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Supplementary Table from δ-Tocotrienol is the Most Potent Vitamin E Form in Inhibiting Prostate Cancer Cell Growth and Inhibits Prostate Carcinogenesis in Ptenp−/− Mice

Vitamin E compounds, consisting of α, β, γ, and δ forms of tocopherols and tocotrienols, display different cancer preventive activities in experimental models. Tocotrienols may have higher potential for clinical use due to their lower effective doses in laboratory studies. However, most studies on tocotrienols have been carried out using cancer cell lines. Strong data from animal studies may encourage the use of tocotrienols for human cancer prevention research. To examine the cancer inhibitory activity of different vitamin E forms, we first investigated their inhibitory activities of different vitamin E forms in prostate cancer cell lines. We found that δ-tocotrienol (δT3) was the most effective form in inhibiting cell growth at equivalent doses. Because of this in vitro potency, δT3 was further studied using prostate-specific Pten−/− (Ptenp−/−) mice. We found that 0.05% δT3 in diet reduced prostate adenocarcinoma multiplicity by 32.7%, featuring increased apoptosis and reduced cell proliferation. The inhibitory effect of 0.05% δT3 in diet was similar to that of 0.2% δ-tocopherol (δT) in diet reported previously. Our further study on the δT3-induced transcriptome changes indicated that δT3 inhibited genes in blood vessel development in the prostate of Ptenp−/− mice, which was confirmed by IHC. Together, our results demonstrate that δT3 effectively inhibits the development of prostate adenocarcinoma in Ptenp−/− mice, which involves inhibition of proliferation and angiogenesis and promotion of apoptosis.Prevention Relevance:We demonstrated that δ-tocotrienol is the most active vitamin E form in inhibiting the growth of several prostate cancer cell lines. In transgenic Ptenp−/− mice, δ-tocotrienol inhibited the formation of prostate cancer. This result would encourage and help design clinical studies for the application of δ-tocotrienol for prostate cancer prevention.

Supplementary Figure from δ-Tocotrienol is the Most Potent Vitamin E Form in Inhibiting Prostate Cancer Cell Growth and Inhibits Prostate Carcinogenesis in Ptenp−/− Mice

Diabetic Retinopathy (DR) is a leading cause of irreversible visual impairment and blindness in both developed and developing countries. Although the merits of DR screening are well recognized, significant variations in screening practices including imaging modality still exists. To evaluate and compare the sensitivity and specificity of mydriatic and non-mydriatic photographic screening methods using 7-Field fundus photography or dilated fundus examination (DFE) by an ophthalmologist as reference standard. A systematic review using PRISMA Guidelines was conducted by online search of MEDLINE, Web of Science, and other repositories of all available studies from 1990 until 2019. A total of 62 studies were included in the meta-analysis from a total of 406 suitable abstracts screened and 95 articles reviewed in full. Data were collected using a standardized extraction form independently, with all authors masked to others’ search results. For the detection of any DR (ADR), sensitivity ranged from 81% with single field to a maximum of 99% for 4–7 fields and wide-angle images. For detection of referable DR (RDR) sensitivity ranged from 76% for single field to 93% for wide-angle photography. Specificity was lowest at 91% for wide-angle images and greatest at 99% for three field photography. Study heterogeneity was noted to be significant, which was partly attributed to the range of DR classification between studies. The sensitivity and specificity of DR screening are positively associated with number of photographic fields. Pooled estimates suggest non-mydriatic two-field photography may be sufficient for screening detection of ADR and RDR.

Vitamin E compounds, consisting of α, β, γ, and δ forms of tocopherols and tocotrienols, display different cancer preventive activities in experimental models. Tocotrienols may have higher potential for clinical use due to their lower effective doses in laboratory studies. However, most studies on tocotrienols have been carried out using cancer cell lines. Strong data from animal studies may encourage the use of tocotrienols for human cancer prevention research. To examine the cancer inhibitory activity of different vitamin E forms, we first investigated their inhibitory activities of different vitamin E forms in prostate cancer cell lines. We found that δ-tocotrienol (δT3) was the most effective form in inhibiting cell growth at equivalent doses. Because of this in vitro potency, δT3 was further studied using prostate-specific Pten−/− (Ptenp−/−) mice. We found that 0.05% δT3 in diet reduced prostate adenocarcinoma multiplicity by 32.7%, featuring increased apoptosis and reduced cell proliferation. The inhibitory effect of 0.05% δT3 in diet was similar to that of 0.2% δ-tocopherol (δT) in diet reported previously. Our further study on the δT3-induced transcriptome changes indicated that δT3 inhibited genes in blood vessel development in the prostate of Ptenp−/− mice, which was confirmed by IHC. Together, our results demonstrate that δT3 effectively inhibits the development of prostate adenocarcinoma in Ptenp−/− mice, which involves inhibition of proliferation and angiogenesis and promotion of apoptosis. Prevention Relevance: We demonstrated that δ-tocotrienol is the most active vitamin E form in inhibiting the growth of several prostate cancer cell lines. In transgenic Ptenp−/− mice, δ-tocotrienol inhibited the formation of prostate cancer. This result would encourage and help design clinical studies for the application of δ-tocotrienol for prostate cancer prevention.

