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1.
Anat Sci Educ ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38954745

ABSTRACT

Reduced hours of instruction are reported within the gross anatomy education literature. Anatomy instruction continues to be challenged with motivating and inspiring learners to value the contribution of gross anatomy knowledge to their career development alongside increased organizational demands for efficiency and effectiveness. To address these demands, this retrospective study sought to understand how the relative timing and amount of gross anatomy instruction were related to examination performance. Undergraduate and graduate students between 2018 and 2022 were assigned to three cohorts determined by enrollment in prosection-based anatomy only (n = 334), concurrent enrollment in prosection- and dissection-based anatomy in the same semester (n = 67), or consecutive enrollment in the courses one year apart (n = 43). Concurrent students had higher prosection-based anatomy examination scores than prosection-only and consecutive students. Consecutively, enrolled students outperformed concurrently enrolled students on the first two dissection examinations but showed no performance differences on the third and fourth dissection examinations. While the results on the timing and presentation of anatomical instruction were inconclusive, the results do support increased instructional time using both prosection and dissection modalities concurrently to improve performance on identification-based gross anatomy examinations.

2.
BMJ Open Diabetes Res Care ; 12(1)2024 01 02.
Article in English | MEDLINE | ID: mdl-38167606

ABSTRACT

INTRODUCTION: Diabetic retinopathy (DR) is a leading cause of preventable blindness among working-age adults, primarily driven by ocular microvascular complications from chronic hyperglycemia. Comprehending the complex relationship between microvascular changes in the eye and disease progression poses challenges, traditional methods assuming linear or logistical relationships may not adequately capture the intricate interactions between these changes and disease advances. Hence, the aim of this study was to evaluate the microvascular involvement of diabetes mellitus (DM) and non-proliferative DR with the implementation of non-parametric machine learning methods. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study that included optical coherence tomography angiography (OCTA) images collected from a healthy group (196 eyes), a DM no DR group (120 eyes), a mild DR group (71 eyes), and a moderate DR group (66 eyes). We implemented a non-parametric machine learning method for four classification tasks that used parameters extracted from the OCTA images as predictors: DM no DR versus healthy, mild DR versus DM no DR, moderate DR versus mild DR, and any DR versus no DR. SHapley Additive exPlanations values were used to determine the importance of these parameters in the classification. RESULTS: We found large choriocapillaris flow deficits were the most important for healthy versus DM no DR, and became less important in eyes with mild or moderate DR. The superficial microvasculature was important for the healthy versus DM no DR and mild DR versus moderate DR tasks, but not for the DM no DR versus mild DR task-the stage when deep microvasculature plays an important role. Foveal avascular zone metric was in general less affected, but its involvement increased with worsening DR. CONCLUSIONS: The findings from this study provide valuable insights into the microvascular involvement of DM and DR, facilitating the development of early detection methods and intervention strategies.


Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Adult , Humans , Diabetic Retinopathy/etiology , Diabetic Retinopathy/diagnosis , Retrospective Studies , Retinal Vessels/diagnostic imaging , Tomography, Optical Coherence/methods , Microvessels
3.
Microbiol Resour Announc ; 13(1): e0095423, 2024 Jan 17.
Article in English | MEDLINE | ID: mdl-38032190

ABSTRACT

We describe the genome of a lytic phage EKq1 isolated on Klebsiella quasipneumoniae, with activity against Klebsiella pneumoniae. EKq1 is an unclassified representative of the class Caudoviricetes, similar to Klebsiella phages VLCpiS8c, phiKp_7-2, and vB_KleS-HSE3. The 48,244-bp genome has a GC content of 56.43% and 63 predicted protein-coding genes.

