPGES-1 inhibitor abrogated cell repopulation. Moreover, inhibition of mPGES-1 potentiated the cytotoxic effect of vincristine on established neuroblastoma allografts in mice. In conclusion, we established a 3D neuroblastoma model, highlighting the potential of combining stromal targeting of mPGES-1 with tumor cell targeting drugs like vincristine.

ObjectivesTo assess if improvement of working conditions related to heat stress was associated with improved kidney health outcomes among sugarcane harvest workers in Chichigalpa, Nicaragua, a region heavily affected by the epidemic of chronic kidney disease of non-traditional origin.MethodsBased on our findings during the 2017–2018 harvest (harvest 1), recommendations that enhanced the rest schedule and improved access to hydration and shade were given before the 2018–2019 harvest (harvest 2). Actual work conditions during harvest 2 were then observed. Serum creatinine (SCr) was measured before and at end-harvest, and cross-harvest changes in estimated glomerular filtration rate (eGFR) and incident kidney injury (IKI, ie, SCr increase by ≥0.30 mg/dL or ≥1.5 times the baseline value) were compared between harvest 1 and harvest 2 for three jobs with different physical workloads using regression modelling. Workers who left during harvest were contacted at home, to address the healthy worker selection effect.ResultsIn burned cane cutters, mean cross-harvest eGFR decreased 6 mL/min/1.73 m2 (95% CI 2 to 9 mL/min/1.73 m2) less and IKI was 70% (95% CI 90% to 50%) lower in harvest 2 as compared with harvest 1 data. No such improvements were seen among seed cutters groups with less successful intervention implementation.ConclusionKidney injury risk was again elevated in workers with strenuous jobs. The results support further efforts to prevent kidney injury among sugarcane workers, and other heat-stressed workers, by improving access to water, rest and shade. The distinction between design and implementation of such interventions should be recognised.

Objective To evaluate change in fear of movement and the relationship of fear of movement and pain intensity to low back disability and general health-related quality of life over a 2-year period. Methods Consecutive patients scheduled for lumbar spine surgery were included. In addition to clinical background variables, back pain intensity, fear of movement, low back disability, and general health-related quality of life were assessed at baseline, 1 year, and 2 years after surgery. Linear mixed-effects models were used to analyze data. Results In total, 348 patients were included in the final analyses. There was a significant reduction in fear of movement and a significant interaction between fear of movement and low back disability across assessments, showing that greater levels of fear of movement were related to greater levels of disability over the 2-year period. Similarly, greater levels of back pain intensity were related to lower levels of general health-related quality of life during this period. Conclusions We found that greater levels of fear of movement were related to greater levels of low back disability, following lumbar spine surgery, in a longitudinal study. This shows the need to address fear of movement in prehabilitation/rehabilitation pre- or postsurgically to improve health outcomes for patients who undergo lumbar spine surgery.

Objective In this work we aim to investigate the origins and genetic affinities of Bronze Age populations (2,400-1,100 BC) from the region of southern Poland and to trace maternal kinship patterns present in the burials of those populations by the use of complete mitochondrial genomes. Materials and methods We performed ancient DNA analyses for Bronze Age individuals from present-day Poland associated with the Strzyzow culture, the Mierzanowice culture, and the Trzciniec Cultural circle. To obtain complete mitochondrial genomes, we sequenced genomic libraries using Illumina platform. Additionally, hybridization capture was used to enrich some of the samples for mitochondrial DNA. AMS 14 C-dating was conducted for 51 individuals to verify chronological and cultural attribution of the analyzed samples. Results Complete ancient mitochondrial genomes were generated for 80 of the Bronze Age individuals from present-day Poland. The results of the population genetic analyses indicate close maternal genetic affinity between Mierzanowice, Trzciniec, and Corded Ware culture-associated populations. This is in contrast to the genetically more distant Strzyzow people that displayed closer maternal genetic relation to steppe populations associated with the preceding Yamnaya culture and Catacomb culture, and with later Scythians. Potential maternal kinship relations were identified in burials of Mierzanowice and Trzciniec populations analyzed in this study. Discussion Results revealed genetic continuity from the Late Neolithic Corded Ware groups to Bronze Age Mierzanowice and Trzciniec-associated populations, and possible additional genetic contribution from the steppe to the formation of the Strzyzow-associated group at the end of 3rd millennium BC. Mitochondrial patterns indicated several pairs of potentially maternally related individuals mostly in Trzciniec-associated group.

To analyse the risk of rhegmatogenous retinal detachment (RRD) after cataract surgery, and to identify possible risk factors.Observational cohort study of patients undergoing cataract surgery in Region Skåne, southern Sweden, during 2015-2017 were retrieved from the Swedish National Cataract Register. These were then cross-referenced with cases of retinal detachment surgery performed at the Skåne University Hospital in Lund from 2015 to 2020. The main outcome was RRD after cataract surgery. The influence of sex, age, axial length of the eye, rupture of the posterior capsule, patient comorbidity and other cataract complications were analysed.Among the 58 624 cases of cataract surgery, a total of 298 RRDs (0.51%) were identified up to the end of 2020. The mean time from cataract surgery to RRD was 667 days. The mean age was 65.3 years, compared to 74 years in the control group. A strong correlation was found between RDD and age:60 years, incidence = 0.50%; 60-75 years, incidence = 0.14%; and75 years, incidence = 0.04%. The correlation with axial length was also very strong: mean value 23.73 mm in those without RRD, and 25.13 mm in those with RRD (p 0.001). Sex was also strongly correlated to RDD; 68.8% of cases of RRD being men. Among men younger than 60 years of age, with an axial length ≥25 mm, 9.46% exhibited RRD within the follow-up period (mean 4.7 years). Rupture of the posterior capsule was found in 2.01% of RRD patients compared to 0.74% in the control group. Diabetes, glaucoma or pseudoexfoliation had no impact on the prevalence of RRD.The three main risk factors for RRD following cataract surgery were found to be sex, age and axial length. The highest incidence of RRD (9.46%) were identified among men younger than 60 years of age and an axial length ≥25 mm.

Background The distal radius fracture (DRF) is the most common fracture in adults. With an ageing population, the number of wrist fractures in the superelderly (≥ 80 years) is expected to rise. Optimal treatment for displaced DRFs remains controversial, especially in the superelderly group. In addition, basic knowledge of the outcome after a DRF in this heterogenic group is lacking. The aim of this study was to study injury characteristics, treatment and outcome of DRFs in superelderly patients using data from a large national register. Methods We used prospectively collected data from the Swedish Fracture Register. All distal radius fractures registered between April 2012 and December 2018 in patients ≥ 80 years of age were included. Data on epidemiology, fracture type, trauma mechanism and treatment are registered by the physician treating the patient. Patients are also sent a subjective outcome questionnaire including EQ-5D, EQ-VAS and Short Musculoskeletal Function Assessment questionnaire (SMFA-score) at the time of injury and after 12 months. The 12-month questionnaire was sent to those who had completed the questionnaire at the time of injury. A Mann–Whitney U-test was used to assess differences between treatment methods. Results Mean age for this population was 86 years (80–105 years), a majority of the patients were female (86.7%). The dominating injury mechanism was a simple fall (74.6%) in the patient’s residence. The majority of fractures were AO type A (70%) followed by AO type C (20.9%) and type B (8.6%). The incidence of open fractures was significantly higher in females (2.6%) compared to males (1.5%). A majority of the fractures were treated with a cast (87.5%) with volar locking plate as the second most common treatment method (6.6%). Patient-reported outcome measures (PROMs) EQ-5D, EQ-VAS and the Arm Hand Function Index of the SMFA-score deteriorated somewhat one year after injury compared to pre-injury. PROMs did not correlate to treatment with cast or a volar plate. Conclusions This nationwide register study provides detailed data on DRFs in the superelderly regarding epidemiology, treatment and self-reported outcome. A good self-reported outcome is possible, but many patients do not recover completely. PROMs did not correlate to type of treatment. The frequency of open fractures was significantly higher in females. The reason for this is unclear but different skin thickness in older males versus females may be one explanation.

