The relation of plasmacytoid dendritic cells (pDCs) and regulatory t-cells (Tregs) with HPV persistence in HIV-Infected and HIV-Uninfected women

Other than CD4+ count, the immunologic factors that underlie the relationship of HIV/AIDS with persistent oncogenic HPV (oncHPV) and cervical cancer are not well understood. Plasmacytoid dendritic cells (pDCs) and regulatory T-cells (Tregs) are of particular interest. pDCs have both effector and antigen presenting activity and, in HIV-positive patients, low pDC levels are associated with opportunistic infections. Tregs downregulate immune responses, and are present at high levels in HIV-positives. The current pilot study shows for the first time that low pDC and high Treg levels may be significantly associated with oncHPV persistence in both HIV-positive and HIV-negative women. Larger studies are now warranted

Eliminating Preventable HIV-Related Maternal Mortality in Sub-Saharan Africa: What Do We Need to Know?

Introduction: HIV makes a significant contribution to maternal mortality, and women living in sub-Saharan Africa are most affected. International commitments to eliminate preventable maternal mortality and reduce HIV-related deaths among pregnant and postpartum women by 50% will not be achieved without a better understanding of the links between HIV and poor maternal health outcomes and improved health services for the care of women living with HIV (WLWH) during pregnancy, childbirth, and postpartum. Methods: This article summarizes priorities for research and evaluation identified through consultation with 30 international researchers and policymakers with experience in maternal health and HIV in sub-Saharan Africa and a review of the published literature. Results: Priorities for improving the evidence about effective interventions to reduce maternal mortality and improve maternal health among WLWH include better quality data about causes of maternal death among WLWH, enhanced and harmonized program monitoring, and research and evaluation that contributes to improving: (1) clinical management of pregnant and postpartum WLWH, including assessment of the impact of expanded antiretroviral therapy on maternal mortality and morbidity, (2) integrated service delivery models, and (3) interventions to create an enabling social environment for women to begin and remain in care. Conclusions: As the global community evaluates progress and prepares for new maternal mortality and HIV targets, addressing the needs of WLWH must be a priority now and after 2015. Research and evaluation on maternal health and HIV can increase collaboration on these 2 global priorities, strengthen political constituencies and communities of practice, and accelerate progress toward achievement of goals in both areas

Randomized Trial of Antibiotics in Addition to Tocolytic Therapy to Treat Preterm Labor

Objective: The objective of this study was to assess whether antibiotic therapy plus tocolysis given to women in preterm labor would prolong pregnancy compared with tocolysis alone

Cervical Antibodies to Herpes Simplex Virus Proteins in Pregnancy and Puerperium: A Pilot Study

Objective: This study was undertaken to evaluate the changes in total and anti-herpes simplex virus (HSV)-specific cervical IgA and IgG antibody profiles during and after pregnancy

Smartphone and medical related App use among medical students and junior doctors in the United Kingdom (UK): a regional survey

Background: Smartphone usage has spread to many settings including that of healthcare with numerous potential and realised benefits. The ability to download custom-built software applications (apps) has created a new wealth of clinical resources available to healthcare staff, providing evidence-based decisional tools to reduce medical errors. Previous literature has examined how smartphones can be utilised by both medical student and doctor populations, to enhance educational and workplace activities, with the potential to improve overall patient care. However, this literature has not examined smartphone acceptance and patterns of medical app usage within the student and junior doctor populations. Methods: An online survey of medical student and foundation level junior doctor cohorts was undertaken within one United Kingdom healthcare region. Participants were asked whether they owned a Smartphone and if they used apps on their Smartphones to support their education and practice activities. Frequency of use and type of app used was also investigated. Open response questions explored participants’ views on apps that were desired or recommended and the characteristics of apps that were useful. Results: 257 medical students and 131 junior doctors responded, equating to a response rate of 15.0% and 21.8% respectively. 79.0% (n=203/257) of medical students and 74.8% (n=98/131) of junior doctors owned a smartphone, with 56.6% (n=115/203) of students and 68.4% (n=67/98) of doctors owning an iPhone. The majority of students and doctors owned 1–5 medical related applications, with very few owning more than 10, and iPhone owners significantly more likely to own apps (Chi sq, p<0.001). Both populations showed similar trends of app usage of several times a day. Over 24hours apps were used for between 1–30 minutes for students and 1–20 minutes for doctors, students used disease diagnosis/management and drug reference apps, with doctors favouring clinical score/calculator apps. Conclusions: This study found a high level of smartphone ownership and usage among medical students and junior doctors. Both groups endorse the development of more apps to support their education and clinical practice

