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Complement component 3 (C3) deficiency has recently been reported as one of the novel causes of constipation. To identify a unique gene specific to constipation caused by C3 deficiency, the total RNA extracted from the mid colon of C3 knockout (C3 KO) mice was hybridized to oligonucleotide microarrays, and the function of the candidate gene was verified in in vitro and in vivo models. C3 KO mice used for microarrays showed definite phenotypes of constipation. Overall, compared to the wild type (WT), 1237 genes were upregulated, and 1292 genes were downregulated in the C3 KO mice. Of these, the major genes included were lysine (K)-specific demethylase 5D (KDM5D), olfactory receptor 870 (Olfr870), pancreatic lipase (PNLIP), and alkaline phosphatase intestinal (ALPI). Specifically, the ALPI gene was selected as a novel gene candidate based on alterations during loperamide (Lop)-induced constipation and intestinal bowel disease (IBD). The upregulation of ALPI expression treated with acetate recovered the expression level of mucin-related genes in primary epithelial cells of C3 KO mice as well as most phenotypes of constipation in C3 KO mice. These results indicate that ALPI plays an important role as the novel gene associated with C3 deficiency-induced constipation. [ABSTRACT FROM AUTHOR]

Despite the improved outcomes in patients with hematological malignancies, infections caused by multidrug-resistant organisms (MDROs) pose a new threat to these patients. We retrospectively reviewed the patients with hematological cancer and bacterial bloodstream infections (BSIs) at a tertiary hospital between 2003 and 2022 to assess the impact of MDROs on outcomes. Among 328 BSIs, 81 (24.7%) were caused by MDROs. MDRO rates increased from 10.3% (2003–2007) to 39.7% (2018–2022) (P < 0.001). The 30-day mortality rate was 25.0%, which was significantly higher in MDRO-infected patients than in non-MDRO-infected patients (48.1 vs. 17.4%; P < 0.001). The observed trend was more pronounced in patients with newly diagnosed diseases and relapsed/refractory disease but less prominent in patients in complete remission. Among MDROs, carbapenem-resistant Gram-negative bacteria exhibited the highest mortality, followed by vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus, and extended-spectrum β-lactamase-producing Enterobacteriaceae. Multivariate analysis identified independent risk factors for 30-day mortality as age ≥ 65 years, newly diagnosed disease, relapsed/refractory disease, MDROs, polymicrobial infection, CRP ≥ 20 mg/L, and inappropriate initial antibiotic therapy. In conclusion, MDROs contribute to adverse outcomes in patients with hematological cancer and bacterial BSIs, with effects varying based on the underlying disease status and causative pathogens. Appropriate initial antibiotic therapy may improve patient outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To provide an updated analysis of the long-term outcomes of patients with acute primary angle closure (APAC) and to investigate the risk factors for visual field (VF) loss progression. Study Design: Retrospective, clinical cohort study Methods: One hundred and forty-six APAC patients with a minimum of 1-year follow-up were included. The presenting features and the treatment utilized were recorded. The visual and intraocular pressure (IOP) outcomes were analyzed. The main outcome measures were the proportion of blindness and IOP at the final visit. A subset of patients with sufficient VF results was divided into a stable and progressive group based on mean deviation (MD) loss rate. Univariate and multivariate logistic regression analyses were performed to identify predictors of progression. Results: Nine patients (6.2%) were blind, and 76.0% (111/146) had final decimal visual acuity greater than or equal to 0.5. All patients had normal final IOP, and 65.1% (95/146) were medication-free. 64.4% (94/146) underwent cataract surgery at a median 4 months after their APAC attack. The use of topical hypotensive medications (OR = 8.029, P = 0.012) was the only significant predictor of fast MD loss in the multivariate regression. Conclusions: The long-term outcomes of APAC in recent years have been more promising. All patients maintained normal IOP several years following their APAC attack, and fewer than half required hypotensive agents. The incidence of blindness was low. These findings suggest that current practice patterns in the management of APAC are beneficial. [ABSTRACT FROM AUTHOR]

Purpose: To compare the efficacy and safety of omidenepag isopropyl (OMDI) 0.002% with latanoprost 0.005% once daily in Asian subjects with open-angle glaucoma (OAG)/ocular hypertension (OHT). Methods: In this Phase III randomized, observer-masked, active-controlled, multinational trial (NCT02981446), subjects aged ≥ 18 years with OAG/OHT in both eyes and baseline intraocular pressure (IOP) ≥ 22 mmHg and ≤ 34 mmHg were randomized 1:1 to OMDI or latanoprost. IOP was measured at 9AM, 1PM, and 5PM at baseline, 1 week, 6 weeks, and 3 months. Adverse events (AEs) were recorded. Non-inferiority of OMDI to latanoprost was tested for primary and key secondary endpoints. Results: Each group included 185 subjects. Mean diurnal IOP from baseline to month 3 was reduced 7.1 mmHg (28.8%) with OMDI and 7.8 mmHg (31.3%) with latanoprost, with the least-squares mean difference (OMDI minus latanoprost) being 0.6 mmHg (95% CI: 0.0, 1.2 mmHg; p = 0.0366), indicating non-inferiority. Mean IOP reductions at the nine timepoints were − 5.8 to − 7.3 mmHg (23.5– 29.5%) for OMDI and − 6.1 to − 7.9 mmHg (24.3– 31.7%) for latanoprost. Non-inferiority per FDA criteria was also met. Rates of all AEs, ocular AEs, and ocular AEs associated with treatment were 40.0%, 36.8%, and 23.2%, respectively, for OMDI and 29.7%, 21.1%, and 11.9%, respectively, for latanoprost. Conjunctival hyperemia rates were higher with OMDI than latanoprost (11.9% vs 5.4%). Most AEs were mild, with no serious ocular AEs. Conclusion: OMDI safely and effectively reduces IOP in Asian subjects with OAG/OHT, with mean diurnal IOP at Month 3 and per-timepoint IOP reductions non-inferior to those of latanoprost. Plain Language Summary: PEONY Study: Testing How Well and How Safely Omidenepag Isopropyl Eye Drops Treat People with Glaucoma or Ocular Hypertension Compared with Latanoprost. Who took part in the study? Three hundred and seventy participants average age of 57 years, from 34 centers across four Asian countries who had glaucoma or high pressure in both eyes were randomly divided into two groups. One group (185 people; 50%) was given OMDI, and the other group (185 people; 50%) latanoprost for 3 months. The intraocular pressure of both eyes was measured in all participants at three time points (9 AM, 1 PM, and 5 PM) after 1 week, 6 weeks, and 3 months of treatment. The primary endpoint was the average of the daily eye pressure after 3 months of treatment. The safety of OMDI was also assessed. Study results. After 3 months of treatment, OMDI decreased the eye pressure by 29%. This was similar to latanoprost, which decreased the eye pressure by 31% over the same time period. OMDI was safe and well tolerated by those participants who received it. The most common side-effect in people receiving OMDI or latanoprost was conjunctival hyperemia (red eye) (experienced by 22 people receiving OMDI, and 10 people receiving latanoprost). Conclusions After 3 months of use, OMDI was found to safely reduce high eye pressure to a similar level as latanoprost in Asian people with glaucoma or high eye pressure. [ABSTRACT FROM AUTHOR]