Background Supraclavicular block (SCB) with long-acting local anaesthetic is commonly used for surgical repair of distal radial fractures (DRF). Studies have shown a risk for rebound pain when the block fades. This randomised single-centre study aimed to compare pain and opioid consumption the first three days post-surgery between SCB-mepivacaine vs. SCB-ropivacaine, with general anaesthesia (GA) as control. Methods Patients (n = 90) with ASA physical status 1–3 were prospectively randomised to receive; SCB with mepivacine 1%, 25–30 ml (n = 30), SCB with ropivacaine 0.5%, 25–30 ml (n = 30) or GA (n = 30) with propofol/fentanyl/sevoflurane. Study objectives compared postoperative pain with Numeric Rating Scale (NRS) and sum postoperative Opioid Equivalent Consumption (OEC) during the first 3 days post-surgery between study-groups. Results The three groups showed significant differences in postoperative pain-profile. Mean NRS at 24 h was significantly lower for the SCB-mepivacaine group (p = 0.018). Further both median NRS and median OEC day 0 to 3 were significanly lower in the SCB-mepivacaine group as compared to the SCB-ropivacaine group during the first three days after surgery; pain NRS 1 (IQR 0.3–3.3) and 2.7 (IQR 1.3–4.2) (p = 0.017) and OEC 30 mg (IQR 10–80) and 85 mg (IQR 45–125) (p = 0.004), respectively. The GA-group was in between both in pain NRS and median sum OEC. Unplanned healthcare contacts were highest among SCB-ropivacaine patients (39.3%) vs. SCB-mepivacaine patients (0%) and GA-patients (3.4%). Conclusions The potential benefit of longer duration of analgesia, associated to a long-acting local anaesthetic agent, during the early postoperative course must be put in perspective of potential worse pain progression following block resolution. Trial registration NCT03749174 (clinicaltrials.gov, Nov 21, 2018, retrospectively registered).

This paper explores essential characteristics of current nursing practice from the perspectives of clinically experienced registered nurses in various fields of health care in Sweden. Nursing practice has been the subject of much debate in the past and because of its complexity as well as continuous changes in society it is important to continue the debate. A qualitative study, including 16 group interviews with altogether 74 participants, was conducted. Nursing practice was viewed as a multifaceted field. The participants struggled to define nursing but were able to describe it using concrete examples. The analysis, using interpretive description, identified current practice as essentially consisting of: ‘A practice pervaded by comprehensive responsibility’, ‘A practice that recognises a patient's unique needs’, ‘A practice based on multifaceted knowledge’ and ‘A practice that mediates between traditional values and changing demands’. Current nursing practice can be understood as striving to be in close proximity to the patient, but in tension with pervasive requirements and societal changes. Going forward, it is necessary to continue to reflect on and discuss the nature of nursing practice in an interprofessional context. Studies from primary and home care are also needed to broaden the understanding of nursing practice.

BACKGROUND AND AIM: The drinking water in parts of Ronneby municipality was heavily contaminated with perfluoroalkyl substances (PFAS) for decades. Although PFAS has endocrine-disrupting properties and may interfere with breastfeeding, the supporting epidemiologic literature is conflicting and based solely on populations with background levels of exposure. The effects on breastfeeding in populations with a point source of exposure are unknown. The aim was to investigate the potential associations between high PFAS exposure and 1) initiation and 2) duration of breastfeeding in a population-based cohort. METHODS: We retrieved data on infant feeding practices for 2,374 children born between 1999 and 2009 from Child Health Care centers in Ronneby and Karlshamn, a nearby municipality with background levels of exposure. Maternal residential address before delivery was used as a proxy for exposure, and confounder data were obtained from charts and national registers. We used modified Poisson regressions to estimate the risk of not initiating breastfeeding and, among initiators, the risks of not breastfeeding exclusively after 3 months and not breastfeeding at all at 6 months. RESULTS:Mothers who had received the contaminated water at their residential address had a 2.4 times higher risk (95% CI: 0.8, 6.7) of not initiating breastfeeding. Among initiators, primiparous mothers from the exposed area were at a 1.2 times increased risk (95% CI: 0.9, 1.6) of not exclusively breastfeeding at 3 months and a 1.6 times increased risk (95% CI: 1.2, 2.1) of not breastfeeding at all at 6 months. Multiparous women seemed less vulnerable to these effects, although we observed slightly increased risk estimates towards the end of the study period. CONCLUSIONS:Exposure to high levels of PFAS was associated with increased risks of not initiating breastfeeding as well as with shorter breastfeeding duration. Initiation among primiparous mothers was the most critical outcome, and targeted intervention might be warranted. (Less)

Medulloblastoma (MB) is one of the most common malignant central nervous system tumors of childhood. Despite intensive treatments that often leads to severe neurological sequelae, the risk for resistant relapses remains significant. In this study we have evaluated the effects of the ω3-long chain polyunsaturated fatty acids (ω3-LCPUFA) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on MB cell lines and in a MB xenograft model.Effects of ω3-LCPUFA treatment of MB cells were assessed using the following: WST-1 assay, cell death probes, clonogenic assay, ELISA and western blot. MB cells were implanted into nude mice and the mice were randomized to DHA, or a combination of DHA and EPA treatment, or to control group. Treatment effects in tumor tissues were evaluated with: LC-MS/MS, RNA-sequencing and immunohistochemistry, and tumors, erythrocytes and brain tissues were analyzed with gas chromatography.ω3-LCPUFA decreased prostaglandin E2 (PGEOur findings suggest that addition of DHA and EPA to the standard MB treatment regimen might be a novel approach to target inflammation in the tumor microenvironment.

