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Context: Lung cancer surgery is among the surgical procedures associated with the highest prevalence of pain, but prospective longitudinal studies after the pain trajectory are scarce., Objectives: We aimed to describe the pain trajectory in patients undergoing surgery for primary lung cancer and investigate whether distinct groups of patients could be identified based on different pain trajectories., Methods: Patients (n = 264; 95% thoracotomies) provided data on the average and worst pain intensity, pain location, and comorbidities before, and at one month and five, nine, and 12 months after surgery. Pain profiles were analyzed by latent class mixed models., Results: The occurrence of any pain increased from 40% before surgery to 69% after one month and decreased to 56%, 57%, and 55% at five, nine, and 12 months, respectively. Latent class mixed models identified two classes both for average and worst pain; one class started low with high ratings after one month, then returning to a level slightly higher than baseline. The other class started higher with similar scores through the trajectory. Patients reporting no pain (8%) were placed in a separate class. Higher comorbidity score, preoperative use of both pain and psychotropic medicine characterized the class with overall highest pain for average and/or worst pain., Conclusion: Pain was highly prevalent after surgery, and subgroups could be identified based on different pain trajectories. Patients reported both postoperative pain and pain from chronic conditions. Knowledge about vulnerable patients and risk factors for pain is important to tailor interventions and information about pain., (Copyright © 2019 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Several risk prediction models for coronary heart disease (CHD) are available today, however, they only explain a modest proportion of the incidence. Circulating microRNAs (miRs) have recently been associated with processes in CHD development, and may therefore represent new potential risk markers. The aim of the study was to assess the incremental value of adding circulating miRs to the Framingham Risk Score (FRS)., Methods: This is a case-control study with a 10-year observation period, with fatal and non-fatal myocardial infarction (MI) as endpoint. At baseline, ten candidate miRs were quantified by real-time polymerase chain reaction in serum samples from 195 healthy participants (60-79 years old). During the follow-up, 96 participants experienced either a fatal (n = 36) or a non-fatal MI (n = 60), whereas the controls (n = 99) remained healthy. By using best subset logistic regression, we identified the miRs that together with the FRS for hard CHD best predicted future MI. The model evaluation was performed by 10-fold cross-validation reporting area under curve (AUC) from the receiver operating characteristic curve (ROC)., Results: The best miR-based logistic regression risk-prediction model for MI consisted of a combination of miR-21-5p, miR-26a-5p, mir-29c-3p, miR-144-3p and miR-151a-5p. By adding these 5 miRs to the FRS, AUC increased from 0.66 to 0.80. In comparison, adding other important CHD risk factors (waist-hip ratio, triglycerides, glucose, creatinine) to the FRS only increased AUC from 0.66 to 0.68., Conclusions: Circulating levels of miRs can add value on top of traditional risk markers in predicting future MI in healthy individuals., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Patients with moderate traumatic brain injury (TBI) often are studied together with patients with severe TBI, even though the expected outcome of the former is better. Therefore, we aimed to describe patient characteristics and 12-month outcomes, and to develop a prognostic model based on admission data, specifically for patients with moderate TBI., Methods: Patients with Glasgow Coma Scale scores of 9-13 and age ≥16 years were prospectively enrolled in 2 level I trauma centers in Europe. Glasgow Outcome Scale Extended (GOSE) score was assessed at 12 months. A prognostic model predicting moderate disability or worse (GOSE score ≤6), as opposed to a good recovery, was fitted by penalized regression. Model performance was evaluated by area under the curve of the receiver operating characteristics curves., Results: Of the 395 enrolled patients, 81% had intracranial lesions on head computed tomography, and 71% were admitted to an intensive care unit. At 12 months, 44% were moderately disabled or worse (GOSE score ≤6), whereas 8% were severely disabled and 6% died (GOSE score ≤4). Older age, lower Glasgow Coma Scale score, no day-of-injury alcohol intoxication, presence of a subdural hematoma, occurrence of hypoxia and/or hypotension, and preinjury disability were significant predictors of GOSE score ≤6 (area under the curve = 0.80)., Conclusions: Patients with moderate TBI exhibit characteristics of significant brain injury. Although few patients died or experienced severe