4.
J Clin Microbiol ; 61(12): e0061423, 2023 12 19.
Article in English | MEDLINE | ID: mdl-37962552

ABSTRACT

Standardized approaches to phage susceptibility testing (PST) are essential to inform selection of phages for study in patients with bacterial infections. There is no reference standard for assessing bacterial susceptibility to phage. We compared agreement between PST performed at three centers: two centers using a liquid assay standardized between the sites with the third, a plaque assay. Four Pseudomonas aeruginosa phages: PaWRA01ø11 (EPa11), PaWRA01ø39 (EPa39), PaWRA02ø83 (EPa83), PaWRA02ø87 (EPa87), and a cocktail of all four phages were tested against 145 P. aeruginosa isolates. Comparisons were made within measurements at the two sites performing the liquid assay and between these two sites. Agreement was assessed based on coverage probability (CP8), total deviation index, concordance correlation coefficient (CCC), measurement accuracy, and precision. For the liquid assay, there was satisfactory agreement among triplicate measurements made on different days at site 1, and high agreement based on accuracy and precision between duplicate measurements made on the same run at site 2. There was fair accuracy between measurements of the two sites performing the liquid assay, with CCCs below 0.6 for all phages tested. When compared to the plaque assay (performed once at site 3), there was less agreement between results of the liquid and plaque assays than between the two sites performing the liquid assay. Similar findings to the larger group were noted in the subset of 46 P. aeruginosa isolates from cystic fibrosis. Results of this study suggest that reproducibility of PST methods needs further development.


Subject(s)
Bacteriophages , Cystic Fibrosis , Pseudomonas Infections , Humans , Pseudomonas aeruginosa , Reproducibility of Results , Pseudomonas Infections/drug therapy , Cystic Fibrosis/microbiology , Anti-Bacterial Agents/therapeutic use
5.
Microbiol Resour Announc ; 12(9): e0034123, 2023 Sep 19.
Article in English | MEDLINE | ID: mdl-37607055

ABSTRACT

We describe the genome of a lytic phage EAb13 isolated from sewage, with broad activity against multidrug-resistant Acinetobacter baumannii. EAb13 is an unclassified siphovirus. Its genome consists of 82,411 bp, with 40.15% GC content, 126 protein-coding sequences, 1 tRNA, and 2,177 bp-long direct terminal repeats.

6.
Microbiol Resour Announc ; 12(7): e0019223, 2023 Jul 18.
Article in English | MEDLINE | ID: mdl-37338419

ABSTRACT

We describe the genome of a lytic phage, ESa2, isolated from environmental water and specific for Staphylococcus aureus. ESa2 belongs to the family Herelleviridae and genus Kayvirus. Its genome consists of 141,828 bp, with 30.25% GC content, 253 predicted protein-coding sequences, 3 tRNAs, and 10,130-bp-long terminal repeats.

7.
Anat Histol Embryol ; 52(1): 36-49, 2023 Jan.
Article in English | MEDLINE | ID: mdl-35243669

ABSTRACT

Anatomy faculty with cadaver-based laboratory courses were presented with a significant challenge in March 2020 to create equivalent learning experiences without cadaveric access. The undergraduate domestic animal anatomy course at the Colorado State University was halfway into a 16-week semester when COVID-19 lockdown orders and the transition to remote instruction began. The new course curriculum was critically evaluated using student surveys and course outcome data. Most students (92.5%) agreed that the transition to online learning was a success; however, students who valued face-to-face lectures prior to March were less likely to perceive the transition as a success. Qualitative and quantitative analyses of survey results suggest that the resources perceived as most helpful for the transition to online learning were not the same as those that helped facilitate animal anatomy learning. Most students (92.5%) agreed that the Virtual Animal Anatomy (VAA) helped them learn anatomy, and 82.2% indicated that the VAA was a valuable resource following the transition to online learning. Additional resources associated with transition success included course instructors, weekly quizzes, written descriptions of anatomical structures and open laboratory sessions. In contrast, those resources associated with facilitating learning included guided quizzes and asynchronous lecture recordings. These findings suggest that the VAA can support online anatomy learning when used in conjunction with other best practices for online teaching.


