Ramalingam S, Daughtridge GW, Johnston MJ, Gracz AD, Magness ST. Distinct levels of Sox9 expression mark colon epithelial stem cells that form colonoids in culture.

Microgravity (µXg) leads to a 10-15% loss of bone mass in astronauts during space flight. Osteoclast (OCL) is the multinucleated bone-resorbing cell. In this study, we used the NASA developed ground-based rotating wall vessel bioreactor (RWV), rotary cell culture system (RCCS) to simulate µXg conditions and demonstrated a significant increase (2-fold) in osteoclastogenesis compared to normal gravity control (Xg). Gene expression profiling of RAW 264.7 OCL progenitor cells in modelled µXg by Agilent microarray analysis revealed significantly increased expression of critical molecules such as cytokines/growth factors, proteases and signalling proteins, which play an important role in enhanced OCL differentiation/function. Transcription factors such as c-Jun, MITF and CREB implicated in OCL differentiation are upregulated; however no significant change in the levels of NFATc1 expression in preosteoclast cells subjected to modelled µXg. We also identified high-level expression of calcium-binding protein, S100A8 (calcium-binding protein molecule A8/calgranulin A) in preosteoclast cells under µXg. Furthermore, modelled µXg stimulated RAW 264.7 cells showed elevated cytosolic calcium (Ca(2+)) levels/oscillations compared to Xg cells. siRNA knock-down of S100A8 expression in RAW 264.7 cells resulted in a significant decrease in modelled µXg stimulated OCL differentiation. We also identified elevated levels of phospho-CREB in preosteoclast cells subjected to modelled µXg compared to Xg. Thus, modelled µXg regulated gene expression profiling in preosteoclast cells provide new insights into molecular mechanisms and therapeutic targets of enhanced OCL differentiation/activation to prevent bone loss and fracture risk in astronauts during space flight missions.

In 2012, the US Food and Drug Administration approved Truvada as a pre-exposure prophylaxis (PrEP) for adults at risk of HIV. PrEP is highly effective at preventing HIV when taken daily, but no gold standard exists for consistently administering PrEP to populations at highest risk. The "I Am Men's Health" program used an innovative methodology to generate adherence to PrEP in 23 mostly young men who have sex with men of color (yMSMc), during a 28-week period from February to September 2013. Adherence was measured using weekly medication pickup rates. The average age of the participants was 21 years, and the majority were black and lived below the poverty line. Time on PrEP ranged from 1 to 28 weeks (2723 person-days), and the weighted average adherence was 73%. The methodology used in this study was preliminarily effective at generating adherence to PrEP among high-risk yMSMc in a community setting and may help inform large-scale future HIV prevention interventions.

Background: Pre-exposure prophylaxis (PrEP) is only effective in preventing new HIV infections when taken consistently. In clinical practice, asking a patient about their adherence (self-report) is the predominant method of assessing adherence to PrEP. Although inexpensive and noninvasive, self-report is subject to social desirability and recall biases. Several clinical trials demonstrate a discrepancy between self-reported adherence and biomarker-based recent adherence. Less is known about the accuracy of self-report in real-world clinical settings. This brief report addresses this knowledge gap and describes the concordance between self-reported adherence and biomarker-based adherence in real-world clinical settings. Methods: A liquid chromatography–mass spectrometry urine test for tenofovir was developed and used clinically to detect recent nonadherence (no dose in at least 48 hours) for each individual. Two clinics' standard operating procedures recommend utilization of the urine-based adherence test for patients who self-report that they are not struggling with adherence. Those who self-report struggling with adherence receive enhanced adherence support without the need for additional testing. The number of results indicating recent nonadherence from these 2 clinics were analyzed to assess the concordance between self-reported adherence and biomarker-based adherence. Results: Across 2 clinics, 3987 tests were conducted from patients self-reporting as “adherent,” and 564 [14.1%; 95% confidence interval (CI): 13.1% to 15.2%] demonstrated recent nonadherence with the liquid chromatography–mass spectrometry test. At clinic #1 in Florida, 3200 tests were conducted, and 465 (14.5%; 95% CI: 13.3% to 15.8%) demonstrated recent nonadherence. At clinic #2 in Texas, 787 tests were conducted, and 99 (12.6%; 95% CI: 10.4% to 14.9%) demonstrated recent nonadherence. Conclusions: Utilization of biomarker-based adherence monitoring at these 2 clinics resulted in 564 additional patients receiving enhanced adherence support who otherwise would not have been identified as nonadherent to their prescribed PrEP regimen. These findings suggest that objective adherence monitoring can be used clinically to enable providers to identify nonadherent patients and allocate support services accordingly.

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