Management of autoimmune retinopathy treated with intravitreal dexamethasone implant.

PURPOSE: The purpose of this study is to evaluate clinical outcomes of autoimmune retinopathy (AIR) in the patients treated with intravitreal dexamethasone implant (IDI). METHOD: Twenty-one eyes of 11 AIR patients treated with at least 1 injection of IDI were retrospectively reviewed. Clinical outcomes before and after treatment, including best corrected visual acuity (BCVA), optic coherence tomography (OCT), fundus autofluorescence (FAF), full-field electroretinography (ff-ERG), and visual field (VF) at last visit within 6 and/or 12 months, were recorded. RESULTS: Among all the patients, 3 had cancer-associated retinopathy (CAR) and 8 had non-paraneoplastic-AIR (npAIR) with mean followed up of 8.52 ± 3.03 months (range 4-12 months). All patients achieved improved or stable BCVA within 6 and/or 12 months after the treatment. Cystoid macular edema (CME) in 2 eyes and significant retinal inflammation in 4 eyes were markedly resolved after single injection. Central retinal thickness (CFT) in all eyes without CME, ellipsoid zone (EZ) on OCT in 71.4% of eyes, ERG response in 55% of eyes, and VF in 50% of eyes were stable or improved within 6 months after treatment. At last visit within 12 months, both BCVA and CFT remained stable in the eyes treated with either single or repeated IDI; however, progression of EZ loss and damage of ERG response occurred in some patients with single IDI. CONCLUSION: Clinical outcomes, including BCVA and parameters of OCT, ERG, and VF, were stable or improved after IDI in a majority of AIR patients. Local treatment of AIR with IDI was a good option to initiate the management or an alternative for the patients' refractory to the systemic therapy but with limited side effect.

A New Small-Molecule Compound, Q308, Silences Latent HIV-1 Provirus by Suppressing Tat- and FACT-Mediated Transcription.

Eliminating the latent HIV reservoir remains a difficult problem for creating an HIV functional cure or achieving remission. The "block-and-lock" strategy aims to steadily suppress transcription of the viral reservoir and lock the HIV promoter in deep latency using latency-promoting agents (LPAs). However, to date, most of the investigated LPA candidates are not available for clinical trials, and some of them exhibit immune-related adverse reactions. The discovery and development of new, active, and safe LPA candidates for an HIV cure are necessary to eliminate residual HIV-1 viremia through the block-and-lock strategy. In this study, we demonstrated that a new small-molecule compound, Q308, silenced the HIV-1 provirus by inhibiting Tat-mediated gene transcription and selectively downregulating the expression levels of the facilitated chromatin transcription (FACT) complex. Strikingly, Q308 induced the preferential apoptosis in HIV-1 latently infected cells, indicating that Q308 may reduce the size of the viral reservoir and thus further prevent viral rebound. These findings highlight that Q308 is a novel and safe anti-HIV-1 inhibitor candidate for a functional cure.

You are what you eat: Microplastics in the feces of young men living in Beijing.

PURPOSE: Microplastics have been widely detected in the environment and marine organisms. However, few studies have investigated the presence of microplastics in humans. This preliminary study identified and quantified the microplastic content in human feces. METHODS: A total of 26 young male students aged 18-25 years were recruited from Beijing, China. A self-administered 7-day 24-h fluid intake record was used to document fluid intake, and food intake was recorded for 3 days. Feces were collected by participants using a sterile fecal collector. Microplastics in the remaining fecal residues were measured and identified using fourier transform infrared micro-spectroscopy. RESULTS: Eventually, twenty-four participants completed the study. The fecal samples of 23 (95.8%) participants tested positive for microplastics. In these 23 samples, the abundance of microplastics varied from 1 particle/g to 36 particles/g (size 20 to 800 µm). The summed mass of all microplastic particles per participant ranged from 0.01 to 14.6 mg. Qualitative analysis of the microplastics indicated the presence of one to eight types of microplastics in each sample, with polypropylene (PP) being the most abundant; it was found in 95.8% of fecal samples. We examined associations between water intake habits and the abundance of microplastics in their feces. A moderate correlation was observed between packaged water and beverage intake and microplastic abundance in feces (r = 0.445, P = 0.029). CONCLUSION: Various types of microplastics were detected in human feces, with PP being found in the highest proportion. There may be an association between water intake habits and microplastic abundance in feces.