Subject(s)
Anatomy , COVID-19 , Computer-Assisted Instruction , Animals , Humans , Computer-Assisted Instruction/methods , Pandemics , Educational Measurement , COVID-19/epidemiology , COVID-19/veterinary , Communicable Disease Control , Students , Anatomy/education
8.
Trials ; 23(1): 1057, 2022 Dec 28.
Article in English | MEDLINE | ID: mdl-36578069

ABSTRACT

BACKGROUND: Bacteriophages (phages) are a promising anti-infective option for human disease. Major gaps remain in understanding their potential utility. METHODS: This is a randomized, placebo-controlled, double-blind study of a single dose of intravenous phage in approximately 72 clinically stable adult cystic fibrosis volunteers recruited from up to 20 US sites with Pseudomonas aeruginosa airway colonization. The single dose of phage consists of a mixture of four anti-pseudomonal phages. Six sentinel participants will be sequentially enrolled with dose escalation of the phage mixture by one log10 beginning with 4 × 107 plaque-forming units in an unblinded stage 1. If no serious adverse events related to the study product are identified, the trial will proceed to a double-blinded stage 2. In stage 2a, 32 participants will be randomly assigned to one of three phage dosages or placebo in a 1:1:1:1 allocation. An interim analysis will be performed to determine the phage dosage with the most favorable safety and microbiological activity profile to inform phage dosing in stage 2b. During stage 2b, up to 32 additional volunteers will be randomized 1:1 to the phage or placebo arm. Primary outcomes include (1) the number of grade 2 or higher treatment-emergent adverse events, (2) change in log10 P. aeruginosa total colony counts in sputum, and (3) the probability of a randomly selected subject having a more favorable outcome ranking if assigned to receive phage therapy versus placebo. Exploratory outcomes include (1) sputum and serum phage pharmacokinetics, (2) the impact of phage on lung function, (3) the proportion of P. aeruginosa isolates susceptible to the phage mixture before and after study product administration, and (4) changes in quality of life. DISCUSSION: This trial will investigate the activity of phages in reducing P. aeruginosa colony counts and provide insights into the safety profile of phage therapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT05453578. Registered on 12 July 2022.


Subject(s)
Cystic Fibrosis , Phage Therapy , Adult , Humans , Cystic Fibrosis/therapy , Pseudomonas aeruginosa , Double-Blind Method , Quality of Life , Anti-Bacterial Agents , Randomized Controlled Trials as Topic , Multicenter Studies as Topic , Clinical Trials, Phase II as Topic , Clinical Trials, Phase I as Topic
9.
Antibiotics (Basel) ; 11(11)2022 Nov 19.
Article in English | MEDLINE | ID: mdl-36421303

ABSTRACT

Shigellosis is a leading global cause of diarrheal disease and travelers' diarrhea now being complicated by the dissemination of antibiotic resistance, necessitating the development of alternative antibacterials such as therapeutic bacteriophages (phages). Phages with lytic activity against Shigella strains were isolated from sewage. The genomes of 32 phages were sequenced, and based on genomic comparisons belong to seven taxonomic genera: Teetrevirus, Teseptimavirus, Kayfunavirus, Tequatrovirus, Mooglevirus, Mosigvirus and Hanrivervirus. Phage host ranges were determined with a diverse panel of 95 clinical isolates of Shigella from Southeast Asia and other geographic regions, representing different species and serotypes. Three-phage mixtures were designed, with one possessing lytic activity against 89% of the strain panel. This cocktail exhibited lytic activity against 100% of S. sonnei isolates, 97.2% of S. flexneri (multiple serotypes) and 100% of S. dysenteriae serotypes 1 and 2. Another 3-phage cocktail composed of two myophages and one podophage showed both a broad host range and the ability to completely sterilize liquid culture of a model virulent strain S. flexneri 2457T. In a Galleria mellonella model of lethal infection with S. flexneri 2457T, this 3-phage cocktail provided a significant increase in survival.

10.
PLoS Pathog ; 18(5): e1010500, 2022 05.
Article in English | MEDLINE | ID: mdl-35500035

ABSTRACT

Neutralizing antibodies are important correlates of protection against dengue. Yet, determinants of variation in neutralization across strains within the four dengue virus serotypes (DENV1-4) is imperfectly understood. Studies focus on structural DENV proteins, especially the envelope (E), the primary target of anti-DENV antibodies. Although changes in immune recognition (antigenicity) are often attributed to variation in epitope residues, viral processes influencing conformation and epitope accessibility also affect neutralizability, suggesting possible modulating roles of nonstructural proteins. We estimated effects of residue changes in all 10 DENV proteins on antigenic distances between 348 DENV collected from individuals living in Bangkok, Thailand (1994-2014). Antigenic distances were derived from response of each virus to a panel of twenty non-human primate antisera. Across 100 estimations, excluding 10% of virus pairs each time, 77 of 295 positions with residue variability in E consistently conferred antigenic effects; 52 were within ±3 sites of known binding sites of neutralizing human monoclonal antibodies, exceeding expectations from random assignments of effects to sites (p = 0.037). Effects were also identified for 16 sites on the stem/anchor of E which were only recently shown to become exposed under physiological conditions. For all proteins, except nonstructural protein 2A (NS2A), root-mean-squared-error (RMSE) in predicting distances between pairs held out in each estimation did not outperform sequences of equal length derived from all proteins or E, suggesting that antigenic signals present were likely through linkage with E. Adjusted for E, we identified 62/219 sites embedding the excess signals in NS2A. Concatenating these sites to E additionally explained 3.4% to 4.0% of observed variance in antigenic distances compared to E alone (50.5% to 50.8%); RMSE outperformed concatenating E with sites from any protein of the virus (ΔRMSE, 95%IQR: 0.01, 0.05). Our results support examining antigenic determinants beyond the DENV surface.


Subject(s)
Dengue Virus , Dengue , Amino Acids , Animals , Antibodies, Monoclonal , Antibodies, Neutralizing , Antibodies, Viral , Epitopes/genetics , Thailand , Viral Envelope Proteins
11.
Viruses ; 14(4)2022 03 29.
Article in English | MEDLINE | ID: mdl-35458437

ABSTRACT

Providencia rettgeri is an emerging opportunistic Gram-negative pathogen with reports of increasing antibiotic resistance. Pan-drug resistant (PDR) P. rettgeri infections are a growing concern, demonstrating a need for the development of alternative treatment options which is fueling a renewed interest in bacteriophage (phage) therapy. Here, we identify and characterize phage vB_PreP_EPr2 (EPr2) with lytic activity against PDR P. rettgeri MRSN 845308, a clinical isolate that carries multiple antibiotic resistance genes. EPr2 was isolated from an environmental water sample and belongs to the family Autographiviridae, subfamily Studiervirinae and genus Kayfunavirus, with a genome size of 41,261 base pairs. Additional phenotypic characterization showed an optimal MOI of 1 and a burst size of 12.3 ± 3.4 PFU per bacterium. EPr2 was determined to have a narrow host range against a panel of clinical P. rettgeri strains. Despite this fact, EPr2 is a promising lytic phage with potential for use as an alternative therapeutic for treatment of PDR P. rettgeri infections.


Subject(s)
Bacteriophages , Anti-Bacterial Agents , Host Specificity , Providencia/genetics
12.
Vaccine X ; 10: 100143, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35243320