Metabolic syndrome (MetS) and its four clinical entities, central obesity, insulin resistance, hypertension and dyslipidemia, are implicated in increasing the risk and mortality of cancer in several organs. However, it is unclear how they are associated with increased risk of prostate cancer. To elucidate the mechanistic link between MetS and prostate carcinogenesis, we characterized the development of MetS and prostate adenocarcinoma in prostate-specific Pten−/− (Ptenp−/−) mice fed a high-fat (HF) diet. We found that male Ptenp−/− mice on an HF diet gained excess body weight and elevated blood glucose, insulin and insulin-like growth factor 1 (IGF1) levels at 20 weeks of age and were obese at 40 weeks. Prostate adenocarcinoma multiplicity at 40 weeks was significantly higher in the mice on an HF diet, suggesting that the HF diet promotes the development of prostate adenocarcinoma. Increased cell proliferation and enhanced AKT activation were found in the prostates of mice on an HF diet. Further transcriptome study revealed that receptor tyrosine kinase regulation, which mediates insulin/IGF1 signaling, was one of the top enriched pathways by HF diet-induced transcriptome changes. Together, our results suggest that HF diet-induced hyperinsulinemia leads to increased activation of insulin/IGF1/AKT signaling in lesioned prostates, promoting the development of adenocarcinoma.

Personalized nutrition (PN) approaches have been shown to help drive behavior change and positively influence health outcomes. This has led to an increase in the development of commercially available PN programs, which utilize various forms of individual-level information to provide services and products for consumers. The lack of a well-accepted definition of PN or an established set of guiding principles for the implementation of PN creates barriers for establishing credibility and efficacy. To address these points, the North American Branch of the International Life Sciences Institute convened a multidisciplinary panel. In this article, a definition for PN is proposed: "Personalized nutrition uses individual-specific information, founded in evidence-based science, to promote dietary behavior change that may result in measurable health benefits." In addition, 10 guiding principles for PN approaches are proposed: 1) define potential users and beneficiaries; 2) use validated diagnostic methods and measures; 3) maintain data quality and relevance; 4) derive data-driven recommendations from validated models and algorithms; 5) design PN studies around validated individual health or function needs and outcomes; 6) provide rigorous scientific evidence for an effect on health or function; 7) deliver user-friendly tools; 8) for healthy individuals, align with population-based recommendations; 9) communicate transparently about potential effects; and 10) protect individual data privacy and act responsibly. These principles are intended to establish a basis for responsible approaches to the evidence-based research and practice of PN and serve as an invitation for further public dialog. Several challenges were identified for PN to continue gaining acceptance, including defining the health–disease continuum, identification of biomarkers, changing regulatory landscapes, accessibility, and measuring success. Although PN approaches hold promise for public health in the future, further research is needed on the accuracy of dietary intake measurement, utilization and standardization of systems approaches, and application and communication of evidence.

IMPORTANCE: Cataract is the leading cause of blindness and the second leading cause of vision impairment. The majority of people with vision impairment reside in low-resource settings with limited access to cataract surgery and services. BACKGROUND: Cataract surgery rate (CSR) is a proxy measure for eye care service delivery and estimating the burden of cataract disease. This research aims to evaluate the longitudinal changes of CSR inequality globally and by income groups. DESIGN: Systematic review. PARTICIPANTS: Studies published from January 2000 to December 2015 were considered for inclusion into the review. METHODS: CSR data were retrieved from a systematic review of published literature (OVID Medline, Embase, PubMed, ISI, Web of Science), unpublished reports and data repositories. MAIN OUTCOME MEASURES: Inequality of CSR was measured on a global scale and between countries grouped by income levels using the Gini coefficient and concentration index, with respect to the human development index (HDI). RESULTS: Overall, correlations between HDI and gross domestic product (GDP) per capita vs CSRs were observed with R2 values of 49.2% (β = 5.01, P < 0.001) and 38.9% (β = 0.56, P < 0.001), respectively. Analysis of longitudinal CSR data using generalized estimation equation models revealed strong associations between CSR and HDI (P < 0.001), GDP (P < 0.001) and the proportion of people aged ≥50 (P = 0.001). Overall, the trend of inequality in worldwide CSR remained relatively stable. CONCLUSIONS AND RELEVANCE: Inequalities in cataract service provision were found between countries grouped by income and associated with socioeconomic indicators.

