Retrofitting tractors with rollover protective structures: perspective of equipment dealers.

PubMed

Tonelli, S M; Donham, K J; Leedom-Larson, K; Sanderson, W; Purschwitz, M

2009-10-01

This study was one of a cluster of studies that originated via requests for proposals from the NIOSH National Agricultural Tractor Safety Initiative. The present study design consisted of several steps: (1) formation of an advisory group, (2) development and testing of a standard paper self-responding survey instrument, (3) sample selection of farm equipment dealers, (4) administration of the survey, (5) assessment and analysis of the survey, and (6) in-person response panel of dealers (n = 80) to review results of the questionnaire for further definition and sharpening of the recommendations from the survey. A key finding is that most dealers do not currently sell or install ROPS retrofit kits. Barriers cited by dealers included (1) actual or perceived lack of farmer demand, (2) injury liability, (3) expensive freight for ordering ROPS, (4) lack of dealer awareness of the magnitude of deaths from tractor overturns and the high life-protective factor of ROPS, and (5) difficulty and incursion of non-recoverable expenses in locating and obtaining specific ROPS. Despite not currently selling or installing ROPS, dealers responded favorably about their future potential role in ROPS promotion and sales. Dealers were willing to further promote, sell, and install ROPS if there was demand from farmers. Recommendations include establishing a ROPS "clearing house" that dealers could contact to facilitate locating and obtaining ROPS orders from customers. Additional recommendations include education and social marketing targeting farm machinery dealers as well farmers, manufacturers, and policy makers.

Continuous overturn control of compactors/rollers by rollover protective structures

PubMed Central

Myers, Melvin L.

2009-01-01

The objective of this article is to report on the effectiveness of Rollover Protective Structures (ROPS) in preventing continuous overturns of compactors/rollers. This study is a case-based analysis of government investigation reports of injury-related overturns of compactors/rollers. The overturns were predominately on construction sites including road and embankment construction in the USA. Other sites included driveway and roadway maintenance or repair and transporting of compactors/rollers either by driving or when loading on or unloading from trailers. The principle intervention observed in controlling a continuous overturn (a roll beyond 90° relative to the impact surface) was the presence of a ROPS on a compactor/roller that serves as an anti-roll bar. The main outcome measures are cases of compactor/roller overturns that are restricted to a 90° roll or are continuous (exceed a 90° roll.) All cases of an overturn in which a ROPS was present resulted in no continuous overturn, and the cases involved with no ROPS averaged an overturn of 301°, showing a propensity for a continuous overturn. This case-based analysis identified a ROPS on compactors/rollers as an effective control for reducing the risk of an overturn to 90° relative to the impact plane. PMID:21765649

Encouraging the installation of rollover protective structures in New York State: the design of a social marketing intervention.

PubMed

Sorensen, Julie A; May, John; Ostby-Malling, Ronne; Lehmen, Tom; Strand, John; Stenlund, Hans; Weinehall, Lars; Einehall, Lars W; Emmelin, Maria

2008-11-01

Increasing the percentage of rollover protective structure (ROPS) equipped tractors has been the focus of many agricultural safety campaigns. Traditionally efforts have attempted to persuade farmers through education or community awareness interventions. These efforts have lead to marginal change. In response, a social marketing approach was tested as a means for increasing interest in ROPS retrofitting in New York. An initial phone survey was conducted with a random sample of New York farmers to identify a potential target population. Following target selection, in-depth interviews were conducted to isolate barriers and motivators to retrofitting. This information was used to develop message prototypes which were tested in small focus group discussions. Selected and revised messages, as well as various other incentives developed in response to feedback from interviews, were then tested in a prospective, quasi-randomized controlled trial. Small crop and livestock farms were selected as the intervention target since they represent 86% of New York farms with none or only one ROPS protected tractor. Barriers to retrofitting which were identified in interviews were: 1) constant exposures normalize risk, 2) risk is modeled by significant others and 3) safety in general and retrofitting in particular requires too much time and money. The piloting of ROPS incentives led to a marked increase in ROPS sales in New York. Social Marketing provides a promising framework for the design of agricultural injury prevention programs. The potential implications for other health initiatives seeking to promote behaviour change are also discussed.

