Lisa A Hark

Analysis of 13 cell types reveals evidence for the expression of numerous novel primate- And tissue-specific microRNAs

Significance MicroRNAs (miRNAs) are small ∼22-nt RNAs that are important regulators of posttranscriptional gene expression. Since their initial discovery, they have been shown to be involved in many cellular processes, and their misexpression is associated with disease etiology. Currently, nearly 2,800 human miRNAs are annotated in public repositories. A key question in miRNA research is how many miRNAs are harbored by the human genome. To answer this question, we examined 1,323 short RNA sequence samples and identified 3,707 novel miRNAs, many of which are human-specific and tissue-specific. Our findings suggest that the human genome expresses a greater number of miRNAs than has previously been appreciated and that many more miRNA molecules may play key roles in disease etiology. Two decades after the discovery of the first animal microRNA (miRNA), the number of miRNAs in animal genomes remains a vexing question. Here, we report findings from analyzing 1,323 short RNA sequencing samples (RNA-seq) from 13 different human tissue types. Using stringent thresholding criteria, we identified 3,707 statistically significant novel mature miRNAs at a false discovery rate of ≤0.05 arising from 3,494 novel precursors; 91.5% of these novel miRNAs were identified independently in 10 or more of the processed samples. Analysis of these novel miRNAs revealed tissue-specific dependencies and a commensurate low Jaccard similarity index in intertissue comparisons. Of these novel miRNAs, 1,657 (45%) were identified in 43 datasets that were generated by cross-linking followed by Argonaute immunoprecipitation and sequencing (Ago CLIP-seq) and represented 3 of the 13 tissues, indicating that these miRNAs are active in the RNA interference pathway. Moreover, experimental investigation through stem-loop PCR of a random collection of newly discovered miRNAs in 12 cell lines representing 5 tissues confirmed their presence and tissue dependence. Among the newly identified miRNAs are many novel miRNA clusters, new members of known miRNA clusters, previously unreported products from uncharacterized arms of miRNA precursors, and previously unrecognized paralogues of functionally important miRNA families (e.g., miR-15/107). Examination of the sequence conservation across vertebrate and invertebrate organisms showed 56.7% of the newly discovered miRNAs to be human-specific whereas the majority (94.4%) are primate lineage-specific. Our findings suggest that the repertoire of human miRNAs is far more extensive than currently represented by public repositories and that there is a significant number of lineage- and/or tissue-specific miRNAs that are uncharacterized.

Diabetes eye screening in urban settings serving minority populations: detection of diabetic retinopathy and other ocular findings using telemedicine.

IMPORTANCE The use of a nonmydriatic camera for retinal imaging combined with the remote evaluation of images at a telemedicine reading center has been advanced as a strategy for diabetic retinopathy (DR) screening, particularly among patients with diabetes mellitus from ethnic/racial minority populations with low utilization of eye care. OBJECTIVE To examine the rate and types of DR identified through a telemedicine screening program using a nonmydriatic camera, as well as the rate of other ocular findings. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional study (Innovative Network for Sight [INSIGHT]) was conducted at 4 urban clinic or pharmacy settings in the United States serving predominantly ethnic/racial minority and uninsured persons with diabetes. Participants included persons aged 18 years or older who had type 1 or 2 diabetes mellitus and presented to the community-based settings. MAIN OUTCOMES AND MEASURES The percentage of DR detection, including type of DR, and the percentage of detection of other ocular findings. RESULTS A total of 1894 persons participated in the INSIGHT screening program across sites, with 21.7% having DR in at least 1 eye. The most common type of DR was background DR, which was present in 94.1% of all participants with DR. Almost half (44.2%) of the sample screened had ocular findings other than DR; 30.7% of the other ocular findings were cataract. CONCLUSIONS AND RELEVANCE In a DR telemedicine screening program in urban clinic or pharmacy settings in the United States serving predominantly ethnic/racial minority populations, DR was identified on screening in approximately 1 in 5 persons with diabetes. The vast majority of DR was background, indicating high public health potential for intervention in the earliest phases of DR when treatment can prevent vision loss. Other ocular conditions were detected at a high rate, a collateral benefit of DR screening programs that may be underappreciated.

The Impact of Visual Field Clusters on Performance-based Measures and Vision-Related Quality of Life in Patients With Glaucoma