ABSTRACT

INTRODUCTION: Japanese encephalitis (JE) virus is one of the leading causes of viral encephalitis across temperate and tropical zones of Asia. The live attenuated SA 14-14-2 JE vaccine (CD-JEV) is one of three vaccines prequalified by the World Health Organization (WHO) to prevent JE. WHO currently recommends a single CD-JEV dose for infants in endemic settings. However, in the absence of long-term immunogenicity data, WHO has indicated a need for long-term immunogenicity studies to inform optimal dosing schedules and determine the need for booster doses. METHODS: This Phase 4, open-label clinical study measured neutralizing antibody (NAb) titers in Bangladeshi children three and four years after primary CD-JEV vaccination and 7 and 28 days after a booster CD-JEV vaccination given four years after primary vaccination. The study also assessed the tolerability and safety of the booster dose. A NAb titer of ≥1:10 was considered seroprotective. RESULTS: Of 560 children vaccinated between 10 and 12 months of age with CD-JEV three years earlier and enrolled in this study from 30 July 2015 through 03 January 2016, 52 (9.3%; 95% CI: 7.2-12.0) had a seroprotective titer at enrollment. One year later, of 533 children, 66 (12.4%; 95% CI: 9.9-15.5) had a seroprotective titer before receiving a booster dose. Of 524 children who received a booster CD-JEV dose, 479 (91.4%; 95% CI: 88.7-93.5) and 514 (98.1%; 95% CI: 96.5-99.0) were seroprotected 7 and 28 days later, respectively. The geometric mean titer (GMT) was 6 (95% CI: 6-6) at baseline, 105 (95% CI: 93-119) 7 days post-booster, and 167 (95% CI: 152-183) 28 days post-booster. No vaccine-associated neurologic adverse events or other serious adverse events were noted following the booster dose. CONCLUSIONS: Although most children did not have measurable antibody titers three and four years after a single primary CD-JEV dose, more than 90% of seronegative children had a strong anamnestic response within one week of a booster dose. This suggests that these children were immune despite the absence of measurable NAb prior to their booster.ClinicalTrials.gov Identifier: NCT02514746.

13.
Sci Rep ; 12(1): 1400, 2022 01 26.
Article in English | MEDLINE | ID: mdl-35082345

ABSTRACT

We examined the performance of human Schlemm's canal (SC) imaging using different OCT devices: CIRRUS 5000 (840 nm, spectral-domain (SD)-OCT), PLEX Elite 9000 (1060 nm, swept-source (SS)-OCT) and CASIA SS-1000 (1310 nm, SS-OCT), and analyzed potential impact factors on visualization and the quantitative assessment of SC morphology in a pilot study. Ten healthy subjects were imaged using three OCT devices by a single experienced operator on the same day. Each eye underwent two cubic scans by each device, one on nasal and the other on temporal quadrant. The B-scan showing the largest SC was manually selected for processing. Four quantitative metrics, including one morphological metric as cross-sectional area (CSA), and three performance metrics as contrast, continuity, and coverage, were derived from the datasets. Repeated-measures ANOVA was used to investigate the difference between these parameters from the three devices (P < 0.05). We found the CSA measured from CIRRUS was significantly larger than PLEX, followed by CASIA. The contrast was highest in CIRRUS, followed by PLEX and CASIA. The coverage was also higher in CIRRUS as compared to PLEX and CASIA. No significant difference was seen in the continuity from the three devices. In summary, we showed the measurements from the three devices were not interchangeable.


Subject(s)
Limbus Corneae/diagnostic imaging , Sclera/diagnostic imaging , Tomography, Optical Coherence/instrumentation , Trabecular Meshwork/diagnostic imaging , Adult , Female , Glaucoma, Open-Angle/diagnostic imaging , Glaucoma, Open-Angle/pathology , Healthy Volunteers , Humans , Intraocular Pressure , Limbus Corneae/anatomy & histology , Male , Pilot Projects , Sclera/anatomy & histology , Tomography, Optical Coherence/methods , Trabecular Meshwork/anatomy & histology
14.
Mil Med ; 187(5-6): e655-e660, 2022 05 03.
Article in English | MEDLINE | ID: mdl-33428750