Neutrophils have been classically viewed as a homogenous population. Recently, neutrophils were phenotypically classified into pro-inflammatory N1 and anti-inflammatory N2 sub-populations, but the functional differences between the two subtypes are not completely understood. We aimed to investigate the phenotypic and functional differences between N1 and N2 neutrophils, and to identify the potential contribution of the S100A9 alarmin in neutrophil polarization. We describe distinct transcriptomic profiles and functional differences between N1 and N2 neutrophils. Compared to N2, the N1 neutrophils exhibited: i) higher levels of ROS and oxidative burst, ii) increased activity of MPO and MMP-9, and iii) enhanced chemotactic response. N1 neutrophils were also characterized by elevated expression of NADPH oxidase subunits, as well as activation of the signaling molecules ERK and the p65 subunit of NF-kB. Moreover, we found that the S100A9 alarmin promotes the chemotactic and enzymatic activity of N1 neutrophils. S100A9 inhibition with a specific small-molecule blocker, reduced CCL2, CCL3 and CCL5 chemokine expression and decreased MPO and MMP-9 activity, by interfering with the NF-kB signaling pathway. Together, these findings reveal that N1 neutrophils are pro-inflammatory effectors of the innate immune response. Pharmacological blockade of S100A9 dampens the function of the pro-inflammatory N1 phenotype, promoting the alarmin as a novel target for therapeutic intervention in inflammatory diseases.

Little is known about the demographic/life-style/physiological determinants explaining the variation of serum perfluoroalkyl acid (PFAA) concentrations in children. We identified significant determinants in children and investigated the influence of low-level PFAA-contaminated drinking water (DW) (

Background: Patients with Inflammatory Bowel Disease (IBD) undergo repeated colonoscopies to monitor their lifelong disease.Objective: To describe experiences from repeated colonoscopies in...

We present a literature review of surgical techniques of intraocular lens placement in eyes with insufficient capsular support, focusing on the most recent publications, together with a retrospective multicentre consecutive case series analysis of 103 eyes undergoing pars plana vitrectomy and sutureless intrascleral (SIS) fixation of a standard three-piece PCIOL. Many different approaches appear in the literature without any specific procedure achieving superior outcomes. Advantages and disadvantages vary between techniques. Common complications related to IOL fixation techniques were as follow: anterior chamber IOL: transient/permanent corneal oedema (9-66.6%), uveitis (1.1-39.3%); iris-fixated IOL: pupil ovalization (16-47.7%); and sutured scleral-fixated IOL: suture breakage/exposure (6.1-11%), vitreous haemorrhage: (5.5-16.6%). In our retrospective case series, indications for surgery were postoperative aphakia in 50 eyes (49%), IOL dislocation in 38 eyes (37%) and natural lens dislocation in 15 eyes (14%). Scleral tunnels for haptic fixation were created with (28 eyes, 27.2%) or without (75 eyes, 72.8%) 25 gauge trocar cannulas. Complications included transient hypotony (n = 20; 19.4%), corneal decompensation (n = 7; 6.7%), IOL dislocation (n = 6; 5.8%), cystoid macular oedema (n = 5; 4.8%), vitreous haemorrhage (n = 4; 3.8%) and retinal detachment (n = 4; 3.8%). Mean best corrected visual acuity improved from logMAR 0.65 to 0.36 at the final visit (p = 0.001). In conclusion, SIS fixation provides good anatomical and functional outcomes; however, complications can occur. The number of surgical approaches for IOL dislocation described in the literature indicates that optimal treatment remains to be found.

OBJECTIVE: To investigate how levels of the soluble urokinase plasminogen activator receptor (suPAR) and erythrocyte sedimentation rate (ESR) correlate with disease activity and prognosis in pulmonary tuberculosis (PTB).DESIGN: This was a retrospective analysis of patients with active PTB (n = 500) in Gondar, Ethiopia, for whom the suPAR (n = 301) and ESR (n = 330) were analysed at the start of treatment. Both biomarkers were available for 176 patients. Human immunodeficiency virus (HIV) status, chest X-ray (CXR) findings, classification according to the clinical TBscore and treatment outcome were all recorded.RESULTS: In a multivariable logistic regression analysis adjusted for age, sex and HIV status, surrogate markers of disease activity such as advanced CXR patterns correlated with increased levels of suPAR (adjusted OR [aOR] 8.24, P < 0.001) and of ESR (aOR 1.63, P = 0.030), whereas ESR only correlated significantly with a TBscore >6 points. Increased levels of both suPAR and ESR were associated with unsuccessful treatment outcomes (aOR 2.93, P = 0.013; aOR 2.52, P = 0.025). The highest quartile of suPAR (aOR 13.3, P = 0.029) but not ESR levels correlated independently with increased mortality.CONCLUSION: SuPAR and ESR levels correlate with disease activity in PTB; however, the clinical role of these potentially prognostic biomarkers needs to be verified in prospective studies. OBJECTIVE: To investigate how levels of the soluble urokinase plasminogen activator receptor (suPAR) and erythrocyte sedimentation rate (ESR) correlate with disease activity and prognosis in pulmonary tuberculosis (PTB).DESIGN: This was a retrospective analysis of patients with active PTB (n = 500) in Gondar, Ethiopia, for whom the suPAR (n = 301) and ESR (n = 330) were analysed at the start of treatment. Both biomarkers were available for 176 patients. Human immunodeficiency virus (HIV) status, chest X-ray (CXR) findings, classification according to the clinical TBscore and treatment outcome were all recorded.RESULTS: In a multivariable logistic regression analysis adjusted for age, sex and HIV status, surrogate markers of disease activity such as advanced CXR patterns correlated with increased levels of suPAR (adjusted OR [aOR] 8.24, P < 0.001) and of ESR (aOR 1.63, P = 0.030), whereas ESR only correlated significantly with a TBscore >6 points. Increased levels of both suPAR and ESR were associated with unsuccessful treatment outcomes (aOR 2.93, P = 0.013; aOR 2.52, P = 0.025). The highest quartile of suPAR (aOR 13.3, P = 0.029) but not ESR levels correlated independently with increased mortality.CONCLUSION: SuPAR and ESR levels correlate with disease activity in PTB; however, the clinical role of these potentially prognostic biomarkers needs to be verified in prospective studies.

ObjectivesTo examine the association between workload and kidney injury in a fieldworker cohort with different levels of physically demanding work over a sugarcane harvest, and to assess whether the existing heat prevention efforts at a leading occupational safety and health programme are sufficient to mitigate kidney injury.MethodsBiological and questionnaire data were collected before (n=545) and at the end (n=427) of harvest among field support staff (low workload), drip irrigation workers (moderate), seed cutters (high) and burned sugarcane cutters (very high). Dropouts were contacted (87%) and reported the reason for leaving work. Cross-harvest incident kidney injury (IKI) was defined as serum creatinine increase ≥0.30 mg/dL or ≥1.5 times the baseline value, or among dropouts reporting kidney injury leading to leaving work.ResultsMean cross-harvest estimated glomerular filtration rate change was significantly associated with workload, increasing from 0 mL/min/1.73 m2 in the low-moderate category to −5 mL/min/1.73 m2 in the high and −9 mL/min/1.73 m2 in the very high workload group. A similar pattern occurred with IKI, where low-moderate workload had 2% compared with 27% in the very high workload category. A healthy worker selection effect was detected, with 32% of dropouts reporting kidney injury. Fever and C reactive protein elevation were associated with kidney injury.ConclusionsWorkers considered to have the highest workload had more cross-harvest kidney damage than workers with less workload. Work practices preventing heat stress should be strengthened and their role in preventing kidney damage examined further. Future occupational studies on chronic kidney disease of unknown aetiology should account for a healthy worker effect by pursuing those lost to follow-up.

