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Objective: To investigate the association of meibomian gland dysfunction (MGD) and ocular surface exposure with tear film instability in untreated thyroid eye disease (TED) patients., Methods: A cross-sectional study of TED patients from September 2020 to September 2022 was conducted. Ocular surface parameters included ocular surface disease index (OSDI), tear meniscus height (TMH), non-invasive tear break-up time (NITBUT), partial blinking rate, lipid layer thickness (LLT), meibomian gland dropout (meiboscore), Schirmer's test, and corneal punctate epithelial erosions (PEE). Ocular surface exposure was assessed by the margin reflex distances of the upper and lower eyelid (MRD1 and MRD2), the amount of exophthalmos, lateral flare, and lagophthalmos., Results: In total, 152 eyes from 76 TED patients (64 females and 12 males, age 42.99 ± 12.28 years) and 93 eyes from 61 healthy controls (51 females and 10 males, age 43.52 ± 17.93 years) were examined. Compared with control eyes, TED eyes had higher OSDI, TMH, LLT, and PEE; shorter NITBUT; and worse meiboscore (all p < 0.05). They also had larger amounts of exophthalmos, longer MRD1, more lateral flare, and lagophthalmos. Multivariate analysis identified an association of the tear film instability with lagophthalmos (β = -1.13, 95%CI: -2.08, -0.18) and severe MGD in the lower eyelid (β = -5.01, 95%CI = -7.59, -2.43)., Conclusions: Dry eye in TED is mainly manifested as evaporative dry eye disease. Severe lower eyelid MGD and worse lagophthalmos were significantly associated with tear film instability in treatment-naive TED patients.

Purpose: Central serous chorioretinopathy (CSCR) is a leading cause of central vision impairment in the working-age population with male predilection. Knowledge about the genetic basis of CSCR and its male predilection remained limited. This study aimed to evaluate the association patterns of multiple gene variants in chronic CSCR (cCSCR) in Chinese patients., Methods: This case-control genetic association study included 531 patients with cCSCR and 2383 controls from two independent Chinese cohorts. Nine single-nucleotide polymorphisms (SNPs) of six genes, namely CFH, NR3C2, GATA5, VIPR2, TNFRSF10A, and ARMS2, were genotyped in all subjects. The main outcome measures were the association of individual single-nucleotide polymorphism (SNP) with cCSCR, the sex-stratification effects of individual SNP, and joint effects of different SNPs on cCSCR., Results: Association results in the two cohorts were consistent with low heterogeneities. In the combined analysis, SNPs CFH rs800292 (odds ratio [OR] = 1.25, P = 0.0020), CFH rs1329428 (OR = 1.23, P = 0.0037), and TNFRSF10A rs13278062 (OR = 1.43, P = 0.0014) were significantly associated with cCSCR. In stratification analysis by sex, 3 SNPs in CFH, rs3753394, rs800292, and rs1329428, were associated with cCSCR in male patients, but not in female patients. Joint analysis revealed that subjects homozygous for the risk alleles of CFH rs800292 and TNFRSF10A rs13278062 had over 4-fold of increased risk of cCSCR when compared with subjects homozygous for the non-risk alleles (OR = 4.06, P = 2.30 × 10-5)., Conclusions: This study revealed main and joint effects of SNPs in CFH and TNFRSF10A on cCSCR, and suggested CFH as a potential genetic factor underlying the male predilection of cCSCR. Further replication in other study populations is needed.

Purpose: This study aimed to assess the prevalence and characteristics of the peripapillary gamma zone in myopic, emmetropic, and hyperopic eyes of Chinese children., Methods: Overall, 1274 children aged 6 to 8 years from the Hong Kong Children Eye Study underwent ocular examinations, including measurements of cycloplegic auto-refraction and axial length (AL). The optic disc was imaged using a Spectralis optical coherence tomography (OCT) unit and a protocol involving 24 equally spaced radial B-scans. The Bruch's membrane opening (BMO) was identified in over 48 meridians in each eye. The peripapillary gamma zone was defined as the region between the BMO and the border of the optic disc, identified by the OCT., Results: The prevalence of the peripapillary gamma zone was higher in myopic eyes (36.3%) than in emmetropic (16.1%) and hyperopic eyes (11.5%, P < 0.001). AL (per 1 mm; odds ratio [OR]) = 1.861, P < 0.001) and a more oval disc shape (OR = 3.144, P < 0.001) were associated with the presence of a peripapillary gamma zone after adjusting for demographic, systemic, and ocular variables. In the subgroup analysis, a longer AL was associated with the presence of a peripapillary gamma zone in myopic eyes (OR = 1.874, P < 0.001), but not in emmetropic (OR = 1.033, P = 0.913) or hyperopic eyes (OR = 1.044, P = 0.883). A peripapillary zone was not observed in the region nasal to the optic nerve in myopic eyes, in contrast to its presence in the same region in 1.9% of emmetropic eyes and 9.3% of hyperopic eyes; these intergroup differences were statistically significant (P < 0.001)., Conclusions: Although peripapillary gamma zones were observed in the eyes of both myopic and non-myopic children, their characteristics and distribution patterns were substantially different.

Background: The Wechsler Memory Scale-Fourth Edition (WMS-IV) has been widely used to assess memory function in people with dementia. The older adult battery of the WMS-IV includes four indices and seven subtests. The aims of this study were to examine the practice effect and test-retest reliability and calculate the reliable change index modified for practice (RCIp) for the indices and subtests of the older adult battery of the WMS-IV for people with dementia., Methods: Fifty-six participants completed the WMS-IV twice, two weeks apart. The practice effect was investigated using effect size (Cohen's d) and bootstrapping mixed design analysis of variance while considering the severity of dementia. The test-retest reliability was estimated using intraclass correlation coefficient (ICC)., Results: The results showed non-significant practice effects with Cohen's d < 0.20 in different severities of dementia on two indices and five subtests. The ICC values of these indices and subtests were 0.82-0.85 and 0.57-1.00, respectively. The other two indices (i.e., auditory memory and immediate memory) and two subtests (i.e., logical memory delayed recall and visual reproduction immediate recall) demonstrated small to moderate practice effect (d = 0.46-0.74) for people with mild severity of dementia., Conclusion: On the whole, the WMS-IV has no to moderate practice effects and moderate to excellent test-retest reliability in people with dementia. The values of the RCIp with 95% confidence interval for the indices and subtests were provided in this study, which are useful to clinicians and researchers for interpreting the real score change in persons with dementia. The two indices (i.e., auditory memory and immediate memory) and two subtests (i.e., logical memory delayed recall and visual reproduction immediate recall) with noticeable practice effect should be used with caution when assessing memory function repeatedly in people with mild severity of dementia., (© 2023. The Author(s).)

Introduction: This study aimed to evaluate the habitual reading distance among non-myopic children and also myopic children with undercorrection and with full correction., Methods: This was a population-based cross-sectional study with a total of 2363 children aged 6-8 years who were recruited from the Hong Kong Children Eye Study. Cycloplegic autorefraction, subjective refraction, habitual visual acuity, and best corrected visual acuity were measured. The entire reading process (9 min) was recorded using a hidden video camera placed 5 m away from the reading desk. Reading distances were taken at 6, 7, 8, and 9 min after the child began reading and were measured using a customized computer program developed in MATLAB. The main outcome was the association of habitual reading distances with refraction status. Habitual reading distances of children were documented via video camera footage., Results: The habitual reading distances of undercorrected myopic children (23.37 ± 4.31 cm) were the shortest when compared to non-myopic children (24.20 ± 4.73 cm, P = 0.002) and fully corrected myopic children (24.81 ± 5.21 cm, P < 0.001), while there was no significant difference between the last two children groups (P = 0.17). A shorter reading distance was associated with myopia (OR 1.67; 95% CI 1.11-2.51; P = 0.013) after adjusting for age, sex, height, near work time, outdoor time, and parental myopia. The association of reading distance with myopia did not hold after undercorrected myopic children were excluded (OR 0.97, 95% CI 0.55-1.73; P = 0.92). A shorter reading distance correlated with poorer vision under habitual correction (β = - 0.003, P < 0.001)., Conclusion: A shorter reading distance was present among undercorrected myopic children. Myopia undercorrection is not recommended as a strategy for slowing myopic progression., (© 2022. The Author(s).)