Genital HSV Detection among HIV-1-Infected Pregnant Women in Labor

Objective. To compare genital HSV shedding among HIV-positive and HIV-negative women. Methods. Women with and without known HIV infection who delivered at the University of Washington Medical Center between 1989–1996 had HSV serologies done as part of clinical care. Genital swabs from HSV-2-seropositive women were evaluated by real-time quantitative HSV DNA PCR. Results. HSV-2 seroprevalence was 71% and 30% among 75 HIV-positive and 3051 HIV-negative women, respectively, (P < .001). HSV was detected at delivery in the genital tract of 30.8% of HIV-seropositive versus 9.5% of HIV-negative women (RR = 3.2, 95% CI 1.6 to 6.5, P = .001). The number of virion copies shed per mL was similar (log 3.54 for HIV positive versus 3.90 for HIV negative, P = .99). Conclusions. Our study demonstrated that HIV-, HSV-2-coinfected women are more likely to shed HSV at delivery

Pregnant and breastfeeding women: A priority population for HIV viral load monitoring

With more than 18 million HIV-infected individuals having initiated antiretroviral therapy (ART) in low- and middle-income countries (LMICs) by the end of 2016, ensuring effective HIV care and treatment services is a global public health priority [1]. Viral load (VL) quantification provides a direct measure of the effectiveness of ART, with a consistently elevated VL suggesting poor adherence or treatment failure and the need for intervention. In turn, HIV VL monitoring is now recognised as a key component of ART services in LMICs in World Health Organization (WHO) guidelines, with an emphasis on scaling up access to VL testing for ART programmes [2]. Pregnant and postpartum women are an important population within ART programmes. In many countries, the majority of identified HIV-infected adults are women, and many women of reproductive age are diagnosed with HIV infection during pregnancy through prevention of mother-to-child transmission of HIV (PMTCT) services in antenatal care (ANC) [3]. With universal eligibility for ART for all HIV-infected pregnant and postpartum women (based on the WHO’s 2013 ‘Option B+’ policy [4]), many women of reproductive age initiating ART do so during pregnancy. PMTCT services extend through early infant diagnosis around 6–10 weeks postpartum until the cessation of breastfeeding and documentation of the infant’s final HIV testing status, which may extend well beyond 1 year postpartum based on the recently updated infant feeding recommendations [5]. With ongoing risk of HIV transmission throughout breastfeeding, maintaining ART adherence and viral suppression is especially crucial during this period. Although the importance of routine VL monitoring for HIV-infected individuals on ART is widely recognised [6], there has been minimal attention to VL monitoring in pregnancy and the postpartum period. Here we discuss key considerations for VL monitoring in pregnant and breastfeeding women in the context of expanding access to VL monitoring (summarised in Box 1)

Reconstruction of primary vertices at the ATLAS experiment in Run 1 proton–proton collisions at the LHC

This paper presents the method and performance of primary vertex reconstruction in proton–proton collision data recorded by the ATLAS experiment during Run 1 of the LHC. The studies presented focus on data taken during 2012 at a centre-of-mass energy of √s=8 TeV. The performance has been measured as a function of the number of interactions per bunch crossing over a wide range, from one to seventy. The measurement of the position and size of the luminous region and its use as a constraint to improve the primary vertex resolution are discussed. A longitudinal vertex position resolution of about 30μm is achieved for events with high multiplicity of reconstructed tracks. The transverse position resolution is better than 20μm and is dominated by the precision on the size of the luminous region. An analytical model is proposed to describe the primary vertex reconstruction efficiency as a function of the number of interactions per bunch crossing and of the longitudinal size of the luminous region. Agreement between the data and the predictions of this model is better than 3% up to seventy interactions per bunch crossing

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

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements