Diagnostic Abilities of Three-Dimensional Anterior Segment Optical Coherence Tomography in Detecting Angle Closure.

PRCIS: Three-dimensional (3D) angle parameters and cutoff values for detecting angle closure were proposed. The 3D parameters demonstrated excellent diagnostic performance. Certain horizontal two-dimensional (2D) parameters [ie, trabecular iris space area (TISA)-750, angle opening distance (AOD)-750, and AOD-500] can attain similar performance to their high-performing 3D counterparts. OBJECTIVE: To investigate the diagnostic performance of single horizontal 2D versus 3D angle parameters from swept-source anterior segment optical coherence tomography (CASIA2) in detecting angle closure. MATERIALS AND METHODS: The cross-sectional study included 118 phakic patients (59 open angles, 59 closed angles). AOD, angle recess area (ARA), and TISA at 250, 500, and 750 µm from scleral spur were measured in 360-degree radial-scan images. The 3D information of each measurement was analyzed in 2 patterns: (1) average 3D parameter-the averaged value from 360-degree angle values and (2) estimate 3D parameter-the estimation of surface area of circumferential angle inlet (using AOD) or circumferential angle volume (using ARA and TISA). The areas under the receiver operating characteristic curve [areas under the curve (AUCs)] of eighteen 3D parameters were compared with 2D horizontal parameters. RESULTS: Among 3D parameters, AOD-500 estimate 3D gave the highest AUC (AUC: 0.950, cutoff: 6.09 mm 2 ), followed by AOD-750 estimate 3D (AUC: 0.948, cutoff: 8.26 mm 2 ). 3D parameters significantly increased the AUC of ARA-250 and TISA-250 (all P < 0.02) compared with the 2D parameters. No significant improvement in AUC was demonstrated for AOD-250 and all parameters at 500 and 750 µm. No significant difference in AUC was found among the 6 maximum AUC parameters, which were AOD-750 horizontal 2D, AOD-500 estimate 3D, TISA-750 horizontal 2D, AOD-500 horizontal 2D, AOD-750 estimate 3D, and TISA-750 average 3D. CONCLUSIONS: The 3D-angle parameters had high performance in detecting angle closure. However, comparing a horizontal measurement to 3D parameters, the AUC improvement was mostly insignificant.

Genetic regulation and targeted reversal of lysosomal dysfunction and inflammatory sterol metabolism in pulmonary arterial hypertension.

Vascular inflammation critically regulates endothelial cell (EC) pathophenotypes, particularly in pulmonary arterial hypertension (PAH). Dysregulation of lysosomal activity and cholesterol metabolism have known inflammatory roles in disease, but their relevance to PAH is unclear. In human pulmonary arterial ECs and in PAH, we found that inflammatory cytokine induction of the nuclear receptor coactivator 7 (NCOA7) both preserved lysosomal acidification and served as a homeostatic brake to constrain EC immunoactivation. Conversely, NCOA7 deficiency promoted lysosomal dysfunction and proinflammatory oxysterol/bile acid generation that, in turn, contributed to EC pathophenotypes. In vivo, mice deficient for Ncoa7 or exposed to the inflammatory bile acid 7α-hydroxy-3-oxo-4-cholestenoic acid (7HOCA) displayed worsened PAH. Emphasizing this mechanism in human PAH, an unbiased, metabolome-wide association study (N=2,756) identified a plasma signature of the same NCOA7-dependent oxysterols/bile acids associated with PAH mortality (P<1.1x10-6). Supporting a genetic predisposition to NCOA7 deficiency, in genome-edited, stem cell-derived ECs, the common variant intronic SNP rs11154337 in NCOA7 regulated NCOA7 expression, lysosomal activity, oxysterol/bile acid production, and EC immunoactivation. Correspondingly, SNP rs11154337 was associated with PAH severity via six-minute walk distance and mortality in discovery (N=93, P=0.0250; HR=0.44, 95% CI [0.21-0.90]) and validation (N=630, P=2x10-4; HR=0.49, 95% CI [0.34-0.71]) cohorts. Finally, utilizing computational modeling of small molecule binding to NCOA7, we predicted and synthesized a novel activator of NCOA7 that prevented EC immunoactivation and reversed indices of rodent PAH. In summary, we have established a genetic and metabolic paradigm and a novel therapeutic agent that links lysosomal biology as well as oxysterol and bile acid processes to EC inflammation and PAH pathobiology. This paradigm carries broad implications for diagnostic and therapeutic development in PAH and in other conditions dependent upon acquired and innate immune regulation of vascular disease.