PURPOSE To investigate how visual field (VF) clusters affect performance-based measures of the ability to perform activities of daily living and subjective measures of vision-related quality of life (QoL) in patients with glaucoma. DESIGN Prospective, cross-sectional study. METHODS setting: Institutional - Wills Eye Hospital. STUDY POPULATION 322 eyes of 161 patients with moderate-stage glaucoma. OBSERVATION VF tests were conducted using the Humphrey 24-2 Swedish Interactive Thresholding Algorithm standard perimeter. The VFs of each patient were divided into 5 clusters: nasal, temporal, central, paracentral, and peripheral. The score for each cluster was the averaged total deviation scores of all tested points within the cluster. Each cluster score was correlated with performance-based measures of visual function and subjective assessment of vision-related QoL. MAIN OUTCOME MEASURES The Compressed Assessment of Ability Related to Vision, the National Eye Institute Visual Functioning Questionnaire 25 (NEI VFQ-25), and the Modified Glaucoma Symptom Scale. RESULTS The central VF cluster in the better eye was positively correlated with all Compressed Assessment of Ability Related to Vision (performance-based measure) subscales. The strongest correlation for the better eye was between the central VF cluster and total Compressed Assessment of Ability Related to Vision score (0.39, P < .001). The inferior VF hemisphere in both eyes was positively correlated with most Compressed Assessment of Ability Related to Vision subscales. Central VF clusters in the better eye were positively correlated with a majority of the NEI VFQ-25 subscales. There were no significant correlations between VF clusters and Modified Glaucoma Symptom Scale subscales. CONCLUSIONS Scores of central VF defects in the better eye and inferior hemisphere defects in both eyes were positively correlated with performance-based measures of the ability to perform activities of daily living. Glaucoma patients with central defects in the better eye were more likely to have reduced scores on assessments of vision-related QoL.

Clinical outcomes after injection of a compounded pharmaceutical for prophylaxis after cataract surgery: a large-scale review.

Purpose of review To evaluate relevant clinical outcomes following a transzonular intravitreal injection of a compounded triamcinolone–moxifloxacin–vancomycin (TMV) formulation for postoperative prophylaxis after cataract surgery in a retrospective review of medical records from a private practice, single-specialty ambulatory center in New Jersey, USA. Recent findings The analysis included 1541 cases from 922 patients who underwent cataract surgery with an intravitreal injection of TMV from November 2013 to December 2014. Cataract surgery was performed by a standard clear corneal phacoemulsification technique. Transzonular injection was used to deliver TMV directly into the anterior vitreous after implantation of an intraocular lens. Summary There were no major intraoperative complications associated with the transzonular injection technique. There were no cases of postoperative endophthalmitis. Nearly 92% of cases (n = 1413/1541) did not require supplemental medication after surgery. The rate of breakthrough inflammation at Days 14–21 was 9.2% (n = 132/1429). The rate of visually significant postoperative cystoid macular edema was 2.0% (n = 28/1429). The rate of clinically significant postoperative intraocular pressure increase was low: 0.9% (n = 13/1425) of cases had an at least 10 mmHg increase at Days 14–21 or 90. Four of these cases had intraocular pressure at least 30 mmHg. The rates of infection and inflammation reported in this retrospective review of a transzonular injection of TMV for prophylaxis after cataract surgery appear similar to reported rates with alternative prophylactic therapies such as topical drops. The transzonular injection of TMV may have advantages in terms of patient compliance.

IMPACT OF PHYSICIAN COMMUNICATION ON DIABETIC EYE EXAMINATION ADHERENCE: Results From a Retrospective Cohort Analysis.

Purpose: To evaluate the effect of written communication between an ophthalmologist and a primary care physician (PCP) on patient adherence to diabetic eye examination recommendations. Methods: In a retrospective cohort study of a multiethnic population at an urban ophthalmology center, records of all patients with diabetes and clinic visits between 2007 and 2010 were reviewed. Data collected included patient demographics, insurance status, hemoglobin A1C, severity of diabetic retinopathy, follow-up examinations, and written communication between a patients ophthalmologist and PCP. Statistical analyses were performed to examine the relationship between physician communication and adherence to diabetic eye examination based on the American Academy of Ophthalmology–published recommendations. Results: A total of 1,968 people with diabetes were included. Written communication from an ophthalmologist to a PCP was associated with increased adherence to follow-up eye examination recommendations (Odds Ratio: 1.49; 95% Confidence Interval: 1.16–1.92; P = 0.0018). Communication from a PCP to an ophthalmologist was also associated with increased adherence (Odds Ratio: 1.94; 95% Confidence Interval: 1.37–2.77; P = 0.0002). Multivariable analysis controlling for other factors associated with examination adherence confirmed that communication both to and from an ophthalmologist was independently and significantly associated with increased follow-up adherence. Conclusion: Patients with communication between ophthalmologists and PCPs are more likely to adhere to diabetic eye examinations.

Achieving cultural competency

Achieving cultural competency : , Achieving cultural competency : , کتابخانه دیجیتال جندی شاپور اهواز

Improving Access to Eye Care among Persons at High-Risk of Glaucoma in Philadelphia--Design and Methodology: The Philadelphia Glaucoma Detection and Treatment Project.