A Demonstration Project in New York and Virginia: Retrofitting Cost-Effective Roll-over Protective Structures (CROPS) on Tractors.

PubMed

Hard, D L; McKenzie, E A; Cantis, D; May, J; Sorensen, J; Bayes, B; Madden, E; Wyckoff, S; Stone, B; Maass, J

2015-07-01

The NIOSH cost-effective roll-over protective structure (CROPS) demonstration project sought to determine whether three prototype roll-over protective structures (ROPS) designed to be retrofitted on Ford 8N, Ford 3000, Ford 4000, and Massey Ferguson 135 tractors could be installed in the field and whether they would be acceptable by the intended end users (farmers). There were a total of 50 CROPS. demonstrators (25 in New York and 25 in Virginia), with 45 observers attending the New York CROPS demonstrations and 36 observers attending the Virginia CROPS demonstrations, for a total of 70 participants in New York and 61 in Virginia. The oldest retrofitted tractors were 77 to 62 years old, while the newest retrofitted tractors were 40 to 37 years old. The most frequently retrofitted tractor in the CROPS demonstration project was a Ford 3000 series tractor (n = 19; 38%), followed by Ford 4000 (n = 11; 22%), Massey Ferguson 135 (n = 11; 22%), and Ford 8N (n = 9; 18%). A major issue of CROPS retrofitting was the rear wheel fenders. The effort involved in disassembling the fenders (removing the old bolts was often faster by cutting them with a torch), modifying the fender mounting brackets, and then reinstalling the fenders with the CROPS generally required the most time. In addition, various other semi-permanent equipment attachments, such as front-end loaders, required additional time and effort to fit with the CROPS. Demonstrators were asked to rank the reasons why they had not retrofitted their tractors with ROPS until they had enrolled in the CROPS demonstration program. ROPS "cost too much" was ranked as the primary reason for participants in both states (80% for New York and 88% for Virginia). The second highest ranked reasons were "ROPS wasn't available" for Virginia (80%) and "hassle to find ROPS" for New York (69%). The third highest ranked reasons were "not enough time to find ROPS" for New York (67%) and "hassle to find ROPS" for Virginia (79%). All demonstrators and observers indicated that they were glad to have participated in the CROPS project.

Prominent barriers and motivators to installing ROPS: an analysis of survey responses from Pennsylvania and Vermont.

PubMed

Jenkins, P L; Sorensen, J A; Yoder, A; Myers, M; Murphy, D; Cook, G; Wright, F; Bayes, B; May, J J

2012-04-01

Tractor overturns contribute significantly to the number of work-related deaths that occur every year on U.S. farms. Although the agriculture, forestry, and fishing industries have the highest fatality rates of any industries, researchers predict that the elimination of tractor overturn fatalities could result in a noticeable reduction in the farm fatality rate. Rollover protection structures (ROPS) are 99% effective in preventing overturn fatalities. However, roughly 50% of U.S. tractors do not have a ROPS. In order to identify prominent barriers and motivators to installing ROPS, a phone survey was conducted with a random sample of farmers (n = 327) in Vermont and Pennsylvania, two states interested in developing ROPS installation programs. Results indicated that cost and perceived need were the most frequently highly rated barriers to ROPS installation in both states, while working near hills or ditches and concerns regarding liability were the most frequently highly rated motivators for installing ROPS. Additionally, older farmers identified limited use of a tractor as a highly rated barrier.

Selecting target populations for ROPS retrofit programs in Pennsylvania and Vermont.

