Expression of DC-SIGN and DC-SIGNRs in placentas of HIV-positive patients

Background. Human dendritic cell-specific intracellular adhesion molecule-3 (ICAM3)-grabbing non-integrin (DC-SIGN) is a mannose-binding lectin that initiates interaction between dendritic cells and resting T-lymphocytes. DC-SIGN is highly expressed in placental tissue on dendritic cells and Hofbauer cells, and it is suggested that HIV may become adsorbed to DC-SIGN on Hofbauer cells as part of the mechanism of mother-to-child HIV transmission. A possible mechanism of transfer of the virus from the Hofbauer cells to the fetus is the subsequent adsorption to DC-SIGN-related molecules (DC-SIGNRs), present on immediately adjacent capillary vascular endothelium. However, data on DC-SIGN and DC-SIGNR expression in the placenta are few. Methods. Forty term placentas from HIV-positive mothers and 21 term placentas from HIV-negative mothers underwent immunohistochemistry staining for DC-SIGN and DC-SIGNR expression. Five random sets of 10 villi were assessed, and the average number of positive cells were counted in each case. In addition, where possible, maternal and cord blood viral loads and maternal CD4+ counts were performed in the HIV-positive group only. Results. The median maternal CD4+ count was 377 cells/μl and 27% of participants had undetectable viral loads; the median detectable viral load was 3.72 log. Most (97%) of the cord bloods tested in infants from HIV-positive mothers had lower than detectable viral loads. HIV-positive cases had significantly greater expression of both DC-SIGNRs (median values in HIV-positive cases, 14.5 positive cells/10 villi (pc/10villi), compared with 11 pc/10villi in HIV-negative cases, p=0.020) and DC-SIGN (median value in HIV-positive cases, 26.5 pc/10villi, compared with 23 pc/10villi in HIV-negative cases, p=0.037). DC-SIGNR expression was also noted in Hofbauer cells and decidual macrophages in addition to endothelium (reported currently). There was no difference in expression of DC-SIGN and DC-SIGNRs in patients with or without chorioamnionitis, but there was an inverse relationship between DC-SIGN and DC-SIGNR expression and maternal CD4+ counts in HIV-positive cases. Conclusion. Both DC-SIGN and DC-SIGNR expression were higher in placentas from HIV-positive mothers compared with HIV-negative cases. These lectins may be potential new therapeutic targets for preventing vertical transmission of HIV

Expression of DC-SIGN and DC-SIGNRs in placentas of HIV-positive patients

Background. Human dendritic cell-specific intracellular adhesion molecule-3 (ICAM3)-grabbing non-integrin (DC-SIGN) is a mannose-binding lectin that initiates interaction between dendritic cells and resting T-lymphocytes. DC-SIGN is highly expressed in placental tissue on dendritic cells and Hofbauer cells, and it is suggested that HIV may become adsorbed to DC-SIGN on Hofbauer cells as part of the mechanism of mother-to-child HIV transmission. A possible mechanism of transfer of the virus from the Hofbauer cells to the fetus is the subsequent adsorption to DC-SIGN-related molecules (DC-SIGNRs), present on immediately adjacent capillary vascular endothelium. However, data on DC-SIGN and DC-SIGNR expression in the placenta are few. Methods. Forty term placentas from HIV-positive mothers and 21 term placentas from HIV-negative mothers underwent immunohistochemistry staining for DC-SIGN and DC-SIGNR expression. Five random sets of 10 villi were assessed, and the average number of positive cells were counted in each case. In addition, where possible, maternal and cord blood viral loads and maternal CD4+ counts were performed in the HIV-positive group only. Results. The median maternal CD4+ count was 377 cells/µl and 27% of participants had undetectable viral loads; the median detectable viral load was 3.72 log. Most (97%) of the cord bloods tested in infants from HIV-positive mothers had lower than detectable viral loads. HIV-positive cases had significantly greater expression of both DC-SIGNRs (median values in HIV-positive cases, 14.5 positive cells/10 villi (pc/10villi), compared with 11 pc/10villi in HIV-negative cases, p=0.020) and DC-SIGN (median value in HIV-positive cases, 26.5 pc/10villi, compared with 23 pc/10villi in HIV-negative cases, p=0.037). DC-SIGNR expression was also noted in Hofbauer cells and decidual macrophages in addition to endothelium (reported currently). There was no difference in expression of DC-SIGN and DC-SIGNRs in patients with or without chorioamnionitis, but there was an inverse relationship between DC-SIGN and DC-SIGNR expression and maternal CD4+ counts in HIV-positive cases.  Conclusion. Both DC-SIGN and DC-SIGNR expression were higher in placentas from HIV-positive mothers compared with HIV-negative cases. These lectins may be potential new therapeutic targets for preventing vertical transmission of HIV

