Combined ChIP-Seq and transcriptome analysis identifies AP-1/JunD as a primary regulator of oxidative stress and IL-1β synthesis in macrophages

10.1186/1471-2164-14-92BMC Genomics1419

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Masyarakat, Kependudukan, dan Kebijakan di Indonesia #KB

xix, 225 hal; ilus

Ilmu Sosial dan Kekuasaan di Indonesia: Masyarakat, Kependudukan, dan Kebijakan di Indonesia

xxvi, 225 Hlm; Ilus

Aspek Sosial Budaya Pengambilan Keputusan dalam Keluarga Berencana di Nusa Tenggara Timur

8 ha

A review of research on the price, cost and value of children in Indonesia

33 p.; 28 cm

From Concubines to Prostitutes. A Partial History of Trade in Sexual Services in Indonesia

The history of sex work in Indonesia is filled with contradictions and conflicts. Women from poor families were recruited by nobles to take the position of concubines to serve the twin roles of domestic and sexual servants. Foreign traders, soldiers and officials also exploited the opportunity to recruit poor women to maintain temporary households, and petty officials took on the role of pimps to organize sex workers for increasingly commercialised operations. The complaints of religious leaders from both the Christian churches of the colonisers and the Islamic and Hindu believers among indigenous people put pressure on the state to regulate or forbid sex work, largely unsuccessfully. In a detailed review of the history of prostitution up to the end of the New Order this article traces the transformation of sex work from a largely socially acceptable practice into a widely condemned, but begrudgingly accepted social reality.L’histoire du travail du sexe en Indonésie est pleine de contradictions et de conflits. Les femmes issues de familles pauvres ont été recrutées par les nobles pour occuper la place de concubines et jouer ainsi le double rôle de domestique et de servante sexuelle. Les commerçants étrangers, les soldats et les employés administratifs ont également exploité l’opportunité de recruter des femmes pauvres pour entretenir des ménages temporaires ; de petits fonctionnaires ont endossé le rôle de proxénètes pour organiser les travailleurs du sexe afin de mener des opérations de plus en plus commercialisées. Les plaintes des dirigeants religieux des églises chrétiennes des colonisateurs et des croyants islamiques et hindous parmi les populations autochtones firent pression sur l’État pour qu’il règle ou interdise le travail sexuel, mais en vain la plupart du temps. Au cours d’un examen détaillé de l’histoire de la prostitution jusqu’à la fin de l’Ordre Nouveau, cet article retrace le passage du travail du sexe d’une pratique généralement acceptable sur le plan social à une réalité sociale largement condamnée mais acceptée à contrecœur