PubMed

Yoder, A M; Sorensen, J A; Foster, F; Myers, M; Murphy, D; Cook, G; May, J; Jenkins, P

2013-07-01

Agriculture has the highest injury and fatality rates when compared with other U.S. industries, and tractor overturns remain the leading cause of agricultural fatalities. Rollover protection structures (ROPS) are the only proven devices to protect a tractor operator in the event of an overturn. These devices are 99% effective when used with a seatbelt. Nearly 49% of tractors in the U.S. are not equipped with a ROPS. Interventions such as social marketing, community awareness campaigns, and financial incentives have been directed at encouraging farmers to install ROPS on their unprotected tractors. The purpose of this study was to conduct similar comparisons of ROPS protection and readiness to retrofit in different segments of the Vermont and Pennsylvania farm communities. A telephone survey was used to collect data on ROPS prevalence, farm demographic characteristics, and farmer's stage of change relative to installing ROPS on farm tractors. Our data provide new and unique information on the prevalence of ROPS-equipped tractors relative to commodity, farm size, and a variety of other demographic variables. Extrapolating from these data, the commodities studied account for roughly 162,072 tractors across the two states. Of these, 85,927 (53%) do not have ROPS. Of these unprotected tractors, 77,203 are in Pennsylvania and 8,724 are in Vermont. Our other two research questions dealt with the farmer's stage of change and possible ways to segment this population. The stage of change portion of our work demonstrates that most Pennsylvania and Vermont farmers are not contemplating ROPS retrofitting in the near future. Since no major differences were found in the stage of change, the number of unprotected tractors was examined for each of the commodity groups. In Pennsylvania, 29% of all unprotected tractors were found on cash crop farms. This trend was even more apparent on smaller farms than large farms. This led to the selection of smaller cash crop farms as the target audience for social marketing messages. In contrast, researchers in Vermont found a bimodal distribution of unprotected tractors. Of all the commodity groups surveyed in Vermont, vegetable and cash crop farmers were least likely to have even one protected tractor to use on the farm. Probably the most encouraging finding from this study is that over 85% of Pennsylvania farms and over 87% of Vermont farms surveyed had at least one tractor available that had ROPS protection. Of those farms, 25.5% of the Pennsylvania farms and 46% of the Vermont farms have ROPS on all of their tractors. Both of these findings were greater than the findings from a 2006 survey of New York State farms, which found that 75% of surveyed New York farms have ROPS on at least one tractor and 18% have ROPS on all tractors. Even with these encouraging data, the goal of 100% of tractors with ROPS is far from being met. There are still an estimated 90,000 unprotected tractors on Pennsylvania and Vermont farms, and these farm owners are currently unmotivated to install ROPS. However as demonstrated in New York State, it may be possible to use social marketing that combines persuasive messages and cost-sharing to persuade these farmers that ROPS are indeed important and accessible.

The NIOSH CROPS Demonstration Project: A Study in New York and Virginia with an Emphasis on Youth

PubMed Central

Hard, David L.; McKenzie, Eugene A.; Cantis, Douglas; May, John; Sorensen, Julie; Bayes, Barbara; Madden, Erin; Stone, Bruce; Maass, Jimmy

2016-01-01

The agriculture, forestry, and fishing (AgFF) industry sector has had the highest rate of work-related deaths over the past several years. Tractors are the single largest source of occupational fatalities in this industry sector, and tractor rollovers are the largest category of tractor fatalities. The risk of death due to tractor rollovers has been found to be reduced considerably when rollover protective structures (ROPS) are used in conjunction with seatbelts. Increasing the number of tractors with ROPS and seatbelts is one way in which tractor rollover fatalities can be mitigated. The NIOSH cost-effective rollover protective structure (CROPS) project was designed as a demonstration project to determine if CROPS, a type of ROPS, could be retrofitted in the field and were acceptable to farmers. To this end, the CROPS project was successful, with 50 tractors being retrofitted with CROPS in the field. All study participants were asked to complete a pretest, test, and posttest regarding the CROPS retrofit demonstration and their knowledge and attitudes toward ROPS. CROPS demonstrators were the participants who retrofitted their tractors with CROPS. Demonstrators were asked to recruit three to five other participants, known as observers, to watch the demonstration. The rationale was to generate interest in ROPS/CROPS among other farmers and community leaders. Overall, 16% of the participants had youth operating tractors on their farms. Participants reported that 44 youth operated tractors on their farms, more than 25% of these young tractor operators were 4 to 10 years old, and half of the youth operating tractors on participant farms were 13 years old or younger. Only one participant group (demonstrators) included individuals who had all of their tractors protected with ROPS/CROPS for young tractor operators (28%), but they accounted for only one farm each among the New York and Virginia demonstrators. The survey question on ROPS importance did not show an overall increase after respondents participated in the CROPS demonstration project. However, one Virginia observer asked to become a Virginia demonstrator and installed a CROPS on his tractor. Additionally, the questions on attitude toward ROPS showed a general increase in mean scores, with the some of the lowest response categories on the follow-up survey not being selected by respondents, indicating a potentially positive impact on participants' safety attitudes toward ROPS. For the safety attitude questions, the majority remained the same. This study indicates there is still much work to be done to reduce the number of deaths in production agriculture due to tractor rollovers. CROPS could be a valuable addition to the efforts of retrofitting ROPS on tractors in order to reduce the number of deaths due to tractor rollovers. PMID:27857511