Clinical relevance: Ocular biometry is key to understanding the determinants of ocular development and pathology changes, especially for the thriving myopic population in Asia. Investigating biometric data in highly myopic eyes within a wide age spectrum is therefore of high importance.Background: To report the magnitude of change in spherical equivalent for each unit of change in the ocular biometry parameters in a highly myopic population in China.Methods: Highly myopic patients aged 7 to 70 years were recruited from the Zhongshan Ophthalmic Center, China. Each patient had a cycloplegic refraction and a measurement of ocular biometry.Results: Data from 823 right eyes were available for analysis, with a mean age of 22.7 years and a median spherical equivalent of -8.88 D. Axial length and lens thickness increased with age, while anterior chamber depth (ACD) decreased in older subjects. There was a significant trend of increasing axial length, lens thickness, vitreous chamber depth (VCD) and decreasing ACD and calculated lens power over spherical equivalent quartiles (all p

The number of Individuals that use dietary supplements and herbal medicine products are continuous to increase in many countries. The context of usage of a dietary supplement varies widely from country-to-country; in some countries supplement use is just limited to general health and well-being while others permit use for medicinal purposes. To date, there is little consensus from country to country on the scope, requirements, definition, or even the terminology in which dietary supplement and herbal medicines categories could be classified. Transparent science-based quality standards for the ingredients across these regulatory frameworks/definitions becomes even more important given the international supply chain. Meanwhile, there has been a rapid advancement in emerging technologies and data science applied to the field. This review was conceived at the Global Summit on Regulatory Sciences that took place in Beijing on September 2018 (GSRS2018) which is organized by Global Coalition for Regulatory Science Research (GCRSR) that consists of the global regulatory agencies from over ten countries including the European Union. This review summarizes a significant portion of discussions relating to a longitudinal comparison of the status for dietary supplements and herbal medicines among the different national jurisdictions and to the extent of how new tools and methodologies can improve the regulatory application.

IMPORTANCE: Understanding the longitudinal intraocular pressure (IOP) changes and potential risk factors in adults is important for future glaucoma control in the aging society. BACKGROUND: Limited longitudinal studies exist in Asia investigating the longitudinal IOP changes and with varying results. DESIGN: Population-based cohort study. PARTICIPANTS: 1405 baseline participants from the Liwan Eye Study. METHODS: All baseline participants were invited for the 10-year follow-up examination in 2013. IOP (by Tonopen), central corneal thickness (CCT; by ultrasound), refractive error (by autorefractor), blood pressure, height and weight were measured per standardized protocol and the presence of hypertension or diabetes was collected by questionnaire. Follow-up examinations were conducted using the same equipment with proper calibration. Linear regression analysis was used to assess the association between IOP change and potential risk factors. MAIN OUTCOME MEASURES: 10-year IOP change. RESULTS: Of the 791 participants at the 10-year follow-up, IOP data were available for 602 participants with a mean age of 60.9 years (55.5% female). The average IOP change over 10 years was an increase of 1.44 mmHg (95% confidence interval, 1.12-1.75). Linear regression showed that 10-year IOP change was not associated with baseline age, gender, body mass index (BMI), CCT, spherical equivalence (SE), hypertension or diabetes. However, it was positively associated with longitudinal increase of BMI when longitudinal changes of BMI and SE were included in the model (P < 0.001). CONCLUSIONS AND RELEVANCE: We observed a small increase in IOP over 10 years in this adult Chinese population, which was positively related to the longitudinal change in BMI.