Background: To compare the prevalence of refractive (RA), corneal (CA), and internal astigmatism (IA) in Hong Kong children and adults and evaluate the role of IA in compensating for total astigmatism and its relations to myopic traits., Methods: The Hong Kong Children Eye Study is a population-based cross-sectional study. Totally 3704 school children (mean age 7.5 ± 1.0 years) and 5577 adults (mean age 41.1 ± 7.5 years), who were their parents, were recruited. Cycloplegic and non-cycloplegic refractive cylinders were obtained from children and adults, respectively. Spearman correlation was applied to detect associations between astigmatism, ocular biometrics, refraction, and lens power. Astigmatism compensation factor (CF) was derived from the power vector analysis J0 and J45., Results: The prevalence of RA (≤-1.0 D), CA (≥+1.0 D) and IA (≥+1.0 D) was 21.9%, 63.9%, and 9.9% in children, and 30.9%, 39.5%, and 23.7% in adults respectively. The mean RA, CA and IA values in children and adults were -0.69 ± 0.66 D, +1.14 ± 0.61 D, +0.62 ± 0.32 D, and -0.80 ± 0.74 D, +0.97 ± 0.69 D, and +0.76 ± 0.43 D, respectively. In adults and children, IA was negatively correlated with axial length (p < 0.0001), but positively correlated with spherical values and equivalent (p < 0.0001), suggesting an association of astigmatism with myopic traits. A greater proportion of children exhibited compensation by IA than adults in J0 (86.6% vs. 66.0%, p < 0.0001) and J45 components (55.5% vs. 41.7%, p < 0.0001)., Conclusions: Chinese children in Hong Kong exhibit a higher prevalence of RA and CA than in other cities. Children displayed a greater compensation by IA than adults, suggesting an age-related attenuation of IA compensation. IA is associated with myopic traits., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Background: Although biological aging has been proposed as a more accurate measure of aging, few biological aging measures have been developed for Asians, especially for young adults., Methods: A total of 521 656 participants were enrolled in the MJ cohort (1996-2011) and were followed until death, loss-to-follow-up, or December 31, 2011, whichever came first. We selected 14 clinical biomarkers, including chronological age, using a random forest algorithm, and developed a multidimensional aging measure (MDAge). Model performance was assessed by area under the curve (AUC) and internal calibration. We evaluated the associations of MDAge and residuals from regressing MDAge on chronological age (MDAgeAccel) with mortality and morbidity, and assessed the robustness of our findings., Results: MDAge achieved an excellent AUC of 0.892 in predicting all-cause mortality (95% confidence interval [CI]: 0.889-0.894). Participants with higher MDAge at baseline were at a higher risk of death (per 5 years, hazard ration [HR] = 1.671, 95% CI: 1.662-1.680), and the association remained after controlling for other variables and in different subgroups. Furthermore, participants with higher MDAgeAccel were associated with shortened life expectancy. For instance, compared to men who were biologically younger (MDAgeAccel ≤ 0) at baseline, men in the highest tertiles of MDAgeAccel had shortened life expectancy by 17.23 years. In addition, higher MDAgeAccel was associated with having chronic disease either cross-sectionally (per 1-standard deviation [SD], odds ratio [OR] = 1.564, 95% CI: 1.552-1.575) or longitudinally (per 1-SD, OR = 1.218, 95% CI: 1.199-1.238)., Conclusion: MDAge accurately predicted mortality and morbidity, which has great potential in the early identification of individuals at higher risk and therefore promoting early intervention., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The androgen-dependent or -independent pathways are regarded as primary therapeutic targets for the neoplasm of the prostate. Mucosa-associated lymphoid tissue 1 (MALT1) acting as a paracaspase in the regulation of nuclear factor κB (NF-κB) signal transduction plays a central role in inflammation and oncogenesis in cancers. This study confirmed the potential linkages between androgen and NF-κB activation by inducing MALT1 in the androgen receptor-full length (ARFL)-positive LNCaP and 22Rv1 prostate cancer cells. Although androgen did not stimulate MALT1 expression in AR-null or ectopic ARFL-overexpressed PC-3 cells, the ectopic overexpression of the AR splicing variant 7 (ARv7) upregulated MALT1 to activate NF-κB activities in 22Rv1 and PC-3 cells. Since the nuclear translocation of p50 and p65 was facilitated by ARv7 to motivate NF-κB activity, the expressions of MALT1, prostate-specific antigen (PSA), and N-myc downstream regulated 1 (NDRG1) were therefore induced in ectopic ARv7-overexpressed prostate cancer cells. Ectopic ARv7 overexpression not only enhanced 22Rv1 or PC-3 cell growth and invasion in vitro but also the tumor growth of PC-3 cells in vivo. These results indicate that an androgen receptor induces MALT1 expression androgen-dependently and -independently in ARFL- or ARv7-overexpressed prostate cancer cells, suggesting a novel ARv7/MALT1/NF-κB-signaling pathway may exist in the cells of prostate cancer.

Purpose: This study aims to investigate the effectiveness of interventions to control myopia progression. In this systematic review, the primary outcomes were mean differences (MD) between treatment and control groups in myopia progression (D) and axial length (AL) elongation (mm)., Results: The following interventions were found to be effective ( p  < 0.001): highly aspherical lenslets (HAL, 0.80 D, 95% CI, 0.77-0.83; -0.35 mm, 95% CI -0.36 to -0.34), MiSight contact lenses (0.66 D, 95% CI, 0.63-0.69; -0.28 mm, 95% CI -0.29 to -0.27), low dose atropine 0.05% (0.54 D, 95% CI, 0.38-0.70; -0.21 mm, 95% CI-0.28 to -0.14), Biofinity +2.50 D (0.45 D, 95% CI, 0.29, 0.61; -0.24 mm, 95% CI -0.33 to -0.15), defocus incorporated multiple segments [DIMS] (0.44 D, 95% CI, 0.42-0.46; -0.34 mm, 95% CI -0.35 to -0.33) and ortho-k lenses (-0.24 mm, 95% CI -0.33 to -01.5)., Conclusion: Low-dose atropine 0.01% was not effective in reducing AL progression in two studies. Treatment efficacy with low-dose atropine of 0.05% showed good efficacy. Spectacles (HAL and DIMS) and contact lenses (MiSight and Biofinity) may confer a comparable treatment benefit compared to atropine, to slow myopia progression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lanca, Pang and Grzybowski.)

The surface effects on running biomechanics have been greatly investigated. However, the effects on rearfoot strike runners remain unknown. The purpose of this study was to investigate the effects of surfaces on the running kinematics, kinetics, and lower-limb stiffness of habitual rearfoot strikers. Thirty healthy male runners were recruited to run at 3.3 ± 0.2 m/s on a customized runway covered with three different surfaces (artificial grass, synthetic rubber, or concrete), and their running kinematics, kinetics, and lower-limb stiffness were compared. Differences among the three surfaces were examined using statistical parametric mapping and one-way repeated-measure analysis of variance. There were no statistical differences in the lower-limb joint motion, vertical ground reaction force (GRF), loading rates, and lower-limb stiffness when running on the three surfaces. The braking force (17%-36% of the stance phase) and mediolateral GRF were decreased when running on concrete surface compared with running on the other two surfaces. The moments of ankle joint in all three plane movement and frontal plane hip and knee joints were increased when running on concrete surface. Therefore, habitual rearfoot strikers may expose to a higher risk of running-related overuse injuries when running on a harder surface., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Myopia is the most common ocular disorder worldwide with an increasing prevalence over the past few decades. It is a refractive error associated with excessive growth of the eyeball. Individuals with myopia, especially high myopia, are prone to develop sight-threatening complications. Currently, atropine is the only drug that is used to slow myopia progression in clinical practice. However, there are still areas of uncertainty such as treatment strategy, optimal concentration when considering risk-benefit ratio and active treatment period. Since the prevalence of myopia is much higher in Asian countries, most of the research on myopia control has been conducted in Asia. Data on the efficacy and tolerability to atropine eye drops in the non-Asian population remains limited. In this review, we summarize the results of published clinical trials on the effectiveness and tolerability of atropine eye drops for myopia control in non-Asian regions. The efficacy was evaluated by the mean change in spherical equivalent (SE) or axial length (AL). The tolerability of atropine eye drops was analyzed based on patients complains and adverse events. The results of this review suggest that 0.01% atropine eye drops are effective in non-Asian regions achieving less side effects compared to 0.5% concentration.

Purpose: To elucidate the clinical implications of corneal striae (CS) in thyroid associated orbitopathy (TAO) patients., Methods: In this cross-sectional study, the presence of CS was confirmed after topical fluorescein staining on a slit lamp for consecutive treatment-naive TAO patients. Orbital parameters, including margin reflex distances, lagophthalmos, exophthalmos, intraocular pressure and radiological measurements, were compared between eyes with and without CS. The largest cross-sectional areas of each rectus muscle were measured by segmenting the T1-weighted (T1W) magnetic resonance images (MRI). The logistic regression analyses were used to evaluate the associations between CS and orbital parameters and rectus muscle measurements., Results: Fifty-three consecutive TAO patients (presenting age 46.47 ± 14.73 years, clinical activity score 1.77 ± 1.25) who had unilateral CS were enrolled. In univariate analysis, both the degree of lagophthalmos and the area of the levator palpebrae superioris-superior rectus complex (LPS/SR) on T1W MRI were significantly larger in CS eyes compared to eyes without CS ( p < 0.05). Multivariate analyses showed that CS in TAO patients were significantly associated with the degree of lagophthalmos (OR = 1.75, 95% CI: 1.18-2.61, p < 0.05) and LPS/SR area (OR = 19.27, 95% CI: 1.43-259.32, p < 0.05) but not with the other parameters. CS could predict LPS/SR enlargement and larger lagophthalmos in TAO ( p < 0.05). The largest cross-sectional areas of LPS/SR and inferior rectus were positively correlated with clinical activity scores ( p < 0.05)., Conclusions: The presence of CS in TAO eye is significantly associated with LPS/SR enlargement and worse lagophthalmos. CS might be evaluated further as a potential ocular surface biomarker to identify upper lid and LPS/SR involvement in TAO.

Importance: Individuals with prediabetes have a higher risk of death than healthy individuals. However, previous findings have suggested that individuals with reversion from prediabetes to normoglycemia may not have a lower risk of death compared with individuals with persistent prediabetes., Objectives: To investigate the associations between changes in prediabetes status and risk of death and to elucidate the roles of modifiable risk factors in these associations., Design, Setting, and Participants: This population-based prospective cohort study used data from 45 782 participants with prediabetes from the Taiwan MJ Cohort Study who were recruited between January 1, 1996, and December 31, 2007. Participants were followed up from the second clinical visit to December 31, 2011, with a median (IQR) follow-up of 8 (5-12) years. Participants were categorized into 3 groups according to changes in their prediabetes status within a 3-year period after initial enrollment: reversion to normoglycemia, persistent prediabetes, and progression to diabetes. Cox proportional hazards regression models were used to examine the associations between changes in prediabetes status at baseline (ie, the second clinical visit) and risk of death. Data analysis was performed between September 18, 2021, and October 24, 2022., Main Outcomes and Measures: All-cause mortality, cardiovascular disease (CVD)-related mortality, and cancer-related mortality., Results: Of 45 782 participants with prediabetes (62.9% male; 100% Asian; mean [SD] age, 44.6 [12.8] years), 1786 (3.9%) developed diabetes and 17 021 (37.2%) reverted to normoglycemia. Progression from prediabetes to diabetes within a 3-year period was associated with higher risks of all-cause death (hazard ratio [HR], 1.50; 95% CI, 1.25-1.79) and CVD-related death (HR, 1.61; 95% CI, 1.12-2.33) compared with persistent prediabetes, while reversion to normoglycemia was not associated with a lower risk of all-cause death (HR, 0.99; 95% CI, 0.88-1.10), cancer-related death (HR, 0.91; 95% CI, 0.77-1.08), or CVD-related death (HR, 0.97; 95% CI, 0.75-1.25). Among individuals who were physically active, reversion to normoglycemia was associated with a lower risk of all-cause death (HR, 0.72; 95% CI, 0.59-0.87) compared with those with persistent prediabetes who were physically inactive. Among individuals with obesity, risk of death varied between those who experienced reversion to normoglycemia (HR, 1.10; 95% CI, 0.82-1.49) and those who had persistent prediabetes (HR, 1.33; 95% CI, 1.10-1.62)., Conclusions and Relevance: In this cohort study, although reversion from prediabetes to normoglycemia within a 3-year period did not mitigate the overall risk of death compared with persistent prediabetes, risk of death associated with reversion to normoglycemia varied based on whether individuals were physically active or had obesity. These findings highlight the importance of lifestyle modification among those with prediabetes status.