Background: Human induced pluripotent stem cells (hiPSCs) and their differentiated cell types have a great potential for tissue repair and regeneration. While the primary focus of using hiPSCs has historically been to regenerate damaged tissue, emerging studies have shown a more potent effect of hiPSC-derived paracrine factors on tissue regeneration. However, the precise contents of the transplanted hiPSC-derived cell secretome are ambiguous. This is mainly due to the lack of tools to distinguish cell-specific secretome from host-derived proteins in a complex tissue microenvironment in vivo. Methods: In this study, we present the generation and characterization of a novel hiPSC line, L274G-hiPSC, expressing the murine mutant methionyl-tRNA synthetase, L274GMmMetRS, which can be used for tracking the cell specific proteome via biorthogonal non-canonical amino acid tagging (BONCAT). We assessed the trilineage differentiation potential of the L274G-hiPSCs in vitro and in vivo. Furthermore, we assessed the cell-specific proteome labelling in the L274G-hiPSC derived cardiomyocytes (L274G-hiPSC-CMs) in vitro following co-culture with wild type human umbilical vein derived endothelial cells and in vivo post transplantation in murine hearts. Results: We demonstrated that the L274G-hiPSCs exhibit typical hiPSC characteristics and that we can efficiently track the cell-specific proteome in their differentiated progenies belonging to the three germ lineages, including L274G-hiPSC-CMs. Finally, we demonstrated cell-specific BONCAT in transplanted L274G-hiPSC-CMs. Conclusion: The novel L274G-hiPSC line can be used to study the cell-specific proteome of hiPSCs in vitro and in vivo, to delineate mechanisms underlying hiPSC-based cell therapies for a variety of regenerative medicine applications. [ABSTRACT FROM AUTHOR]

This study investigated intraocular pressure (IOP) in Dutch belted rabbits using two different tonometers, rebound tonometry (TonoVet Plus; TVP) and a Tonopen (Tono-Pen AVIA Vet; TPA). Post-pubescent male Dutch belted rabbits aged 36 weeks (n = 10 animals) were used in the study. IOP measurements were conducted every 2 weeks for 22 weeks using TVP and TPA on both eyes of each rabbit. The average IOP measurements were compared by the paired Student’s t-test. Pairwise Pearson’s correlation coefficients and Bland–Altman statistics were used. The overall mean IOP measured with TPA was significantly higher than that with TVP (23.5 ± 4.9 vs. 21.8 ± 2.4 mmHg for the right eyes; P = 0.045, and 23.0 ± 4.7 vs. 21.5 ± 2.4 mmHg for the left eyes; P = 0.047). Both tonometers tended to show increased IOP readings with age, and positive correlations between IOP and age were observed with both TPA (r = 0.95, P < 0.001 for right eyes; r = 0.95, P < 0.001 for left eyes) and TVP (r = 0.91, P < 0.001 for right eyes; r = 0.64, P = 0.024 for left eyes). The average bias calculated by subtracting TPA from TVP was − 1.60 (95% confidence intervals − 1.927, − 1.281) mmHg. IOP in post-pubescent Dutch belted rabbits tended to increase with age throughout the 22 week study. [ABSTRACT FROM AUTHOR]

This prospective cross-sectional study investigated the visual function of preperimetric glaucoma (PPG) patients based on hemifield (HF) pattern electroretinogram (PERG) amplitudes. Thirty-two (32) normal subjects and 33 PPG patients were enrolled in control and PPG groups, respectively. All of the participants had undergone full ophthalmic examinations, including spectral-domain optical coherence tomography (SD-OCT), visual field (VF) examination and pattern electroretinography (PERG). The PERG parameters along with the HF ratios of SD-OCT and PERG were compared between the control and PPG groups. Pairwise Pearson's correlation coefficients and linear regression models were fitted to investigate the correlations. The PERG N95 amplitudes were significantly lower in the PPG group (P < 0.001). The smaller/larger HF N95 amplitude ratio of the PPG group was found to be smaller than that of the control group (0.73 ± 0.20 vs. 0.86 ± 0.12; P = 0.003) and showed positive correlations with affected HF average ganglion cell-inner plexiform layer (GCIPL) thickness (r = 0.377, P = 0.034) and with average GCIPL thickness (r = 0.341, P = 0.005). The smaller/larger HF N95 amplitude ratio did not significantly change with age (β = − 0.005, P = 0.195), whereas the full-field N95 amplitude showed a negative correlation with age (β = − 0.081, P < 0.001). HF analysis of PERG N95 amplitudes might be particularly useful for patients with early glaucoma. [ABSTRACT FROM AUTHOR]

The combination of aztreonam (ATM) and ceftazidime–avibactam (CAZ-AVI; CZA) has shown therapeutic potential against serine-β-lactamase (SBL)- and metallo-β-lactamase (MBL)-producing Enterobacterales. However, the ability of CZA to restore the antibiotic activity of ATM is severely limited in MBL-producing multidrug-resistant (MDR) Pseudomonas aeruginosa strains because of the myriad of intrinsic and acquired resistance mechanisms associated with this pathogen. We reasoned that the simultaneous inhibition of multiple targets associated with multidrug resistance mechanisms may potentiate the antibiotic activity of ATM against MBL-producing P. aeruginosa. During a search for the multitarget inhibitors through a molecular docking study, we discovered that di-F-Q, the previously reported efflux pump inhibitor of MDR P. aeruginosa, binds to the active sites of the efflux pump (MexB), as well as various β-lactamases, and these sites are open to the 3-O-position of di-F-Q. The 3-O-substituted di-F-Q derivatives were thus synthesized and showed hereto unknown multitarget MDR inhibitory activity against various ATM-hydrolyzing β-lactamases (AmpC, KPC, and New Delhi metallo-β-lactamase (NDM)) and the efflux pump of P. aeruginosa, presumably by forming additional hydrophobic contacts with the targets. The multitarget MDR inhibitor 27 effectively potentiated the antimicrobial activity of ATM and reduced the MIC of ATM more than four-fold in 19 out of 21 MBL-producing P. aeruginosa clinical strains, including the NDM-producing strains which were highly resistant to various combinations of ATM with β-lactamase inhibitors and/or efflux pump inhibitors. Our findings suggest that the simultaneous inhibition of multiple MDR targets might provide new avenues for the discovery of safe and efficient MDR reversal agents which can be used in combination with ATM against MBL-producing MDR P. aeruginosa. [ABSTRACT FROM AUTHOR]

Little is known about the diagnostic utility of three-dimensional neuroretinal rim thickness (3D-NRRT) for differentiating patients with superior segmental optic nerve hypoplasia (SSOH) from normal-tension glaucoma (NTG). Since SSOH is defined by characteristic optic nerve head features, investigation of diagnostic usefulness of 3D-NRRT is necessary. In this cross-sectional study, 49 SSOH eyes, 52 NTG eyes, and 41 normal eyes were enrolled. Retinal nerve fiber layer thickness (RNFLT) and 3D-NRRT values, as obtained in the right-eye orientation by optical coherence tomography (OCT), were recorded. On RNFLT clock-hour comparison, the 11–3 clock-hour sectors were significantly thinner for SSOH than for NTG (all P < 0.01). As for 3D-NRRT, whereas the 1 and 2 sectors were significantly thinner for SSOH (P < 0.001, P = 0.004), the 6–11 sectors were significantly thinner for NTG (all P < 0.01). The area under receiver operating characteristic (AUROC) curves of the superior and nasal quadrants of RNFLT (0.838, 0.729) were significantly greater than those of 3D-NRRT (0.518, 0.588; P < 0.001, P = 0.043). However, the AUROCs of the inferior and temporal quadrants were significantly greater for 3D-NRRT (0.728, 0.760) than for RNFLT (0.527, 0.550; P = 0.008, P = 0.019). The appropriate use of 3D-NRRT can be useful in differentiating SSOH from NTG. [ABSTRACT FROM AUTHOR]