Local magnetism of isolated Mo atoms at substitutional and interstitial sites in Yb metal : Experiment and Theory

Using TDPAD experiment and local spin density calculations, we have observed large 4d moments on isolated Mo atoms at substitutional and octahedral interstitial lattice sites in Yb metal, showing Curie-Weiss local susceptibility and Korringa like spin relaxation rate. As a surprising feature, despite strong hybridization with the Yb neighbours, interstitial Mo atoms show high moment stability with small Kondo temperature. While, magnetism of Mo, at substitutional site is consistent with Kondo type antiferromagnetic d-sp exchange interaction, we suggest that moment stability at the interstitial site is strongly influenced by ferromagnetic polarization of Yb-4f5d band electrons.Comment: 4 pages, 4 figure

Strengthening implant provision and acceptance in South Africa with the ‘Any woman, any place, any time’ approach: An essential step towards reducing unintended pregnancies

Progress in reducing unintended pregnancies in South Africa is slow. The implant, introduced in 2014, expanded the range of available longacting reversible contraceptives (LARCs) and held much promise. Uptake, however, has declined precipitously, in spite of its ‘unmatched effectiveness’ and high levels of satisfaction for most users. We propose policy and provider interventions to raise implant use, underscored by a ‘LARC-first’ approach. Contraceptive counselling should focus on the particular benefits of LARCs and methods be presented in order of effectiveness. Moreover, implants hold particular advantages for certain groups, especially adolescents and young women, in whom it is considered first-line contraception. Provision of immediate postpartum and post-abortion implants is safe and highly acceptable, yet remains under-utilised. Implant services at HIV and tuberculosis clinics are a key priority, as is inclusion of LARC provision within school health services. Implants could also be delivered by existing mobile outreach services, for example in sex worker programmes. Services could be built around nurses dedicated solely to providing implants, with other health workers receiving brief refresher training. Women who experience side-effects, especially abnormal bleeding, require timely interventions, following a standardised protocol, including use of medications. Encouraging return for side-effects, follow-up phone calls and home visits would raise continuation rates. Removal services require doctor support or designated nurses at specific centres. Limited access to removal services, health workers’ resistance or botched procedures will further undermine implant provision. Rapid implant demonstration projects in postpartum wards, schools, outreach services and by dedicated providers may rapidly advance the field. Together, the actions outlined here will ensure that the implant fulfils its potential and reinvigorates family planning services

Teaching in the time of COVID-19: Shared perspectives from South Africa and the USA

In line with keeping people safe, social distancing has become a civilised norm across the world. Compulsory lockdowns have meant that universities closed their doors to students and staff, thus causing widespread disruption across the higher-education landscape. Pharmacy education is no exception. As pharmacy educators from institutions in different countries, with an existing partnership, we have identified common challenges between our different educational environments and have benefited from sharing possible solutions

Antiretroviral therapy to prevent HIV acquisition in serodiscordant couples in a hyperendemic community in rural South Africa

Background. Antiretroviral therapy (ART) was highly efficacious in preventing human immunodeficiency virus (HIV) transmission in stable serodiscordant couples in the HPTN-052 study, a resource-intensive randomized controlled trial with near-perfect ART adherence and mutual HIV status disclosure among all participating couples. However, minimal evidence exists of the effectiveness of ART in preventing HIV acquisition in stable serodiscordant couples in "real-life" population-based settings in hyperendemic communities of sub-Saharan Africa, where health systems are typically resource-poor and overburdened, adherence to ART is often low, and partners commonly do not disclose their HIV status to each other. Methods. Data arose from a population-based open cohort in KwaZulu-Natal, South Africa. A total of 17 016 HIV-uninfected individuals present between January 2005 and December 2013 were included. Interval-censored time-updated proportional hazards regression was used to assess how the ART status affected HIV transmission risk in stable serodiscordant relationships. Results. We observed 1619 HIV seroconversions in 17 016 individuals, over 60 349 person-years follow-up time. During the follow-up period, 1846 individuals had an HIV-uninfected and 196 had an HIV-infected stable partner HIV incidence was 3.8/100 person-years (PY) among individuals with an HIV-infected partner (95% confidence interval [CI], 2.3-5.6), 1.4/100 PY (.4-3.5) among those with HIV-infected partners receiving ART, and 5.6/100 PY (3.5-8.4) among those with HIV-infected partners not receiving ART. Use of ART was associated with a 77% decrease in HIV acquisition risk among serodiscordant couples (adjusted hazard ratio, 0.23; 95% CI,. 07-.80). Conclusions. ART initiation was associated with a very large reduction in HIV acquisition in serodiscordant couples in rural KwaZulu-Natal. However, this "real-life" effect was substantially lower than the effect observed in the HPTN-052 trial. To eliminate HIV transmission in serodiscordant couples, additional prevention interventions are probably needed