ABSTRACT Purpose: The Wills Eye Glaucoma Research Center initiated a 2-year demonstration project to develop and implement a community-based intervention to improve detection and management of glaucoma in Philadelphia. Methods: The glaucoma detection examination consisted of: ocular, medical, and family history; visual acuity testing; corneal pachymetry; biomicroscopy of the anterior segment; intraocular pressure (IOP) measurement; gonioscopy; funduscopy; automated visual field testing; and fundus-color photography. Treatment included laser surgery and/or IOP-lowering medication. A cost analysis was conducted to understand resource requirements. Outcome measures included; prevalence of glaucoma-related pathology and other eye diseases among high-risk populations; the impact of educational workshops on level of knowledge about glaucoma (assessed by pre- and post-test evaluation); and patient satisfaction of the glaucoma detection examinations in the community (assessed by satisfaction survey). Treatment outcome measures were change in IOP at 4–6 weeks and 4–6 months following selective laser trabeculoplasty treatment, deepening of the anterior chamber angle following laser-peripheral iridotomy treatment, and rate of adherence to recommended follow-up examinations. Cost outcomes included total program costs, cost per case of glaucoma detected, and cost per case of ocular disease detected. Results: This project enrolled 1649 participants (African Americans aged 50+ years, adults 60+ years and individuals with a family history of glaucoma). A total of 1074 individuals attended a glaucoma educational workshop and 1508 scheduled glaucoma detection examination appointments in the community setting. Conclusions: The Philadelphia Glaucoma Detection and Treatment Project aimed to improve access and use of eye care and to provide a model for a targeted community-based glaucoma program.

An Education- and Telephone-Based Intervention to Improve Follow-up to Vision Care in Patients With Diabetes A Prospective, Single-Blinded, Randomized Trial

The aim was to evaluate the effectiveness of a multipronged intervention on diabetic dilated fundus examination (DFE) adherence. In a prospective trial, 521 patients with diabetes who were due for follow-up DFEs were randomized to usual care or the intervention group. Usual care received a form letter reminder to schedule and an automated reminder phone call prior to their appointment. Intervention participants received an educational brochure about diabetic eye disease and a personalized letter reminder to schedule. A research assistant called intervention participants to help schedule the appointment, and they received a reminder letter and an automated phone call prior to the scheduled visit. Patients in the intervention group were significantly more likely to schedule (63% vs 40%; P < .0001) and complete their appointment (48% vs 30%; P < .0001) compared with usual care. A multipronged intervention, including an educational mailing and telephone assistance with scheduling an appointment, significantly improved diabetic DFE adherence.

Non-adherence to eye care in people with diabetes

Objective Evaluate individual factors that impact adherence to eye care follow-up in patients with diabetes. Design and methods A 4-year retrospective chart review was conducted for 1968 patients with diabetes over age 40 from an urban academic center. Data collected included demographics, insurance, visual acuity, smoking status, medications, dates of dilated fundus examinations (DFE), and reported hemoglobin A1C and blood glucose levels. The primary outcome was timely DFE follow-up adherence following the initial eye exam visit. Results Overall, 41.6% of patients adhered to initial follow-up eye care recommendations. Multivariable analysis demonstrated that patients with severe diabetic retinopathy (DR) were more adherent than patients with mild DR (OR 1.86). Other variables associated with increased adherence were visual impairment and reported A1C or blood glucose. Smoking was associated with decreased adherence. Ethnicity and insurance were also significantly associated with adherence. Longitudinal follow-up rates were influenced by additional factors, including ethnicity and neighborhood deprivation index. Conclusions Patients with moderate to severe DR and/or visual impairment were more likely to adhere to timely DFE follow-up. This could relate to the presence of visual symptoms and/or other systemic manifestations of diabetes. Smokers were less likely to adhere to timely DFE follow-up. One hypothesis is patients who smoke have other symptomatic health problems which patients prioritize over asymptomatic ocular disorders. In order to reduce vision loss from DR, practitioners should be aware that patients with mild and moderate DR, patients with normal vision, and smokers are at greater risk for poor follow-up eye care adherence.

Evaluation of Nonmydriatic Hand-held Optic Disc Photography Grading in the Philadelphia Glaucoma Detection and Treatment Project.

Purpose:To determine the reproducibility of optic disc photograph grading obtained by a hand-held fundus camera and to determine the diagnostic value of these photographs in detecting patients with glaucoma in a community-based glaucoma-detection program. Materials and Methods:Patients underwent slit-lamp examination by an ophthalmologist who graded each patient’s optic discs using 2 methods: cup-to-disc ratio (CDR) and disc damage likelihood scale (DDLS). After a comprehensive glaucoma evaluation, patients were diagnosed as having “glaucoma,” “glaucoma suspect,” or “no glaucoma.” Nonmydriatic, monoscopic optic disc photographs were then taken with a portable digital imaging device. On a different day, the same examiner and a second observer graded the disc photographs in a masked manner and determined a diagnostic impression based only on the disc photographs. Results:Of the 1649 patients examined, 119 subjects were randomly selected according to 3 groups of diagnoses: “glaucoma” (n=36), “glaucoma suspect” (n=50), and “no glaucoma” (n=33). For CDR, the intraobserver agreement was 0.71 and the interobserver agreement was 0.69. For disc DDLS, the intraobserver agreement was 0.65 and the interobserver agreement was 0.67. The area under the receiver-operating characteristic distinguishing between normal and glaucoma was 0.88 and 0.86 for CDR and disc DDLS, respectively. Conclusions:Nonmydriatic, monoscopic disc photographs obtained by a hand-held camera had only moderate disc grading reproducibility. This could be due to a reduced quality of images, making interpretation more challenging, due to taking photographs through small pupils by a hand-held camera and the high percentage of patients with significant cataracts.