ABSTRACT

INTRODUCTION: Dengue fever, caused by any of the four dengue viruses (DENV1-4), is endemic in more than 100 countries around the world. Each year, up to 400 million people get infected with dengue virus. It is one of the most important arthropod-borne viral diseases. Dengue's global presence poses a medical threat to deploying military personnel and their dependents. An accurate diagnosis followed by attentive supportive care can improve outcomes in patients with severe dengue disease. Dengue diagnostic tests based on PCR and ELISA platforms have been developed and cleared by the U.S. FDA. However, these diagnostic assays are laborious and usually require highly trained personnel and specialized equipment, which presents a significant challenge when conducting operations in austere and resource-constrained areas. InBios International, Inc. (Seattle, WA) has developed two rapid and instrument-free immunochromatographic test prototype devices (multiplex and traditional formats) for dengue diagnosis. MATERIALS AND METHODS: To determine the performance of the InBios immunochromatographic tests, 183 clinical samples were tested on both prototype devices. Both assays were performed without any instruments and the results were read in 20 minutes. RESULTS: The traditional format had better overall performance (sensitivity: 97.4%; specificity: 90%) than the multiplex format (sensitivity: 86.9%; specificity: 63.3%). The traditional format was superior in serotype-specific detection with 100% overall sensitivity for DENV1, DENV3, and DENV4 and 93.3% sensitivity for DENV2 compared to the multiplex format (91.7%, 78.3%, 83.3%, and 96.3% for DENV1, 2, 3, and 4, respectively). The traditional format was easier to read than the multiplex format. The multiplex format was simpler and faster to set up than the traditional format. CONCLUSIONS: The InBios traditional format had a better overall performance and readability profile than the multiplex format, while the multiplex format was easier to set up. Both formats were highly sensitive and specific, were easy to perform, and did not require sophisticated equipment. They are ideal for use in resource-limited settings where dengue is endemic. Based on our overall assessment, the traditional format should be considered for further development and used in the upcoming multicenter clinical trial toward FDA clearance.


Subject(s)
Dengue , Antibodies, Viral , Dengue/diagnosis , Enzyme-Linked Immunosorbent Assay/methods , Humans , Nucleic Acid Amplification Techniques , Sensitivity and Specificity
15.
Br J Ophthalmol ; 106(10): 1387-1392, 2022 10.
Article in English | MEDLINE | ID: mdl-33846160

ABSTRACT

AIMS: To validate a deep learning (DL) algorithm (DLA) for 360° angle assessment on swept-source optical coherence tomography (SS-OCT) (CASIA SS-1000, Tomey Corporation, Nagoya, Japan). METHODS: This was a reliability analysis from a cross-sectional study. An independent test set of 39 936 SS-OCT scans from 312 phakic subjects (128 SS-OCT meridional scans per eye) was analysed. Participants above 50 years with no previous history of intraocular surgery were consecutively recruited from glaucoma clinics. Indentation gonioscopy and dark room SS-OCT were performed. Gonioscopic angle closure was defined as non-visibility of the posterior trabecular meshwork in ≥180° of the angle. For each subject, all images were analysed by a DL-based network based on the VGG-16 architecture, for gonioscopic angle-closure detection. Area under receiver operating characteristic curves (AUCs) and other diagnostic performance indicators were calculated for the DLA (index test) against gonioscopy (reference standard). RESULTS: Approximately 80% of the participants were Chinese, and more than half were women (57.4%). The prevalence of gonioscopic angle closure in this hospital-based sample was 20.2%. After analysing a total of 39 936 SS-OCT scans, the AUC of the DLA was 0.85 (95% CI:0.80 to 0.90, with sensitivity of 83% and a specificity of 87%) to classify gonioscopic angle closure with the optimal cut-off value of >35% of circumferential angle closure. CONCLUSIONS: The DLA exhibited good diagnostic performance for detection of gonioscopic angle closure on 360° SS-OCT scans in a glaucoma clinic setting. Such an algorithm, independent of the identification of the scleral spur, may be the foundation for a non-contact, fast and reproducible 'automated gonioscopy' in future.


Subject(s)
Deep Learning , Glaucoma, Angle-Closure , Algorithms , Anterior Eye Segment , Cross-Sectional Studies , Female , Glaucoma, Angle-Closure/diagnosis , Glaucoma, Angle-Closure/surgery , Gonioscopy , Humans , Intraocular Pressure , Male , Reproducibility of Results , Tomography, Optical Coherence/methods
16.
Microbiol Resour Announc ; 10(19)2021 May 13.
Article in English | MEDLINE | ID: mdl-33986073

ABSTRACT

Here, we describe genome sequences of 17 Pseudomonas aeruginosa phages, including therapeutic candidates. They belong to the families Myoviridae, Podoviridae, and Siphoviridae and six different genera. The genomes ranged in size from 42,788 to 88,805 bp, with G+C contents of 52.5% to 64.3% and numbers of coding sequences from 58 to 179.