Complement component 3 (C3) deficiency has recently been known as a cause of constipation, without studies on the therapeutic efficacy. To evaluate the therapeutic agents against C3-deficiency-induced constipation, improvements in the constipation-related parameters and the associated molecular mechanisms were examined in FVB/N-C3em1Hlee/Korl knockout (C3 KO) mice treated with uridine (Urd) and the aqueous extract of Liriope platyphylla L. (AEtLP) with laxative activity. The stool parameters and gastrointestinal (GI) transit were increased in Urd- and AEtLP-treated C3 KO mice compared with the vehicle (Veh)-treated C3 KO mice. Urd and AEtLP treatment improved the histological structure, junctional complexes of the intestinal epithelial barrier (IEB), mucin secretion ability, and water retention capacity. Also, an improvement in the composition of neuronal cells, the regulation of excitatory function mediated via the 5-hydroxytryptamine (5-HT) receptors and muscarinic acetylcholine receptors (mAChRs), and the regulation of the inhibitory function mediated via the neuronal nitric oxide synthase (nNOS) and inducible NOS (iNOS) were detected in the enteric nervous system (ENS) of Urd- and AEtLP-treated C3 KO mice. Therefore, the results of the present study suggest that C3-deficiency-induced constipation can improve with treatment with Urd and AEtLP via the regulation of the mucin secretion ability, water retention capacity, and ENS function. [ABSTRACT FROM AUTHOR]

We investigated the internal morphology of filtration blebs after XEN gel stent implantation using anterior segment optical coherence tomography (AS-OCT) and identified factors related to intraocular pressure (IOP) postoperatively. Eighteen eyes of 18 patients who had undergone XEN gel stent implantation were analyzed. Blebs were imaged using Visante OCT (Carl Zeiss Meditec AG, Germany) at 6 months and 1 year after surgery and evaluated for quantitative parameters including bleb height, maximum height of internal cavity, maximum bleb wall thickness, and maximum bleb epithelial thickness. Subjects were classified into two groups according to the presence or absence of a definite internal cavity between the conjunctiva and sclera using AS-OCT imaging. Nine eyes (50%) were assigned to the internal cavity group and 9 (50%) to the uniform group. Postoperative IOP was significantly lower in the internal cavity group than in the uniform group both at 6 months and 1 year after surgery (p = 0.024 and p = 0.040). Postoperative IOP showed statistically significant negative correlations with bleb height and the height of the internal cavity (Spearman correlation coefficient r = −0.518, p = 0.028 and r = −0.453, p = 0.034, respectively). AS-OCT facilitates analysis of bleb morphology after XEN gel stent implantation. A larger height of the internal cavity of the bleb appeared to correlate with lower IOP after XEN implantation. [ABSTRACT FROM AUTHOR]

Background and Objective: Our previous studies demonstrated that MG53 protein can protect the myocardium, but its use as a therapeutic is challenging due to its short half-life in blood circulation. This study aimed to investigate the cardioprotective role of MG53 on human induced pluripotent stem cell-derived cardiomyocytes (HiPSC-CMs) in the context of myocardial ischemia/reperfusion (I/R). Methods: In vitro: HiPSC-CMs were transfected with adenoviral MG53 (HiPSC-CMsMG53), in which the expression of MG53 can be controlled by doxycycline (Dox), and the cells were then exposed to H2O2 to mimic ischemia/reperfusion injury. In vivo: HiPSC-CMsMG53 were transplanted into the peri-infarct region in NSG™ mice after I/R. After surgery, mice were treated with Dox (+ Dox) to activate MG53 expression (sucrose as a control of -Dox) and then assessed by echocardiography and immunohistochemistry. Results: MG53 can be expressed in HiPSC-CMMG53 and released into the culture medium after adding Dox. The cell survival rate of HiPSC-CMMG53 was improved by Dox under the H2O2 condition. After 14 and 28 days of ischemia/reperfusion (I/R), transplanted HiPSC-CMsMG53 + Dox significantly improved heart function, including ejection fraction (EF) and fractional shortening (FS) in mice, compared to HiPSC-CMsMG53-Dox, and reduced the size of the infarction. Additionally, HiPSC-CMMG53 + Dox mice demonstrated significant engraftment in the myocardium as shown by staining human nuclei-positive cells. In addition, the cell survival-related AKT signaling was found to be more active in HiPSC-CMMG53 + Dox transplanted mice's myocardium compared to the HiPSC-CMMG53-Dox group. Notably, the Dox treatment did not cause harm to other organs. Conclusion: Inducible MG53 expression is a promising approach to enhance cell survival and engraftment of HiPSC-CMs for cardiac repair. [ABSTRACT FROM AUTHOR]

The rates, patterns and associated factors for false-positive classification of deviation maps by Cirrus optical coherence tomography (OCT) have been reported. However, research on OCT layer-by-layer deviation maps is lacking. We aimed to determine the rates and associated factors for false-positive classification of segmented macular layers and retinal nerve fiber layer (RNFL) deviation maps of Spectralis OCT, and to identify false-positive patterns on segmented macular layers deviation maps. 118 healthy eyes of 118 normal participants who had undergone Spectralis OCT imaging were included. False-positive classification was determined by the area and location of yellow or red color-coded regions on the deviation map. The false-positive rates on the deviation maps were the highest on the ganglion cell layer map, followed by the inner plexiform layer, retinal layer, and RNFL maps. More myopic/less hyperopic refractive error was a factor significantly associated with higher false-positive classification on the RNFL deviation map, and three false-positive patterns were found on the segmented macular layers deviation maps. Spectralis OCT deviation maps should be interpreted carefully to avoid misdiagnosis, especially for eyes with higher degrees of myopic refractive error on the RNFL map, for which purpose, recognizing the characteristic false-positive patterns would be helpful in clinical practice. [ABSTRACT FROM AUTHOR]

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Macular OCT angiography (OCTA) measurements have been reported to be useful for glaucoma diagnostics. However, research on highly myopic glaucoma is lacking, and the diagnostic value of macular OCTA measurements versus OCT parameters remains inconclusive. We aimed to evaluate the diagnostic ability of the macular microvasculature assessed with OCTA for highly myopic glaucoma and to compare it with that of macular thickness parameters, using deep learning (DL). A DL model was trained, validated and tested using 260 pairs of macular OCTA and OCT images from 260 eyes (203 eyes with highly myopic glaucoma, 57 eyes with healthy high myopia). The DL model achieved an AUC of 0.946 with the OCTA superficial capillary plexus (SCP) images, which was comparable to that with the OCT GCL+ (ganglion cell layer + inner plexiform layer; AUC, 0.982; P = 0.268) or OCT GCL++ (retinal nerve fiber layer + ganglion cell layer + inner plexiform layer) images (AUC, 0.997; P = 0.101), and significantly superior to that with the OCTA deep capillary plexus images (AUC, 0.779; P = 0.028). The DL model with macular OCTA SCP images demonstrated excellent and comparable diagnostic ability to that with macular OCT images in highly myopic glaucoma, which suggests macular OCTA microvasculature could serve as a potential biomarker for glaucoma diagnosis in high myopia. [ABSTRACT FROM AUTHOR]