Importance: Childhood myopia increased during the COVID-19 pandemic. Limited evidence exists about whether myopia development was reversed or worsened after the lockdown., Objective: To determine the prevalence of myopia and its associated factors before, during, and after COVID-19 restrictions., Design, Setting, and Participants: This population-based, repeated cross-sectional study evaluated children aged 6 to 8 years from the Hong Kong Children Eye Study between 2015 and 2021 in 3 cohorts: before COVID-19 (2015-2019), during COVID-19 restrictions (2020), and after COVID-19 restrictions were lifted (2021)., Exposures: All the children received ocular examinations, including cycloplegic autorefraction and axial length. Data about the children's lifestyle, including time spent outdoors, near-work time, and screen time, were collected from a standardized questionnaire., Main Outcomes and Measures: The main outcomes were the prevalence of myopia, mean spherical equivalent refraction, axial length, changes in lifestyle, and the associated factors over 7 years. Data were analyzed using descriptive statistics, logistic regression, and generalized estimating equations., Results: Of 20 527 children (mean [SD] age, 7.33 [0.89] years; 52.8% boys and 47.2% girls), myopia prevalence was stable from 2015 to 2019 (23.5%-24.9%; P = .90) but increased to 28.8% (P < .001) in 2020 and 36.2% (P < .001) in 2021. The mean (SD) time spent outdoors was much lower in 2020 (0.85 [0.53] h/d; P < .001) and 2021 (1.26 [0.48] h/d; P < .001) compared with pre-COVID-19 levels (1.40 [0.47]-1.46 [0.65] h/d). The trend was reversed for total near-work time and screen time. High myopia prevalence was associated with the COVID-19 pandemic (odds ratio [OR], 1.40; 95% CI, 1.28-1.54; P < .001), younger age (OR, 1.84; 95% CI, 1.76-1.93; P < .001), male sex (OR, 1.11; 95% CI, 1.03-1.21; P = .007), lower family income (OR, 1.05; 95% CI, 1.00-1.09; P = .04), and parental myopia (OR, 1.61; 95% CI, 1.52-1.70; P < .001). During the pandemic, mean (SD) near-work and screen times in children from lower-income families were 5.16 (2.05) h/d and 3.44 (1.97) h/d, more than from higher-income families (4.83 [1.85] and 2.90 [1.61] h/d, respectively)., Conclusions and Relevance: The findings of this cross-sectional study revealed that after COVID-19 restrictions were lifted in Hong Kong, myopia prevalence among children was higher than before the pandemic, and lifestyle did not return to pre-COVID-19 levels. Younger children and those from low-income families were at a higher risk of myopia development during the pandemic, suggesting that collective efforts for myopia control should be advocated for these groups.

Significance Statement: The kidney failure risk equation (KFRE) uses age, sex, GFR, and urine albumin-to-creatinine ratio (ACR) to predict 2- and 5-year risk of kidney failure in populations with eGFR <60 ml/min per 1.73 m 2 . However, the CKD-EPI 2021 creatinine equation for eGFR is now recommended for use but has not been fully tested in the context of KFRE. In 59 cohorts comprising 312,424 patients with CKD, the authors assessed the predictive performance and calibration associated with the use of the CKD-EPI 2021 equation and whether additional variables and accounting for the competing risk of death improves the KFRE's performance. The KFRE generally performed well using the CKD-EPI 2021 eGFR in populations with eGFR <45 ml/min per 1.73 m 2 and was not improved by adding the 2-year prior eGFR slope and cardiovascular comorbidities., Background: The kidney failure risk equation (KFRE) uses age, sex, GFR, and urine albumin-to-creatinine ratio (ACR) to predict kidney failure risk in people with GFR <60 ml/min per 1.73 m 2 ., Methods: Using 59 cohorts with 312,424 patients with CKD, we tested several modifications to the KFRE for their potential to improve the KFRE: using the CKD-EPI 2021 creatinine equation for eGFR, substituting 1-year average ACR for single-measure ACR and 1-year average eGFR in participants with high eGFR variability, and adding 2-year prior eGFR slope and cardiovascular comorbidities. We also assessed calibration of the KFRE in subgroups of eGFR and age before and after accounting for the competing risk of death., Results: The KFRE remained accurate and well calibrated overall using the CKD-EPI 2021 eGFR equation. The other modifications did not improve KFRE performance. In subgroups of eGFR 45-59 ml/min per 1.73 m 2 and in older adults using the 5-year time horizon, the KFRE demonstrated systematic underprediction and overprediction, respectively. We developed and tested a new model with a spline term in eGFR and incorporating the competing risk of mortality, resulting in more accurate calibration in those specific subgroups but not overall., Conclusions: The original KFRE is generally accurate for eGFR <45 ml/min per 1.73 m 2 when using the CKD-EPI 2021 equation. Incorporating competing risk methodology and splines for eGFR may improve calibration in low-risk settings with longer time horizons. Including historical averages, eGFR slopes, or a competing risk design did not meaningfully alter KFRE performance in most circumstances., (Copyright © 2023 by the American Society of Nephrology.)

Many complex forms of retinal diseases are common and pan-ethnic in occurrence. Among them, neovascular age-related macular degeneration, polypoidal choroidal vasculopathy, and central serous choroid retinopathy involve both choroidopathy and neovascularization with multifactorial etiology. They are sight-threatening and potentially blinding. Early treatment is crucial to prevent disease progression. To understand their genetic basis, candidate gene mutational and association analyses, linkage analysis, genome-wide association studies, transcriptome analysis, next-generation sequencing, which includes targeted deep sequencing, whole-exome sequencing, and whole genome sequencing have been conducted. Advanced genomic technologies have led to the identification of many associated genes. But their etiologies are attributed to complicated interactions of multiple genetic and environmental risk factors. Onset and progression of neovascular age-related macular degeneration and polypoidal choroidal vasculopathy are affected by aging, smoking, lifestyle, and variants in over 30 genes. Although some genetic associations have been confirmed and validated, individual genes or polygenic risk markers of clinical value have not been established. The genetic architectures of all these complex retinal diseases that involve sequence variant quantitative trait loci have not been fully delineated. Recently artificial intelligence is making an impact in the collection and advanced analysis of genetic, investigative, and lifestyle data for the establishment of predictive factors for the risk of disease onset, progression, and prognosis. This will contribute to individualized precision medicine for the management of complex retinal diseases., Competing Interests: The authors have no funding or conflicts of interest to declare., (Copyright © 2023 Asia-Pacific Academy of Ophthalmology. Published by Wolters Kluwer Health, Inc. on behalf of the Asia-Pacific Academy of Ophthalmology.)

The rising prevalence of myopia is a major global public health concern. Economic evaluation of myopia interventions is critical for maximizing the benefits of treatment and the healthcare system. This systematic review aimed to evaluate the cost-effectiveness of interventions for treating myopia. Five databases were searched - Embase, Emcare, PubMed, Web of Science, and ProQuest - from inception to July 2022 and a total of 2,099 articles were identified. After careful assessments, 6 studies met the eligibility criteria. The primary outcomes of this systematic review were costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). The secondary outcomes included utility values and net monetary benefits (NMB). One study determined the cost-effectiveness of photorefractive screening plus treatment with 0.01% atropine, 2 studies examined cost-effectiveness of corneal refractive surgery, and 3 studies evaluated cost-effectiveness of commonly used therapies for pathologic myopia. Corneal refractive surgeries included laser in situ keratomileusis (LASIK), femtosecond laser-assisted in situ keratomileusis (FS-LASIK), photorefractive keratectomy (PRK), and small-incision lenticule extraction (SMILE). Interventions for pathologic myopia included ranibizumab, conbercept, and photodynamic therapy (PDT). At an incremental cost of NZ$ 18 (95% CI 15, 20) (US$ 11) per person, photorefractive screening plus 0.01% atropine resulted in an ICER of NZ$ 1,590/QALY (US$ 1,001/QALY) (95% CI NZ$ 1,390, 1,791) for an incremental QALY of 0.0129 (95% CI 0.0127, 0.0131). The cost of refractive surgery in Europe ranged from €3,075 to €3,123 ([US$4,046 to $4,109 - adjusted to 2021 inflation). QALYs associated with these procedures were 23 (FS-LASIK) and 24 (SMILE and PRK) with utility values of 0.8 and ICERs ranging from approximately €14 (US$17)/QALY to €19 (US$23)/QALY. The ICER of LASIK was US$683/diopter gained (inflation-adjusted). The ICER of ranibizumab and PDT were £8,778 (US$12,032)/QALY and US$322,460/QALY respectively, with conbercept yielding a saving of 541,974 RMB (US$80,163)/QALY, respectively. The use of 0.01% atropine and corneal refractive surgery were cost-effective for treating myopia. Treating pathologic myopia with ranibizumab and conbercept were more cost-effective than PDT. Prevention of myopia progression is more cost-effective than treating pathologic myopia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Agyekum, Chan, Zhang, Huo, Yip, Ip, Tham, Chen, Zhang, Pang and Yam.)

