Reductions in HIV Stigma as Measured by Social Distance: Impact of a Stigma Reduction Campaign in a Historically Black University

We evaluated the effectiveness of a small media campaign intervention on a historically African American college campus aimed to lower social distance (willingness to interact) for people with HIV.  A modified version of the Bogardus Social scale was used to measure social distance. The survey included questions regarding HIV transmission knowledge and sympathy felt towards those with HIV. Time between pre-test (n= 207) and post-test (n=210) was 1 month. There was significant change in social distance from pre- to post-test only among women (p<.001).  In a regression analysis transmission knowledge (p=.027), sympathy towards those with HIV (p=.000) and gender (p=.000) were significantly related to social distance.  There was a significance difference between men and women for transmission knowledge (p=.001) and sympathy (p=.001). Small media campaigns can be effective at lowering social distance among female African American students but may need to be modified to be effective among males

Reductions in HIV Stigma as Measured by Social Distance: Impact of a Stigma Reduction Campaign in a Historically Black University

We evaluated the effectiveness of a small media campaign intervention on a historically African American college campus aimed to lower social distance (willingness to interact) for people with HIV.  A modified version of the Bogardus Social scale was used to measure social distance. The survey included questions regarding HIV transmission knowledge and sympathy felt towards those with HIV. Time between pre-test (n= 207) and post-test (n=210) was 1 month. There was significant change in social distance from pre- to post-test only among women (p<.001).  In a regression analysis transmission knowledge (p=.027), sympathy towards those with HIV (p=.000) and gender (p=.000) were significantly related to social distance.  There was a significance difference between men and women for transmission knowledge (p=.001) and sympathy (p=.001). Small media campaigns can be effective at lowering social distance among female African American students but may need to be modified to be effective among males

The Moon Zoo citizen science project: preliminary results for the Apollo 17 landing site

Moon Zoo is a citizen science project that utilises internet crowd-sourcing techniques. Moon Zoo users are asked to review high spatial resolution images from the Lunar Reconnaissance Orbiter Camera (LROC), onboard NASA’s LRO spacecraft, and perform characterisation such as measuring impact crater sizes and identify morphological ‘features of interest’. The tasks are designed to address issues in lunar science and to aid future exploration of the Moon. We have tested various methodologies and parameters therein to interrogate and reduce the Moon Zoo crater location and size dataset against a validated expert survey. We chose the Apollo 17 region as a test area since it offers a broad range of cratered terrains, including secondary-rich areas, older maria, and uplands. The assessment involved parallel testing in three key areas: (1) filtering of data to remove problematic mark-ups; (2) clustering methods of multiple notations per crater; and (3) derivation of alternative crater degradation indices, based on the statistical variability of multiple notations and the smoothness of local image structures. We compared different combinations of methods and parameters and assessed correlations between resulting crater summaries and the expert census. We derived the optimal data reduction steps and settings of the existing Moon Zoo crater data to agree with the expert census. Further, the regolith depth and crater degradation states derived from the data are also found to be in broad agreement with other estimates for the Apollo 17 region. Our study supports the validity of this citizen science project but also recommends improvements in key elements of the data acquisition planning and production

Multiple mechanisms disrupt the let-7 microRNA family in neuroblastoma

Poor prognosis in neuroblastoma is associated with genetic amplification of MYCN. MYCN is itself a target of let-7, a tumour suppressor family of microRNAs implicated in numerous cancers. LIN28B, an inhibitor of let-7 biogenesis, is overexpressed in neuroblastoma and has been reported to regulate MYCN. Here we show, however, that LIN28B is dispensable in MYCN-amplified neuroblastoma cell lines, despite de-repression of let-7. We further demonstrate that MYCN messenger RNA levels in amplified disease are exceptionally high and sufficient to sponge let-7, which reconciles the dispensability of LIN28B. We found that genetic loss of let-7 is common in neuroblastoma, inversely associated with MYCN amplification, and independently associated with poor outcomes, providing a rationale for chromosomal loss patterns in neuroblastoma. We propose that let-7 disruption by LIN28B, MYCN sponging, or genetic loss is a unifying mechanism of neuroblastoma development with broad implications for cancer pathogenesis.United States. National Institutes of Health (R01GM107536)Alex's Lemonade Stand FoundationHoward Hughes Medical InstituteBoston Children's Hospital. Manton Center for Orphan Disease ResearchNational Institute of General Medical Sciences (U.S.) (T32GM007753

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Structure of a β-Alanine-linked Polyamide Bound to a Full Helical Turn of Purine Tract DNA in the 1:1 Motif

Polyamides composed of N-methylpyrrole (Py), N-methylimidazole (Im) and N-methylhydroxypyrrole (Hp) amino acids linked by β-alanine (β) bind the minor groove of DNA in 1:1 and 2:1 ligand to DNA stoichiometries. Although the energetics and structure of the 2:1 complex has been explored extensively, there is remarkably less understood about 1:1 recognition beyond the initial studies on netropsin and distamycin. We present here the 1:1 solution structure of ImPy–β–Im–β–ImPy–β-Dp bound in a single orientation to its match site within the DNA duplex 5′-CCAAAGAGAAGCG-3′·5′-CGCTTCTCTTTGG-3′ (match site in bold), as determined by 2D 1H NMR methods. The representative ensemble of 12 conformers has no distance constraint violations greater than 0.13 Å and a pairwise RMSD over the binding site of 0.80 Å. Intermolecular NOEs place the polyamide deep inside the minor groove, and oriented N–C with the 3′–5′ direction of the purine-rich strand. Analysis of the high-resolution structure reveals the ligand bound 1:1 completely within the minor groove for a full turn of the DNA helix. The DNA is B-form (average rise=3.3 Å, twist=38°) with a narrow minor groove closing down to 3.0–4.5 Å in the binding site. The ligand and DNA are aligned in register, with each polyamide NH group forming bifurcated hydrogen bonds of similar length to purine N3 and pyrimidine O2 atoms on the floor of the minor groove. Each imidazole group is hydrogen bonded via its N3 atom to its proximal guanine's exocyclic amino group. The important roles of β-alanine and imidazole for 1:1 binding are discussed