Women's Perceptions of HIV- and Sexuality-Related Stigma in Relation to PrEP: Qualitative Findings from the Masibambane Study, Durban, South Africa.

Daily oral pre-exposure prophylaxis (PrEP) offers effective HIV prevention. In South Africa, PrEP is publicly available, but use among young women remains low. We explored young women's perceptions of PrEP to inform a gender-focused intervention to promote PrEP uptake. Six focus group discussions and eight in-depth interviews exploring perceptions of PrEP were conducted with forty-six women not using PrEP, ages 18-25, from central Durban. Data were thematically analyzed using a team-based consensus approach. The study was conducted among likely PrEP users: women were highly-educated, with 84.8% enrolled in post-secondary education. Qualitative data revealed intersecting social stigmas related to HIV and women's sexuality. Women feared that daily PrEP pills would be confused with anti-retroviral treatment, creating vulnerability to misplaced HIV stigma. Women also anticipated that taking PrEP could expose them to assumptions of promiscuity from the community. To address these anticipated community-level reactions, women suggested community-facing interventions to reduce the burden on young women considering PrEP. Concerns around PrEP use in this group of urban, educated women reflects layered stigmas that may inhibit future PrEP use. Stigma-reducing strategies, such as media campaigns and educational interventions directed at communities who could benefit from PrEP, should re-frame PrEP as an empowering and responsible choice for young women.

Iceland is an episodic source of atmospheric ice-nucleating particles relevant for mixed-phase clouds.

Ice-nucleating particles (INPs) have the potential to remove much of the liquid water in climatically important mid- to high-latitude shallow supercooled clouds, markedly reducing their albedo. The INP sources at these latitudes are very poorly defined, but it is known that there are substantial dust sources across the high latitudes, such as Iceland. Here, we show that Icelandic dust emissions are sporadically an important source of INPs at mid to high latitudes by combining ice-nucleating active site density measurements of aircraft-collected Icelandic dust samples with a global aerosol model. Because Iceland is only one of many high-latitude dust sources, we anticipate that the combined effect of all these sources may strongly contribute to the INP population in the mid- and high-latitude northern hemisphere. This is important because these emissions are directly relevant for the cloud-phase climate feedback and because high-latitude dust emissions are expected to increase in a warmer climate.

Contributions of biogenic material to the atmospheric ice-nucleating particle population in North Western Europe.

A minute fraction of atmospheric particles exert a disproportionate effect on the phase of mixed-phase clouds by acting as ice-nucleating particles (INPs). To understand the effects of these particles on weather and climate, both now and into the future, we must first develop a quantitative understanding of the major INP sources worldwide. Previous work has demonstrated that aerosols such as desert dusts are globally important INPs, but the role of biogenic INPs is unclear, with conflicting evidence for their importance. Here, we show that at a temperate site all INPs active above -18 °C at concentrations >0.1 L-1 are destroyed on heating, consistent with these INPs being of biological origin. Furthermore, we show that a global model of desert dust INPs dramatically underestimates the measured INP concentrations, but is consistent with the thermally-stable component. Notably, the heat sensitive INPs are active at temperatures where shallow cloud layers in Northern Europe are frequently observed to glaciate. Hence, we suggest that biogenic material is important for primary ice production in this region. The prevalence of heat sensitive, most likely biogenic, INPs in this region highlights that, as a community, we need to quantify the sources and transport of these particles as well as determine their atmospheric abundance across the globe and at cloud altitudes.

Novel analogs targeting histone deacetylase suppress aggressive thyroid cancer cell growth and induce re-differentiation.