disability, 44% did not experience good recovery, indicating that follow-up is needed. The model is a first step in development of prognostic models for moderate TBI that are valid across centers., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Studies of preterm and term-born infants have shown absent fidgety movements and an abnormal movement character to be related to brain lesions and unfavourable neurological outcomes., Aims: The present study examines what effect a parent-administered early intervention program applied to preterm infants in a randomised control trial (RCT) between 34 and 36weeks gestational age has on their fidgety movements and overall movement character at three months of age., Study Design: The study was part of the RCT in an early intervention programme including preterm infants born between 2010 and 2014 at three Norwegian university hospitals., Subjects: 130 preterm infants participated in the study, with 59 of them in the control group and 71 in the intervention group., Outcome Measures: Fidgety movements and overall movement character at three months corrected age., Results: No difference was found between the intervention group and the control group in terms of fidgety movements or movement character. Approximately half of the infants in both groups showed an abnormal movement character., Conclusion: No evidence was found in this RCT to suggest that an intervention at 34 to 37weeks gestational age has a significant effect on the fidgety movements or overall movement character of preterm infants. This is in line with the assumption that absent fidgety movements and an abnormal movement character are due to permanent brain injury and are therefore good predictors for later neurological impairments., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: Excessive placental inflammation is associated with pregnancy complications. Toll-like receptors (TLRs) are sensors for danger signals from infections and damaged tissue and initiate inflammation. Trophoblasts in the placenta broadly express TLRs. Trophoblast cell lines are used as surrogates for primary trophoblasts for in vitro studies, but the inflammatory translatability of trophoblast cell lines warrants examination. We aimed to assess TLR1-10 gene expression and activation in seven trophoblast cell lines and compare this to primary trophoblasts., Methods: The five choriocarcinoma trophoblast cell lines BeWo, JAR, JEG-3, AC1M-32 and ACH-3P, and the two SV40 transfected trophoblast cell lines HTR-8/SVneo and SGHPL-5 were included and compared to primary first trimester trophoblasts (n = 6). TLR1-10 gene expression was analyzed by RT-qPCR. Cells were stimulated by specific TLR1-9 ligands for 24 h and cytokine release was measured by a 10-plex immunoassay., Results: All choriocarcinoma cell lines demonstrated broad TLR gene expression, but lacked functional cytokine response to TLR ligand activation. In contrast, SV40 transfected cell lines showed restricted TLR gene expression, but SGHPL-5 cells displayed significantly increased levels of interleukin (IL)-6, IL-8, IL-12 and vascular endothelial growth factor A after TLR3 and/or TLR4 activation (P < 0.01), while TLR2 activation increased IL-6 and IL-8 levels (P < 0.05). HTR8/SVneo cells responded to TLR3 activation by increased IL-6 and interferon (IFN)-γ (P < 0.05). The SGHPL-5 TLR profile most closely resembled primary trophoblast., Discussion: The characterized trophoblast cell line TLR profiles serve as a reference and warrant caution when selecting trophoblast cell lines as in vitro models for immune responses in primary trophoblasts., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Polyunsaturated fatty acids (PUFAs) are normal constituents of the diet, but have properties different from other fatty acids (e.g., through generation of signaling molecules). N-3 PUFAs reduce cancer cell growth, but no unified mechanism has been identified. We show that docosahexaenoic acid (DHA; 22:6 n-3) causes extensive changes in gene expression patterns at mRNA level in the colon cancer cell line SW620. Early changes include unfolded protein response (UPR) and increased levels of phosphorylated eIF2alpha as verified at protein level. The latter is considered a hallmark of endoplasmic reticulum (ER) stress and is abundantly present already after 3 h. It may coordinate many of the downstream changes observed, including signaling pathways for cell cycle arrest/apoptosis, calcium homeostasis, cholesterol metabolism, ubiquitination, and proteasomal degradation. Also, eicosapentaenoic acid (EPA), but not oleic acid (OA), induced key mediators of ER stress and UPR at protein level. Accumulation of esterified cholesterol was not compensated for by increased total levels of cholesterol, and mRNAs for cholesterol biosynthesis as well as de novo synthesis of cholesterol were reduced. These results suggest that cytotoxic effects of DHA are associated with signaling pathways involving lipid metabolism and ER stress.