The NIOSH CROPS Demonstration Project: A Study in New York and Virginia with an Emphasis on Youth.

PubMed

Hard, David L; McKenzie, Eugene A; Cantis, Douglas; May, John; Sorensen, Julie; Bayes, Barbara; Madden, Erin; Stone, Bruce; Maass, Jimmy

2016-01-01

The agriculture, forestry, and fishing (AgFF) industry sector has had the highest rate of work-related deaths over the past several years. Tractors are the single largest source of occupational fatalities in this industry sector, and tractor rollovers are the largest category of tractor fatalities. The risk of death due to tractor rollovers has been found to be reduced considerably when rollover protective structures (ROPS) are used in conjunction with seatbelts. Increasing the number of tractors with ROPS and seatbelts is one way in which tractor rollover fatalities can be mitigated. The NIOSH cost-effective rollover protective structure (CROPS) project was designed as a demonstration project to determine if CROPS, a type of ROPS, could be retrofitted in the field and were acceptable to farmers. To this end, the CROPS project was successful, with 50 tractors being retrofitted with CROPS in the field. All study participants were asked to complete a pretest, test, and posttest regarding the CROPS retrofit demonstration and their knowledge and attitudes toward ROPS. CROPS demonstrators were the participants who retrofitted their tractors with CROPS. Demonstrators were asked to recruit three to five other participants, known as observers, to watch the demonstration. The rationale was to generate interest in ROPS/CROPS among other farmers and community leaders. Overall, 16% of the participants had youth operating tractors on their farms. Participants reported that 44 youth operated tractors on their farms, more than 25% of these young tractor operators were 4 to 10 years old, and half of the youth operating tractors on participant farms were 13 years old or younger. Only one participant group (demonstrators) included individuals who had all of their tractors protected with ROPS/CROPS for young tractor operators (28%), but they accounted for only one farm each among the New York and Virginia demonstrators. The survey question on ROPS importance did not show an overall increase after respondents participated in the CROPS demonstration project. However, one Virginia observer asked to become a Virginia demonstrator and installed a CROPS on his tractor. Additionally, the questions on attitude toward ROPS showed a general increase in mean scores, with the some of the lowest response categories on the follow-up survey not being selected by respondents, indicating a potentially positive impact on participants' safety attitudes toward ROPS. For the safety attitude questions, the majority remained the same. This study indicates there is still much work to be done to reduce the number of deaths in production agriculture due to tractor rollovers. CROPS could be a valuable addition to the efforts of retrofitting ROPS on tractors in order to reduce the number of deaths due to tractor rollovers.

Systematic review and meta-analysis of human milk intake and retinopathy of prematurity: a significant update.