Importance: Early onset of myopia is associated with high myopia later in life, and myopia is irreversible once developed., Objective: To evaluate the efficacy of low-concentration atropine eyedrops at 0.05% and 0.01% concentration for delaying the onset of myopia., Design, Setting, and Participants: This randomized, placebo-controlled, double-masked trial conducted at the Chinese University of Hong Kong Eye Centre enrolled 474 nonmyopic children aged 4 through 9 years with cycloplegic spherical equivalent between +1.00 D to 0.00 D and astigmatism less than -1.00 D. The first recruited participant started treatment on July 11, 2017, and the last participant was enrolled on June 4, 2020; the date of the final follow-up session was June 4, 2022., Interventions: Participants were assigned at random to the 0.05% atropine (n = 160), 0.01% atropine (n = 159), and placebo (n = 155) groups and had eyedrops applied once nightly in both eyes over 2 years., Main Outcomes and Measures: The primary outcomes were the 2-year cumulative incidence rate of myopia (cycloplegic spherical equivalent of at least -0.50 D in either eye) and the percentage of participants with fast myopic shift (spherical equivalent myopic shift of at least 1.00 D)., Results: Of the 474 randomized patients (mean age, 6.8 years; 50% female), 353 (74.5%) completed the trial. The 2-year cumulative incidence of myopia in the 0.05% atropine, 0.01% atropine, and placebo groups were 28.4% (33/116), 45.9% (56/122), and 53.0% (61/115), respectively, and the percentages of participants with fast myopic shift at 2 years were 25.0%, 45.1%, and 53.9%. Compared with the placebo group, the 0.05% atropine group had significantly lower 2-year cumulative myopia incidence (difference, 24.6% [95% CI, 12.0%-36.4%]) and percentage of patients with fast myopic shift (difference, 28.9% [95% CI, 16.5%-40.5%]). Compared with the 0.01% atropine group, the 0.05% atropine group had significantly lower 2-year cumulative myopia incidence (difference, 17.5% [95% CI, 5.2%-29.2%]) and percentage of patients with fast myopic shift (difference, 20.1% [95% CI, 8.0%-31.6%]). The 0.01% atropine and placebo groups were not significantly different in 2-year cumulative myopia incidence or percentage of patients with fast myopic shift. Photophobia was the most common adverse event and was reported by 12.9% of participants in the 0.05% atropine group, 18.9% in the 0.01% atropine group, and 12.2% in the placebo group in the second year., Conclusions and Relevance: Among children aged 4 to 9 years without myopia, nightly use of 0.05% atropine eyedrops compared with placebo resulted in a significantly lower incidence of myopia and lower percentage of participants with fast myopic shift at 2 years. There was no significant difference between 0.01% atropine and placebo. Further research is needed to replicate the findings, to understand whether this represents a delay or prevention of myopia, and to assess longer-term safety., Trial Registration: Chinese Clinical Trial Registry: ChiCTR-IPR-15006883.

Myopic tilted disc is a common structural change of myopic eyes. With advancing ocular imaging technology, the associated structural changes of the eye, particularly the optic nerve head, have been extensively studied. These structural changes may increase patients' susceptibility to axonal damage and the risk of developing serious optic neuropathies including glaucoma. They also lead to diagnostic difficulties of disease suspects and treatment dilemmas of patients, which implicate clinical practice and subsequently the health care system. In the context of the mounting prevalence of myopia worldwide and its implications to irreversible visual impairment and blindness, it is essential to gain a thorough understanding of the structural changes of myopia. Myopic tilted disc has been extensively investigated by different study groups. However, generalizing the knowledge could be difficult because of the variable definitions of myopic tilted disc utilized in these studies and the complexities of the changes. The current review aimed to clarify the concepts and discuss various aspects of myopic tilted disc, including the definitions, association with other myopia-related changes, mechanism of tilted disc development, structural and functional changes, and clinical implications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chan, Zhang and Pang.)

Bleeding during endoscopic prostate surgery is often overlooked, and appropriate measurement techniques are rarely applied. We proposed a simple and convenient method for assessing the severity of bleeding during endoscopic prostate surgery. We determined the factors affecting bleeding severity and whether they affected the surgical results and functional outcomes. Records from March 2019 to April 2022 were obtained for selected patients who underwent endoscopic prostate enucleation through either 120-W Vela XL Thulium:YAG laser or bipolar plasma enucleation of the prostate. The bleeding index was measured using the following equation: irrigant hemoglobin (Hb) concentration (g/dL) × irrigation fluid volume (mL)/preoperative blood Hb concentration (g/dL) × enucleated tissue (g). Our research revealed that patients who underwent surgery employing the thulium laser, those aged over 80 years, and those with a preoperative maximal flow rate (Qmax) of more than 10 cc/s experienced less surgical bleeding. The patients' treatment outcomes differed depending on the severity of the bleeding. Enucleating prostate tissue was easier in the patients with less severe bleeding, who also had a lower risk of developing urinary tract infections and an improved Qmax.

Genetic counselling (GC) provides information to the patient and the family to make informed choices. Among the advanced Western countries and a few Asian countries, there are certified or trained professionals who perform GC. The Human Genome Project and next-generation sequencing diagnostics have provided an opportunity for increased genetic testing in the field of ophthalmology. The recent interventional therapeutic research strategies have also generated additional interest to seek GC globally, including in Asia. However, GC has several barriers to practise in the developing countries in Asia, namely, (a) shortage of qualified or trained genetic counsellors, (b) poor knowledge and reluctance in clinical adoption of genomics among the physicians in clinical practice, (c) overstretched public health services, and (d) negligible ophthalmic GC-related research and publications. The GC inadequacy in Asia is glaring in the most populous countries like China and India. Cultural differences, religious beliefs, misogyny, genetic discrimination, and a multitude of languages in Asia create unique challenges that counsellors in the West may only encounter with the immigrant minorities. Since there are currently 500 or more specific Mendelian genetic eye disorders, it is important for genetic counsellors to translate the genetic results at a level that the patient and family understand. There is therefore a need for governmental and healthcare organisations to train genetic counsellors in Asia and especially this practice must be included in the routine comprehensive ophthalmic care practice., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Treatment wearing-off has been reported for calcitonin gene-related peptide-pathway monoclonal antibodies, including erenumab, specifically in the last week of the monthly dosing cycle., Objective: We sought to determine the consistency of erenumab effect throughout the monthly treatment cycle., Methods: In this post hoc analysis of four pivotal double-blind, randomized controlled studies of erenumab in episodic and chronic migraine, we assessed wearing-off based on change in weekly migraine days at week 4 versus average over weeks 1-3 in each monthly dosing cycle. Analyses were conducted at each monthly dosing cycle in all patients, in responders (≥50% reduction in weekly migraine days), and in consistent responders (response in ≥2monthly cycles)., Results: There was no evidence of wearing-off in the full study populations of two global studies (N = 946 and N = 656) and two Japan studies (N = 475 and N = 261). In the full study population, mean change in weekly migraine days at week 4 compared with the average over week 1-3 ranged from 0.15 days improvement to 0.19 days worsening in the placebo group and 0.08 days improvement to 0.20 days worsening in the erenumab groups. A subgroup of responders experienced wearing-off, but the extent of wearing-off did not differ between erenumab and placebo groups. The mean change in weekly migraine days at week 4 compared with the average over weeks 1-3 ranged from 0.34 to 0.61 days worsening in the placebo group and 0.27 to 0.78 days worsening in the erenumab groups. Few patients had persistent wearing-off in ≥2 consecutive monthly treatment cycles. For erenumab-treated responders, serum erenumab concentrations were similar among patients experiencing wearing-off and those maintaining response., Conclusion: No systematic wearing-off with erenumab was identified. Further research is needed to determine if wearing-off reported for some patients in clinical practice reflects a true treatment response pattern or normal fluctuations in migraine frequency., (© 2022 The Authors. Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.)