17.
Diagnostics (Basel) ; 11(4)2021 Apr 01.
Article in English | MEDLINE | ID: mdl-33916081

ABSTRACT

Detection and quantification of viruses in laboratory and clinical samples are standard assays in dengue virus (DENV) studies. The quantitative reverse transcription polymerase chain reaction (qRT-PCR) is considered to be the standard for DENV detection and quantification due to its high sensitivity. However, qRT-PCR offers only quantification relative to a standard curve and consists of several "in-house" components resulting in interlaboratory variations. We developed and optimized a protocol for applying one-step RT-droplet digital PCR (RT-ddPCR) for DENV detection and quantification. The lower limit of detection (LLOD95) and the lower limit of quantification (LLOQ) for RT-ddPCR were estimated to be 1.851 log10-copies/reaction and 2.337 log10-copies/reaction, respectively. The sensitivity of RT-ddPCR was found to be superior to qRT-PCR (94.87% vs. 90.38%, p = 0.039) while no false positives were detected. Quantification of DENV in clinical samples was independently performed in three laboratories showing interlaboratory variations with biases <0.5 log10-copies/mL. The RT-ddPCR protocol presented here could help harmonize DENV quantification results and improve findings in the field such as identifying a DENV titer threshold correlating with disease severity.

18.
Br J Ophthalmol ; 105(3): 426-431, 2021 03.
Article in English | MEDLINE | ID: mdl-32461263

ABSTRACT

BACKGROUND/IMS: To compare the retinal vessel diameter measurements obtained from the swept-source optical coherence tomography angiography (OCTA; Plex Elite 9000, Carl Zeiss Meditec, USA) and adaptive optics ophthalmoscope (AOO; RTX1, Imagine Eyes, France). METHODS: Fifteen healthy subjects, 67% women, mean age (SD) 30.87 (6.19) years, were imaged using OCTA and AOO by a single experienced operator on the same day. Each eye was scanned using two OCTA protocols (3×3 mm2 and 9×9 mm2) and two to five AOO scans (1.2×1.2 mm2). The OCTA and AOO scans were scaled to the same pixel resolution. Two independent graders measured the vessel diameter at the same location on the region-of-interest in the three coregistered scans. Differences in vessel diameter measurements between the scans were assessed. RESULTS: The inter-rater agreement was excellent for vessel diameter measurement in both OCTA protocols (ICC=0.92) and AOO (ICC=0.98). The measured vessel diameter was widest from the OCTA 3×3 mm2 (55.2±16.3 µm), followed by OCTA 9×9 mm2 (54.7±14.3 µm) and narrowest by the AOO (50.5±15.6 µm; p<0.001). Measurements obtained from both OCTA protocols were significantly wider than the AOO scan (OCTA 3×3 mm2: mean difference Δ=4.7 µm, p<0.001; OCTA 9×9 mm2: Δ=4.2 µm, p<0.001). For vessels >45 µm, it appeared to be larger in OCTA 3×3 mm2 scan than the 9×9 mm2 scan (Δ=1.9 µm; p=0.005), while vessels <45 µm appeared smaller in OCTA 3×3 mm2 scan (Δ=-1.3 µm; p=0.009) CONCLUSIONS: The diameter of retinal vessels measured from OCTA scans were generally wider than that obtained from AOO scans. Different OCTA scan protocols may affect the vessel diameter measurements. This needs to be considered when OCTA measures such as vessel density are calculated.


Subject(s)
Fluorescein Angiography/methods , Fovea Centralis/diagnostic imaging , Ophthalmoscopes , Retinal Vessels/diagnostic imaging , Tomography, Optical Coherence/methods , Adult , Equipment Design , Female , Follow-Up Studies , Fundus Oculi , Healthy Volunteers , Humans , Male , Reproducibility of Results , Retrospective Studies
19.
Ophthalmology ; 128(3): 393-400, 2021 03.
Article in English | MEDLINE | ID: mdl-32739337