Expression of chicken epidermal growth factor (cEGF) in Escherichia coli regulates the microflora structure of the duodenum to improve growth performance and intestinal morphogenesis in broilers.

1. A study used gene synthesis to obtain the functional domains of chicken epidermal growth factor (cEGF) and examined their impact on broiler growth performance, small intestinal morphology, digestive enzyme activities in the intestinal contents and the structure of duodenal microflora.2. The pET-32a-cEGF recombinant expression vector was constructed. The specific band at 26 KDa was shown by SDS-PAGE analysis and WB results. The purified protein content was shown to be 1687 µg/ml by assay.3. A total of 180 healthy, one-day-old Arbor Acres male, white-feathered broilers were randomly divided into three dietary treatment groups (six replicate pens, 10 birds per replicate): A control diet (ND); cEGF diet (cEGF), control supplemented with 250 mg/kg cEGF and the control diet (CD) supplemented with 250 mg/kg chlortetracycline.4. The results showed that feeding the cEGF and CD diet reduced FCR of broilers aged 1-21 d, average daily feed intake (ADFI) at 22-42 d, and the FCR in the whole period (1-42 d; p < 0.05). Compared with the ND group, the cEGF diet increased duodenal α-amylase and alkaline phosphatase activities in the 1-21 d, duodenal lipase, alkaline phosphatase, and ileal alkaline phosphatase activities in the post-period and increased villus height in the duodenum and ileum (p < 0.05). In addition, the ACE and Chao1 index for the birds fed cEGF were higher than the ND group (p < 0.05). At the phyla level, Firmicutes and Proteobacteria were dominant in all groups. At the genus level, the dominant genus was Lactobacillus. The LEfSe analysis showed that the cEGF group was enriched by 11 species including Brevibacillus, Eisenbergiella, Cloacibacterium, Butyricoccus spp.5. The addition of 250 mg/kg cEGF to the diet can increase growth performance by improving intestinal development and digestive enzyme activity, which may be related to the duodenal intestinal microflora. Therefore, cEGF is an effective alternative to antibiotics in broiler farming.

[Disseminated nocardiosis caused by Nocardia otitidiscaviarum in an immunocompetent host: a case report].

Nocardiosis can be caused by various Nocardia spp., including Nocardia asteroides, Nocardia brasiliensis, Nocardia cyriacigeorgica, Nocardia farcinica and Nocardia otitidiscaviarum. As compared with the other Nocardia spp., Nocardia otitidiscaviarum appears to be rare which can spread through the bloodstream and affect multiple organs. The disease is usually seen in immunocompromised patients' but may also occur in immunocompetent patients. The clinical symptoms and laboratory and imaging examinations of the disease are nonspecific.Here, we reported a case of disseminated nocardiosis caused by infection with Nocardiosis otitidiscaviarum in an immunocompetent host to improve the knowledge and diagnosis of nocardiosis.

[Incidence and prognosis of olfactory and gustatory dysfunctions related to infection of SARS-CoV-2 Omicron strain: a national multi-center survey of 35 566 population].

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.

Lithium chloride promotes neural functional recovery after local cerebral ischaemia injury in rats through Wnt signalling pathway activation.