PurposeTo describe the prevalence of age-related macular degeneration (AMD) among older adults in rural southern mainland China.MethodsEligible persons aged 50 years or over were identified by geographically defined cluster sampling from Yangxi County, Guangdong Province, China. Participants underwent a standardised interview and comprehensive eye examinations from August to November in 2014. Digital retinal photographs were graded for AMD lesions using the Clinical Classification of Age-Related Macular Degeneration developed by the Beckman Initiative for Macular Research Classification Committee. Age-standardised prevalence of AMD and AMD lesions was calculated using the 2010 world population data and compared with those of other populations.ResultsOf 5825 subjects who participated (90.7% response rate), 4881 (83.8%) had fundus photographs gradable for AMD. Early, intermediate and late AMD were present in 2003 (41.0%), 879 (18.0%) and 42 (0.86%) participants. The age-standardised prevalence of early, intermediate and late AMD was 40.4% (95% CI 39.6% to 41.2%), 17.6% (95% CI 17.0% to 18.2%) and 0.79% (95% CI 0.65% to 0.95%), respectively. Total AMD was more prevalent in men than in women (62.8% vs 57.1%).ConclusionsAMD is an important public health concern for rural southern China, and the prevalence of AMD was higher in men than in women.

Purpose To investigate the progression of near vision loss and the cumulative incidence of near vision impairment (NVI) 6 years after initial examination of an urban Chinese cohort. Design Population-based, prospective cohort study. Participants People aged ≥35 years examined at baseline in the Yuexiu District of Guangzhou, China. Methods Participants examined at baseline were invited for 2-year and 6-year follow-up examinations in 2010 and 2014, respectively. Examinations included noncycloplegic autorefraction and binocular near visual acuity (NVA) with and without current near correction measured at 40 cm using a LogMAR ETDRS near vision tumbling E chart. Those with uncorrected binocular NVA (UCNVA) ≤20/40 underwent subjective refraction to obtain best-corrected binocular NVA (BCNVA). Main Outcome Measures Change in UCNVA between baseline and 2014 follow-up examinations and the 6-year cumulative incidence of vision impairment based on 3 definitions: NVA ≤20/40, ≤20/50, and ≤20/63. Results Among the 1817 baseline participants, 1595 (87.8%) were reexamined in 2010 and 1427 (78.5%) in 2014. Mean vision loss between baseline and the 2014 follow-up was 1.54 (±1.74) lines of UCNVA. Vision loss was associated with age 80 years or older, less education, and better baseline UCNVA. The 6-year cumulative incidence of uncorrected binocular NVI (UCNVI) across the 3 vision impairment definitions was 55.2% (95% confidence interval [CI], 46.1%–64.3%), 51.3% (95% CI, 44.0%–58.7%), and 42.4% (95% CI, 35.5%–49.3%), respectively. With best-corrected binocular NVI (BCNVI), incidence was 6.89% (95% CI, 4.28%–9.50%), 5.17% (95% CI, 2.89%–7.44%), and 2.62% (95% CI, 1.11%–4.12%), respectively. A higher incidence of UCNVI was associated with worse baseline UCNVA for all 3 impairment definitions. Similarly, incidence of BCNVI was associated with worse baseline BCNVA, but also with older age and education at the primary level or less. Gender was not significant for either UCNVI or BCNVI. Conclusions Approximately half of those aged 35 years or older develop UCNVI in 6 years, the overwhelming majority of whom can be corrected with spectacles. Cost-effective strategies to provide spectacles to this at-risk population remains an issue requiring further study.

ObjectivesTo investigate the longitudinal changes in intraocular pressure (IOP) and its associations with refractive error and systemic determinants in a Chinese geriatric population.DesignProspective cohort study.SettingGuangzhou Government Servant Physical Check-up Center, Guangzhou, China.Participants4413 government employees aged no less than 40 years (41.9% female) attending annual physical and eye examinations were included in this study. The inclusion criterion was having attended the 2010 follow-up examination. The exclusion criteria include glaucoma or intraocular surgery history, IOP >21 mm Hg at any visit or without available IOP data at all visits from 2010 to 2014.Primary and secondary outcome measuresThe outcome measure was IOP at each follow-up visit from 2010 to 2014. Mixed-effect model was used to assess the relationship between longitudinal changes in IOP and potential risk factors.ResultsFor the 2653 participants who had available IOP data at both the 2010 and 2014 follow-up visits, the average change in IOP was an increase of 0.43 (95% CI 0.36 to 0.50) mm Hg. For the whole study population and in the optimised mixed model, there was a non-linear increase of IOP with age (PConclusionsIn this cohort of elderly Chinese adults, IOP increases non-linearly with ageing. People with increasing blood pressure, BMI, FPG and myopic progression are more likely to have IOP elevation over time.