Background: COVID-19 has been shown to affect the onset and severity of various diseases. We examined whether the clinical characteristics of Bell's palsy differed between before and during the COVID-19 pandemic. Methods: From January 2005 to December 2021, 1839 patients were diagnosed and treated for Bell's palsy at Kyung Hee University Hospital. These patients were divided into a pre-COVID period group and COVID-19 period group, and the clinical characteristics of the two groups were compared. Results: There were 1719 patients in the pre-COVID period group and 120 patients in the COVID-19 period group. There were no between-group differences in sex (p = 0.103) or in the presence of underlying hypertension (p = 0.632) or diabetes (p = 0.807). Regarding symptoms, there were no significant between-group differences in otalgia, dizziness, tinnitus, hyperacusis, or hearing loss (p = 0.304, p = 0.59, p = 0.351, p = 0.605, and p = 0.949). There were also no significant between-group differences in electroneurography results (p = 0.398), electromyography results (p = 0.331), House–Brackmann Grade at visit (p = 0.634), or recovery rate after treatment (p = 0.525). Conclusions: Contrary to our expectation that Bell's palsy cases during the COVID-19 pandemic would show different clinical features than those occurring before COVID-19, the present study found no differences in clinical features or prognosis. [ABSTRACT FROM AUTHOR]

The lingual retractor is an appliance with esthetic advantages and biomechanical superiority in the retraction of anterior teeth, when used in combination with temporary skeletal anchorage devices (TSADs). These appliances can address the patients' chief complaint during the early stages of bialveolar protrusion treatment. This narrative review presents the clinical applications and biomechanics of various lingual retractors with TSADs.This review includes all research and case reports related to various lingual retractors such as the C-lingual retractor (CLR), double J retractor (DJR), and antero-posterior lingual retractor (APLR). Anterior torque and vertical control can be achieved with all three types of lingual retractors by changing the length of the lever arms and the position of the TSADs. Torquing springs in DJR are designed to slide along palatal mini-implants or to apply intermaxillary elastics to counteract retroclination of the incisors during space closure. APLR allows three-dimensional control of the anterior tooth movement with anterior lever arms, guide bars, posterior tubes, and position of TSADs. Various lingual retractors with TSADs are effectively proper anterior torque and vertical control. [ABSTRACT FROM AUTHOR]

Little is known about the myopic characteristics of lamina cribrosa (LC) curvature. As such, we investigated nasal and temporal LC curvatures in myopia. In this retrospective, cross-sectional study, 144 myopic eyes (refraction < − 2D) and 88 non-myopic eyes (refraction > − 0.5D) underwent swept-source optical coherence tomography scanning of the LC. The anterior border of LC curvature was delineated with 17 points and interpolated with the "cardinal spline" curve-fitting method. The average curvature indices of the temporal and nasal sides were presented as the temporal and nasal curvatures. Myopic eyes had a mean refraction of − 6.7 ± 2.8D, while for non-myopic eyes, the value was 0.3 ± 1.0D. Nasal LC curvature was visible in 54 myopia (37.5%) and 42 non-myopia (47.7%) cases (P = 0.126), and temporal LC curvature was visible in 142 myopia (98.6%) and 68 non-myopia (77.3%) cases (P = 0.001). The nasal LC curvature was significantly larger in myopia than in non-myopia (P < 0.001). Contrastingly, the temporal LC curvature was significantly smaller in myopia than in non-myopia (P < 0.001). Axial length was associated with larger nasal LC curvature, smaller temporal LC curvature, and larger nasal–temporal LC curvature difference (all P's < 0.05). In myopic relative to non-myopic eyes, LC curvature was decreased temporally and increased nasally. [ABSTRACT FROM AUTHOR]

Background: Development of a macular sector‐wise decision tree model (DTM) for the prediction of parafoveal scotoma. Methods: This prospective study enrolled 126 patients with early‐stage open‐angle glaucoma (mean deviation ≥−6 decibels) without the signs of parafoveal scotoma on the 24‐2 visual field (VF) test (i.e., any abnormalities at the four innermost points). Based on the central 36 points of the 10‐2 pattern deviation plot, patients were classified as being with or without 10‐2 parafoveal scotoma. For the discrimination of patients from those without 10‐2 parafoveal scotoma, a macular ganglion cell‐inner plexiform layer (mGCIPL) sector‐wise DTM analysis was performed. Results: Among 126 eyes without 24‐2 parafoveal scotoma, 10‐2 parafoveal scotoma was detected in 77 (61.1%) eyes. The balanced accuracy of DTM was best in the inferotemporal sector (0.9286; 95% CI, 0.7458–0.9697) and worst in the inferior sector (0.8373; 0.6484–0.9204). DTM revealed that even in the absence of VF abnormalities at the innermost 4 points on the 24‐2 test, (1) 10‐2 parafoveal scotoma should be strongly suspected when the adjacent 24‐2 perifoveal point in the correlated sector is abnormal; (2) if the 24‐2 perifoveal point is normal, and if the probability colour codes of the correlated mGCIPL sector are green, the probability of 10‐2 parafoveal scotoma is very low. Conclusions: In clinical practice, the evaluation of the 24‐2 perifoveal test points along with the probability colour codes of mGCIPL can be a useful decision‐support tool in determining whether 10‐2 tests are needed for a given patient. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate ocular hypotensive efficacy and the safety of sovesudil (formally known as PHP‐201), a novel Rho‐associated protein kinase (ROCK) inhibitor, in patients with normal‐tension glaucoma (NTG). Design: Multicentre, prospective, double‐masked, randomized, placebo‐controlled, parallel clinical study. Methods: Patients with NTG (unmedicated baseline IOP ≤ 21 mmHg) were randomized in 3 groups and treated with sovesudil in concentrations of 0.25% and 0.5%, or with a placebo three times daily (TID) for 4 weeks. The primary end‐point was the mean diurnal IOP change from the baseline at week 4. Safety was recorded over a 4‐week treatment period and the following 2‐week observation period. Results: A total of 119 patients were included in the primary efficacy analysis. The mean diurnal IOP change from the baseline at week 4 was −1.56 mmHg for the high‐dose group, −1.10 mmHg for the low‐dose group and −0.65 mmHg for the placebo group. The difference between the high‐dose and the placebo groups was −0.91 mmHg (95% confidence intervals: −1.73, −0.09). 0.5% sovesudil TID met the criteria for superiority to the placebo. The most frequent ocular adverse event among sovesudil‐treated patients was conjunctival hyperaemia (24.4% for the high‐dose and 17.5% for the low‐dose group) and predominately classified as mild. Conclusions: Sovesudil 0.25% and 0.5% TID showed statistically significant IOP‐lowering effects and 0.5% concentration's IOP‐lowering effects met the superiority criteria in comparison with the placebo at week 4. Sovesudil was well tolerated with mild adverse events including relatively low incidence of conjunctival hyperaemia in patients with NTG. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate longitudinal changes of circumpapillary retinal nerve fiber layer thickness (cpRNFLT) profile arising in the course of childhood myopia progression. Thirty-six eyes of 36 healthy children who showed myopia progression (spherical equivalent [SE] decrease of ≥ 2.0 diopters [D]) were included. To account for the axial-elongation-induced magnification effect on spectral-domain optical coherence tomography (SD-OCT) measurements, we calculated the proportion of quadrant-cpRNFLT distribution (i.e., the percentage of cpRNFLT within a single quadrant of total cpRNFLT). During 4.1 ± 1.1 years, the mean SE changed from -1.3 ± 0.9 to -4.3 ± 0.8D, and both the optic disc tilt ratio and the torsional angle increased (both P < 0.001). In the temporal quadrant, the cpRNFLT proportion was increased from 19.2 ± 1.86 to 24.4 ± 2.30% (P < 0.001). The cpRNFLT proportion in 3 quadrants (i.e., superior, inferior, nasal) showed decreases (all P < 0.001). Between baseline and follow up, the scan-circle location as determined by OCT was shifted mostly (94%; 34 of 36 eyes) toward the nasal side of the optic disc. With scan-circle repositioning to match the baseline, cpRNFLT distribution proportions did not show any significant difference between the baseline and follow up (all P > 0.05). For longitudinal evaluations of patients with myopia progression, scan-circle alteration should be given due consideration. [ABSTRACT FROM AUTHOR]