Background It has been argued that the significance of personality in relation to students' readiness for interprofessional collaboration is an area where more research is needed. Nursing students in particular seem to be unsure about their role in the interprofessional team. Objective To explore associations between nursing students' readiness for interprofessional learning and personality traits with regard to biological sex, and previous work experience from health care. Design A cross-sectional questionnaire study. Setting Nursing students in year one and three enrolled in a three-year undergraduate bachelor in nursing programme. Participants Nursing students (n = 284) in semester two and six. Methods The participants completed the Readiness for Interprofessional Learning Scale and the Neuroticism, Extraversion, and Openness to experience Five Factor Inventory-3. The data were statistically analyzed by descriptive statistics, t-tests, correlations and linear regressions. Results Four of the five investigated personality traits – Extraversion, Openness to experiences, Agreeableness and Conscientiousness - were associated with nursing students' readiness for interprofessional learning. Moreover, nursing students in semester six were more ready for interprofessional learning regarding Negative professional identity and Roles and responsibilities than students in semester two. Female students were more ready for Teamwork and collaboration than male students. Conclusions Nursing students being more outgoing, open-minded, agreeable or conscientious seem to be more ready for interprofessional learning. Consequently, personality is of significance for nursing students' readiness for interprofessional learning.

Summary: Identifying cellular programs that drive cancers to be stem-like and treatment resistant is critical to improving outcomes in patients. Here, we demonstrate that constitutive extracellular signal-regulated kinase 1/2 (ERK1/2) activation sustains a stem-like state in glioblastoma (GBM), the most common primary malignant brain tumor. Pharmacological inhibition of ERK1/2 activation restores neurogenesis during murine astrocytoma formation, inducing neuronal differentiation in tumorspheres. Constitutive ERK1/2 activation globally regulates miRNA expression in murine and human GBMs, while neuronal differentiation of GBM tumorspheres following the inhibition of ERK1/2 activation requires the functional expression of miR-124 and the depletion of its target gene SOX9. Overexpression of miR124 depletes SOX9 in vivo and promotes a stem-like-to-neuronal transition, with reduced tumorigenicity and increased radiation sensitivity. Providing a rationale for reports demonstrating miR-124-induced abrogation of GBM aggressiveness, we conclude that reversal of an ERK1/2-miR-124-SOX9 axis induces a neuronal phenotype and that enforcing neuronal differentiation represents a therapeutic strategy to improve outcomes in GBM. : Sabelström et al. show that the loss of neurogenesis is reversible during neural stem cell-derived glioma formation. Pharmacological inhibition of ERK1/2 globally regulates miRNAs and induces neuronal differentiation, a process that is dependent on the modulation of an miR-124-SOX9 axis in glioblastoma (GBM) cells. The overexpression of miR-124 induces neuronal differentiation that abrogates GBM aggressiveness. Keywords: brain, cancer, differentiation, glioma, glioblastoma, microRNA, neural stem cell, neurogenesis, neuron, tumor

Age-specific type-distribution of high-risk human papillomavirus (hrHPV) in cervical precancerous lesions is subject to change in the HPV vaccination era. Knowing the pre-vaccination type-distribution helps to anticipate changes induced by mass vaccination and optimize screening.We recruited 1279 women referred to colposcopy for abnormal cytology into a population-based study on HPV type distribution in diagnostic cervical samples (ISRCTN10933736). The HPV genotyping findings were grouped as: HPV16/18+, other hrHPV+ (HPV31/33/35/39/45/51/52/56/58/59/66/68), non-vaccine targeted hrHPV+ (HPV35/39/51/56/59/66/68), low-risk HPV, and HPV negative. We estimated the HPV group-specific prevalence rates according to diagnostic histopathological findings in the age groups of30 (n = 339), 30-44.9 (n = 614), and ≥45 (n = 326).Altogether 503 cases with high grade squamous intraepithelial lesion or worse (HSIL+) were diagnosed. More than half, 285 (56.7%) of HSIL+ cases were associated with HPV16/18: 64.3% (101/157) in women30 years (reference group), 58.4% (157/269) in women 30-44.9 years (risk ratio (RR) 0.91, 95% confidence interval (95% CI) 0.78-1.06), and 35.1% (27/77) in women ≥45 years of age (RR 0.55, 95% CI 0.39-0.75). Conversely, other hrHPV's were associated with 191 (38.0%) of HSIL+: 31.9% (50/157) in women30, 36.8% (99/269) in women 30-44.9 years, 54.6% (42/77) and in women ≥45 (RR 1.71, 95% CI 1.26-2.33). The proportion of non-vaccine targeted hrHPV and HPV negative HSIL+ increased with advancing age.Pre-vaccination HPV type distribution in HSIL+ was distinctly polarised by age with HPV16/18 attributed disease being markedly more prevalent in women aged30. In the older women the other hrHPV types, however, dominated suggesting a need for more age-dependent screening strategies.

Background There is no prognostic test to ascertain whether cervical intraepithelial neoplasias (CINs) regress or progress. The majority of CINs regress in young women, and treatments increase the risk of adverse pregnancy outcomes. We investigated the ability of a DNA methylation panel (the S5 classifier) to discriminate between outcomes among young women with untreated CIN grade 2 (CIN2). Methods Baseline pyrosequencing methylation and human papillomavirus (HPV) genotyping assays were performed on cervical cells from 149 women with CIN2 in a 2-year cohort study of active surveillance. Results Twenty-five lesions progressed to CIN grade 3 or worse, 88 regressed to less than CIN grade 1, and 36 persisted as CIN1/2. When cytology, HPV16/18 and HPV16/18/31/33 genotyping, and the S5 classifier were compared to outcomes, the S5 classifier was the strongest biomarker associated with regression vs progression. The S5 classifier alone or in combination with HPV16/18/31/33 genotyping also showed significantly increased sensitivity vs cytology when comparing regression vs persistence/progression. With both the S5 classifier and cytology set at a specificity of 38.6% (95% confidence interval [CI], 28.4–49.6), the sensitivity of the S5 classifier was significantly higher (83.6%; 95% CI, 71.9–91.8) than of cytology (62.3%; 95% CI, 49.0–74.4; P = 0.005). The highest area under the curve was 0.735 (95% CI, 0.621–0.849) in comparing regression vs progression with a combination of the S5 classifier and cytology, whereas HPV genotyping did not provide additional information. Conclusions The S5 classifier shows high potential as a prognostic biomarker to identify progressive CIN2., Many cervical intraepithelial neoplasias (CINs) regress spontaneously or persist, but to date there is no method to predict progression. In this study, we show that a DNA methylation classifier can predict progression or regression of untreated CIN grade 2.