Cataract blindness accounts for a substantial proportion of blindness worldwide. Understanding the correlations between national levels of socioeconomic development with the quantity and quality of cataract surgery may provide insight for the prioritization and resource allocation for blindness prevention programs.The relationships between human development index (HDI), gross domestic product (GDP) per capita, and cataract surgical coverage (CSC) and visual outcome of cataract surgery were examined in a multinational study utilizing secondary data from the repository for Rapid Assessment of Avoidable Blindness (RAAB), World Health Organization, Global Burden of Disease, United Nations, and the World Bank.A total of 266 RAAB studies across 73 countries/territories were retrieved. Linear regression model results revealed strong associations of HDI with prevalence of cataract blindness (β = -7.056, P0.001), CSC (β = 60.808, P = 0.004), proportion of intraocular lens (IOL) implantation (β = 87.040, P = 0.001), and proportion of cases with good vision outcomes among operated eyes (β = 73.351, P0.001) in studies performed between 1995 and 2009. Similar associations were observed for studies performed between 2010 and 2015. In addition, countries with lower GDP per capita showed a higher rate of cataract blindness (β = -0.527, P = 0.001), lower CSC (β = 9.800, P0.001), lower percentage of IOL implantation (β = 6.871, P = 0.001), and fewer patients with good vision outcomes after surgery (β = 7.959, P0.001). After controlling survey year, country, and other factors, GDP per capita and HDI were also found to be significantly associated with CSC and visual outcomes after cataract surgery (all P0.05).We documented the strong associations of socioeconomic indices with quantity and quality of cataract surgery. These socioeconomic indicators should be considered as important factors for developing strategies aimed to improve worldwide cataract surgery service delivery.

The science of lipid research continues to rapidly evolve and change. New knowledge enhances our understanding and perspectives on the role of lipids in health and nutrition. However, new knowledge also challenges currently held opinions. The following are the proceedings of the 2013 Canadian Nutrition Society Conference on the Advances in Dietary Fats and Nutrition. Content experts presented state-of-the-art information regarding our understanding of fish oil and plant-based n-3 polyunsaturated fatty acids, nutrigenomics, pediatrics, regulatory affairs, and trans fats. These important contributions aim to provide clarity on the latest advances and opinions regarding the role of different types of fats in health.

ObjectivesTo investigate mobile health product use in Australia and societal and clinician perceptions towards smartphone based visual acuity (VA) assessment tools.DesignQuantitative analysis of a cross-sectional survey delivered to the general public and thematic analysis of in-depth interviews of eye health clinicians.SettingOnline survey within Australia and face-to-face in-depth interviews of clinicians.Participants1016 adults were recruited via Survey Monkey Audience, social media (Facebook and Twitter), Rotary Australia and Lions Clubs Australia. Six clinicians were recruited from private and public settings in Melbourne, Australia.Primary and secondary outcome measuresThe study assessed socio-demographic characteristics, history of mobile health product use and perceived advantages and potential drawbacks of smartphone based VA assessment tools.ResultsA total of 14.4% of the study population had previously used a mobile-based health product. After adjusting for covariates, younger age (p=0.001), male gender (p=0.01) and higher income (>$45 000) were associated with increased likelihood of having used a mobile health product (p=0.005). Seventy-two per cent of participants would use an automated smartphone based VA assessment tool, provided that the accuracy was on par to that of human assessors. Convenience (37.3%) and cost-savings (15.5%) were ranked as the greatest perceived advantages. While test accuracy (50.6%), a lack of personal contact with healthcare providers (18.3%) and data security (11.9%) were the greatest concerns. Themes to emerge from clinician qualitative data included the potential benefits for identifying refractive error in patients, as well as the ability to self-monitor vision. Concerns were raised over the potential misuse of self-testing vision apps and the inability to detect pathology.ConclusionOur findings suggest that a substantial proportion of the Australian population do not use mobile health products. Furthermore, there remains notable concerns, including test accuracy and data privacy, with smartphone-based VA assessment tools by both clinicians and the public.

Myopia has become epidemic, particularly in East Asia, and is a major cause of visual impairment worldwide. Twin studies are an important resource to investigate the genetics and the gene-environment interaction in myopia. This article aims to provide an overview of major findings regarding myopia from different types of twin studies, from the heritability of myopia-related traits to novel findings of genome-wide association studies. In the postgenomic era, twin studies will continue to serve as a unique method in the investigation of gene-environment interaction.

