A Randomized Trial of Photobiomodulation Therapy for Center-Involved Diabetic Macular Edema with Good Visual Acuity (Protocol AE).

PURPOSE: To determine if treatment with a photobiomodulation (PBM) device results in greater improvement in central subfield thickness (CST) than placebo in eyes with center-involved diabetic macular edema (CI-DME) and good vision. DESIGN: Phase 2 randomized clinical trial. PARTICIPANTS: Participants had CI-DME and visual acuity (VA) 20/25 or better in the study eye and were recruited from 23 clinical sites in the United States. METHODS: One eye of each participant was randomly assigned 1:1 to a 670-nm light-emitting PBM eye patch or an identical device emitting broad-spectrum white light at low power. Treatment was applied for 90 seconds twice daily for 4 months. MAIN OUTCOME MEASURES: Change in CST on spectral-domain OCT at 4 months. RESULTS: From April 2019 to February 2020, 135 adults were randomly assigned to either PBM (n = 69) or placebo (n = 66); median age was 62 years, 37% were women, and 82% were White. The median device compliance was 92% with PBM and 95% with placebo. OCT CST increased from baseline to 4 months by a mean (SD) of 13 (53) µm in PBM eyes and 15 (57) µm in placebo eyes, with the mean difference (95% confidence interval [CI]) being -2 (-20 to 16) µm (P = 0.84). CI-DME, based on DRCR Retina Network sex- and machine-based thresholds, was present in 61 (90%) PBM eyes and 57 (86%) placebo eyes at 4 months (adjusted odds ratio [95% CI] = 1.30 (0.44-3.83); P = 0.63). VA decreased by a mean (SD) of -0.2 (5.5) letters and -0.6 (4.6) letters in the PBM and placebo groups, respectively (difference [95% CI] = 0.4 (-1.3 to 2.0) letters; P = 0.64). There were 8 adverse events possibly related to the PBM device and 2 adverse events possibly related to the placebo device. None were serious. CONCLUSIONS: PBM as given in this study, although safe and well-tolerated, was not found to be effective for the treatment of CI-DME in eyes with good vision.

The NIH Human Microbiome Project.

The Human Microbiome Project (HMP), funded as an initiative of the NIH Roadmap for Biomedical Research (http://nihroadmap.nih.gov), is a multi-component community resource. The goals of the HMP are: (1) to take advantage of new, high-throughput technologies to characterize the human microbiome more fully by studying samples from multiple body sites from each of at least 250 "normal" volunteers; (2) to determine whether there are associations between changes in the microbiome and health/disease by studying several different medical conditions; and (3) to provide both a standardized data resource and new technological approaches to enable such studies to be undertaken broadly in the scientific community. The ethical, legal, and social implications of such research are being systematically studied as well. The ultimate objective of the HMP is to demonstrate that there are opportunities to improve human health through monitoring or manipulation of the human microbiome. The history and implementation of this new program are described here.

A transcriptional initiator overlaps with a conserved YY1 binding site in the long control region of human papillomavirus type 16.

A single promoter has so far been found in the long control region (LCRs) of human papillomavirus-16 (HPV-16). Multiple promoters exist in the LCRs of several other papillomaviruses, which are spliced to become mRNAs for late and some early genes. Here we have investigated whether such promoters exist in the LCR of HPV-16. In in vitro transcription experiments, we detected a strong transcript starting 280 bp downstream from the 3' end of the L1 gene between a nuclear matrix attachment region and the epithelial-specific enhancer. Promoter activity coincides with a GCCATTTT motif, which binds the transcription factor YY1 (YY1-7436). The A of this motif is the first nucleotide of the transcripts and identifies YY1-7436 as an initiator. Genomic segments with YY1-7436 initiate expression of a luciferase reporter gene in transfection experiments. Mutational analysis of YY1-7436 suggests, however, that promoter function originates from another factor but YY1, which can contact overlapping sequences. Promoter activity of YY1-7436 is modulated by upstream A-T-rich sequences, which bind the basal transcription factor TFIID, and it is stimulated by the viral E2 protein binding to a downstream E2 binding site. In differentiating W12 cells, which contain episomal HPV-16 copies, we detected transcripts including LCR sequences downstream of YY1-7436, which were differentially spliced to early and late genes. However, we could not detect 5' ends mapping to YY1-7436, but we detected two novel HPV-16 promoters within the L1 gene. Conservation of the arrangement of the YY1 and E2 binding sites suggests a role in important biological functions, which, however, is difficult to confirm in every type of cell culture. The study of W12 cells complements the examination of YY1-7436 and points to yet undetected promoters upstream of the LCR.