Aims: The 2021 European Society of Cardiology (ESC) guideline on cardiovascular disease (CVD) prevention categorizes moderate and severe chronic kidney disease (CKD) as high and very-high CVD risk status regardless of other factors like age and does not include estimated glomerular filtration rate (eGFR) and albuminuria in its algorithms, systemic coronary risk estimation 2 (SCORE2) and systemic coronary risk estimation 2 in older persons (SCORE2-OP), to predict CVD risk. We developed and validated an 'Add-on' to incorporate CKD measures into these algorithms, using a validated approach., Methods: In 3,054 840 participants from 34 datasets, we developed three Add-ons [eGFR only, eGFR + urinary albumin-to-creatinine ratio (ACR) (the primary Add-on), and eGFR + dipstick proteinuria] for SCORE2 and SCORE2-OP. We validated C-statistics and net reclassification improvement (NRI), accounting for competing risk of non-CVD death, in 5,997 719 participants from 34 different datasets., Results: In the target population of SCORE2 and SCORE2-OP without diabetes, the CKD Add-on (eGFR only) and CKD Add-on (eGFR + ACR) improved C-statistic by 0.006 (95%CI 0.004-0.008) and 0.016 (0.010-0.023), respectively, for SCORE2 and 0.012 (0.009-0.015) and 0.024 (0.014-0.035), respectively, for SCORE2-OP. Similar results were seen when we included individuals with diabetes and tested the CKD Add-on (eGFR + dipstick). In 57 485 European participants with CKD, SCORE2 or SCORE2-OP with a CKD Add-on showed a significant NRI [e.g. 0.100 (0.062-0.138) for SCORE2] compared to the qualitative approach in the ESC guideline., Conclusion: Our Add-ons with CKD measures improved CVD risk prediction beyond SCORE2 and SCORE2-OP. This approach will help clinicians and patients with CKD refine risk prediction and further personalize preventive therapies for CVD., Competing Interests: Conflict of interest: Ku.M. reports grants from NIDDK; grants and personal fees from Kyowa Kirin, personal fees from Akebia outside the submitted work. M.G. reports grants from NIH and National Kidney Foundation outside the submitted work. J.A. reports personal fees from AstraZeneca, Novartis, and Boerhinger Ingelheim outside the submitted work. A.R.C. reports personal fees from Novartis, Reata, and Amgen; grants from Novo Nordisk outside the submitted work. N.E. reports personal fees from Bayer and AG Leverkusen outside the submitted work. K.E. reports grants from Amgen, Astra Zenceca, Bayer, Evotec, and Vifor; personal fees from Akebia, Astra Zeneca, Bayer, Otsuka, and Retrophin outside the submitted work. S.K.J reports salary support from US Government and Department of Veterans Affairs during the conduct of the study. C.K. reports personal fees from Bayer, Abbott, Astra-Zeneca, Takeda, Tricida, Akebia, Cara Therapeutics, Vifor, Rockwell, CSL Behring, Reata, Boehringer Ingelheim, and GSK outside the submitted work. A.S.L. reports grants and contracts from NIH and NKF for studies in CKD and a contract from AstraZeneca for DSMB for clinical trials of dapagliflozin. Ka.M. reports grants from Ministry of Health, Labor, and Welfare, Japan. G.N.N reports personal fees from Renalytix, Daiichi Sankyo, Menarini Medical, Qiming Capital, and Variant Bio; other fees from Pensieve Health, Nexus I Connect outside the submitted work; patent KidneyIntelX pending to Renalytix. M.G.S. reports grants from NIH- NIA/NIDDK/NHLBI during the conduct of the study; personal fees from Cricket Health, Intercept Pharmaceuticals, Bayer Pharmaceuticals, AztraZeneca, Boeringer Ingelheim; grants from Bayer Pharmaceuticals outside the submitted work. M.D.S reports a honoraria from AstraZeneca outside the submitted work. N.S. is a current employee of GSK and employed at AMGA. M.W. reports personal fees from Amgen and Freeline outside the submitted work. J.C. reports grants from National Institute of Health and National Kidney Foundation, during the conduct of the study; personal fees from Healthy.io and SomaLogic outside the submitted work. No other potential conflicts of interest relevant to this article were reported. All other authors report no potential conflicts., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: There is limited research investigating the diagnostic strength of 3-dimensional computed tomography (3D-CT) and multidirectional CT arthrography (CTA) for femoroacetabular impingement (FAI) and related hip lesions., Purpose: To evaluate the diagnostic strength of combined 3D-CT and CTA in patients with FAI and related hip lesions by comparing it with hip arthroscopic surgery findings., Study Design: Cohort study (diagnosis); Level of evidence, 2., Methods: This study included patients who were suspected of having FAI and related hip lesions and who underwent a combination of 3D-CT and CTA and subsequent hip arthroscopic surgery between December 2013 and December 2017. The CT and intraoperative arthroscopic findings were recorded and compared. The sensitivity, specificity, and accuracy of 3D-CT for FAI and those of CTA for related hip lesions were calculated., Results: A total of 114 patients with 114 hips were included in our study. There were 101 patients with positive findings and 13 patients with negative findings for FAI (including cam, pincer, and combined morphology) according to 3D-CT. The sensitivity, specificity, and accuracy of 3D-CT for FAI were 91.58%, 57.14%, and 89.47%, respectively. The sensitivity, specificity, and accuracy of CTA for labral tears were 94.64%, 100.00%, and 94.73%, respectively. For acetabular cartilage defects, the sensitivity, specificity, and accuracy of CTA were 60.71%, 91.37%, and 76.31%, respectively. For femoral cartilage defects, the sensitivity, specificity, and accuracy of CTA were 82.22%, 76.81%, and 78.94%, respectively., Conclusion: The study results indicated that 3D-CT was able to provide excellent accuracy for FAI compared with hip arthroscopic surgery findings. In addition, multidirectional CTA demonstrated promising diagnostic strength for hip lesions such as labral tears and chondral defects., Competing Interests: The authors declared that there are no conflicts of interest in the authorship and publication of this contribution. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2023.)

Purpose: Clinical phenotypes in Immunoglobulin G4-related disease (IgG4-RD) according to the patterns of affecting organs have different risks of malignancies. We attempt to determine the association of malignancies with IgG4-related ophthalmic disease (IgG4-ROD)., Design: Retrospective cohort study., Methods: Review of medical records, orbital images and histopathology reports in a territory-wide cohort of biopsy proven IgG4-ROD patients from 2005-2019., Findings: Among 122 patients who had biopsies taken from adnexal lesions including lacrimal glands (n = 108), orbital mass (n = 30), infiltrated orbital fat (n = 10), conjunctiva (n = 2) or extraocular muscles (n = 3), 13% (16/122) developed malignancies over 73 ± 48months' follow-up. There were 9 cases of ocular adnexal lymphoma (OAL) and 7 extra-orbital malignancies. Compared with the general population, the incidence of OAL was significantly higher (standardized incidence ratios, SIRs = 10.0, 95%CI = 4.5-17.6) while that of extra-orbital malignancies was similar. The SIRs was highest within the first year (SIR = 46.7, 95%CI = 18.5-87.6) when 7 OAL were concomitantly diagnosed. Patients who developed OAL or extra-orbital malignancies were older than other patients at IgG4-ROD diagnosis (64.9 ± 7.1, 68.3 ± 8.5 versus 55.2 ± 15.0 years, P < 0.05). Asymmetric lacrimal gland enlargement (78% versus 13%), lack of frontal (0% versus 12%) or infraorbital nerve enlargement (0% versus 36%) were associated with OAL (all P < 0.05). Pre-treatment serum IgG4 level or extra-orbital IgG4-RD involvement was similar among patients with or without malignancies., Conclusion: In this biopsy-proven IgG4-ROD cohort, 7% developed OAL which was 10 times higher than the general population. Patients with asymmetric lacrimal gland enlargement or without trigeminal nerves involvement radiologically were associated with OAL.

Background: Chest compressions are the basis of cardiopulmonary resuscitation (CPR), and high-quality chest compressions can improve survival rate in patients with out-of-hospital cardiac arrest. Although many efforts have been made to improve the quality of CPR in inexperienced adults, the results are still not high, especially during emergencies. The primary purpose of this study is to investigate whether a brief instructional chest compression-only CPR video could improve chest compression quality in inexperienced adults. Methods: One hundred adults with no CPR experience (age: 20.28 ± 2.28 years; women: 50, men: 50) participated in this study. Participants completed body composition and handgrip strength measurements, and performed two CPR quality tests on the Laerdal ® Little Anne QCPR Manikin, namely without video-CPR (WV-CPR) and video-CPR (V-CPR). The WV-CPR quality test was performed first. After 2 minutes of continuous chest compression, the participants rested for 10 seconds and repeated 3 cycles (phase 1, phase 2, and phase 3). After resting for more than 72 hours, V-CPR quality test was conducted. During the V-CPR with video intervention, the participants also continued to compress the chest for 2 minutes, and then rested for 10 seconds, repeating 3 cycles. Results: In phase 1, compared with WV-CPR, the V-CPR has a significant increase ( p < 0.001) in chest compression fraction (CCF) (56.31 ± 33.22% vs. 41.82 ± 32.30%) and percent of correct compression rate (PCCR) (96.17 ± 8.45% vs. 26.31 ± 37.55%). In addition, the V-CPR has significantly lower ( p < 0.001) chest compression rate (CCR) (110.85 ± 2.40 cpm vs. 128.86 ± 24.52 cpm) and rating of perceived exertion (RPE) (11.89 ± 2.25 vs. 12.87 ± 2.25). For phases 2 through 3, V-CPR and WV-CPR achieved significant differences in CCF, CCD, CCR, PCCR, and RPE ( p < 0.01). There were significant differences ( p < 0.05) in CCF, CCD, chest compression rebound rate, and RPE among the different administration stages of both WV-CPR and V-CPR. Conclusions: The results of this study revealed that a brief instructional chest compression-only CPR video could improve chest compression quality for inexperienced adults by reducing fatigue and CCR, and increasing CCF and PCCR., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Cyclic GMP-AMP (cGAMP) synthase (cGAS), a sensor of cytosolic DNA, recognizes cytoplasmic nucleic acids to activate the innate immune responses via generation of the second messenger cGAMP and subsequent activation of the stimulator of interferon genes (STINGs). The cGAS-STING signaling has multiple immunologic and physiological functions in all human vital organs. It mediates protective innate immune defense against DNA-containing pathogen infection, confers intrinsic antitumor immunity via detecting tumor-derived DNA, and gives rise to autoimmune and inflammatory diseases upon aberrant activation by cytosolic leakage of self-genomic and mitochondrial DNA. Disruptions in these functions are associated with the pathophysiology of various immunologic and neurodegenerative diseases. Recent evidence indicates important roles of the cGAS-STING signaling in mediating inflammatory responses in ocular inflammatory and inflammation-associated diseases, such as keratitis, diabetic retinopathy, age-related macular degeneration, and uveitis. In this review, we summarize the recently emerging evidence of cGAS-STING signaling in mediating ocular inflammatory responses and affecting pathogenesis of these complex eye diseases. We attempt to provide insightful perspectives on future directions of investigating cGAS-STING signaling in ocular inflammation. Understanding how cGAS-STING signaling is modulated to mediate ocular inflammatory responses would allow future development of novel therapeutic strategies to treat ocular inflammation and autoimmunity., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Treating lower extremity malalignment-related knee osteoarthritis, especially valgus alignment, is a challenge. A high revision rate was observed with patients who underwent unicompartmental knee arthroplasty, so distal femur osteotomy has regained its popularity. This research aimed to evaluate the radiographic and functional outcomes of arthroscopy-assisted lateral open-wedge distal femur osteotomy (LOWDFO) for patients with lateral compartment osteoarthritis and valgus knees with a minimum follow-up of 2 years. Our study retrospectively included isolated lateral osteoarthritis (Outerbridge grade 3 and grade 4) of the knee related to valgus alignment and a young age (<65 y/o) with the demand for a high-impact activity event. Preoperative and postoperative radiographic and functional outcomes were evaluated. Significant pre-operative and postoperative mechanical correction was observed with mechanical axis deviation (preop/postop: −28.77 ± 12.98/−9.45 ± 7.36, p < 0.001), hip-knee angle (preop/postop: 7.64 ± 3.62/2.68 ± 2.04, p < 0.001), and mechanical lateral distal femoral angle (mLDFA, preop/postop: 10.9 ± 4.14/5.66 ± 3.71, p < 0.001). The International Knee Documentation Committee (IKDC) score also showed improvement after the operation (preop/postop: 57.36 ± 11.98/79.02 ± 4.58, p = 0.002). In conclusion, lateral open-wedge distal femur osteotomy is effective in treating patients with lateral compartment osteoarthritis and valgus knees with a low complication rate and excellent outcome.