Purpose.To compare the use of the halo fixation device in our hospital before and after implementation of a new compliance protocol.Methods.From 2003 to 2008, 17 (47%) of 36 patients had dislodgement of their halo fixation device. All rings and vests and some of the pins were reused. Documentation of poundage assessment and change of skull pins before dislodgement was lacking. There was no protocol for assessing superstructure throughout the course of the application. To improve the standard of care, knowledge about the application of the halo fixation device in orthopaedic and orthotic departments was reinforced and compliance documented. From September 2008 to April 2010, 15 patients used the halo fixation device for cervical immobilisation. Patients were reminded to minimise shoulder shrugging and report any discomfort. Poundage checking was strictly observed during and after application. The integrity of the device was regularly checked by orthotists. The conditions of the skull pins, halo ring, and vest were also documented after removal.Results.Two (13%) of the 15 patients had ring dislodgement. One occurred a day after application owing to malposition of a posterior skull pin, and the other was related to a fall in a toilet at week 4. Both involved reused skull pins. 45% of the skull pins were new, whereas 44% were found defective after removal of rings. Compliance with the new assessment form was satisfactory.Conclusion.Clinical audit improved outcome achieved with the halo fixation device. Reuse of titanium skull pins should be avoided. Re-torquing of the pin should be avoided when the tip is blunted or hooked. The new assessment form enabled compliance with the principle of application by orthotists and patients.

IMPORTANCE: Vision loss is the third most common impairment worldwide. Although cost-effective interventions are available for preventing or curing most causes of vision loss, availability of these interventions varies considerably between countries and districts. Knowledge of the association between vision loss and socioeconomic factors is informative for public health planning. OBJECTIVES: To explore correlations of the prevalence of visual impairment with socioeconomic factors at country levels and to model and estimate a socioeconomic-adjusted disease burden based on these data. DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, the following data were collected from 190 countries and territories: the age-standardized prevalence of moderate to severe visual impairment (MSVI) and blindness from January 1 to December 31, 2010, across countries, human development index (HDI), gross domestic product (GDP) per capita, total health expenditure, total health expenditure as percentage of GDP (total health expenditure/GDP), public health expenditure as percentage of total health expenditure (public/total health expenditure), and out-of-pocket expenditure as percentage of total health expenditure (out-of-pocket/total health expenditure). Countries were divided into 4 levels (low, medium, high, and very high) by HDI. Data analysis was conducted from September 1, 2016, to July 1, 2017. MAIN OUTCOMES AND MEASURES: The correlations between prevalence data and socioeconomic indices were assessed. RESULTS: A strong negative association between prevalence rates of MSVI and blindness and socioeconomic level of development was observed. The mean (SD) age-standardized prevalence of MSVI decreased from 4.38% (1.32%) in low-HDI regions to 1.51% (1.00%) in very-high-HDI regions (P

All over the world, authorities responsible for the assessment and surveillance of foods and feeds derived using gene technology and the environmental impacts of genetically modified organisms (GMO) have chosen specific strategies to assess their safety. Although different regulatory frameworks are in place, almost all adopted risk assessment strategies are based on a common set of principles and guidelines. Here we provide some examples of these strategies and we compare them to highlight areas where an international consensus exists. Our hope is that even if limited, this short review can represent a first step towards the recognition of an international consensus and a broader dialog on GMOs regulation worldwide.

We report the case a 15-year-old boy who presented with retinopathy caused by a green-diode (class IIIB) laser. The patient was followed over a period of 8 weeks. Visual acuity on day 1 was 6/7.5, with central scotoma in the right eye, and 6/5 in the left eye. Macular optical coherence tomography of the right eye day 1 showed focal subfoveal disruption of the photoreceptor ellipsoid and myoid zones extending through the external limiting membrane to the outer nuclear layer. At week 8, visual acuity was 6/6 right eye and 6/5 in the left eye. Disruption of the ellipsoid and myoid layers, though still present, had improved.

Odontogenic orbital cellulitis, although uncommon, has the potential to cause severe vision loss if unsuspected and untreated. Compared to non-odontogenic bacteriology, odontogenic orbital abscesses typically feature a heavy mixed growth with anaerobic organisms. We review the literature and discuss the case of a 26-year-old male who presented with anaerobic orbital cellulitis for treatment.