GLH8NDE, a derivative of eupatilin, is currently under development to treat dry eye disease. We conducted a randomized, double‐masked, placebo‐controlled, single‐ and multiple‐day study to evaluate safety, tolerability, pharmacodynamics, and pharmacokinetics of ocular GLH8NDE in healthy male adults. Subjects randomly received topical ocular dosing of GLH8NDE or its matching placebo for a day, then for 7 consecutive days with a 62‐h washout at one of the following daily doses: 9, 18, 36 (Koreans), and 36 mg (Whites). The study drug was administered in divided doses over 10 h with 2‐ or 5‐h intervals. Thirty‐nine (97.5%) out of 40 subjects completed the study. A total of 17 subjects experienced 31 treatment‐emergent adverse events, all of which were mild in severity and recovered without sequelae. Neither pathological changes in eye compartments nor clinically significant systemic effects were observed. GLH8NDE was rapidly absorbed reaching the peak concentration within 0.25–0.75 h postdose. The systemic exposure as measured by area under the concentration‐time curve from time of administration up to the time of the last quantifiable concentration (AUClast) after single‐day administration of the same dose was 109% higher in Koreans than in Whites. In conclusion, GLH8NDE was safe and well‐tolerated in healthy Korean and White male adults at 9–36 mg/day after single‐ and multiple‐day administrations. [ABSTRACT FROM AUTHOR]

Purpose: We evaluated the long-term visual outcomes in children with primary congenital glaucoma and determined the factors associated with the final visual outcomes. Methods: Medical records of children with primary congenital glaucoma between 2005 and 2016, seen at Seoul National University Children's Hospital in South Korea, were reviewed. The minimum follow-up period after surgery for primary congenital glaucoma was 3 years. Visual acuity (VA) was categorized into good (≧20/70) and poor (< 20/70). Factors including age, VA, refractive errors, intraocular pressure (IOP), laterality, and cup-to-disc (C/D) ratio were compared between the groups. Results: A total of 71 eyes of 44 patients were included. The patients' age at the time of surgery was 14.7 ± 12.2 months. The mean IOP was 28.3 ± 7.0 mmHg. During 6.7 ± 2.7 years of mean follow-up after surgery, 39 eyes (54.9%) needed occlusion treatment. After occlusion, patients with lower IOP values, lesser additional surgeries, reversal of optic disc cupping, and better initially measured VA achieved a better visual outcome. At the final assessment, the mean age was 7.8 ± 2.6 years, and the mean VA gain was 15.0 ± 19.4 letters. There were 44 eyes (62.0%) with VA ≧20/70. Conclusions: In children with primary congenital glaucoma, IOP control and the optic disc configuration over time are important factors associated with visual outcome. Regular follow-up and correction of refractive errors—along with occlusion for those with difference in VA between the two eyes—might be helpful for achieving better visual outcomes. [ABSTRACT FROM AUTHOR]

Background: Nonrandom multiple respiratory virus (RV) detection provides evidence for viral interference among respiratory viruses. However, little is known as to whether it occurs randomly.Methods: The prevalence of dual RV detection (DRVD) in patients with acute respiratory illnesses (ARIs) at 4 academic medical centers was investigated; data about the prevalence of 8 RVs were collected from the Korean national RV surveillance dataset. Linear regression analysis was performed to assess the correlation between observed and estimated prevalence of each type of DRVD.Results: In total, 108 patients with ARIs showing DRVD were included in this study between 2011 and 2017. In several types of regression analysis, a strong correlation was observed between the observed and estimated prevalence of each type of DRVD. Excluding three DRVD types (influenza/picornavirus, influenza/human metapneumovirus, and adenovirus/respiratory syncytial virus), the slope of the regression line was higher than that of the line of random occurrence (1.231 > 1.000) and the 95% confidence interval of the regression line was located above the line of random occurrence.Conclusions: Contrary to the results of previous epidemiologic studies, most types of DRVD occur more frequently than expected from the prevalence rates of individual RV, except for three underrepresented pairs above. [ABSTRACT FROM AUTHOR]

Introduction: Current medical therapy for glaucoma consists of topical agents that lower intraocular pressure (IOP). Prostaglandin F2α analogues, the most commonly used class of IOP-lowering drugs, bind to prostaglandin FP receptors in tissues of the uveoscleral pathway. This binding increases the expression of matrix metalloproteinases, which degrade the extracellular matrix of the ciliary body, creating inter-muscular spaces allowing aqueous humor to exit the eye. Drawbacks to prostaglandin F2α analogues include cosmetic side effects, especially prostaglandin-associated periorbitopathy (PAP) syndrome. Areas covered: This review describes the novel prostaglandin E2 receptor antagonist, omidenepag isopropyl, which reduces IOP by improving drainage of uveoscleral and trabecular outflow, increasing the facility of outflow. In contrast to prostaglandin F2α analogues, omidenepag does not inhibit adipogenesis or promote eyelash growth. This review describes preclinical studies of omidenepag, published results of phase I–III clinical trials, and preliminary results of phase III trials currently in progress. Expert opinion: Omidenepag appears to provide IOP reductions comparable to those of prostaglandin F2α analogues, but without the cosmetic side effects common to prostaglandin F2α analogues, especially PAP syndrome. The lack of association between omidenepag and PAP suggests that long-term use of this agent may have advantages in patients with glaucoma. [ABSTRACT FROM AUTHOR]