Since excessive alcohol consumption is a shared risk factor for esophageal cancer and liver fibrosis, it is possible that patients with esophageal cancer may develop unknown liver fibrosis or cirrhosis. We applied preoperative transient elastography (TE) to patients without recorded cirrhosis undergoing esophagectomy to clarify the validity in predicting postesophagectomy hepatic failure. The cohort consisted of 107 patients who received TE before esophagectomy between June 2018 and December 2021. Patients were categorized into two groups based on the fibrosis score yielded by preoperative TE (mild group: 0~2, n = 92; severe group: 3~4, n = 15). There was no significant difference in demographic data nor surgical variables between the two groups. None of the cohort encountered hepatic failure, yet the severe fibrosis group had a significantly higher rate of pleural effusion (40.0% versus 15.2%, p = 0.03). The areas under the curve (AUCs) of TE in predicting postoperative complications and 180-day mortality were 0.60 (95% CI: 0.46-0.74) and 0.67 (95% CI: 0.51-0.83), respectively. In conclusion, stratification of patients with esophageal cancer who had liver fibrosis by preoperative TE demonstrates significant validity in predicting postoperative pleural effusions. Recruitment of noncirrhotic patients with higher TE scores is warranted to examine its power in other parameters.

Background: Kidney diseases are viewed as continuously progressing diseases from microalbuminuria and chronic kidney disease (CKD), to end-stage renal disease (ESRD) and its mortality including deaths. The report on the association between prolonged sitting and kidney diseases is limited., Methods: We examined a cohort of 455,506 participants in a screening program in Taiwan conducted between 1996 and 2017. Data on occupational sedentary behavior and physical activity were collected with a standardized questionnaire. The outcomes of ESRD and death were identified by linking with the Catastrophic Illness Dataset and Cause of Death Data. The association between prolonged sitting and CKD, the incidence of ESRD, and death were assessed using logistic regression models to compute odds ratios (ORs) and Cox proportional hazards models for hazard ratios (HRs)., Results: More than half of the participants, i.e., 265,948 (58.4%), were categorized as "prolonged sitting" during their work. During a median of 13 years of follow-up, we identified 2227 individuals undergoing dialysis and 25,671 deaths. Prolonged occupational sitting was significantly associated with a higher risk of CKD (OR: 1.26, 95% confidence interval: 1.21, 1.31), ESRD (HR: 1.19, 95% CI 1.03, 1.38), and kidney-specific mortality (HR: 1.43, 95% CI 1.07, 1.91) compared to mostly standing participants after controlling for physical activity and other risk factors. Inactive prolonged sitting carries a significantly higher risk of ESRD than physically active mostly standing participants (HR: 1.34, 95% CI 1.04, 1.73). However, active prolonged sitting decreased the risk of ESRD (HR: 1.03, 95% CI 0.79, 1.34) compared to inactive prolonged sitting., Conclusion: The results suggest that prolonged occupational sitting is associated with a greater risk of the spectrum of kidney disease, proteinuria, CKD, dialysis (ESRD), and mortality for all causes and kidney diseases. Physical activity, even at a minimal level of 15 min/day (90 min/week) of moderate-intensity exercise, was associated with a reduction in these risks., (© 2022. The Author(s).)

Both inflammation and anti-inflammation are involved in the protection of retinal cells. Antagonists of the hypothalamic growth hormone-releasing hormone receptor (GHRHR) have been shown to possess potent anti-inflammatory properties in experimental disease models of various organs, some with systemic complications. Such effects are also found in ocular inflammatory and neurologic injury studies. In experimental models of mice and rats, both growth hormone-releasing hormone receptor agonists and antagonists may alleviate death of ocular neural cells under certain experimental conditions. This review explores the properties of growth hormone-releasing hormone receptor agonists and antagonists that lead to its protection against inflammatory responses induced by extrinsic agents or neurologic injures in ocular animal models.

Background: The impacts of social restrictions for COVID-19 on children's vision and lifestyle remain unknown., Aims: To investigate myopia incidence, spherical equivalent refraction (SER) and lifestyle changes among schoolchildren during the COVID-19 pandemic., Methods: Two separate longitudinal cohorts of children aged 6-8 years in Hong Kong were included. The COVID-19 cohort was recruited at the beginning of the COVID-19 outbreak, whereas the pre-COVID-19 cohort was recruited before the COVID-19 pandemic. All children received ocular examinations, and answered a standardised questionnaire relating to their lifestyle, including time spent on outdoor activities and near work, both at baseline and at follow-up visits., Results: A total of 1793 subjects were recruited, of whom 709 children comprised the COVID-19 cohort with 7.89±2.30 months of follow-up, and 1084 children comprised the pre-COVID-19 cohort with 37.54±3.12 months of follow-up. The overall incidence was 19.44% in the COVID-19 cohort, and 36.57% in pre-COVID-19 cohort. During the COVID-19 pandemic, the change in SER and axial length was -0.50±0.51 D and 0.29±0.35 mm, respectively; the time spent on outdoor activities decreased from 1.27±1.12 to 0.41±0.90 hours/day (p<0.001), while screen time increased from 2.45±2.32 to 6.89±4.42 hours/day (p<0.001)., Conclusions: We showed a potential increase in myopia incidence, significant decrease in outdoor time and increase in screen time among schoolchildren in Hong Kong during the COVID-19 pandemic. Our results serve to warn eye care professionals, and also policy makers, educators and parents, that collective efforts are needed to prevent childhood myopia-a potential public health crisis as a result of COVID-19., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: To determine the prevalence of amblyopia and the factors associated with delayed diagnosis among school-aged children in Hong Kong., Methods: Completed comprehensive ophthalmoscopic examinations were conducted among 4.273 children aged 6-8 years in the population-based Hong Kong Children Eye Study. New and previous diagnoses of amblyopia were identified. Socioeconomic status was surveyed through questionnaires., Results: According to criteria from the Multi-Ethnic Pediatric Eye Disease Study (MEPEDS), amblyopia was present in 43 out of 4,273 children (1.01%; 95% CI, 0.71-1.31). Among them, 33 (0.77%) were newly detected cases that were more likely from families living in Public Rental Housing or subdivided flats (OR, 4.22; P = .012), with lower paternal (OR 6.68, P = .008) and maternal education levels (OR, 4.38; P = .039). Multivariate analysis revealed associations of amblyopia with hyperopia (≥+2.00D; OR, 6.23; 95% CI, 2.86-13.56, P < .001), astigmatism (≥+2.00D; OR, 24.88; 95% CI, 10.69-57.91, P < .001) and anisometropia (≥2.00D; OR, 14.49; 95% CI, 5.93-37.63, P < .001)., Conclusion: These children with delayed diagnoses of amblyopia were more likely to come from lower socioeconomic backgrounds. Public education aimed at increasing awareness and utilization of child vision screening among such families is needed.

Importance: Parental astigmatism is a factor associated with risk for development of child astigmatism; however, the magnitude of the association has not been determined., Objective: To determine the association between parental and child astigmatism., Design, Setting, and Participants: This population-based, cross-sectional study included participants from familial trios, each comprising a child aged 6 to 8 years and both parents, recruited from the Hong Kong Children Eye Study. No restriction criteria were set on the children in terms of refractive status. Data were analyzed from February to June 2022., Exposures: Cycloplegic autorefraction and autokeratometry were conducted on the children, whereas noncycloplegic autorefraction and autokeratometry were conducted on their parents. The children were categorized into 6 groups on the basis of the severity of astigmatism of both parents. Information on parental education, family income, and children's outdoor and near work time were obtained by questionnaires., Main Outcomes and Measures: The primary outcome was the odds of child astigmatism among the 6 categories of children. Associations of factors with child astigmatism were evaluated by logistic regression analyses., Results: A total of 17 124 participants from 5708 trios (2964 boys and 2754 girls) at a mean (SD) age of 7.32 (0.87) years, and 11 416 parents were examined. Astigmatism of 1.0 D or greater in both parents was associated with greater odds of refractive astigmatism (RA) (odds ratio [OR], 1.62; 95% CI, 1.15-2.26) and corneal astigmatism (CA) (OR, 1.94; 95% CI, 1.50-2.50) in the child. The respective ORs increased to 3.10 (95% CI, 1.34-7.21) and 4.31 (95% CI, 1.76-10.55) when both parents had astigmatism 2.0 D or greater. Higher parental astigmatism conferred higher risks for both RA and CA in children (P for trend <.001). Parental astigmatism was significantly associated with greater odds of corresponding child astigmatism (maternal RA: OR, 0.76; 95% CI, 0.68-0.84; paternal RA: OR, 0.82; 95% CI, 0.74-0.91; maternal CA: OR, 1.70; 95% CI, 1.51-1.93; paternal CA: OR, 1.33; 95% CI, 1.19-1.49)., Conclusions and Relevance: The findings of this cross-sectional study suggest that parental astigmatism may confer an independent and dose-dependent association with child astigmatism. Children with parents with astigmatism should have early eye examinations for timely detection of astigmatism to facilitate age-appropriate vision correction and visual development.

This prospective study investigated how exercise impacted chronological changes in anthropometrics, body composition, prostate-specific antigen (PSA) level and prognostic nutrition index (PNI) in high-risk prostate cancer (PCa) patients on androgen deprivation therapy (ADT). The patients were divided into either the usual care or exercise group. All patients received measurements a week before ADT initiation, six- and twelve months after treatment. The exercise group received both aerobic and resistance training. The analysis was conducted using appropriate statistical methods. There were 45 males enrolled (age 67.4 ± 8 years and BMI 25.5 ± 3.6 kg/m 2 ). Profound changes were observed at six months follow-up. The exercise group showed a significant increase in the trunk and leg lean mass, and a lesser loss of total and arm lean mass. A significant decrease in PSA was also observed among the exercise group. PNI and PSA were significantly associated with regional lean mass. Exercise can prevent loss or even increase lean mass in high-risk PCa, especially in the early stage of ADT treatment. Moreover, a strong bond between lean mass and PNI and PSA further underscores the importance of early and continuous exercise interventions.

Background: We evaluated the impact of endoscopic enucleation of the prostate on testosterone levels in hypotestosteronemic patients with bladder outlet obstruction. Methods: We enrolled 294 men with lower urinary tract symptoms (LUTS) who received surgery between January 2019 and December 2020 in simple tertiary centre. The inclusion criteria were as follows: being a male patient aged 45−95 years and having recurrent urinary tract infection, having previously failed medical treatment for LUTS or urine retention, and undergoing bipolar or thulium laser enucleation of the prostate. The preoperative and postoperative data were retrospectively reviewed. Results: This study included 112 men with a mean age of 69.4 years. The mean preoperative and postoperative testosterone levels were 4.8 and 4.98, respectively. Of the patients, 88 (78.6%) received ThuLEP and 24 received BipolEP. We divided the patients into two groups according to preoperative serum testosterone levels: normal-testosterone (≥3 ng/mL) and low-testosterone (<3 ng/mL) groups. A significant change in testosterone levels (p = 0.025) was observed in the low-testosterone group. In contrast, no significant difference in testosterone levels was noted in the normal-testosterone group (p = 0.698). Conclusions: Endoscopic enucleation surgery of the prostate could improve postoperative testosterone levels in hypotestosteronemic patients with bladder outlet obstruction., Competing Interests: The authors declare no conflict of interest.

Snakebites from Protobothrops mucrosquamatus (Taiwan habus) and Viridovipera stejnegeri (green bamboo vipers) account for the most venomous snakebites in Taiwan. The bivalent freeze-dried hemorrhagic (FH) antivenom is employed to treat these two snakebite patients without a strict clinical trial. We evaluated the clinical usefulness of Taiwan bivalent freeze-dried hemorrhagic (FH) antivenom in Taiwan habu- and green bamboo viper-envenomed patients. We checked ELISA- based serum venom antigen levels before and after FH antivenom to evaluate FH's ability to neutralize patients' serum snake venom and its usefulness in reducing limb swelling after snakebites. Patients who had higher serum venom antigen levels had more severe limb swelling. Of the 33 enrolled patients, most of their snake venom antigen levels were undetected after the appliance of antivenom. Most enrolled patients (25/33) had their limb swelling subside within 12 h after antivenom treatment. The failure to reduce limb swelling was probably due to an inadequate antivenom dose applied in more severely envenomated patients. Our data indicate the feasibility of the FH antivenom in effectively eliminating venom and resolving the affected limb swelling caused by Taiwan habu and green bamboo viper bites.

Background: Before major non-pharmaceutical interventions were implemented, seasonal incidence of influenza in Hong Kong showed a rapid and unexpected reduction immediately following the early spread of COVID-19 in mainland China in January 2020. This decline was presumably associated with precautionary behavioral changes (e.g., wearing face masks and avoiding crowded places). Knowing their effectiveness on the transmissibility of seasonal influenza can inform future influenza prevention strategies., Methods: We estimated the effective reproduction number ( R t ) of seasonal influenza in 2019/20 winter using a time-series susceptible-infectious-recovered (TS-SIR) model with a Bayesian inference by integrated nested Laplace approximation (INLA). After taking account of changes in underreporting and herd immunity, the individual effects of the behavioral changes were quantified., Findings: The model-estimated mean R t reduced from 1.29 (95%CI, 1.27-1.32) to 0.73 (95%CI, 0.73-0.74) after the COVID-19 community spread began. Wearing face masks protected 17.4% of people (95%CI, 16.3-18.3%) from infections, having about half of the effect as avoiding crowded places (44.1%, 95%CI, 43.5-44.7%). Within the current model, if more than 85% of people had adopted both behaviors, the initial R t could have been less than 1., Conclusion: Our model results indicate that wearing face masks and avoiding crowded places could have potentially significant suppressive impacts on influenza., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lin, Dorigatti, Tsui, Xie, Ling and Yuan.)

Primary open-angle glaucoma (POAG) is the most common form of glaucoma, for which elevated intraocular pressure (IOP) is a major risk factor. IOP is mainly regulated by dynamic balance of aqueous humor (AH) production and outflow via the conventional trabecular meshwork/Schlemm's canal (TM/SC) pathway. Dysfunctions of TM cells due to endoplasmic reticulum (ER) stress have been demonstrated to increase the resistance of AH outflow, resulting in IOP elevation. Epigallocatechin-3-gallate (EGCG), the most abundant polyphenolic component in green tea, has been shown to alleviate ER stress in several diseases while its potential roles in alleviating ER stress in TM cells have not been determined. In this study, we investigate the mitigation of tunicamycin-induced ER stress in TM cells by EGCG. MTT assay was used to measure the cell viability of human TM (HTM) cells and primary porcine TM (PTM) cells. ER stress levels in both HTM cells and primary PTM cells were detected by quantitative real-time PCR. The primary PTM cells isolated from porcine TM tissues were characterized by immunostaining. We found that 40  μ M and 80  μ M EGCG pretreatment substantially promoted HTM cell survival under 3  μ M tunicamycin-induced ER stress. Pretreatment of 40  μ M EGCG markedly reduced the expression of ER stress markers ATF4 , HSPA5 , and DDIT3, evoked by 3  μ M tunicamycin in HTM cells. Furthermore, 40  μ M EGCG pretreatment significantly decreased the expressions of ATF4 , HSPA5 , and DDIT3 at the mRNA level induced by 3  μ M tunicamycin and improved cell viability in primary PTM cells. Our results show that EGCG is capable of protecting TM cells from ER stress. EGCG provides a promising therapeutic option for POAG treatment., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2022 Linbin Zhou et al.)

Background: Personal Activity Intelligence (PAI) is a physical activity metric that translates heart rate during physical activity into a simple score, where a weekly score of 100 or greater is associated with a lower risk of cardiovascular disease and mortality. Here, we prospectively investigated the association between PAI and ischemic heart disease (IHD) mortality in a large healthy population from China., Methods: Using data from the China Kadoorie Biobank, we studied 443,792 healthy adults (60% women). The weekly PAI score of each participant was estimated based on the questionnaire data and divided into four groups (PAI scores of 0, ≤50, 51-99, or ≥100). Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for fatal IHD and nonfatal myocardial infraction (MI) related to PAI were estimated using Cox proportional hazard regression analyses., Results: There were 3050 IHD deaths and 1808 MI events during a median follow-up of 8.2 years (interquartile range, 7.3-9.1; 3.6 million person-years). After adjustments for multiple confounders, a weekly PAI score ≥ 100 was associated with a lower risk of IHD (aHR: 0.91 (95% CI: 0.83-1.00)), compared with the inactive group (0 PAI). The corresponding aHR for MI was 0.94 (95% CI: 0.83-1.05). In participants aged 60 years or older at baseline, the aHR associated with a weekly PAI score ≥ 100 was 0.84 (95% CI, 0.75-0.93) for IHD and 0.84 (95% CI, 0.73-0.98) for MI., Conclusion: Among healthy Chinese adults, a weekly PAI score of 100 or greater was associated with a lower risk of IHD mortality across all age groups; moreover, a high PAI score significantly lowered the risk of MI but only in those 60 years and older at baseline. The present findings extend the scientific evidence that PAI may have prognostic significance in diverse settings for IHD outcomes and suggest that the PAI metric may be useful in delineating the magnitude of weekly physical activity needed to reduce the risk of IHD mortality.

Aims: To identify single-nucleotide polymorphisms (SNPs) associated with central serous chorioretinopathy (CSCR) by a systematic review and meta-analysis, and to compare the association profiles between CSCR, neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV)., Methods: We searched the EMBASE, PubMed and Web of Science for genetic studies of CSCR from the starting dates of the databases to 12 September 2020. We then performed meta-analyses on all SNPs reported by more than two studies and calculated the pooled OR and 95% CIs. We also conducted sensitivity analysis and adopted the funnel plot to assess potential publication bias., Results: Totally 415 publications were reviewed, among them 10 were eligible for meta-analysis. We found 10 SNPs that have been reported at least twice. Meta-analysis and sensitivity analysis confirmed significant associations between CSCR and six SNPs in three genes, namely age-related maculopathy susceptibility 2 ( ARMS2 ) (rs10490924, OR=1.37; p=0.00064), complement factor H ( CFH ) (rs800292, OR=1.44; p=7.80×10 -5 ; rs1061170, OR=1.34; p=0.0028; rs1329428, OR=1.40; p=0.012; and rs2284664, OR=1.36; p=0.0089) and tumour necrosis factor receptor superfamily, member 10a ( TNFRSF10A ) (rs13278062, OR=1.34; p=1.44×10 -15 ). Among them, only TNFRSF10A rs13278062 showed the same trend of effect on CSCR, nAMD and PCV, while the SNPs in ARMS2 and CFH showed opposite trends in the SNP associations., Conclusions: This study confirmed the associations of ARMS2 , CFH and TNFRSF10A with CSCR, and revealed that ARMS2 , CFH and TNFRSF10A may affect different phenotypic expressions of CSCR, nAMD and PCV., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The purpose of the study was to determine if aqueous glucose levels rise in a comparable time frame to interstitial fluid and could therefore be suitable for a continuous glucose monitoring (CGM) site., Methods: An intravenous glucose tolerance test was performed on five New Zealand white rabbits. Aqueous humor from the posterior and anterior chamber of the eye and venous blood were sampled for glucose concentration measurement. Glucose concentrations in the interstitial fluids were monitored using a CGM system. A compartment model was created to map the glucose response curves in each compartment. The delay in rising glucose concentrations between blood and interstitial fluid and aqueous humor in the posterior chamber and anterior chamber of the eye were analyzed., Results: The results showed a statistically similar time lag and rate of change in glucose concentrations between blood and interstitial fluids or aqueous humor in either the posterior or anterior chamber., Conclusions: The results of this study add further support to the aqueous humor being used as an alternative CGM site., Translational Relevance: The study provides the basis for developing an intraocular continuous glucose sensor that can overcome limitations of current CGM systems.