Percutaneous fixation of neonatal humeral physeal fracture: A case report and review of the literature.

BACKGROUND: Neonatal distal humeral physeal fractures are rare and difficult to diagnose. Thus, missed diagnoses and delayed healing are possible. Few studies have reported surgical treatment, because a callus may develop at the fracture site 5 d after the fracture, resulting in difficult reduction, and reduction of the limb may cause further physeal injury. Other surgical challenges include the provision of adequate anesthesia and complexity of the operation. However, without appropriate reduction and fixation, a varus elbow deformity may develop. Manual reduction and percutaneous pin fixation are ideal treatment options. CASE SUMMARY: A 4-day-old neonate with left elbow pain accompanied by limited movement for 4 d was admitted, and diagnosed with delayed physeal fracture of the distal humerus based on physical examination, ultrasonography, and magnetic resonance imaging. The patient was treated by manual reduction combined with percutaneous pin fixation under arthrography. Postoperatively, the reduction was successful. The upper limbs could have been lifted and the fingers could have been moved freely on the second day after the operation. CONCLUSION: The techniques of manual reduction and percutaneous pin fixation, to treat neonatal distal humeral physeal fractures, are safe and reliable.

Novel 2-Substituted 3-Hydroxy-1,6-dimethylpyridin-4(1H)-ones as Dual-Acting Biofilm Inhibitors of Pseudomonas aeruginosa.

2-Heptyl-3-hydroxy-4(1H)-quinolone (PQS), a compound from P. aeruginosa, functions as both a quorum sensing (QS) regulator and a potent iron chelator to induce expression of pyoverdine and pyochelin which are involved in high-affinity iron transport systems. A potential dual-acting antibiofilm strategy requires molecules designed to interfere with iron uptake and the QS system of P. aeruginosa. A series of 2-substituted 3-hydroxy-1,6-dimethylpyridin-4-ones have been designed, synthesized, and tested as biofilm inhibitors of P. aeruginosa. One compound, N-((1,3,6-trimethyl-4-oxo-1,4-dihydropyridin-2-yl)methyl)hexanamide (10d), exhibits 68.67% biofilm inhibitory activity at 20 µM. Further mechanistic studies have confirmed that this compound not only inhibits the QS systems of P. aeruginosa but also acts as an iron chelator to compete strongly with pyoverdine, causing iron deficiency in bacteria. The pyoverdine receptor FpvA was revealed as the target of 10d by the Pvds mutant strain, fpvA-overexpressed strain, and in silico studies.

Design, synthesis and biological evaluation of 2-substituted 3-hydroxy-6-methyl-4H-pyran-4-one derivatives as Pseudomonas aeruginosa biofilm inhibitors.

Drug-resistant bacteria associated with biofilm formation are rapidly on the rise, requiring novel therapeutic options to combat biofilm induced drug-resistance. In this study, a class of 3-hydroxy-2-(phenylhydroxy-methyl)-6-methyl-4H-pyran-4-one derivatives (1a-1e) were found by screening of an in-house compound library to be potential Pseudomonas aeruginosa biofilm inhibitors. Thirty one novel 2-substituted 3-hydroxy-6-methyl-4H-pyran-4-one derivatives were synthesized and assayed for their biofilm inhibitory activity. A promising biofilm inhibitor 6a was identified, and showed an obvious biofilm inhibitory effect even at a concentration of 2.5 µM. Further mechanism studies revealed that 6a only shows inhibitory effects on the expression of pqsA-gfp in a fluorescent reporter strain, and the production of a PQS- regulated virulence factor, pyocyanin. This indicates that this type of compound exercises its anti-biofilm activity specifically through the PQS pathway. Novel chemical biofilm inhibitors are described here and guard against biofilm formation associated with Pseudomonas aeruginosa infections.