Glaucoma shares common risk factors with chronic kidney disease (CKD) but previous cross-sectional studies have demonstrated discrepancies in the risk of glaucoma in CKD patients. This study enrolled kidney transplantation recipients (KTRs) (n = 10,955), end stage renal disease (ESRD) patients (n = 10,955) and healthy controls (n = 10,955) from National Health Insurance Service database of the Republic of Korea. A Cox proportional hazard regression model was used to calculate the hazard ratios (HR) for primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG) incidences. The incidence of POAG was higher in ESRD patients (3.36/1,000 person-years, P < 0.0001) and KTRs (3.22 /1,000 person-years, P < 0.0001), than in healthy controls (1.20/1,000 person-years). However, POAG risk showed no significant increase in either ESRD patients (P = 0.07) or KTRs (P = 0.08) when adjusted for the confounding factors. The incidence of PACG was significantly higher in ESRD patients (0.41/1,000 person-years) than in healthy controls (0.14/1,000 person-years, P = 0.008). The PACG incidence was significantly lower in KTRs than in ESRD patients (HR = 0.35, P = 0.015). In conclusion, this nationwide cohort study demonstrated that kidney transplantation can reduce the risk of PACG but not POAG in ESRD patients. [ABSTRACT FROM AUTHOR]

Biocreative Orthodontic Strategy (BOS) is designed to establish a physiologically stable occlusion in harmony with masticatory and TMJ function and healthy supporting tissues with strategic use of temporary skeletal anchorage devices (TSADs). This narrative review surveys current research that demonstrates how BOS with TSADs uses a target approach to overcome the limitations experienced with conventional orthodontic treatment. A narrative review article including research on TSADs orthodontics in the permanent dentition. This review is a brief survey of five BOS principles for contemporary TSAD orthodontics: elegant selection of TSADs, bracket prescription to enhance TSAD orthodontics, antero-posterior dimension control, transverse dimension control and airway control issues. Severe malocclusion and craniofacial dysmorphology can be treated with Biocreative Orthodontic Strategy with a minimum number of TSADs. In order to achieve successful treatment outcome using TSADs, it is critical to understand the key diagnosis and treatment principles of BOS and how to develop a target approach for the tooth and bone movement. [ABSTRACT FROM AUTHOR]

Purpose: To assess the 12-month efficacy and safety of fixed-combination brimonidine tartrate 0.2%/timolol maleate 0.5% (FCBT) with or without bimatoprost 0.01% (BIM) in primary open-angle glaucoma (POAG), including normal-tension glaucoma (NTG). Study design: Prospective, multicenter, open-label study. Methods: FCBT was self-administered twice daily after applicable washout (study eye). Intraocular pressure (IOP) was measured at baseline and months 1, 3, 6, 9, and 12. BIM could be added for IOP ≥ 21 mmHg, IOP reduction from baseline < 20%, or the investigator deemed it necessary. Primary endpoint: mean (11-a.m.) month-12 IOP change from baseline. Secondary endpoints included mean IOP changes from baseline at other visits, median time to achieving and patients (%) achieving target IOP reduction with FCBT, and visual field (VF) progression rate over 12 months. Safety was assessed at each visit. Results: Of 118 eyes with POAG (NTG, n = 93), 87 used FCBT; 31 required FCBT + BIM. Mean IOP changes from baseline (16.8 and 15.3 mmHg) to month 12 were − 4.1 mmHg (FCBT, n = 62) and − 3.5 mmHg (FCBT + BIM, n = 15), respectively (both P < 0.0001). Patients who achieved target IOP reduction with FCBT did so in 1 month (median). VF progression rates were 0.17%/year (FCBT, P = 0.8367) and − 0.08%/year (FCBT + BIM, P = 0.9410). Ocular treatment-emergent adverse events occurred in 42.5% (FCBT) and 71.0% (FCBT + BIM) of patients; most were mild and included ocular hyperemia (9.2% and 41.9%, respectively). Conclusions: Despite low mean baseline IOP, ≥ 20% IOP reduction from baseline persisted over 12 months with FCBT and FCBT + BIM, without clinically significant VF progression. Tolerability was consistent with reported drug safety profiles. [ABSTRACT FROM AUTHOR]

Biocreative Orthodontic Strategy (BOS) is designed to establish a physiologically stable occlusion in harmony with masticatory and TMJ function and healthy supporting tissues with strategic use of temporary skeletal anchorage devices (TSADs). This narrative review surveys current research that demonstrates how BOS with TSADs uses a target approach to overcome the limitations experienced with conventional orthodontic treatment. A narrative review article including research on TSADs orthodontics in the permanent dentition. This review is a brief survey of five BOS principles for contemporary TSAD orthodontics: elegant selection of TSADs, bracket prescription to enhance TSAD orthodontics, antero‐posterior dimension control, transverse dimension control and airway control issues. Severe malocclusion and craniofacial dysmorphology can be treated with Biocreative Orthodontic Strategy with a minimum number of TSADs. In order to achieve successful treatment outcome using TSADs, it is critical to understand the key diagnosis and treatment principles of BOS and how to develop a target approach for the tooth and bone movement. [ABSTRACT FROM AUTHOR]

Burkholderia cepacia complex (BCC) is an emerging pathogen of nosocomial infection in chronic or critically ill patients without cystic fibrosis (CF). The objective was to evaluate the management and outcomes of BCC bacteremia in patients without CF. We conducted a retrospective study of non-CF adult patients with BCC bacteremia between January 1997 and December 2016 at 4 tertiary hospitals in South Korea. A total of 216 non-CF patients with BCC bacteremia were identified. Most cases were hospital-acquired (79.2%), and the most common source was a central venous catheter (CVC) (42.1%). The rates of susceptibility to trimethoprim-sulfamethoxazole and piperacillin-tazobactam of BCC isolates were high as 92.8% and 90.3%, respectively. The rates of susceptibility to ceftazidime, meropenem, and levofloxacin were 75.5%, 72.3%, and 64.1%, respectively. The 14-day, 30-day, and in-hospital mortality rate was 19.4%, 23.1%, and 31.0%, respectively. Female (OR = 3.1; 95% CI, 1.4–6.8), liver cirrhosis (OR = 6.2; 95% CI, 1.6–16.6), septic shock (OR = 11.2; 95% CI, 5.1–24.8), and catheter-related infection (OR = 2.6, 95% CI, 1.2–5.8) were the independent risk factors for 30-day mortality. The outcome did not differ according to type of antibiotics used. Among 91 patients with CVC-related BCC bacteremia, delayed CVC removal (> 3 days) had a higher rate of persistent bacteremia (54.5 vs. 26.1%; P = 0.03) and lower rate of clinical response (49.0 vs. 71.9%; P = 0.04), compared with early CVC removal (within 3 days). BCC bacteremia occurring in non-CF patients was mostly hospital-acquired and CVC-related. Early removal of the catheter is crucial in treatment of CVC-related BCC bacteremia. [ABSTRACT FROM AUTHOR]

Optic-disc photography (ODP) has proven to be very useful for optic nerve evaluation in glaucoma. In real clinical practice, however, limited patient cooperation, small pupils, or media opacities can limit the performance of ODP. The purpose of this study was to propose a deep-learning approach for increased resolution and improved legibility of ODP by contrast, color, and brightness compensation. Each high-resolution original ODP was transformed into two counterparts: (1) down-scaled 'low-resolution ODPs', and (2) 'compensated high-resolution ODPs' produced via enhancement of the visibility of the optic disc margin and surrounding retinal vessels using a customized image post-processing algorithm. Then, the differences between these two counterparts were directly learned through a super-resolution generative adversarial network (SR-GAN). Finally, by inputting the high-resolution ODPs into SR-GAN, 4-times-up-scaled and overall-color-and-brightness-transformed 'enhanced ODPs' could be obtained. General ophthalmologists were instructed (1) to assess each ODP's image quality, and (2) to note any abnormal findings, at 1-month intervals. The image quality score for the enhanced ODPs was significantly higher than that for the original ODP, and the overall optic disc hemorrhage (DH)-detection accuracy was significantly higher with the enhanced ODPs. We expect that this novel deep-learning approach will be applied to various types of ophthalmic images. [ABSTRACT FROM AUTHOR]