BACKGROUND: Lithium chloride (LiCl) has a significant neuroprotective effect in cerebral ischaemia. However, to date, there is a paucity of evidence on the role of LiCl in neural restoration after brain ischaemia and the signalling pathways involved remain unclear. MATERIALS AND METHODS: Therefore, to address this gap, the middle cerebral artery occlusion (MCAO) rat model was used to simulate human ischaemia stroke. Male Sprague-Dawley rats were given MCAO for 90 min followed by reperfusion, and Dickkopf-1 (DKK1, 5.0 µg/kg) was administered half an hour before MCAO. Rats were then treated with hypodermic injection of LiCl (2.0 mmol/kg) twice a day for 1 week. After treatment, cognitive impairment was assessed by the Morris water maze test. Neurological deficit score, 2,3,5-triphenyl tetrazolium chloride staining, brain water content, and histopathology were used to evaluate brain damage. Enzyme-linked immunosorbent assay was used to measure oxidative stress damage and inflammatory cytokines. Apoptosis of the hippocampal neurons was tested by western blot. The key factors of Wnt signalling pathway in the ischaemic penumbra were detected by immunofluorescence staining and quantitative real-time polymerase chain reaction. RESULTS: Current experimental results showed that LiCl treatment significantly improved the impaired spatial learning and memory ability, suppressed oxidative stress, inflammatory reaction, and neuron apoptosis accompanied by attenuating neuronal damage, which subsequently decreased the brain oedema, infarct volume and neurological deficit. Furthermore, the treatment of LiCl activated Wnt signalling pathway. Interestingly, the aforementioned effects of LiCl treatment were markedly reversed by administration of DKK1, an inhibitor of Wnt signalling pathway. CONCLUSIONS: These results indicate that LiCl exhibits neuroprotective effects in focal cerebral ischaemia by Wnt signalling pathway activation, and it might have latent clinical application for the prevention and treatment of ischaemic stroke.

Ciliochoroidal effusion and its association with the outcomes of micropulse transscleral laser therapy in glaucoma patients: a pilot study.

We investigate the development of ciliochoroidal effusion following micropulse transscleral laser therapy (MPTLT) and evaluate the relationship between the early postoperative ciliochoroidal effusion (ECE) and short-term treatment outcomes. Glaucoma patients who underwent MPTLT were assessed for ciliochoroidal effusion by anterior segment optical coherence tomography (AS-OCT) at postoperative 1, 4, 12 weeks. The subjects were classified based on AS-OCT findings at postoperative 1 week into eyes with and without ECE. The absolute intraocular pressure (IOP), IOP reduction and number of antiglaucoma medications were compared between eyes with and without ECE. A total of 50 eyes were included, of which 23 (46%) developed ciliochoroidal effusion at postoperative 1 week. Almost all effusion resolved at 4 weeks. At 12 weeks, the mean IOP (SD) significantly decreased from 28.5 (12.8) mmHg to 17.8 (10.5) mmHg (p < 0.001), and the mean number of medications (SD) decreased from 4.1 (0.9) to 3.3 (1.1) (p < 0.001). Eyes with ECE had significantly greater IOP reduction (p = 0.009) and lower absolute IOP (p = 0.008) at the 4-week visit. There was no significant difference in number of medications between the groups. In conclusion, ciliochoroidal effusion was commonly observed following MPTLT. Eyes with ECE had overall greater IOP reduction during early post-operation.

Dephosphorylation of Y228 and Y217 and phosphorylation of Y335 in p120 catenin activate convergent extension during zebrafish gastrulation.

BACKGROUND: The cadherin-associated protein p120 catenin regulates convergent extension through interactions with cadherin proteins, Cdc42, and Rac1, as we previously showed in zebrafish (Danio rerio). Phosphorylation of p120 catenin changes the nature of its activity in vitro but is virtually unexplored in embryos. We used our previously developed antisense RNA splice-site morpholino targeted to endogenous p120 catenin-δ1 to cause defects in axis elongation probing the functions of three p120 catenin tyrosine-phosphorylation sites in gastrulating zebrafish embryos. RESULTS: The morpholino-induced defects were rescued by co-injections with mouse p120 catenin-δ1-3A mRNAs mutated at residues Y228 and Y217 to a non-phosphorylatable phenylalanine (F) or mutated at residue Y335 to a phosphomimetic glutamic acid (E). Co-injection of the complementary mutations Y228E, Y217E, or Y335F mRNAs partially rescued embryos whereas dual mutation to Y228E-Y217E blocked rescue. Immunopurification showed Y228F mutant proteins preferentially interacted with Rac1, potentially promoting cell migration. In contrast, the phosphomimetic Y228E preferentially interacted with E-cadherin increasing adhesion. Both Y228F and Y335F strongly bind VAV2. CONCLUSIONS: p120 catenin serves dual roles during gastrulation of zebrafish. Phosphorylation and dephosphorylation of tyrosine residues Y217, Y228, and Y335 precisely balance cell adhesion and cell migration to facilitate somite compaction and axis elongation.

[A pedigree study of Loeys-Dietz syndrome type 4 with skeletal deformity related to a novel TGFß2 mutation].