PubMed

Bharwani, S K; Green, B F; Pezzullo, J C; Bharwani, S S; Bharwani, S S; Dhanireddy, R

2016-11-01

Two recent meta-analyses have studied the association of exclusive or mainly human milk intake (HMI) on retinopathy of prematurity (ROP). One of these meta-analysis found a protective effect of only or mainly HMI on Severe ROP but not on any stage ROP. However, both these meta-analyses did not find protection from any stage ROP or Severe ROP with any amount of HMI. The objective of this study was to study the association between any amount of HMI and the development of All ROP and Severe ROP in very-low birth weight infants (VLBWI) and extremely low birth weight infants (ELBWI) by systematic review using PRISMA-P guidelines and meta-analysis. Exposure, controls and outcomes studied were any amount of HMI vs no HMI and All ROP/Severe ROP in VLBWI/ELBWI. All ROP was defined as all stages of ROP pooled together, and Severe ROP as ⩾stage 3 ROP and ROP requiring intervention. Results and effect sizes are expressed as odds ratio (OR), relative risk (RR), risk difference (RD) and number needed to treat (NNT) with 95% confidence intervals (95% CI). Data sources used were PubMed, MEDLINE, EMBASE, Cochrane Central Register of Clinical Trials, Scopus and CINAHL until 24 April 2015. Extracted data were pooled using a fixed effects model. Heterogeneity was assessed. Sensitivity analysis was performed. Five hundred nine of 1701 infants who received any amount of HMI developed All ROP vs 310 of 760 infants without HMI developed All ROP with a pooled OR 0.63* (0.51,0.78), RR 0.76* (0.67,0.86) and RD -0.09* (-0.13,-0.05). The NNT with any amount of HMI was 11* (8,20) (*P<0.0001) to prevent one case of All ROP. 204 of 2465 infants who received any amount of HMI developed Severe ROP vs 85 of 764 infants without HMI developed Severe ROP with a pooled OR 0.74* (0.56,0.98), RR 0.77* (0.60,0.98) and RD -0.03* (-0.05,-0.00). The NNT with any amount of HMI was 33* (*P=0.04) to prevent one case of Severe ROP. Any amount of HMI is strongly associated with the protection from All ROP and Severe ROP.

Cost effectiveness of a dealer's intervention in retrofitting rollover protective structures

PubMed Central

Myers, M; Cole, H; Westneat, S

2005-01-01

Objective: To evaluate the cost effectiveness of a 4.5 year education campaign that promoted farmers' adoption of rollover protective structures (ROPS) to prevent tractor overturn injuries. Design: Randomized controlled trial, decision analysis, and cost effectiveness analysis. Setting: One treatment county and one control county in the State of Kentucky. Intervention: A campaign by a local tractor and equipment dealership to encourage farmers to purchase and install ROPS and seatbelt retrofit kits for older tractors. Main outcome measures: Number of injuries averted and cost per injury averted. Results: The dealership's 4.5 year intervention was shown to potentially reduce both fatal (0.26) and non-fatal (1.50) injuries by 2.6% in its county over the intervention period using a 20 year analytic horizon. When extrapolated statewide, 6.7 lives would be saved and 39 non-fatal injuries would be averted over the combined 24.5 year combined intervention period and analytic horizon. The intervention for this period was cost effective with a "savings" of $35 713 per injury (fatal plus non-fatal) averted at a 4% discount rate. Conclusions: Tractor manufacturer promotions can influence their dealerships to promote ROPS retrofits by their customers. A manufacturer backed dealer ROPS retrofit campaign was cost effective in reducing overturn related injuries. PMID:15933410

Possible roles of bilirubin and breast milk in protection against retinopathy of prematurity.

PubMed

Kao, Joanna S; Dawson, Jeffrey D; Murray, Jeffrey C; Dagle, John M; Berends, Susan K; Gillen, Susan B; Bell, Edward F

2011-03-01

To explore the association of serum bilirubin level and breast milk feeding with retinopathy of prematurity (ROP) in preterm infants. We conducted a case-control study to examine the independent and combined effects of serum bilirubin and breast milk feeding on ROP risk in infants <32 weeks gestation or with birth weight <1500 g. Cases (66 infants with ROP) were matched with controls (66 infants without ROP) based on factors known to affect ROP risk. When analysed using the paired t-test, the peak bilirubin levels were lower in ROP cases than in controls (mean 7.2 vs. 7.9 mg/dL; p = 0.045). Using conditional logistic regression, we found a negative association between highest serum bilirubin level and risk of ROP (OR = 0.82 per 1-mg/dL change in bilirubin; p = 0.06). There was no significant association between breast milk feeding and risk of ROP. Bilirubin may help to protect preterm infants against ROP. © 2010 The Author(s)/Acta Paediatrica © 2010 Foundation Acta Paediatrica.