Introduction and hypothesis: The aim of this study was to compare the long-term subjective outcomes of an adjustable single-incision sling (Ajust®) vs standard mid-urethral slings (SMUS) for the treatment of women with stress urinary incontinence. Methods: This study was designed as a multicenter prospective randomized trial. Women under 60 years old with objectively verified stress urinary incontinence were included from seven centers in three countries. Women with mixed urinary incontinence were also included. Randomization was held in blocks for operation with either Ajust® or SMUS. Women analyzed at 1-year follow-up received the International Consultation on Incontinence Questionnaire Urinary Incontinence Short Form (ICIQ-UI-SF), International Consultation on Incontinence Questionnaire Overactive Bladder, Pelvic Organ Prolapse/Urinary Incontinence/Sexual Function Questionnaire-12, Patient Global Impression of Severity, and Patient Global Impression of Improvement questionnaires, together with a bladder diary to fill out at least 3 years after the procedure. The main outcome evaluated was the subjective cure rate as reported through the ICIQ-UI-SF questionnaire at 3 years. Results: In total, 205 women participated in the 3-year follow-up: 107 in the Ajust® and 98 in the SMUS group. No significant difference was observed between the groups regarding subjective cure rate (50.9% vs 51.5%, p = 0.909) or dyspareunia. Both groups demonstrated similar postoperative perception of improvement in addition to reduced urgency and urge urinary incontinence. The postoperative improvement remained at the same level after 3 years as it was at 1-year follow-up for both Ajust® and SMUS. Conclusions: Ajust® appears to be equally effective and safe as SMUS with regard to long-term follow-up of patient-reported outcomes.

Purpose: To examine whether patients’ experiences could be improved during colonoscopy by designing the examination room to include a digital screen showing calm nature films. Background: Colonoscopy is the gold standard for examination of the large intestine and the rectum. Around 50% of individuals invited for colorectal cancer screening choose to refrain from the screening due to fear and anxiety. It is therefore important to improve patients’ comfort during the procedure. Method: One of the four endoscopy rooms was rebuilt to include a large digital screen showing calm nature films. Patients were randomized to intervention (i.e., the room showing films) or control. During the colonoscopy, pulse and oxygen saturation were measured and the patients graded the intensity of pain and anxiety. Blood samples were taken regularly during the examination and were analyzed for glucose, cortisol, and prolactin. Results: The presence of calm nature films during colonoscopy decreased the release of cortisol, increased prolactin levels, and enhanced oxygen saturation. These effects were more apparent in patients who were unfamiliar with the procedure and the environment, patients who underwent the examination without analgesics or sedation, and patients whose examination procedure was relatively difficult and took a long time. Conclusions: The intervention described in this study is easy to implement and might help improve the patient experience during colonoscopy. However, this study was performed in a single health institution, and more studies are needed to further explore the role of film interventions in endoscopic and other medical procedures.

The aim of this study was to evaluate how the cytokine profiles differed between autoantibody based subgroups of systemic lupus erythematosus (SLE). SLE is a systemic autoimmune disease, characterized by periods of flares (active disease) and remission (inactive disease). The disease can affect many organ systems, e.g., skin, joints, kidneys, heart, and the central nervous system (CNS). SLE patients often have an overproduction of cytokines, e.g., interferons, chemokines, and interleukins. The high cytokine levels are part of the systemic inflammation, which can lead to tissue injury. In the present study, SLE patients were divided into five groups based on their autoantibody profiles. We thus defined these five groups: ANA negative, antiphospholipid (aPL) positive, anti-Sm/anti-RNP positive, Sjögren's syndrome (SS) antigen A and B positive, and patients positive for more than one type of autoantibodies (other SLE). Cytokines were measured using Mesoscale Discovery (MSD) multiplex analysis. On the basis of the cytokine data, ANA negative patients were the most deviating subgroup, with lower levels of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-12/IL-23p40, and interferon gamma-induced protein (IP)-10. Despite low cytokine levels in the ANA negative group, autoantibody profiles did not discriminate between different cytokine patterns.

Background Prehabilitation programs have led to improved postoperative outcomes in several surgical contexts, but there are presently no guidelines for the prehabilitation phase before lumbar fusion surgery. Objective The objective was to investigate whether a person-centered physical therapy prehabilitation program, based on a cognitive-behavioral approach, is more effective than conventional care in reducing disability and improving functioning after lumbar fusion surgery in patients with degenerative disk disease. Design This study was a randomized controlled trial. Setting The study took place at 2 private spine clinics and 1 university hospital. Patients We prospectively enrolled 118 patients scheduled for lumbar fusion surgery. Intervention The active intervention used a person-centered perspective and focused on promoting physical activity and targeting psychological risk factors before surgery. The control group received conventional preoperative care. Measurements The primary outcome was the Oswestry Disability Index score. Secondary outcomes were back and leg pain intensity, catastrophizing, kinesiophobia, self-efficacy, anxiety, depression, health-related quality of life, and patient-specific functioning, physical activity, and physical capacity. Data were collected on 6 occasions up to 6 months postoperatively. A linear mixed model was used to analyze the change scores of each outcome. Results No statistically significant between-group difference was found on the primary outcome (disability) over time (baseline to 6 months). Among secondary outcome measures, a statistically significant interaction effect (“Group × Time”) was seen for the European Quality of Life 5 Dimensions Questionnaire. The largest between-group difference on the European Quality of Life 5 Dimensions Questionnaire index was seen 1 week prior to surgery and favored the active intervention. The largest between-group effect sizes at the 6-month follow-up favored the active intervention, and were seen for physical activity intensity, steps per day, and the One Leg Stand Test. Both groups reached the minimal important change for the primary outcome and, in several secondary outcomes (pain intensity, back and leg; pain catastrophizing; anxiety; health-related quality of life [EQ5D VAS]), already at 8-week follow-up. Limitations The participants’ preoperative level of disability was lower than normative values, which suggests selection bias. Conclusions Both interventions led to clinically important changes, but it is not clear what kind of prehabilitation program is the most effective.

Although child mortality is decreasing in Sweden, an increase in suicide rates has been previously observed among children and adolescents collectively. To increase knowledge about trends, demographics, and means in child suicides, data including all child ( 18 years) suicides in Sweden in 2000 through 2018 were retrieved from the Swedish National Board of Forensic Medicine. In all, a total of 416 child suicides were found in a 19-year period, accounting for an annual suicide rate of 1.1/100,000 child population. The number of suicides increased with 2.2% by each successive year during the study period (p 0.001). The mean age in both sexes was 16 years; boys accounted for 55% and girls for 45% of all study cases. The majority of the children who died by suicide (96%) were teenagers (13-17 years old) and suicides in children younger than 10 years were uncommon. Suicide methods were 59% hanging, 20% lying/jumping in front of a moving object, 8% jumping from a height, 7% firearm injury, 4% poisoning, and 2% other methods. Sex differences were significant (p 0.001) only for firearms being preferably used by boys. The vast majority of firearms used were licensed long-barreled weapons.Conclusion: The number of child suicides in Sweden is relatively low but increasing. Most of the children used a violent and highly lethal method. Prevention of premature mortality is an urgent concern with an emphasis on resolutely reducing the availability of suicide means. What is Known: • Suicide is a significant cause of death globally among children, bringing tragic consequences for young individuals, their family, and the entire society. • Suicide rates and distribution of suicide methods in children differ between countries and settings, but studies of time trends are scarce. What is New: • Increasing number of minors' suicides and the predominance of violent methods emphasize the importance of prevention strategies tailored for a child population. • Even in a setting of very restrictive firearm laws, firearm suicides in children must not be overlooked.