Objective: Loeys-Dietz syndrome is a rare type of hereditary connective tissue disease. This study was aimed to analyze the clinical characteristics and gene mutations in a family of Loeys-Dietz syndrome with skeletal deformity. Methods: Clinical data of the proband and family members were collected and biochemical measurements and radiological examinations were conducted. Genomic DNA was extracted from peripheral blood of the family members. Whole-exome sequencing was performed to determine the mutation sites in the proband, and Sanger sequencing was applied to verify the candidate mutation in the other family members. Results: The proband is a 34-year-old man with deformities of lower extremities for more than 30 years. Physical examinations showed dolichostenomelia, pes planus, joint laxity and scoliosis. Echocardiography revealed the dilatation of aortic root at the level of the sinuses of Valsalva. A heterozygous missense mutation (c. 220A>C, p.Thr74Pro) in exon 1 of TGFß2 gene was identified in the proband. The same mutation was detected in his sister and niece with similar clinical features such as deformities of lower extremities and pes planus. This novel mutation has not been reported in ExAC or 1000G and was predicted to be deleterious, supporting a diagnosis of Loeys-Dietz syndrome type 4. Conclusions: Loeys-Dietz syndrome type 4 is caused by TGFß2 mutations. Skeletal deformity is one of the distinctive features. Genetic testing is helpful for the early diagnosis and differential diagnosis from other connective tissue diseases.

Association between Daily Niacin Intake and Glaucoma: National Health and Nutrition Examination Survey.

BACKGROUND AND AIMS: To determine the relationship between dietary intake of niacin and glaucoma using the data from the 2005 to 2008 National Health and Nutrition Examination Survey (NHANES). METHODS: Subjects aged 40 years and older who participated in the dietary intake interview and vision health questionnaire of NHANES were included in the study. Glaucoma diagnosis by self-report was utilized. Additionally, glaucoma diagnosis by fundus imaging and International Society Geographical and Epidemiological Ophthalmology (ISGEO) criteria was used in subjects with available qualified retinal imaging. Survey logistic regression analyses were used to examine the association between daily niacin consumption and glaucoma. RESULTS: A total of 5768 participants were included in the study. There was a significant decrease in the crude odds of self-reported glaucoma in the third (OR 0.57, 95% Cl 0.43-0.76; p < 0.001) and fourth (OR 0.57, 95% Cl 0.37-0.90; p = 0.018) quartiles of daily niacin consumption, which equated to 21.01 to 28.22 mg/day and greater than 28.22 mg/day, respectively. A similar trend was found using fundus imaging of subjects with niacin intake in the third (OR 0.42, 95% Cl 0.25-0.72; p = 0.002) and fourth (OR 0.36, 95% Cl 0.20-0.67; p = 0.002) quartiles. After adjusting for covariates, the odds of glaucoma based on fundus imaging remained significantly lower for niacin intake in the third (OR 0.49, 95% Cl 0.28-0.87; p = 0.016) and fourth (OR 0.48, 95% Cl 0.26-0.89; p = 0.022) quartile levels. Using ISGEO criteria, there was no significant association between glaucoma and daily niacin consumption. CONCLUSIONS: Greater niacin intake may be associated with a lower chance of developing glaucoma.

Individuals with and without normal tension glaucoma exhibit comparable performance on tests of cognitive function.

AIM: To evaluate aspects of cognition impacted by individuals with and without normal tension glaucoma. METHODS: Fifty normal tension glaucoma (NTG) and 50 control patients ≥50y of age were recruited from the UCSF Department of Ophthalmology. Demographic data and glaucoma parameters were extracted from electronic medical records for both groups. Tests of executive function [Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (EXAMINER)] and learning and memory [California Verbal Learning Test-Second Edition (CVLT-II)] were administered to both NTG and controls. Race, handedness, best-corrected visual acuity, maximum intraocular pressure, optic nerve cup-to-disc ratio, visual field and optic nerve optical coherence tomography parameters, and a measure of general health (Charlson Comorbidity Index) were compared between NTG and controls as well as within NTG subgroups. Multivariate linear regression was used to compare group performances on the EXAMINER battery and CVLT-II while controlling for age, sex, and years of education. RESULTS: NTG and controls were comparable with respect to age, sex, race, education, handedness, and the Charlson Comorbidity Index (P>0.05 for all). Performance on the EXAMINER composite score and the CVLT-II did not differ between NTG and controls (P>0.05 for both). CONCLUSION: This is the first prospective study in which the cognitive function of subject with NTG were evaluated using a comprehensive, computerized neurocognitive battery. Subjects with NTG do not perform worse than unaffected controls on tests of executive function, learning, and memory. Results do not support the hypothesis that individuals with NTG are at higher risk for cognitive dysfunction and/or dementia.