The purpose of this study was to investigate whether modeling within separate body mass index (BMI) stratifications improves the accuracy of maximal oxygen uptake (VO 2max ) prediction compared to a model developed regardless of adults' BMIs. A total of 250 Taiwanese adults (total group, TOG) aged 22-64 years participated in this study, and were stratified into a normal group (NOG: 135), an overweight group (OVG: 69), and an obesity group (OBG: 46), according to the BMI classification recommended by the Taiwan Ministry of Health and Welfare. VO 2max was directly measured on an electromagnetic bicycle ergometer. Using the participant's heart rate in the 3-min incremental step-in-place test and demographic parameters, VO 2max prediction models established for four groups were TOG model, NOG model, OVG model, and OBG model, respectively. Compared with the TOG model, the OVG and OBG models had higher coefficients of determination and lower standard error of estimates (SEEs), or %SEEs. The validities of the NOG (r = 0.780), OVG (r = 0.776), and OBG (r = 0.791) models for BMI subgroups increased by 1.79%, 4.64%, and 8.22% respectively, and the reliabilities (NOG model: ICC = 0.755; OVG model: ICC = 0.765; OBG model: ICC = 0.779) increased by 3.18%, 3.27%, and 9.63%, respectively. These results suggested using separate models established in BMI stratifications can effectively improve the prediction of VO 2max ., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

(-)-Epigallocatechin-gallate octaacetate (pro-EGCG), a prodrug of epigallocatechin-gallate (EGCG), has been used for pre-clinical study for the treatment of endometriosis. A validated analytical method has been developed for the determination of plasma pro-EGCG and its metabolites after oral administration using ultra-performance-liquid-chromatography coupled to quadrupole-time-of-flight-mass-spectrometry (UPLC-Qtof-MS). This method is more robust, rapid, sensitive, simpler, and able to detect pro-EGCG metabolites compared to our previous method. Pro-EGCG in the plasma was stabilized from rapid degradation by formic acid, extracted by isopropanol/methyl-tert-butyl ether mixture, separated by UPLC core column, and quantified by an exact mass method with Qtof-MS. The lower limit of quantification (LLOQ), intra-day and inter-day precision, and accuracy for the range of 0.01-2.5 μg/mL were within acceptable limits. The sensitivity was improved by 25 folds using pro-EGCG ammonium adduct [M + NH4] + . This is the first report on the pharmacokinetics of oral administration with maximum-concentration (Cmax) was 0.067 ± 0.04 μg/mL, time-of-maximum-concentration (Tmax) was 1.33 h, area-under-curve (AUC) was 0.20 ± 0.05 h × µg/mL, and elimination-rate was 0.20 ± 0.11 hr -1 . The pharmacokinetic profiles of pro-EGCG metabolites, (-)-epigallocatechin-gallate (EGCG) diacetates and EGCG triacetates, were also presented. This method is robust, rapid, and sensitive for the pharmacokinetic study of pro-EGCG and metabolites., Competing Interests: WT was empolyed by Aptorum Group Limited. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chu, Man, Hung, Chan, Lee, Chan, Pang and Wang.)

Background: To determine the association of the ANGPT2 gene with primary open-angle glaucoma (POAG) in Chinese., Methods: Six single-nucleotide polymorphisms (SNPs) in ANGPT2 (rs2515487, rs2922869, rs13255574, rs4455855, rs13269021, and rs11775442) were genotyped in a total of 2601 study subjects from two cohorts. One is a Hong Kong Chinese cohort of 484 high tension glaucoma (HTG) and 537 normal tension glaucoma (NTG) patients, and 496 non-glaucoma control subjects. Another cohort is a Shantou Chinese cohort of 403 HTG and 135 NTG patients, and 543 non-glaucoma control subjects. Subgroup analysis by sex was conducted. Outcomes from different cohorts were combined for meta-analysis., Results: The association of SNP rs11775442 with NTG in the Hong Kong cohort [P = 0.0498, OR = 1.24, 95% confidence interval (CI) 1.00-1.55] after adjusting for age and sex did not reach statistical significance after Bonferroni correction. Other SNPs were not significantly associated with NTG, HTG and POAG in individual cohort or in the combined analyses (P > 0.05). In the subgroup analysis by sex, SNP rs13269021 in the Shantou cohort, but not in the Hong Kong cohort, was significantly associated with NTG in males (P = 0.0081, OR = 1.67, 95% CI: 1.14-2.43) but not in females (P = 0.874). In the combined analyses by sex, no SNPs were significantly associated with NTG, HTG and POAG., Conclusions: In the subgroup analysis by sex, a significant association was shown in SNP rs13269021 with NTG in Shantou males, but not in Hong Kong males. Further studies are needed to verify the association between ANGPT2 locus (rs13269021) and NTG in Chinese males., (© 2022. The Author(s).)

Background: Caffeic acid phenethyl ester (CAPE), a bioactive component of propolis, has beneficial effects on cancer prevention. Growth differentiation factor 15 (GDF15) is an antitumor gene of bladder cancer. Therefore, this study investigated the anti-cancer effect of CAPE on bladder carcinoma cells and related mechanisms., Methods: The expressions of GDF15, N-myc downstream-regulated gene 1 (NDRG1), and maspin, and the activations of extracellular signal regulated kinase (ERK), c-jun Nterminal kinase (JNK), p38, and 50 adenosine monophosphate-activated protein kinase (AMPK) α1/2 in human bladder cells after gene transfection or knockdown were determined by immunoblot, real-time reverse transcriptase-polymerase chain reaction (RT-qPCR), and reporter assays. The assays of 5-ethynyl-2'-deoxyuridine (EdU), CyQUANT cell proliferation, and Matrigel invasion, and the xenograft animal study were used to assess the cell proliferation, invasion, and tumorigenesis., Results: GDF15 expression in epithelial cells was negatively correlated with neoplasia in vitro. Also, GDF15 exhibits in bladder fibroblasts and smooth muscle cells. CAPE-induced expressions of NDRG1 and maspin decreased cell proliferation and invasion of bladder carcinoma cells in a GDF15-dependent manner in vitro. The xenograft animal study suggesting CAPE attenuated tumor growth in vivo. CAPE increased phosphorylation of ERK, JNK, p38, and AMPKα1/2 to modulate the GDF15 expressions. Pretreatments with ERK, JNK, or p38 inhibitors partially inhibited the CAPE effects on the inductions of GDF15, NDRG1, or maspin. Knockdown of AMPKα1/2 attenuated the CAPE-induced GDF15 expression and cell proliferation in bladder carcinoma cells., Conclusions: Our findings indicate that CAPE is a promising agent for anti-tumor growth in human bladder carcinoma cells via the upregulation of GDF15., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2021 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Background/purpose: Alzheimer's disease (AD) is a neurodegenerative disorder and the most common form of dementia. The etiology for AD includes age, genetic susceptibility, neuropathology, and infection. Periodontitis is an infectious and inflammatory disease which mainly causes alveolar bone destruction and tooth loss. The evidence of a link between AD and periodontitis remains controversial. Thus far, studies reviewing the association between AD and periodontal disease have been insufficient from the viewpoint of the oral microbiome. The aim of this review was to focus on studies that have explored the relationship between the oral microbiome and AD development by using the next-generation sequencing technique., Materials and Methods: A comprehensive electronic search of MEDLINE via PubMed, EMBASE, Scopus, and Google Scholar was conducted. The keywords included dementia, Alzheimer's disease, cognitive impairment, periodontitis, periodontal disease, and oral microbiome., Results: This review included 26 articles based on the eligibility criteria. Epidemiologic researches and post-mortem studies showed that the presence of periodontitis is associated with cognitive decline, suggesting a possible role of periodontal pathogens in the pathogenesis of AD. The reported microbiome was inconsistent with those in gene sequencing studies. Nevertheless, Gram-negative species may be possible candidates., Conclusion: This review suggests that periodontal infection is associated with AD. The contributing microbiome remains unconfirmed, possibly because of different microbiome sampling sites or methods. Additional large-scale studies with periodontal intervention and longitudinal follow-up are warranted to clarify the relationship between periodontal disease and AD., (© 2022 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

The WNT1 inducible signaling pathway protein 1 (WISP1), a member of the connective tissue growth factor family, plays a crucial role in several important cellular functions in a highly tissue-specific manner. Results of a RT-qPCR indicated that WISP1 expressed only in cells of the human prostate fibroblasts, HPrF and WPMY-1, but not the prostate carcinoma cells in vitro. Two major isoforms (WISP1v1 and WISP1v2) were identified in the HPrF cells determined by RT-PCR and immunoblot assays. The knock-down of a WISP1 blocked cell proliferation and contraction, while treating respectively with the conditioned medium from the ectopic WISP1v1- and WISPv2-overexpressed 293T cells enhanced the migration of HPrF cells. The TNFα induced WISP1 secretion and cell contraction while the knock-down of WISP1 attenuated these effects, although TNFα did not affect the proliferation of the HPrF cells. The ectopic overexpression of WISP1v1 but not WISP1v2 downregulated the N-myc downstream regulated 1 (NDRG1) while upregulating N-cadherin, slug, snail, and vimentin gene expressions which induced not only the cell proliferation and invasion in vitro but also tumor growth of prostate carcinoma cells in vivo. The results confirmed that WISP1 is a stroma-specific secreting protein, enhancing the cell migration and contraction of prostate fibroblasts, as well as the proliferation, invasion, and tumor growth of prostate carcinoma cells.