Introduction Peripartum hysterectomy is applied as a surgical intervention of last resort for major obstetric hemorrhage. It is performed in an emergency setting except for women with a strong suspicion of placenta accreta spectrum (PAS), where it may be anticipated before cesarean section. The aim of this study was to compare management strategies in the case of obstetric hemorrhage leading to hysterectomy, between nine European countries participating in the International Network of Obstetric Survey Systems (INOSS), and to describe pooled maternal and neonatal outcomes following peripartum hysterectomy. Material and methods We merged data from nine nationwide or multi-regional obstetric surveillance studies performed in Belgium, Denmark, Finland, France, Italy, the Netherlands, Slovakia, Sweden and the UK collected between 2004 and 2016. Hysterectomies performed from 22 gestational weeks up to 48 h postpartum due to obstetric hemorrhage were included. Stratifying women with and without PAS, procedures performed in the management of obstetric hemorrhage prior to hysterectomy between countries were counted and compared. Prevalence of maternal mortality, complications after hysterectomy and neonatal adverse events (stillbirth or neonatal mortality) were calculated. Results A total of 1302 women with peripartum hysterectomy were included. In women without PAS who had major obstetric hemorrhage leading to hysterectomy, uterotonics administration was lowest in Slovakia (48/73, 66%) and highest in Denmark (25/27, 93%), intrauterine balloon use was lowest in Slovakia (1/72, 1%) and highest in Denmark (11/27, 41%), and interventional radiology varied between 0/27 in Denmark and Slovakia to 11/59 (79%) in Belgium. In women with PAS, uterotonics administration was lowest in Finland (5/16, 31%) and highest in the UK (84/103, 82%), intrauterine balloon use varied between 0/14 in Belgium and Slovakia to 29/103 (28%) in the UK. Interventional radiology was lowest in Denmark (0/16) and highest in Finland (9/15, 60%). Maternal mortality occurred in 14/1226 (1%), the most common complications were hematologic (95/1202, 8%) and respiratory (81/1101, 7%). Adverse neonatal events were observed in 79/1259 (6%) births. Conclusions Management of obstetric hemorrhage in women who eventually underwent peripartum hysterectomy varied greatly between these nine European countries. This potentially life-saving procedure is associated with substantial adverse maternal and neonatal outcome.

BACKGROUND: In December 2013, it was discovered that drinking water supplied to one third of the households in Ronneby, southern Sweden, was highly contaminated by PFAS (sum level >10,000 ng/L) originated from firefighting foams used at a nearby military airport.OBJECTIVES: To report serum PFAS levels of Ronneby residents participating in a biomonitoring program, and to describe the variation by age, sex and calendar period for residential exposure. In addition, a reference group living in a neighboring municipality without PFAS contaminated drinking water was examined.METHODS: Blood samples and demographic data were collected for 3297 Ronneby residents and 226 individuals from the reference group. Yearly residence addresses were available for 3086 Ronneby residents from the national population registry. Serum concentrations of PFHxS, PFOS and PFOA were determined in all participants, with additional PFHpA, PFNA and PFDA in subsets of the participants.RESULTS: The population geometric means for serum PFHxS, PFOS and PFOA were 114, 135 and 6.8 ng/mL for all Ronneby residents, i.e.135, 35 and 4.5 times higher than for the reference group. Ronneby residents who resided in the area with contaminated water supply during 2005-2013 showed much higher PFAS levels in 2014 than those exposed only before 2005. Ronneby residents who never resided in the area with contaminated water supply also had higher serum PFAS levels than the reference group. All three PFAS were highly correlated (rs > 0.9 for each pair). Serum PFAS levels were lowest in teenage years and then increased with age. Adult females had lower PFAS levels on average than males under the age of 60 but higher above 60.DISCUSSION: The results reveal high serum PFAS levels dominated by PFHxS and PFOS in the Ronneby residents highly exposed to PFAS originated from firefighting foams. The PFAS exposure in Ronneby permits studies of associations to a range of health parameters, as well as studies of the toxicokinetics of PFAS exposure. (Less)

Per- and polyfluoroalkyl substances (PFAS) are persistent substances with surfactant and repellent properties. Municipal drinking water contaminated with PFAS had been distributed for decades to one third of households in Ronneby, Sweden. The source was firefighting foam used in a nearby airfield since the mid-1980s. Clean water was provided from December 16, 2013.The purpose was to estimate serum half-lives and their determinants in the study population for different PFAS.Up to ten blood samples were collected between 2014 and 2018 from 114 participants (age 4-84 years at entry, 53% female). 19 PFAS were analysed. Linear mixed models were used to estimate the half-lives.Eight PFAS were increased in Ronneby: perfluorooctanoic acid (PFOA), perfluoropentane sulfonate (PFPeS), perfluorohexane sulfonate (PFHxS), perfluoroheptane sulfonate (PFHpS), linear perfluorooctane sulfonate (L-PFOS) and three branched perfluorooctane sulfonates (1 m-PFOS, 3/4/5m-PFOS and 2/6m-PFOS). The mean estimated half-lives (in years) were 0.94 (95 %CI 0.86-1.02) for PFPeS, 2.47 (2.27-2.7) for PFOA, 2.67 (2.51-2.85) for 2/6m-PFOS, 2.73 (2.55-2.92) for L-PFOS, 3.43 (3.19-3.71) for 3/4/5m-PFOS, 4.52 (4.14-4.99) for PFHxS, 4.55 (4.14-5.06) for PFHpS, and 5.01 (4.56-5.55) for 1 m-PFOS. The most important determinants of a shorter half-life were young age, and better kidney function measured by estimated glomerular filtration rate and ratio of paired urine and serum PFAS levels, followed by female sex during their fertile period aged 15-50. Markers of gut inflammation and reduced permeability i.e. zonulin and calprotectin were also possibly associated with shorter half-life. The results also suggested a time-dependent PFAS elimination process, with more rapid elimination in the first year after the end of exposure.The half-life estimates are in line with past estimates for some PFAS such as PFOA, and the novel results for different PFOS isomers. These results provide observational support for elimination routes - renal, fecal and maternal.

Aims and objectives To evaluate aspects of patient safety before and after a person-centred (PC) inpatient care intervention. Background Transitioning from disease-centred to person-centred care requires great effort but can improve patient safety. Design A quasi-experimental study with data collection preceding and 12 months after a PC inpatient care intervention. Methods The study consecutively recruited adult patients (2014, n = 263; 2015/2016, n = 221) admitted to an inpatient care unit. The patients reported experiences of care at discharge and their perceived pain at admission and discharge. Medical records were reviewed to gather data on medications, planned care and clinical observations. The study is reported according to TREND guidelines. Results At discharge, patients receiving PC inpatient care reported competent medical-technical care. Patients receiving PC inpatient care reported more effective pain relief. Updated prescribed medications at the ward were maintained, and patients were made aware of planned medical care to higher extent during PC inpatient care. The assessment of pulse and body temperature was maintained, but fewer elective care patients had their blood pressure taken during PC inpatient care. Weight assessment was not prioritised during usual or PC inpatient care. Conclusions Patients receiving PC inpatient care reported that they were given the best possible care and had less pain at discharge. The PC inpatient care included improved documentation and communication of planned medical care to the patients. Vital signs were more frequently recorded for patients admitted for acute care than patients admitted for elective care. PC inpatient care had no effect on frequency of weight measurements. Relevance to clinical practice PC inpatient care seems beneficial for the patients. Aspects of patient safety such as prescribed medications were maintained, and PC inpatient care seems to enhance the continuity of care. Inpatient clinical observations need further evaluation as healthcare transitions from disease-centred to person-centred care.

Significance A new phenomenon of constructing distinctive funerary monuments, collectively known as megalithic tombs, emerged around 4500 BCE along the Atlantic façade. The megalithic phenomenon has attracted interest and speculation since medieval times. In particular, the origin, dispersal dynamics, and the role of these constructions within the societies that built them have been debated. We generate genome sequence data from 24 individuals buried in five megaliths and investigate the population history and social dynamics of the groups that buried their dead in megalithic monuments across northwestern Europe in the fourth millennium BCE. Our results show kin relations among the buried individuals and an overrepresentation of males, suggesting that at least some of these funerary monuments were used by patrilineal societies., Paleogenomic and archaeological studies show that Neolithic lifeways spread from the Fertile Crescent into Europe around 9000 BCE, reaching northwestern Europe by 4000 BCE. Starting around 4500 BCE, a new phenomenon of constructing megalithic monuments, particularly for funerary practices, emerged along the Atlantic façade. While it has been suggested that the emergence of megaliths was associated with the territories of farming communities, the origin and social structure of the groups that erected them has remained largely unknown. We generated genome sequence data from human remains, corresponding to 24 individuals from five megalithic burial sites, encompassing the widespread tradition of megalithic construction in northern and western Europe, and analyzed our results in relation to the existing European paleogenomic data. The various individuals buried in megaliths show genetic affinities with local farming groups within their different chronological contexts. Individuals buried in megaliths display (past) admixture with local hunter-gatherers, similar to that seen in other Neolithic individuals in Europe. In relation to the tomb populations, we find significantly more males than females buried in the megaliths of the British Isles. The genetic data show close kin relationships among the individuals buried within the megaliths, and for the Irish megaliths, we found a kin relation between individuals buried in different megaliths. We also see paternal continuity through time, including the same Y-chromosome haplotypes reoccurring. These observations suggest that the investigated funerary monuments were associated with patrilineal kindred groups. Our genomic investigation provides insight into the people associated with this long-standing megalith funerary tradition, including their social dynamics.

Background Perfluorinated substances (PFAS) are chemicals with endocrine disruptive properties that may interfere with the female reproductive system. However, few studies have explored the association between benign gynecological diseases and high PFAS exposure. Objectives The aim of this study was to investigate the possible associations between PFAS exposure and subsequent diagnosis of polycystic ovarian syndrome (PCOS), uterine leiomyoma (fibroids), and endometriosis in a cohort exposed to PFAS through drinking water. Material and methods In 2013, high levels (with sum of PFAS above 10,000 ng/L), dominated by perfluorooctanesulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS), were found in the drinking water from one of the two waterworks in Ronneby, Sweden. The contamination came from firefighting foams used at a nearby airfield. Females of all ages (n = 29,106) who had ever resided in the municipality between 1985 and 2013 formed a cohort. Individual exposure was assessed based on municipality waterworks distribution data linked to annual residential address data; 27% of the females had ever lived at an address with PFAS-contaminated water. Gynecological health outcomes were retrieved from the Swedish National Patient Register. The Cox proportional hazards model was used to estimate the association between exposure and each diagnosis. Results There were in all 161 cases of PCOS, 1,122 cases of uterine leiomyoma, and 373 cases of endometriosis. In women aged 20–50 years (n = 18,503), those with the highest estimated PFAS exposure had increased hazard ratios (HR) for PCOS (HR = 2.18; 95% confidence interval (CI) 1.43, 3.34) and uterine leiomyoma (HR = 1.28; 95% CI 0.95, 1.74). No increased HR for endometriosis was found (HR = 0.74; 95% CI 0.42, 1.29). Conclusions Exposure to high levels of PFAS in drinking water was associated with increased risk of PCOS and possibly uterine leiomyoma, but not endometriosis. The findings for PCOS are consistent with prior studies reporting positive associations between PCOS and PFAS exposure at background levels.

[EN] Few complete human genomes from the European Early Upper Palaeolithic (EUP) have been sequenced. Using novel sampling and DNA extraction approaches, we sequenced the genome of a woman from ‘‘Pesxtera Muierii,’’ Romania who lived 34,000 years ago to 13.53 coverage. The genome shows similarities to modern- day Europeans, but she is not a direct ancestor. Although her cranium exhibits both modern human and Neanderthal features, the genome shows similar levels of Neanderthal admixture ( 3.1%) to most EUP humans but only half compared to the 40,000-year-old Pesxtera Oase 1. All EUP European hunter-gatherers display high genetic diversity, demonstrating that the severe loss of diversity occurred during and after the Last Glacial Maximum (LGM) rather than just during the out-of-Africa migration. The prevalence of genetic diseases is expected to increase with low diversity; however, pathogenic variant load was relatively constant from EUP to modern times, despite post-LGM hunter-gatherers having the lowest diversity ever observed among Europeans. The computations were performed on resources provided by SNIC through Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX). Sequencing was performed by the SNP&SEQ Technology Platform in Uppsala. T.G. was supported by a grant from the Swedish Research Council Vetenskapsra° det (2017-05267). M.G.N. was supported by a Spinoza grant of the Netherlands Organisation for Scientific Research and an ERC Advanced Grant (no. 833247). M.J. was supported by an ERC Starting Grant and the Knut and Alice Wallenberg Foundation. C.R. was supported by a Basque Government Grant to Research Groups of the Basque University System (IT1138-16).

Background Previous studies have shown that approximately 20% of hospital readmissions can be medication-related and 70% of these readmissions are possibly preventable. This retrospective medical records study aimed to find risk factors associated with medication-related readmissions to hospital within 30 days of discharge in older adults (≥65 years). Methods 30-day readmissions (n = 360) were assessed as being either possibly or unlikely medication-related after which selected variables were used to individually compare the two groups to a comparison group (n = 360). The aim was to find individual risk factors of possibly medication-related readmissions focusing on living arrangements, polypharmacy, potentially inappropriate medication therapy, and changes made to medication regimens at initial discharge. Results A total of 143 of the 360 readmissions (40%) were assessed as being possibly medication-related. Charlson Comorbidity Index (OR 1.15, 95%CI 1.5–1.25), excessive polypharmacy (OR 1.74, 95%CI 1.07–2.81), having adjustments made to medication dosages at initial discharge (OR 1.63, 95%CI 1.03–2.58) and living in your own home, alone, were variables identified as risk factors of such readmissions. Living in your own home, alone, increased the odds of a possibly medication-related readmission 1.69 times compared to living in your own home with someone (p-value 0.025) and 2.22 times compared to living in a nursing home (p-value 0.037). Conclusion Possibly medication-related readmissions within 30 days of discharge, in patients 65 years and older, are common. The odds of such readmissions increase in comorbid, highly medicated patients living in their own home, alone, and if having medication dosages adjusted at initial discharge. These results indicate that care planning before discharge and the provision of help with, for example, managing medications after discharge, are factors especially important if aiming to reduce the amount of medication-related readmissions among this population. Further research is needed to confirm this hypothesis.