Displacement between anterior chamber width obtained by swept-source anterior segment optical coherence tomography and white-to-white distance.

PURPOSE: To determine the relationship between the external limbal location, represented by white-to-white (WTW) distance, and the actual angle location, represented by spur-to-spur (STS) and angle-to-angle (ATA) distances. METHODS: 166 eyes from 166 participants were imaged using CASIA2 anterior chamber optical coherence tomography (AS-OCT) and LenStar LS 900 optical biometer. The horizontal ATA and STS were measured using the swept-source Fourier-domain AS-OCT (CASIA2). The horizontal WTW was automatically measured using LenStar. The displacement lengths (DL) between WTW-STS and WTW-ATA were calculated. Bland-Altman plots and intraclass correlation were performed. RESULTS: The study showed that WTW has a positive correlation with STS (ICC = 0.82, p<0.001) and ATA (ICC = 0.82, p<0.001). The Bland-Altman analysis demonstrated that the mean difference of WTW-STS is 0.10 mm (95% CI 0.06 to 0.14 mm) with limits of agreement of -0.42 to 0.63 mm between WTW and STS, and the mean difference of WTW-ATA is 0.10 mm (95% CI 0.06 to 0.15 mm) with limits of agreement of -0.48 to 0.64 mm between WTW and ATA. Linear regression with adjustment showed that a WTW value greater than 12.07 mm is associated with a greater DL (WTW-STS DL ß 0.18, p = 0.003; WTW-ATA DL ß 0.14, p = 0.03). CONCLUSIONS: Greater WTW was significantly associated with higher displacement of WTW from the two distances representing anterior chamber width. External limbal location may not accurately represent the actual angle location in eyes with larger WTW.

Simultaneous Pharmacologic Inhibition of Yes-Associated Protein 1 and Glutaminase 1 via Inhaled Poly(Lactic-co-Glycolic) Acid-Encapsulated Microparticles Improves Pulmonary Hypertension.

Background Pulmonary hypertension (PH) is a deadly disease characterized by vascular stiffness and altered cellular metabolism. Current treatments focus on vasodilation and not other root causes of pathogenesis. Previously, it was demonstrated that glutamine metabolism, as catalyzed by GLS1 (glutaminase 1) activity, is mechanoactivated by matrix stiffening and the transcriptional coactivators YAP1 (yes-associated protein 1) and transcriptional coactivator with PDZ-binding motif (TAZ), resulting in pulmonary vascular proliferation and PH. Pharmacologic inhibition of YAP1 (by verteporfin) or glutaminase (by CB-839) improved PH in vivo. However, systemic delivery of these agents, particularly YAP1 inhibitors, may have adverse chronic effects. Furthermore, simultaneous use of pharmacologic blockers may offer additive or synergistic benefits. Therefore, a strategy that delivers these drugs in combination to local lung tissue, thus avoiding systemic toxicity and driving more robust improvement, was investigated. Methods and Results We used poly(lactic-co-glycolic) acid polymer-based microparticles for delivery of verteporfin and CB-839 simultaneously to the lungs of rats suffering from monocrotaline-induced PH. Microparticles released these drugs in a sustained fashion and delivered their payload in the lungs for 7 days. When given orotracheally to the rats weekly for 3 weeks, microparticles carrying this drug combination improved hemodynamic (right ventricular systolic pressure and right ventricle/left ventricle+septum mass ratio), histologic (vascular remodeling), and molecular markers (vascular proliferation and stiffening) of PH. Importantly, only the combination of drug delivery, but neither verteporfin nor CB-839 alone, displayed significant improvement across all indexes of PH. Conclusions Simultaneous, lung-specific, and controlled release of drugs targeting YAP1 and GLS1 improved PH in rats, addressing unmet needs for the treatment of this deadly disease.

Frataxin deficiency promotes endothelial senescence in pulmonary hypertension.