ABSTRACT

PURPOSE: To evaluate the association between different classes of antihypertensive medication with retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL) thickness in a nonglaucomatous multiethnic Asian population. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: A total of 9144 eyes for RNFL analysis (2668 Malays, 3554 Indians, and 2922 Chinese) and 8549 eyes for GC-IPL analysis (2460 Malays, 3230 Indians, and 2859 Chinese) aged 44 to 86 years. METHODS: Participants underwent standardized systemic and ocular examinations and interviewer-administered questionnaires for collection of data on medication and other variables. Intraocular pressure (IOP) readings were obtained by Goldmann applanation tonometry before pupil dilation for fundoscopy and OCT imaging. Blood pressure (BP) was measured with an automatic BP monitor. Mean arterial pressure (MAP) was defined as diastolic BP plus 1/3 (systolic BP - diastolic BP). Regression models were used to investigate the association of antihypertensive medication with OCT measurements of RNFL and GC-IPL. MAIN OUTCOME MEASURES: Average and sectoral RNFL and GC-IPL thickness. RESULTS: After adjusting for age, gender, ethnicity, MAP, IOP, body mass index (BMI), and presence of diabetes, we found that participants taking any type of antihypertensive medication (ß = -0.83; 95% confidence interval [CI], -1.46 to -0.02; P = 0.01), specifically angiotensin-converting enzyme inhibitors (ACEIs) (ß = -1.66; 95% CI, -2.57 to -0.75; P < 0.001) or diuretics (ß = -1.38; 95% CI, -2.59 to -0.17; P < 0.05), had thinner average RNFL in comparison with participants who were not receiving antihypertensive treatment. Use of a greater number of antihypertensive medications was significantly associated with thinner average RNFL (P for trend = 0.001). This association was most evident in the inferior RNFL quadrant in participants using ACEIs (ß = -2.44; 95% CI, -3.99 to -0.89; P = 0.002) or diuretics (ß = -2.76; 95% CI, -4.76 to -0.76; P = 0.007). A similar trend was noted in our analysis of macular GC-IPL thickness. CONCLUSIONS: Use of 2 or more antihypertensive medications, ACEI, and diuretics were associated with a loss of structural markers of retinal ganglion cell health in a multiethnic Asian population.


Subject(s)
Angiotensin-Converting Enzyme Inhibitors/adverse effects , Antihypertensive Agents/adverse effects , Diuretics/adverse effects , Nerve Fibers/drug effects , Retinal Diseases/chemically induced , Retinal Ganglion Cells/drug effects , Retinal Neurons/drug effects , Adult , Aged , Aged, 80 and over , Arterial Pressure/drug effects , Blood Pressure/drug effects , Cross-Sectional Studies , Female , Humans , Intraocular Pressure , Male , Middle Aged , Nerve Fibers/pathology , Retinal Diseases/diagnosis , Retinal Ganglion Cells/pathology , Retinal Neurons/pathology , Surveys and Questionnaires , Tomography, Optical Coherence , Tonometry, Ocular
20.
Ann Transl Med ; 8(18): 1205, 2020 Sep.
Article in English | MEDLINE | ID: mdl-33241054

ABSTRACT

Optical coherence tomography (OCT) has revolutionized the field of ophthalmology in the last three decades. As an OCT extension, OCT angiography (OCTA) utilizes a fast OCT system to detect motion contrast in ocular tissue and provides a three-dimensional representation of the ocular vasculature in a non-invasive, dye-free manner. The first OCT machine equipped with OCTA function was approved by U.S. Food and Drug Administration in 2016 and now it is widely applied in clinics. To date, numerous methods have been developed to aid OCTA interpretation and quantification. In this review, we focused on the workflow of OCTA-based interpretation, beginning from the generation of the OCTA images using signal decorrelation, which we divided into intensity-based, phase-based and phasor-based methods. We further discussed methods used to address image artifacts that are commonly observed in clinical settings, to the algorithms for image enhancement, binarization, and OCTA metrics extraction. We believe a better grasp of these technical aspects of OCTA will enhance the understanding of the technology and its potential application in disease diagnosis and management. Moreover, future studies will also explore the use of ocular OCTA as a window to link ocular vasculature to the function of other organs such as the kidney and brain.

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