We sought to investigate the association between consumption of coffee, tea, or soft drinks and risk of open-angle glaucoma (OAG) among Koreans using nationwide population-based data. This cross-sectional survey was performed through the Korea National Health and Nutrition Examination Survey 2010 to 2011. Participants older than 19 years were included in the sample for analysis after excluding those with any missing data. The diagnosis of OAG was based on the International Society of Geographical and Epidemiological Ophthalmology criteria, and participants without glaucomatous optic neuropathy served as controls. The frequency of beverage consumption during the past 12 months was obtained through a questionnaire. Multivariate logistic regression models were used to determine the relationship between consumption of each type of beverage and prevalence of OAG. A total of 6,681 participants was included in the analysis. The prevalence of OAG was 4.4% (n = 323), including 5.4% (n = 169) among men and 3.5% (n = 154) among women. After adjusting for multiple covariates, coffee consumption was significantly associated with OAG, while no significant association was found between consumption of tea or soft drinks and OAG. Participants who drank coffee had a higher risk of having OAG compared with those who did not drink coffee (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.22–4.72; p = 0.011). In sex-stratified analyses, the robust association of coffee consumption with OAG was observed in men (OR, 3.98; 95% CI, 1.71–9.25; p = 0.001) but not in women. Our results suggest that coffee consumption may affect the risk of OAG, particularly in men. [ABSTRACT FROM AUTHOR]

TRIM family proteins play integral roles in the innate immune response to virus infection. MG53 (TRIM72) is essential for cell membrane repair and is believed to be a muscle-specific TRIM protein. Here we show human macrophages express MG53, and MG53 protein expression is reduced following virus infection. Knockdown of MG53 in macrophages leads to increases in type I interferon (IFN) upon infection. MG53 knockout mice infected with influenza virus show comparable influenza virus titres to wild type mice, but display increased morbidity accompanied by more accumulation of CD45+ cells and elevation of IFNβ in the lung. We find that MG53 knockdown results in activation of NFκB signalling, which is linked to an increase in intracellular calcium oscillation mediated by ryanodine receptor (RyR). MG53 inhibits IFNβ induction in an RyR-dependent manner. This study establishes MG53 as a new target for control of virus-induced morbidity and tissue injury. TRIM proteins are known to play critical roles in the context of viral infection. Here the authors establish MG53 (TRIM72) suppresses IFN and inflammation by modulation of ryanodine receptor related intracellular calcium induction. [ABSTRACT FROM AUTHOR]

Objectives: To investigate significant intraocular pressure (IOP) levels associated with the risk of open-angle glaucoma (OAG) in the treatment-naïve Korean population. Methods: Participants ≥20 years of age in Korea National Health and Nutrition Examination Survey 2010–2011 were divided into two groups, those with higher and lower IOP values, compared with the reference IOP value. We compared the risk of OAG in each group using regression analyses. The IOP value that yielded the highest statistical significance was determined as an IOP significantly associated with the OAG risk. Results: A total of 7,650 participants (7,292 control, 358 OAG) were included. The mean IOP was significantly higher in OAG group (14.4 ± 2.9 mmHg), compared to control group (13.9 ± 2.7 mmHg, P = 0.022). In association with an increased risk of OAG, the significant IOP value was 18 mmHg (Odds ratio [OR] = 1.79, 95% confidence interval [CI] 1.14–2.80, P = 0.011). Additionally, sex-difference was identified and they were 19 mmHg (OR = 2.79, 95% CI 1.27–6.16, P = 0.011) in men and 18 mmHg (OR = 2.65, 95% CI 1.32–5.33, P = 0.006) in women. The IOP values associated with significantly decreased risk of glaucoma were determined to be 14 mmHg in men (OR = 0.68, 95% CI 0.47–0.99, P = 0.042) and 16 mmHg in women (OR = 0.47, 95% CI 0.27–0.81, P = 0.007). Conclusions: In consideration of the risk to benefit ratio, the reference IOP level for screening or setting the target IOP for treatment could be considered different from traditional 21 mmHg in Korean population. [ABSTRACT FROM AUTHOR]

Low ocular perfusion pressure (OPP) has been proposed as an important risk factor for glaucoma development and progression, but controversy still exists between studies. Therefore, we conducted a systematic review and meta-analysis to analyze the association between OPP and open-angle glaucoma (OAG). Studies were identified by searching PubMed and EMBASE databases. The pooled absolute and standardised mean difference in OPP between OAG patients and controls were evaluated using the random-effects model. Meta-regression analysis was conducted to investigate the factors associated with OPP difference between OAG patients and controls. A total of 43 studies were identified including 3,009 OAG patients, 369 patients with ocular hypertension, and 29,502 controls. The pooled absolute mean difference in OPP between OAG patients and controls was −2.52 mmHg (95% CI −4.06 to −0.98), meaning significantly lower OPP in OAG patients (P = 0.001). Subgroup analyses showed that OAG patients with baseline IOP > 21 mmHg (P = 0.019) and ocular hypertension patients also had significantly lower OPP than controls (P < 0.001), but such difference in OPP was not significant between OAG patients with baseline IOP of ≤21 mmHg and controls (P = 0.996). In conclusion, although no causal relationship was proven in the present study, our findings suggest that in patients with high baseline IOP, who already have a higher risk of glaucoma, low OPP might be another risk factor. [ABSTRACT FROM AUTHOR]

Purpose: To quantitatively analyze the topographic features of localized retinal nerve fiber layer (RNFL) defects according to baseline intraocular pressure (IOP) level in cases of early primary open-angle glaucoma (POAG). Study design: Retrospective comparative study. Methods: POAG patients meeting the following conditions were consecutively included: (1) baseline office-hour diurnal IOP ≤ 21 mmHg, (2) 1 localized RNFL defect as observed on red-free fundus photography, and (3) corresponding visual field defect. Defects' approximations to the macula (angle α) and width (angle ß) as well as the angle between the disc long axis and the vertical meridian line (angle Ɣ) were measured on red-free fundus photography. The corrected angle α was calculated as the difference between angles α and Ɣ. The defect area's RNFL thickness was calculated by means of optical coherence tomography's Advanced Extraction analysis utility. Results: Comparative analysis was performed between 2 groups: 45 eyes of 45 patients with low-teen IOP (group A: highest IOP ≤ 15 mmHg) and 49 eyes of 49 patients with high-teen IOP (group B: lowest IOP > 15 mmHg). In group A, the mean baseline IOP was lower (12.9 ± 1.3 vs 17.1 ± 1.0 mmHg; P <.001), the corrected angle α was smaller (32.4 ± 15.1 vs 39.5 ± 13.1 degrees; P =.017), and the defect area's RNFL thickness was thinner (66.3 ± 16.8 vs 76.3 ± 14.9 μm; P =.003) than in group B; angle ß showed no intergroup difference (P =.230). Conclusions: In POAG patients with low-teen IOP relative to those with high-teen IOP, localized RNFL defects were closer to the macula. In addition, the RNFL thickness of the defect area was markedly thinner. [ABSTRACT FROM AUTHOR]