ObjectiveThis study was to aggregate the prevalence and risks of epiretinal membranes (ERMs) and determine the possible causes of the varied estimates.DesignSystematic review and meta-analysis.Data sourcesThe search strategy was designed prospectively. We searched PubMed, Embase and Web of Science databases from inception to July 2016. Reference lists of the included literatures were reviewed as well.Study selectionSurveys published in English language from any population were included if they had a population-based design and reported the prevalence of ERM from retinal photography with or without optical coherence tomography. Eligibility and quality evaluation was conducted independently by two investigators.Data extractionThe literature search generated 2144 records, and 13 population-based studies comprising 49 697 subjects were finally included. The prevalence of ERM and the ORs of potential risk factors (age, sex, myopia, hypertension and so on) were extracted.ResultsThe pooled age-standardised prevalence estimates of earlier ERM (cellophane macular reflex (CMR)), advanced ERM (preretinal macular fibrosis (PMF)) and any ERM were 6.5% (95% CI 4.2% to 8.9%), 2.6% (95% CI 1.8% to 3.4%) and 9.1% (95% CI 6.0% to 12.2%), respectively. In the subgroup analysis, race and photography modality contributed to the variation in the prevalence estimates of PMF, while the WHO regions and image reading methods were associated with the varied prevalence of CMR and any ERM. Meta-analysis showed that only greater age and female significantly conferred a higher risk of ERMs.ConclusionsOur findings suggest that ERMs are relatively common among aged population. Race, image taking and reading methodology may play important roles in influencing the large variability of ERM prevalence estimates.

Purpose: Cataract is the leading cause of blindness and cataract surgical rate (CSR) is used as a proxy indicator of access to cataract services in a country. The aim of this study was to explore the associations between the CSR and the economic development of countries in terms of gross domestic product per capital (GDP/P) and gross national income per capita (GNI/P). Methods: We systematically searched OVID (Medline and Embase), Pubmed, Embase.com, ISI Web of Science, and Cochrane Library databases, and retrieved additional data from unpublished reports. Cataract surgical rates and economic indicators (GDP/P, GNI/P) were collected for each country from 2005 to 2014. Complete data were used for the 50 largest countries according to World Health Organization (WHO) population estimates. Linear correlations between GDP/P and CSR were calculated. Cataract surgical rate data over two periods were used for analysis: 2005 to 2009 and 2010 to 2014 (CSR in 2009 or nearest year, CSR in 2014 or nearest year). Results: Over the study period, CSR data were available for 152 countries across both time periods. Most of the CSR data were obtained from nongovernment organization (NGO) reports, including WHO reports. A good linear correlation between CSR and GDP/P was found overall, nearest to 2009 (β = 0.162, Linear: y = 0.162x + 282.242; R2 = 0.665, P < 0.001). Regression analysis of CSR nearest to 2014 produced similar findings, with significant correlations between CSR and GDP/P (Linear: y = 0.208x + 94.008; R2 = 0.785, P < 0.001). When using GNI/P as an economic indicator, similarly excellent lines of fit were obtained. After adjusting for time and country, CSR was significantly associated with GDP/P (Coefficient = 0.147, R2 = 0.759, P < 0.001), and GNI/P (Coefficient = 0.152, R2 = 0.757, P < 0.001). Most countries had an increase in CSRs over time, with the greatest increases observed for Iran and Argentina. Conclusion: Cataract surgical rate and economic indicators are closely associated, indicating the strong influence of resource availability on healthcare delivery. Considering this relationship, it is important to be innovative in delivery of low-cost services and invest strategically in capacity development to meet cataract surgical need in low-resource settings.

Antibiotic resistance in bacteria can arise due to the acquisition of extrachromosomal genetic elements, and/or loss or reduction in normal gene function through mutations and enzymatic modifications. The drug resistance phenotypes conferred by these genetic determinants are usually drug and mechanism specific. The first such adaptive mechanism discovered was mapped to the multiple antibiotic resistance mar locus at 34.05 min of the Escherichia coli linkage map. As such, the discovery of the mar locus is significant for two reasons: first, it confers a multidrug resistance phenotype and second, recent findings have demonstrated that this locus controls genes in cellular metabolism, physiology, and virulence. The E. coli mar locus comprises two transcriptional units that are divergently transcribed from a common operator region, marO. Transcriptional unit 1 (TU 1) encodes MarC, which has a hydropathy profile suggestive of a putative integral transmembrane protein with six transmembrane helices. Despite MarR mediated repression, low-levels of marA are still detectable in unmutated strains, where this basal constitutive expression of marA may be needed for some expression of the marRAB locus and other members of the regulon. The gene arrangement of the marRAB locus appears to be conserved in 14 out of 53 species of Enterobacteriaceae, as was shown by Southern hybridization. Southern hybridization analysis with an E. coli marRAB probe has demonstrated that the marRAB locus is widespread and highly conserved among members of Enterobacteriaceae such as Shigella flexneri, Citrobacter freundii, Klebsiella pneumoniae, Klebsiella oxytoca, and Enterobacter cloacae.