The dynamic regulation of endothelial pathophenotypes in pulmonary hypertension (PH) remains undefined. Cellular senescence is linked to PH with intracardiac shunts; however, its regulation across PH subtypes is unknown. Since endothelial deficiency of iron-sulfur (Fe-S) clusters is pathogenic in PH, we hypothesized that a Fe-S biogenesis protein, frataxin (FXN), controls endothelial senescence. An endothelial subpopulation in rodent and patient lungs across PH subtypes exhibited reduced FXN and elevated senescence. In vitro, hypoxic and inflammatory FXN deficiency abrogated activity of endothelial Fe-S-containing polymerases, promoting replication stress, DNA damage response, and senescence. This was also observed in stem cell-derived endothelial cells from Friedreich's ataxia (FRDA), a genetic disease of FXN deficiency, ataxia, and cardiomyopathy, often with PH. In vivo, FXN deficiency-dependent senescence drove vessel inflammation, remodeling, and PH, whereas pharmacologic removal of senescent cells in Fxn-deficient rodents ameliorated PH. These data offer a model of endothelial biology in PH, where FXN deficiency generates a senescent endothelial subpopulation, promoting vascular inflammatory and proliferative signals in other cells to drive disease. These findings also establish an endothelial etiology for PH in FRDA and left heart disease and support therapeutic development of senolytic drugs, reversing effects of Fe-S deficiency across PH subtypes.

Comparative Analysis of Fiber Alignment Methods in Electrospinning.

Fabrication of anisotropic materials is highly desirable in designing biomaterials and tissue engineered constructs. Electrospinning has been broadly adopted due to its versatility in producing non-woven fibrous meshes with tunable fiber diameters (from 10 nanometers to 10 microns), microarchitectures, and construct geometries. A myriad of approaches have been utilized to control fiber alignment of electrospun materials to achieve complex microarchitectures, improve mechanical properties, and provide topographical cellular cues. This review provides a comparative analysis of the techniques developed to generate fiber alignment in electrospun materials. A description of the underlying mechanisms that drive fiber alignment, setup variations for each technique, and the resulting impact on the aligned microarchitecture is provided. A critical analysis of the advantages and limitations of each approach is provided to guide researchers in method selection. Finally, future perspectives of advanced electrospinning methodologies are discussed in terms of developing a scalable method with precise control of microarchitecture.

Ethnicity-Specific Database Improves the Diagnostic Ability of Peripapillary Retinal Nerve Fiber Layer Thickness to Detect Glaucoma.

PURPOSE: To determine the changes in optical coherence tomography (OCT) color probability codes and diagnostic ability for peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell complex (GCC) analysis after applying Chinese and white subjects normative databases. DESIGN: Cross-sectional study. METHODS: This study enrolled 219 healthy eyes (108 white and 111 Chinese patients) to construct an ethnicity-specific normative database for pRNFL and macular GCC thickness, which was tested then in 180 eyes with or without glaucoma (102 white and 78 Chinese patients). The percent of change of color probability codes were evaluated after applying the original built-in and the ethnicity-specific normative databases, respectively. Sensitivity and specificity were calculated to evaluate the change in diagnostic ability to detect glaucoma. RESULTS: Healthy white subjects had a thinner pRNFL than Chinese subjects in the overall average thickness as well as the superior, inferior, and temporal quadrants (P < .001). Macular GCC did not differ between ethnicities. After applying an ethnicity-specific normative database, the percent of pRNFL abnormal color code labels decreased significantly for the overall average thickness in the white subjects. This resulted in a significant increase in the specificity to detect glaucoma in the white population (P < .001). No significant changes were seen when applying an ethnicity-specific normative database for macular GCC thickness. CONCLUSIONS: After applying an ethnicity-specific normative database, the percent of pRNFL abnormal color codes decreased significantly, improving the specificity to detect glaucoma in the white population. These findings suggest there may be utility in having ethnicity-specific normative databases for pRNFL thickness.

Intraocular Pressure Changes after Cataract Surgery in Patients with and without Glaucoma: An Informatics-Based Approach.

