High-Throughput Image-Based Aggresome Quantification.

Aggresomes are subcellular perinuclear structures where misfolded proteins accumulate by retrograde transport on microtubules. Different methods are available to monitor aggresome formation, but they are often laborious, time-consuming, and not quantitative. Proteostat is a red fluorescent molecular rotor dye, which becomes brightly fluorescent when it binds to protein aggregates. As this reagent was previously validated to detect aggresomes, we have miniaturized its use in 384-well plates and developed a method for high-throughput imaging and quantification of aggresomes. Two different image analysis methods, including one with machine learning, were evaluated. They lead to similar robust data to quantify cells having aggresome, with satisfactory Z' factor values and reproducible EC50 values for compounds known to induce aggresome formation, like proteasome inhibitors. We demonstrated the relevance of this phenotypic assay by screening a chemical library of 1280 compounds to find aggresome modulators. We obtained hits that present similarities in their structural and physicochemical properties. Interestingly, some of them were previously described to modulate autophagy, which could explain their effect on aggresome structures. In summary, we have optimized and validated the Proteostat detection reagent to easily measure aggresome formation in a miniaturized, automated, quantitative, and high-content assay. This assay can be used at low, middle, or high throughput to quantify changes in aggresome formation that could help in the understanding of chemical compound activity in pathologies such as protein misfolding disorders or cancer.

State of knowledge on smartphone applications concerning contraception: A systematic review.

AIM: Women's knowledge of contraception is incomplete and a wide variety of information sources are used. Since the advent of smartphones, 325,000 healthcare apps have become available. Our aim is to conduct a literature review on smartphone applications for contraception. METHODS: 15 databases in English, Spanish and French were examined, which included studies published between 2007 and 2018 that describe or compare mobile applications for reversible contraceptive methods and interventional studies. The quality of the studies was assessed using the Cochrane scale or a scale created by the authors. RESULTS: 1786 articles were listed and 22 were included in the main text. In two randomised controlled trials, apps did not influence the choice of a contraceptive method. Two studies showed a significant improvement in knowledge after using an app. Comparative studies reported a large number of apps, the majority of which contained only incomplete information and few interactive features. CONCLUSION: Many applications deal with contraception, but few have reliable and exhaustive information. Further studies are needed to measure the impact of apps on observing compliance.