Apoptosis, a process recently implicated as the cellular mechanism underlying ovarian follicular atresia and luteal regression, is characterized by the internucleosomal degradation of DNA by a Ca2+/Mg2+-dependent endonuclease. Although hormones and growth factors have been demonstrated to modulate the DNA degradation associated with ovarian follicular apoptosis, the nature and identity of the endonuclease involved is not known. Ca 2 '/Mg2+-dependent endonuclease activity has a developmental pattern of expression in rat granulosa and luteal cell nuclei. Thus, the present study was conducted to establish the presence of an endonuclease in the nuclei of ovarian granulosa and luteal cells and to examine the biochemical properties of the enzyme relevant to apoptosis. Nuclei from diethylstilbestrol (DES)-, eCG-, and hCG-primed rat ovaries were isolated and exposed to Ca 2+ and Mg 2+ in vitro. Nuclei from rat ovaries primed with eCG and hCG, but not DES, substantially degraded their DNA in an apoptotic fashion, and this DNA degradation was Ca 2 +/Mg 2+ dependent and inhibited by Zn 2+ . Protein extracts from the nuclei of DES-, eCG-, and hCG-treated rat ovaries were tested for endonuclease activity by a plasmid degradation assay. The extracts were found to contain endonuclease activity with the same developmental pattern and cation dependency as found in intact nuclei. These protein extracts were assessed for nuclease activity by zymography, and three nuclease activities were identified depending on the type of DNA used in the gel and the electrophoresis conditions used for protein separation. A doublet of 32/34 kDa was found to have the same developmental pattern and cation dependency as that demonstrated with the plasmid degradation assay and apoptotic DNA production in intact nuclei. A nuclease activity of 27 kDa was also present but was active only on single-stranded DNA and was Mg 2 -, but not Ca 2+ -, dependent. True nuclease activity was distinguished from false positive histone effects by silver staining the DNA in the zymographic gel, a new technique that avoids the use of isotopically labeled DNA. The 32/34-kDa activity had molecular size, cation dependency, and optimal substrate and electrophoresis requirements similar to those of DNase I from bovine pancreas. These experiments suggest that the capacity of rat ovarian cells to undergo apoptosis (as measured by DNA degradation) is developmentally regulated such that differentiated granulosa and luteal cell nuclei, but not undifferentiated granulosa cell nuclei, possess an endogenous DNase I-like endonuclease activity. This Dnase I-like endonuclease may be responsible for the characteristic DNA degradation observed during follicular atresia and luteal regression.

Constitutive expression of the mar operon (marRAB) in Escherichia coli produces a multiple antibiotic resistance phenotype mediated by the expression of multiple genetic loci in response to regulatory proteins in the operon. A mar-specific DNA probe was used to search for the operon in bacterial strains representing 53 species and 27 genera. Among these, 6 other Enterobacteriaceae, Salmonella, Shigella, Klebsiella, Citrobacter, Hafnia, and Enterobacter species, contained DNA sequences that hybridized to the probe under high-stringency conditions. By use of a selection protocol developed to obtain multiple antibiotic resistant mutants of E. coli, multiply resistant mutants that showed increased expression of mar-specific RNA were obtained from Enterobacter agglomerans and Salmonella species.

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Agarose-immobilized chromosomal DNA from the nalidixic-acid-resistant Campylobacter coli strain UA417 and its streptomycin-resistant (StrR) derivative, UA417R, were digested with the restriction enzymes SalI (GTCGAC) and SmaI (CCCGGG). The sizes of the resulting fragments were determined using pulsed-field gel electrophoresis. The two genomes showed similar restriction patterns of seven and 13 fragments for the two respective enzymes and the total genome size was determined to be approx. 1.7 Mb. Analysis of partial digestion fragments, as well as Southern-blot hybridization, were used to construct a physical map of the C. coli UA417R genome. Natural transformation studies using DNA fragments extracted from UA417R, as well as the erythromycin-resistant (EryR) C. coli strain UA585, were used to locate the StrR and EryR resistance markers on the genomic map.

Genomic DNA from 12 different Campylobacter jejuni and 10 Campylobacter coli isolates was digested with SmaI and analyzed by pulsed-field gel electrophoresis (PFGE) and 16S rRNA hybridization studies. Although the two Campylobacter species displayed species-specific restriction and hybridization patterns, significant intraspecies differences were observed. Combined PFGE and hybridization pattern analysis failed to provide any more epidemiologic information than was obtained from PFGE restriction profiles alone. Therefore, results from these studies indicate that PFGE analysis of SmaI-restricted genomic DNA provides a reliable means of differentiating C. jejuni from C. coli and may represent a more practical approach to epidemiologic studies than combining conventional DNA restriction digestion pattern with RNA hybridization procedures.