To develop novel therapies for aggressive thyroid cancers, we have synthesized a collection of histone deacetylase (HDAC) inhibitor analogs named AB1 to AB13, which have different linkers between a metal chelating group and a hydrophobic cap. The purpose of this study was to screen out the most effective compounds and evaluate the therapeutic efficacy. AB2, AB3 and AB10 demonstrated the lowest half-maximal inhibitory concentration (IC50) values in one metastatic follicular and two anaplastic thyroid cancer cell lines. Treatment with each of the three ABs resulted in an increase in apoptosis markers, including cleaved poly adenosine diphosphate ribose polymerase (PARP) and cleaved caspase 3. Additionally, the expression of cell-cycle regulatory proteins p21(WAF1) and p27(Kip1) increased with the treatment of ABs while cyclin D1 decreased. Furthermore, AB2, AB3 and AB10 were able to induce thyrocyte-specific genes in the three thyroid cancer cell lines indicated by increased expression levels of sodium iodide symporter, paired box gene 8, thyroid transcription factor 1 (TTF1), TTF2 and thyroid-stimulating hormone receptors. AB2, AB3 and AB10 suppress thyroid cancer cell growth via cell-cycle arrest and apoptosis. They also induce cell re-differentiation, which could make aggressive cancer cells more susceptible to radioactive iodine therapy.

Thiocoraline activates the Notch pathway in carcinoids and reduces tumor progression in vivo.

Carcinoids are slow-growing neuroendocrine tumors (NETs) that are characterized by hormone overproduction; surgery is currently the only option for treatment. Activation of the Notch pathway has previously been shown to have a role in tumor suppression in NETs. The marine-derived thiodepsipeptide thiocoraline was investigated in vitro in two carcinoid cell lines (BON and H727). Carcinoid cells treated with nanomolar concentrations of thiocoraline resulted in a decrease in cell proliferation and an alteration of malignant phenotype evidenced by decrease of NET markers, achaete-scute complex like-1, chromogranin A and neurospecific enolase. Western blotting analysis demonstrated the activation of Notch1 on the protein level in BON cells. Additionally, thiocoraline activated downstream Notch targets HES1, HES5 and HEY2. Thiocoraline effectively suppressed carcinoid cell growth by promoting cell cycle arrest in BON and H727 cells. An in vivo study demonstrated that thiocoraline, formulated with polymeric micelles, slowed carcinoid tumor progression. Thus the therapeutic potential of thiocoraline, which induced activation of the Notch pathway, in carcinoid tumors was demonstrated.

Sex differences in force attenuation: a clinical assessment of single-leg hop performance on a portable force plate.

OBJECTIVE: Impaired biomechanics and neuromuscular control have been suggested as probable links to female sex bias in the onset of patellofemoral pain syndrome. There are limited objective, clinical measures for assessment of impaired biomechanics and neuromuscular control. The primary objective of this investigation was to examine sex differences in vertical ground reaction force (vGRF) and force loading rate in young athletes performing maximum, repeated vertical single-leg hops (RVSHs). The authors hypothesised that females would demonstrate greater vGRF and force loading rate than males and show interlimb differences in force attenuation. DESIGN: Cross-sectional study. SETTING: Paediatric sports medicine clinic. PARTICIPANTS: 109 Healthy high school, soccer and basketball athletes. ASSESSMENT OF RISK FACTORS: Participants performed RVSHs for 15 seconds on a portable force plate with a sampling rate of 400 Hz (Accupower; AMTI, Watertown, Massachusetts, USA). MAIN OUTCOME MEASUREMENTS: Raw vGRF was filtered with a generalised cross-validation spline using a 50-Hz cutoff frequency and then normalised to potential energy. Force loading rate was calculated by dividing normalised vGRF by time-to-peak force. Group means were compared using analysis of variance. RESULTS: The females demonstrated significantly greater normalised vGRF (p<0.001) and force loading rate (p<0.001) during landing than their male counterparts. Neither sex demonstrated significant interlimb differences in force attenuation (p>0.05). CONCLUSIONS: The female athletes may have altered force attenuation capability during RVSHs as identified by increased vGRF and force loading rate compared with the male athletes. Portable force plates may be potential tools to identify altered force attenuation in clinical settings.