PURPOSE: To evaluate changes in intraocular pressure (IOP) after cataract surgery among patients with or without glaucoma using automated extraction of data from electronic health records (EHRs). DESIGN: Retrospective cohort study. PARTICIPANTS: Adults who underwent standalone cataract surgery at a single academic center from 2009-2018. METHODS: Patient information was identified from procedure and billing codes, demographic tables, medication orders, clinical notes, and eye examination fields in the EHR. A previously validated natural language processing pipeline was used to identify laterality of cataract surgery from operative notes and laterality of eye medications from medication orders. Cox proportional hazards modeling evaluated factors associated with the main outcome of sustained postoperative IOP reduction. MAIN OUTCOME MEASURES: Sustained post-cataract surgery IOP reduction, measured at 14 months or the last follow-up while using equal or fewer glaucoma medications compared with baseline and without additional glaucoma laser or surgery on the operative eye. RESULTS: The median follow-up for 7574 eyes of 4883 patients who underwent cataract surgery was 244 days. The mean preoperative IOP for all patients was 15.2 mmHg (standard deviation [SD], 3.4 mmHg), which decreased to 14.2 mmHg (SD, 3.0 mmHg) at 12 months after surgery. Patients with IOP of 21.0 mmHg or more showed mean postoperative IOP reduction ranging from -6.2 to -6.9 mmHg. Cataract surgery was more likely to yield sustained IOP reduction for patients with primary open-angle glaucoma (hazard ratio [HR], 1.19; 95% confidence interval, 1.05-1.36) or narrow angles or angle closure (HR, 1.21; 95% confidence interval, 1.08-1.34) compared with patients without glaucoma. Those with a higher baseline IOP were more likely to achieve postoperative IOP reduction (HR, 1.06 per 1-mmHg increase in baseline IOP; 95% confidence interval, 1.05-1.07). CONCLUSIONS: Our results suggest that patients with primary open-angle glaucoma or with narrow angles or chronic angle closure were more likely to achieve sustained IOP reduction after cataract surgery. Patients with higher baseline IOP had increasingly higher odds of achieving reduction in IOP. This evidence demonstrates the potential usefulness of a pipeline for automated extraction of ophthalmic surgical outcomes from EHR to answer key clinical questions on a large scale.

Comparison of 1-Year Effectiveness of Trabecular Microbypass Stent implantation (iStent) in Conjunction With Phacoemulsification Among Mild, Moderate, and Severe Primary Open-angle Glaucoma Patients.

PRECIS: The study compared 1-year effectiveness of single trabecular microbypass stent (iStent) implantation with phacoemulsification among glaucoma severities in primary open-angle glaucoma. The study found that mild glaucoma had greater success rate and lower number of medications compared with moderate and severe glaucoma. PURPOSE: To evaluate the effectiveness of iStent implantation in combination with cataract surgery in moderate to severe glaucoma compared with mild glaucoma. METHODS: Medical charts of primary open-angle glaucoma subjects undergoing 1 iStent implantation were retrospectively reviewed. Glaucoma was classified on the basis of mean deviation (MD) of the preoperative standard automated perimetry into mild (MD>-6 dB), moderate (MD -6 to -12 dB), and severe (MD<-12 dB). Mixed effect regression models were performed to determine the effect of iStent at 1 year. The outcomes included as follows: (1) intraocular pressure (IOP) and the number of medications, (2) eyes with IOP ≤ severity-based target (18 mm Hg for mild, 15 mm Hg for moderate, 12 mm Hg for severe) (2A) without medication, and (2B) with medication reduction. RESULTS: In total, 104 eyes from 89 subjects were analyzed. Cataract combined with iStent surgery significantly lowered the number of medications in all groups and significantly decreased IOP in moderate and severe glaucoma (P<0.05). There was significantly higher number of medications in moderate (ß: 0.58, P=0.002) and severe (ß: 1.20, P<0.001) compared with mild glaucoma. Eyes with moderate glaucoma had significantly lower rate of success (criterion 2A) compared with mild glaucoma [odds ratio (OR): 0.008, P=0.047]. Eyes with moderate and severe glaucoma had significantly lower rates of success (criterion 2B) (moderate vs. mild OR: 0.002, P=0.028; severe vs. mild OR: 0.026, P=0.026). CONCLUSIONS: Combined phacoemulsification with iStent seems to have a better IOP-lowering and medication-lowering effect in mild glaucoma cases versus those with moderate and severe glaucoma. This difference was found in real-world data over one-year follow-up period. Long-term studies with defined IOP goals and medication removal protocols are warranted.