Significance A key link to understand human history in Island Southeast Asia is the Philippine archipelago and its poorly investigated genetic diversity. We analyzed the most comprehensive set of population-genomic data for the Philippines: 1,028 individuals covering 115 indigenous communities. We demonstrate that the Philippines were populated by at least five waves of human migration. The Cordillerans migrated into the Philippines prior to the arrival of rice agriculture, where some remain as the least admixed East Asians carrying an ancestry shared by all Austronesian-speaking populations, thereby challenging an exclusive out-of-Taiwan model of joint farming–language–people dispersal. Altogether, our findings portray the Philippines as a crucial gateway, with a multilayered history, that ultimately changed the genetic landscape of the Asia-Pacific region., Island Southeast Asia has recently produced several surprises regarding human history, but the region’s complex demography remains poorly understood. Here, we report ∼2.3 million genotypes from 1,028 individuals representing 115 indigenous Philippine populations and genome-sequence data from two ∼8,000-y-old individuals from Liangdao in the Taiwan Strait. We show that the Philippine islands were populated by at least five waves of human migration: initially by Northern and Southern Negritos (distantly related to Australian and Papuan groups), followed by Manobo, Sama, Papuan, and Cordilleran-related populations. The ancestors of Cordillerans diverged from indigenous peoples of Taiwan at least ∼8,000 y ago, prior to the arrival of paddy field rice agriculture in the Philippines ∼2,500 y ago, where some of their descendants remain to be the least admixed East Asian groups carrying an ancestry shared by all Austronesian-speaking populations. These observations contradict an exclusive “out-of-Taiwan” model of farming–language–people dispersal within the last four millennia for the Philippines and Island Southeast Asia. Sama-related ethnic groups of southwestern Philippines additionally experienced some minimal South Asian gene flow starting ∼1,000 y ago. Lastly, only a few lowlanders, accounting for

Background: Perfluoroalkyl substances (PFAS) are widespread synthetic substances with various adverse health effects. A potential mechanism of toxicity for PFAS is via epigenetic changes, such as DNA methylation. However, few studies have evaluated associations between PFAS exposure and DNA methylation among adults, and data is especially scarce for women. Furthermore, exposure to environmental pollutants has been associated with epigenetic age acceleration, but no studies have yet evaluated whether PFAS is associated with epigenetic age acceleration. Objectives: To investigate whether exposure to PFAS is associated with alteration of DNA methylation and epigenetic age acceleration among women. Methods: In this observational pilot study, 59 women (aged 20–47 years at enrollment in 2014) from Ronneby, Sweden, an area with historically high PFAS exposure due to local drinking water contamination, were divided into three PFAS exposure groups (low, medium, and high). Genome-wide methylation of whole-blood DNA was analyzed using the Infinium MethylationEPIC BeadChip. Ingenuity Pathway Analysis was used for in silico functional assessment. Epigenetic age acceleration was derived from the DNA methylation data using Horvath's epigenetic skin and blood clock. Results: 117 differentially methylated positions (q < 0.017) and one near-significantly differentially methylated region (S100A13, FWER = 0.020) were identified. In silico functional analyses suggested that genes with altered DNA methylation (q < 0.05) were annotated to cancer, endocrine system disorders, reproductive system disease, as well as pathways such as estrogen receptor signaling, cardiac hypertrophy signaling, PPARα/RXRα activation and telomerase signaling. No differences in epigenetic age acceleration between PFAS exposure groups were noted (p = 0.43). Conclusion: The data suggests that PFAS exposure alters DNA methylation in women highly exposed to PFAS from drinking water. The observed associations should be verified in larger cohorts, and it should also be further investigated whether these changes in methylation also underlie potential phenotypic changes and/or adverse health effects of PFAS. (Less)

Purpose: To describe the outcome of retinal detachment surgery in a population affected by rhegmatogenous retinal detachment (RRD) in southern Sweden 2011–2013. Method: All primary retinal detachments that underwent surgery at the Skane University Hospital were registered during the period of 2011–2013. Age, sex, lens status and the different surgical methods including type of tamponade were recorded. For outcome assessment, no reoperation within 6 months was considered as primary success with one surgery except silicone oil removal. Results: In total, 918 primary retinal detachments were recorded during the 3-year period. Pars plana vitrectomy (PPV) alone was used in 618 eyes (67.3%), whereas an external approach with scleral buckling (SB) was used in 184 cases (20.0%) and a combination of PPV + SB in 116 eyes (12.6%). Pars plana vitrectomy (PPV) in combination with phacoemulsification and IOL implantation was performed in 169 eyes (18.4%), which was 43.6% of the phakic eyes having a PPV procedure. A total of 346 eyes (37.7%) were pseudophakic preoperatively. The success rate of one surgery was 86.9% for the entire cohort. In 120 eyes (13.1%), there was a re-detachment during the 6-month follow-up time. Higher age at the primary surgery turned out to be correlated to an increased risk of primary failure (p = 0.018) but gender was not (p = 0.84). Preoperative lens status did not affect the risk of re-detachment (p = 0.36), and there were no differences in outcome between surgeons (p = 0.27). No surgical procedure – alone or in combination – showed superior outcome as primary surgical approach. Conclusions: There were no significant differences in anatomical outcome between the various surgical procedures in this large cohort of 918 RRD cases.

Despite the progress to understand inflammatory reactions, mechanisms causing their resolution remain poorly understood. Prostanoids, especially prostaglandin E2 (PGE2), are well-characterized mediators of inflammation. PGE2 is produced in an inducible manner in macrophages (Mϕ) by microsomal PGE2-synthase-1 (mPGES-1), with the notion that it also conveys pro-resolving properties. We aimed to characterize the role of mPGES-1 during resolution of acute, zymosan-induced peritonitis. Experimentally, we applied the mPGES-1 inhibitor compound III (CIII) once the inflammatory response was established and confirmed its potent PGE2-blocking efficacy. mPGES-1 inhibition resulted in an incomplete removal of neutrophils and a concomitant increase in monocytes and Mϕ during the resolution process. The mRNA-seq analysis identified enhanced C-X3-C motif receptor 1 (CX3CR1) expression in resident and infiltrating Mϕ upon mPGES-1 inhibition. Besides elevated Cx3cr1 expression, its ligand CX3CL1 was enriched in the peritoneal lavage of the mice, produced by epithelial cells upon mPGES-1 inhibition. CX3CL1 not only increased adhesion and survival of Mϕ but its neutralization also completely reversed elevated inflammatory cell numbers, thereby normalizing the cellular, peritoneal composition during resolution. Our data suggest that mPGES-1-derived PGE2 contributes to the resolution of inflammation by preventing CX3CL1-mediated retention of activated myeloid cells at sites of injury.