Design, synthesis and biological evaluation of novel 5-hydroxy-2-methyl-4H-pyran-4-one derivatives as antiglioma agents.

d-2-Hydroxyglutarate (d-2HG) is frequently found in human brain cancers. Approximately 50-80% of grade II glioma patients have a high level of d-2HG production, which can lead to cancer initiation. In this study, a series of novel 5-hydroxy-2-methyl-4H-pyran-4-one derivatives were designed and synthesized as antiglioma agents, and their related structure-activity relationships are discussed. Among these novel compounds, 4a exhibited promising anti-proliferative activity against glioma HT1080 cells and U87 cells with an IC50 of 1.43 µM and 4.6 µM, respectively. Further studies found that the most active compound (4a) shows an 86.3% inhibitory rate against the intracellular production of d-2HG at 1 µM, and dramatic inhibitory effects, even at 1 µM on the colony formation and migration of U87 and HT1080 cells.

Fibroblast Activation Protein α Activated Tripeptide Bufadienolide Antitumor Prodrug with Reduced Cardiotoxicity.

Bufadienolides are the major pharmacologic constituents of traditional Chinese medicine Chan'su, which is frequently used clinically for cancer treatment in China. Motivated by reducing or avoiding the cardiac toxicity of bufadienolides, we have designed, synthesized, and evaluated the fibroblast activation protein α (FAPα) activated tripeptide arenobufagin prodrugs with the purpose of improving the safety of arenobufagin (a representative bufadienolide). Among these FAPα-activated prodrugs, 3f exhibited the best hydrolytic efficiency by recombinant human FAPα (rhFAPα) and was activated in tumors. The LD50 of 3f was 6.5-fold higher than that of arenobufagin. We also observed that there are nonapparent changes in echocardiography, pathological section of cardiac muscle, and the lactate dehydrogenase activities (LDH) in 3f-treatment tumor-bearing mice, even when the dose reached 3 times the amount of parent drug arenobufagin that was used. Compound 3f also exhibits significant antitumor activity in vitro and in vivo. The improved safety profile and favorable anticancer properties of 3f warrant further studies of the potential clinical implications. Our study suggests that FAPα prodrug strategy is an effective approach for successful increasing the therapeutic window of bufadienolides.

FEATURES OF OPTICAL COHERENCE TOMOGRAPHY FOR THE DIAGNOSIS OF VOGT-KOYANAGI-HARADA DISEASE.

BACKGROUND/PURPOSE: To examine the diagnostic value of optical coherence tomography (OCT) for the detection of acute Vogt-Koyanagi-Harada (VKH) disease. METHODS: Clinical charts and OCT images were retrospectively reviewed for patients consecutively diagnosed with acute VKH, subacute VKH, multifocal central serous chorioretinopathy (CSCR), and posterior scleritis. All patients underwent OCT, fundus photography, and fluorescein angiography (FA) before treatment. The characteristics of OCT and FA were analyzed and recorded. RESULTS: The study included 80 eyes with acute VKH, 32 eyes with subacute VKH, 33 eyes with CSCR, and 13 eyes with posterior scleritis. The most common OCT features of VKH disease were hyperreflective dots (70/80; 88%), subretinal membranous structures (64/80; 80%), retinal detachment higher than 450 µm (63/80; 79%), and retinal pigment epithelium (RPE) folds (44/80; 55%). For the detection of VKH disease, sensitivity and specificity were for subretinal membranous structures 80% and 95.6%, respectively, for high retinal detachment 78.8% and 76.1%, respectively, for subretinal hyperreflective dots, 87.5 and 60.9%, respectively, and for RPE folds 55% and 80.4% respectively. Subretinal membranous structures showed the highest positive predictive value (97.3%) and negative predictive value (65.7%) of all OCT assessed features. CONCLUSION: OCT-related morphological signs have a relatively high predictive value for the diagnosis of acute VKH.

[Effect of "one village, one control strategy" on schistosomiasis control in Qianjiang City].

OBJECTIVE: To evaluate the effect of "one village, one control strategy" on schistosomiasis control in Qianjiang City. METHODS: The villages with human and/or bovine schistosome infection rate being more than 1.5% in 2011 were chosen as the trial villages. According to the epidemic characteristics of schistosomiasis and control difficulties of the villages, the "one village, one control strategy" was performed and the control effects were evaluated. RESULTS: By the end of 2013, the infection rates of human and bovine in the trial villages decreased by 45.91% (χ2 = 469.19, P < 0.01) and 49.38% (χ2 = 11.46, P < 0.01), respectively, and all the infection rates of human and bovine in those villages were less than 1%. CONCLUSION: The "one village, one control strategy" is effective for schistosomiasis control, which can rapidly reduce the prevalence of schistosomiasis.

[Measures and effectiveness of comprehensive schistosomiasis control along Xinglong River in Qianjiang City].

OBJECTIVE: To evaluate the effect of comprehensive control of schistosomiasis along the Xinglong River in Qianjiang City, so as to provide the evidence for improving schistosomiasis control. METHODS: The comprehensive control measures including infection source control and Oncomelania hupensis snail eradication were surveyed along the Xinglong River in Qianjiang City. RESULTS: The prevalence of schistosomiasis was under control, that was the human and cattle infection rates decreased by 53.77% and 100% respectively, the snail area decreased by 26.9%, the mean density of living snails decreased by 25.5%, and no infected snails was found. CONCLUSIONS: The comprehensive control measures along the Xinglong River are effective, and the management and surveillance of snail environments still should be strengthened.

Five-year incidence of age-related macular degeneration: the Beijing Eye Study.

PURPOSE: To examine the incidence of age-related macular degeneration (AMD) and its associated factors in an adult Chinese population. DESIGN: Population-based study. PARTICIPANTS: The Beijing Eye Study, which included 4439 subjects (age ≥ 40 years) in 2001, was repeated in 2006 with 3251 (73.2%) subjects participating. METHODS: Fundus photographs were graded using the International Age-related Maculopathy Epidemiological Study Group grading system. MAIN OUTCOME MEASURES: Incidence of AMD. RESULTS: Gradable slides were available on 3049 (93.9%) subjects who participated in the survey of 2001 and again in 2006. The incidence of early, late, and neovascular AMD per eye was 2.6% (95% confidence interval [CI], 2.2-3.0), 0.1% (95% CI, 0.00-0.2), and 0.1% (95% CI, 0.00-0.2), respectively. The incidence of early, late, and neovascular AMD per person was 4.2 ± 0.4% (95% CI, 3.5-5.0), 0.1 ± 0.1% (95% CI, 0.0-0.2), and 0.1 ± 0.1% (95% CI, 0.0-0.2), respectively. By multivariate analysis, incident early AMD was associated significantly with greater age at baseline (P = 0.01; odds ratio [OR], 1.03; 95% CI, 1.01-1.06), smaller optic disc size (P = 0.007; OR, 0.50; 95% CI, 0.30-0.83), smaller scleral spur distance (P = 0.04; OR, 0.59; 95% CI, 0.36-0.98), and hyperopic refractive error (P = 0.057; OR, 1.15; 95% CI, 1.00-1.33), with the latter being significant only marginally. It was not associated with the systemic parameters of gender, body height, body mass index, region of habitation, level of education, profession, smoking, arterial blood pressure, diabetes mellitus, fasting blood concentrations of glucose, triglycerides, high-density or low-density lipoproteins; or the ocular parameters of intraocular pressure, retinal arterial and vein diameters, retinal microvascular abnormalities, amount of nuclear cataract, cortical cataract or subcapsular cataract, pseudophakia, glaucoma, nonglaucomatous optic neuropathy, retinal vein occlusions, size of the beta zone of parapapillary atrophy, or progression of the zone of atrophy during the follow-up from 2001 to 2006. CONCLUSIONS: Hyperopia, short interscleral spur distance, and small optic disc size were, beside older age, the main factors associated with incident early AMD. This may point to a small globe size, potentially in relation to a firmly attached vitreous, playing a role in early incident AMD. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Separation of low concentration of cesium ion from wastewater by electrochemically switched ion exchange method: experimental adsorption kinetics analysis.

A series of experiments were performed to evaluate the continuous separation of cesium based on an electrochemically switched ion exchange (ESIX) process using a diaphragm-isolated reactor with two identical nickel hexacyanoferrate/porous three-dimensional carbon felt (NiHCF/PTCF) electrodes as working electrodes. The effects of applied potential, initial concentrations and pH values of the simulation solutions on the adsorption of cesium ion were investigated. The adsorption rate of cesium ion in the ESIX process was fitted by a pseudo-first-order reaction model. The experiments revealed that the introduction of applied potential on the electrodes greatly enhanced the adsorption/desorption rate of Cs(+) and increased the separation efficiency. H(3)O(+) was found to play a dual role of electrolyte and competitor, and the adsorption rate constant showed a curve diversification with an increase in pH value. Also, it was found that the electrochemically switched adsorption process of Cs(+) by NiHCF/PTCF electrodes proceeded in two main steps, i.e., an ESIX step with a fast adsorption rate and an ion diffusion step with a slow diffusion rate. Meanwhile, the NiHCF/PTCF film electrode showed adsorption selectivity for Cs(+) in preference to Na(+).

[Molluscicidal effect of LDS in field in marshland areas].

The molluscicidal effects of salt of quinoid-2', 5-dichloro-4'-nitrosalicylanilide (LDS) and 50% wettable powder of niclosamide ethanolamine salt (WPN) were observed by three methods of immersion, insufflations and powdering. The results showed that there was no statistic difference between the snail control effects of LDS and WPN, which suggested that LDS had a good molluscicidal effect in marshland areas.

Prevalence and risk factors for diabetic retinopathy: the Beijing Communities Diabetes Study 6.

BACKGROUND: To examine prevalence and associated factors of diabetic retinopathy in patients with Type 2 diabetes mellitus in urban communities of Beijing. METHODS: The community health care center-based study included subjects with diabetes mellitus and an age of 20 years to 80 years, who were recruited from 15 community health centers in urban Beijing. Diabetes mellitus was defined using the World Health Organization criteria. Fundus photographs were graded using the modified Airlie House classification system. RESULTS: Of 2,642 eligible patients, 2,007 (76.0%) subjects (1,199 women) with a mean age of 64.1 ± 9.0 years participated. The overall prevalence of diabetic retinopathy was 24.7 ± 1.0% (95% confidence interval [CI], 22.8-26.6). In binary logistic analysis, presence of diabetic retinopathy was associated with younger age (odds ratio [OR], 0.97; 95% CI, 0.95-0.98), longer duration of diabetes (OR, 1.10; 95% CI, 1.08-1.12), higher concentration of glycosylated hemoglobin HbA1c (OR, 1.23; 95% CI, 1.14-1.33), higher systolic blood pressure (OR, 1.01; 95% CI, 1.01-1.02), lower body mass index (OR, 0.95; 95% CI, 0.92-0.98), and elevated blood urea concentration (OR, 1.01; 95% CI, 1.00-1.01). Microalbuminuria was an additional associated factor (OR, 1.55; 95% CI, 1.16-2.08). Patients with microalbuminuria were 4.7 times more likely to have a severe or proliferating diabetic retinopathy than those without microalbuminuria. CONCLUSION: In the urban population of Beijing, prevalence of diabetic retinopathy in diabetic patients was 25%. As in whites, increased blood pressure besides elevated plasma glucose concentrations was highly significantly associated with diabetic retinopathy in Chinese. It suggests that in Chinese as also in whites, blood pressure control beside control of plasma glucose levels is important to prevent development or progression of diabetic retinopathy.

Age-related macular degeneration and mortality: the Beijing eye study.

PURPOSE: To assess the association between age-related macular degeneration (AMD) and mortality in a population-based setting. PROCEDURES: At baseline in 2001, the Beijing Eye Study examined 4,378 subjects for AMD with a detected frequency of 110/4,378 (2.5%) subjects for early AMD and of 12/4,378 (0.3%) subjects for late AMD. In 2006, all study participants were re-invited for a follow-up examination. RESULTS: Out of the 4,378 subjects, 3,218 (73.5%) returned for a follow-up examination while 138 (3.2%) were dead and 1,022 (23.3%) did not agree to be re-examined or had moved away. Early AMD and late AMD were not significantly associated with mortality (p = 0.40 and 0.33, respectively), neither in univariate analysis nor in multivariate analysis. CONCLUSIONS: AMD may not be associated with an increased mortality in adult Chinese.

Association of beta zone of parapapillary atrophy with age-related macular degeneration in adult Chinese. The Beijing Eye Study.

BACKGROUND: Since parapapillary atrophy and age-related macular degeneration (AMD) share features of their ophthalmoscopic and histological appearance, such as irregular pigmentation, proliferation and loss of the retinal pigment epithelium, it was the purpose of the study to assess whether parapapillary atrophy, particularly beta zone of parapapillary atrophy, is associated with AMD in a population-based investigation. METHODS: The Beijing Eye Study included 4439 subjects out of 5324 subjects invited to participate (response rate 83.4%) with an age of 40 + years. The present investigation consisted of 3874 (82.3%) subjects for whom readable fundus photographs of at least one eye were available with normal intraocular pressure, a refractive error of >- 8 diopters, and no signs of glaucomatous optic neuropathy. RESULTS: In a multivariate analysis, beta zone of parapapillary atrophy was significantly associated with age (P < 0.001), optic disc size (P < 0.001) and myopic refractive error (P < 0.001). It was not significantly associated with presence of retinal pigment depigmentation (P = 0.20) or hyperpigmentation (P = 0.99), drusen size (P = 0.27), and presence of early AMD (P = 0.72) or late AMD (P = 0.99). CONCLUSIONS: Although beta zone of parapapillary atrophy and age-related macular degeneration have a similar histology with irregularities of the retinal pigment epithelium and eventual closure of the choriocapillaris and loss of retinal pigment epithelium cells, the entities are clinically not significantly associated with each other.

[Adeno-associated virus mediated delivery and expression of GDNF cDNA in cultured bovine iris pigment epithelial cells].

OBJECTIVES: To obtain transgenic bovine iris pigment epithelial cells (IPECs) by adeno-associated virus (AAV) mediated delivery of cDNA of glial cell-line derived neurotrophic factor (GDNF). METHODS: AAV-GDNF was titrated by slot blotting. Cultured bovine passage two IPECs were transfected using AAV-GDNF at dosage of MOI (multiplicity of infection) = 50, then were cultured in DMEM medium complemented with 3% FBS for 4 weeks with no change of medium. The expression of GDNF in culture medium was examined using ELISA test. By using the same methods, cultured passage two IPECs were transfected with AAV-GFP (green fluorescent protein) at dosage of MOI = 50, and then were cultured in DMEM medium complemented with 20% FBS. The expression of GFP in IPECs was examined using fluorescence microscope every 2 days after transfection. RESULTS: (1) GFP expression in IPECs could not be detected until 4 days after transfection. The positive GFP expression in IPECs reached fastigium in day 8 or 10. (2) According to the results of ELISA test, concentration of GDNF in the culture medium was (17.14 +/- 1.10) micro g/L. CONCLUSIONS: AAV-GDNF can effectively transfect cultured IPECs, and the transgenic cells show a high expression of GDNF.

[Prevalence of low vision and blindness in defined populations in rural and urban areas in Beijing].

OBJECTIVE: To investigate the prevalence and causes of low vision and blindness in Beijing residents aged 40 and over. METHODS: 4,451 residents aged 40 and over in 3 rural communities and 5 urban communities in Beijing underwent eye examination, including examination of distant and near visual acuity (VA), best corrected distant and near VA, pinhole VA, and visual field, slit lamp biomicroscopy, and dilated ocular examination in the form of in-home survey by defined population-based sampling. The medical history was surveyed too. The data were analyzed based on the criteria of the World Health Organization. RESULTS: The general prevalence rates of low vision and blindness were 0.99% (95% CI: 0.70-1.28) and 0.39% (95% CI: 0.21-0.57) respectively. The prevalence rate of low vision in females was 1.45%, 2.23 times that of males (0.65%) (OR: 1.97, 95% CI: 1.00-3.95). The prevalence rate of low vision of rural residents was 1.76%, 2.89 times that of urban residents (0.61%) (OR: 2.93, 95% CI: 1.43-6.11). The prevalence rate of blindness in females was 0.64% and 0.37% in males. The prevalence rate of blindness of rural residents was 1.06%, 2.04 times that of the urban residents (0.52%) (OR: 3.77, 95% CI: 1.41-10.62). The 3 major causes of blindness were cataract (37.50%), glaucoma (29.20%), and high myopic macular degeneration (8.30%). The prevalence of blindness increased with age. CONCLUSION: The prevalence rates of low vision and blindness are higher in the rural areas. Cataract, glaucoma, and high myopic macular degeneration are the major causes of blindness. The prevalence of low vision and blindness are influenced by age, sex; area, health care level, educational level, and environmental factors.