S-Adenosyl-L-Methionine protects the probiotic yest, \u3cem\u3eSaccharomyces boulardii\u3c/em\u3e, from acid-induced cell death

Background Saccharomyces boulardii is a probiotic yeast routinely used to prevent and to treat gastrointestinal disorders, including the antibiotic-associated diarrhea caused by Clostridium difficile infections. However, only 1-3% of the yeast administered orally is recovered alive in the feces suggesting that this yeast is unable to survive the acidic environment of the gastrointestinal tract. Results We provide evidence that suggests that S. boulardii undergoes programmed cell death (PCD) in acidic environments, which is accompanied by the generation of reactive oxygen species and the appearance of caspase-like activity. To better understand the mechanism of cell death at the molecular level, we generated microarray gene expression profiles of S. boulardii cells cultured in an acidic environment. Significantly, functional annotation revealed that the up-regulated genes were significantly over-represented in cell death pathways Finally, we show that S-adenosyl-L-methionine (AdoMet), a commercially available, FDA-approved dietary supplement, enhances the viability of S. boulardii in acidic environments, most likely by preventing programmed cell death. Conclusions In toto, given the observation that many of the proven health benefits of S. boulardii are dependent on cell viability, our data suggests that taking S. boulardii and AdoMet together may be a more effective treatment for gastrointestinal disorders than taking the probiotic yeast alone

The Los Alamos Supernova Light Curve Project: Computational Methods

We have entered the era of explosive transient astronomy, in which upcoming real-time surveys like the Large Synoptic Survey Telescope (LSST), the Palomar Transient Factory (PTF) and Panoramic Survey Telescope and Rapid Response System (Pan-STARRS) will detect supernovae in unprecedented numbers. Future telescopes such as the James Webb Space Telescope may discover supernovae from the earliest stars in the universe and reveal their masses. The observational signatures of these astrophysical transients are the key to unveiling their central engines, the environments in which they occur, and to what precision they will pinpoint cosmic acceleration and the nature of dark energy. We present a new method for modeling supernova light curves and spectra with the radiation hydrodynamics code RAGE coupled with detailed monochromatic opacities in the SPECTRUM code. We include a suite of tests that demonstrate how the improved physics is indispensable to modeling shock breakout and light curves.Comment: 18 pages, 19 figures, published in ApJ Supplement

Chronic Nicotine Exposure Alters Uninjured Tendon Vascularity and Viscoelasticity

Background: Although nicotine and tobacco use are well established to have adverse health effects, the effects on tendons are less well understood. The purpose of this study was to investigate the effect of chronic nicotine exposure on Achilles tendon (AT) and supraspinatus tendon (SS) physiologic and mechanical properties in a rodent model. Methods: Sprague-Dawley rats (n = 20) were exposed to either 0.9% saline or 36 mg/mL nicotine through an implantable osmotic pump for 12 weeks. At 12 weeks, the AT was imaged in vivo with contrast-enhanced ultrasound (CE-US) to assess vascularity. Bilateral AT and SS were then harvested for ex vivo biomechanical analysis. Statistical analysis was performed using Student t test and Mann Whitney U test. Results: AT CE-US demonstrated a significantly increased wash-in rate in the nicotine group compared to the saline group, indicating an increase in tissue perfusion rate in the nicotine group. AT percent stress relaxation, a measure of tendon viscoelasticity, was significantly increased in the nicotine group compared to the saline group. Similarly, there was a trend toward increased SS percent stress relaxation in the nicotine group compared to the saline group. No differences in other mechanical properties were observed. Conclusion: AT perfusion rate increased and both AT and SS viscoelasticity were altered with chronic nicotine exposure at a clinically relevant dose that models the average smoker in the United States (14 cigarettes per day). Further studies are necessary to link these properties with tendon degeneration and injury. Clinical Relevance: Chronic nicotine exposure affects tendon health. Patients should be counseled as such

Intersecting stigma and HIV testing practices among urban refugee adolescents and youth in Kampala, Uganda: qualitative findings

Introduction: HIV-related risks may be exacerbated in humanitarian contexts. Uganda hosts 1.3 million refugees, of which 60% are aged under 18. There are knowledge gaps regarding HIV testing facilitators and barriers, including HIV and intersecting stigmas, among urban refugee youth. In response, we explored experiences and perspectives towards HIV testing strategies, including HIV self-testing, with urban refugee youth in Kampala, Uganda. Methods: We implemented a qualitative study with refugee cisgender youth aged 16 to 24 living in Kampala's informal settlements from February-April 2019. We conducted five focus groups with refugee youth, including two with adolescent boys and young men, two with adolescent girls and young women and one with female sex workers. We also conducted five key informant (KI) interviews with government, non-government and community refugee agencies and HIV service providers. We conducted thematic analyses to understand HIV testing experiences, perspectives and recommendations. Results: Participants (n = 49) included young men (n = 17) and young women (n = 27) originally from the Democratic Republic of Congo [DRC] (n = 29), Rwanda (n = 11), Burundi (n = 3) and Sudan (n = 1), in addition to five KI (gender: n = 3 women, n = 2 men; country of origin: n = 2 Rwanda, n = 2 Uganda, n = 1 DRC). Participant narratives revealed stigma drivers included fear of HIV infection; misinformation that HIV is a “Ugandan disease”; and blame and shame for sexual activity. Stigma facilitators included legal precarity regarding sex work, same-sex practices and immigration status, alongside healthcare mistreatment and confidentiality concerns. Stigma experiences were attributed to the social devaluation of intersecting identities (sex work, youth, refugees, sexual minorities, people living with HIV, women). Participants expressed high interest in HIV self-testing. They recommended HIV self-testing implementation strategies to be peer supported and expressed concerns regarding sexual- and gender-based violence with partner testing. Conclusions: Intersecting stigma rooted in fear, misinformation, blame and shame, legal precarity and healthcare mistreatment constrain current HIV testing strategies with urban refugee youth. Findings align with the Health Stigma and Discrimination Framework that conceptualizes stigma drivers and facilitators that devalue intersecting health conditions and social identities. Findings can inform multi-level strategies to foster enabling HIV testing environments with urban refugee youth, including tackling intersecting stigma and leveraging refugee youth peer support.Canadian Institutes of Health Research Project Grant. CHL also supported by the Canada Research Chairs Program, Canada Foundation for Innovation, and Ontario Ministry of Research & Innovation