MG53 is a member of the TRIM protein family that is predominantly expressed in striated muscles and participates in cell membrane repair. Controversy exists regarding MG53's role in insulin signaling and manifestation of diabetes. We generated db/db mice with either whole-body ablation or sustained elevation of MG53 in the bloodstream in order to evaluate the physiological function of MG53 in diabetes. To quantify the amount of MG53 protein in circulation, we developed a monoclonal antibody against MG53 with high specificity. Western blot using this antibody revealed lower or no change of serum MG53 levels in db/db mice or patients with diabetes compared with control subjects. Neither whole-body ablation of MG53 nor sustained elevation of MG53 in circulation altered insulin signaling and glucose handling in db/db mice. Instead, mice with ablation of MG53 were more susceptible to streptozotocin-induced dysfunctional handling of glucose compared with the wild-type littermates. Alkaline-induced corneal injury demonstrated delayed healing in db/db mice, which was restored by topical administration of recombinant human (rh)MG53. Daily intravenous administration of rhMG53 in rats at concentrations up to 10 mg/kg did not produce adverse effects on glucose handling. These findings challenge the hypothetical function of MG53 as a causative factor for the development of diabetes. Our data suggest that rhMG53 is a potentially safe and effective biologic to treat diabetic oculopathy in rodents. [ABSTRACT FROM AUTHOR]

The clinical significance of long-term methicillin-resistant Staphylococcus aureus (MRSA) bacteremia remains unclear. We evaluated the clinical, microbiological characteristics, and clinical outcomes of long-term MRSA bacteremia. A nested case-control study was conducted in a prospective cohort of adult patients with MRSA bacteremia at a tertiary hospital between August 2008 and December 2017. Patients with long-term MRSA bacteremia (≥ 14 days) were compared with control patients, defined as having bacteremia that resolved in less than 3 days. The following variables were documented: heteroresistance phenotype, genotypes, agr dysfunction, and the presence of 41 virulence genes in isolates. Of the total 890 patients studied, 69 patients (7.8%) exhibited long-term MRSA bacteremia and 599 (67.3%) exhibited resolving bacteremia. The most common sources of long-term bacteremia were central venous catheter–related infection (39%) and osteomyelitis (19%). Independent risk factors for long-term MRSA bacteremia included male sex (adjusted odds ratio [aOR] = 2.43), community-acquired bacteremia (aOR = 2.93), the presence of a prosthetic device (aOR = 3.40), and osteomyelitis (aOR = 7.98). Metastatic infections developed more frequently in patients with long-term bacteremia than in those with resolving bacteremia (56.5% vs. 8.0%; P < 0.001). Although there were no significant differences in 30-day, 12-week, or in-hospital mortality rates between the two groups, infection-attributable mortality was higher in the long-term bacteremia group (23.2% vs. 11.5%; P = 0.01). Microbiological characteristics did not differ significantly between the two groups. Clinical factors, including community-acquired bacteremia, the presence of a prosthetic device, and osteomyelitis, appear to contribute to long-term MRSA bacteremia more than microbiological factors. [ABSTRACT FROM AUTHOR]

We developed a hybrid deep learning model (HDLM) algorithm that quantitatively predicts macular ganglion cell-inner plexiform layer (mGCIPL) thickness from red-free retinal nerve fiber layer photographs (RNFLPs). A total of 789 pairs of RNFLPs and spectral domain-optical coherence tomography (SD-OCT) scans for 431 eyes of 259 participants (183 eyes of 114 healthy controls, 68 eyes of 46 glaucoma suspects, and 180 eyes of 99 glaucoma patients) were enrolled. An HDLM was built by combining a pre-trained deep learning network and support vector machine. The correlation coefficient and mean absolute error (MAE) between the predicted and measured mGCIPL thicknesses were calculated. The measured (OCT-based) and predicted (HDLM-based) average mGCIPL thicknesses were 73.96 ± 8.81 µm and 73.92 ± 7.36 µm, respectively (P = 0.844). The predicted mGCIPL thickness showed a strong correlation and good agreement with the measured mGCIPL thickness (Correlation coefficient r = 0.739; P < 0.001; MAE = 4.76 µm). Even when the peripapillary area (diameter: 1.5 disc diameters) was masked, the correlation (r = 0.713; P < 0.001) and agreement (MAE = 4.87 µm) were not changed significantly (P = 0.378 and 0.724, respectively). The trained HDLM algorithm showed a great capability for mGCIPL thickness prediction from RNFLPs. [ABSTRACT FROM AUTHOR]

Purpose: To assess the performance of machine learning classifiers for prediction of progression of normal-tension glaucoma (NTG) in young myopic patients. Study design: Cross-sectional study. Methods: One hundred and fifty-five eyes of 155 myopic NTG patients (axial length [AL] ≥ 24.00 mm and refractive error ≤ − 3.0 D) between the ages of 20 and 40 were enrolled and divided into training (110) and test (45) sets. Sixty-five eyes showed glaucoma progression as defined by standard automated perimetry, while 91 eyes (nonprogressors) had been stable over the course of a follow-up period of at least 3 years. Two machine learning classifiers were built using the random forest and extremely randomized trees (extra-trees) models. Baseline clinical measurements obtained only at the initial visit were used as input features. The area under the receiver operating characteristic curve (AUC) was calculated to evaluate the accuracy of prediction. Results: Mean age and AL did not significantly differ between the 2 groups on either the training or the test set. The extra-trees model achieved an AUC of 0.881 [95% CI 0.814–0.945], higher than that of the random forest model (0.811 [0.731–0.888]; P = 0.010). The extra-trees model also outperformed all the clinical measurements for prediction of NTG progression, including average macular ganglion cell-inner plexiform layer thickness (0.735 [0.639–0.831]) and average circumpapillary retinal nerve fiber layer thickness (0.691 [0.590–0.792]; both P < 0.001). Conclusions: In young myopic patients, the machine learning classifier with the extra-trees model can predict glaucomatous progression more effectively than clinical diagnostic parameters. [ABSTRACT FROM AUTHOR]

The macular ellipsoid zone intensity (mEZi) is a known marker of disease severity in a number of diverse ocular diseases. The purpose of this study was to establish an automated method (AM) for mEZi quantification and to compare the method's performance with that of a manual method (MM) for glaucoma patients and healthy controls. Seventy-one (71) mild-to-moderate glaucoma patients, 71 severe-glaucoma patients, and 51 controls were enrolled. Both calibration (n = 160) and validation (n = 33) image sets were compiled. The correlation of AM to MM quantification was assessed by Deming regression for the calibration set, and a compensation formula was generated. Then, for each image in the validation set, the compensated AM quantification was compared with the mean of five repetitive MM quantifications. The AM quantification of the calibration set was found to be linearly correlated with MM in the normal-to-severe-stage glaucoma patients (R2 = 0.914). The validation set's compensated AM quantification produced R2 = 0.991, and the relationship between the 2 quantifications was AM = 1.004(MM) + 0.139. In the validation set, the compensated AM quantification fell within MM quantification's 95% confidence interval in 96.9% of the images. An AM for mEZi quantification was calibrated and validated relative to MM quantification for both glaucoma patients and healthy controls. [ABSTRACT FROM AUTHOR]