Risk Factors for Retinopathy of Prematurity: Insights from Outlier Infants

PubMed Central

Port, Alexander D.; Chan, R.V. Paul; Ostmo, Susan; Choi, Dongseok; Chiang, Michael F.

2014-01-01

Purpose To investigate the characteristics of outlier infants for insights into ROP risk. Methods Chart data were collected from 1354 infants screened for ROP at Weill Cornell Medical Center and Columbia University Medical Center. ROP exam results and clinical risk factors were recorded. The cohort was stratified by weight, highest ROP stage, and need for ROP treatment. Descriptive and correlational statistics were performed. Results For the overall cohort, regression analysis found that birth weight (OR: 0.741 per 100g; 95% CI: 0.606, 0.905), gestational age at birth (OR: 0.563 per week; 95% CI: 0.454, 0.697), multiple gestation (OR 2.02, 95% CI: 1.15, 3.56), bronchopulmonary dysplasia (OR: 4.68, 95% CI: 1.93, 11.35), and necrotizing enterocolitis (OR 2.80, 95% CI: 1.40, 5.16) were independent risk factors for treatment-requiring ROP. Black race was found to be a protective factor for treatment-requiring ROP (OR 0.244, 95% CI: 0.095, 0.626). Among 15 infants with BW <500g, there were no significant differences in any clinical risk factors between the 12 (80%) with ROP vs. the 3 (20%) without ROP. Similarly, among infants with BW >1500g, the 17 (9%) with ROP only differed from the 166 (91%) without ROP with respect to a higher incidence of necrotizing enterocolitis among those with ROP (11.8% vs 0%). Conclusions Although known clinical risk factors were predictive of ROP stage and need for laser treatment in this cohort, they were not significantly associated with ROP at extremes of birth weight. This suggests that other clinical, maternal, or genetic factors may protect from or predispose to ROP. PMID:25053346

Risk factors for retinopathy of prematurity: insights from outlier infants.

PubMed

Port, Alexander D; Chan, R V Paul; Ostmo, Susan; Choi, Dongseok; Chiang, Michael F

2014-10-01

To investigate the characteristics of outlier infants for insights into ROP risk. Chart data were collected from 1,354 infants screened for ROP at Weill Cornell Medical Center and Columbia University Medical Center. ROP exam results and clinical risk factors were recorded. The cohort was stratified by weight, highest ROP stage, and need for ROP treatment. Descriptive and correlational statistics were performed. For the overall cohort, regression analysis found that birth weight (OR: 0.741 per 100 g; 95 % CI: 0.606, 0.905), gestational age at birth (OR: 0.563 per week; 95 % CI: 0.454, 0.697), multiple gestation (OR 2.02, 95 % CI: 1.15, 3.56), bronchopulmonary dysplasia (OR: 4.68, 95 % CI: 1.93, 11.35), and necrotizing enterocolitis (OR 2.80, 95 % CI: 1.40, 5.16) were independent risk factors for treatment-requiring ROP. Black race was found to be a protective factor for treatment-requiring ROP (OR 0.244, 95 % CI: 0.095, 0.626). Among 15 infants with BW <500 g, there were no significant differences in any clinical risk factors between the 12 (80 %) with ROP vs the three (20 %) without ROP. Similarly, among infants with BW >1500 g, the 17 (9 %) with ROP only differed from the 166 (91 %) without ROP with respect to a higher incidence of necrotizing enterocolitis among those with ROP (11.8 % vs 0 %). Although known clinical risk factors were predictive of ROP stage and need for laser treatment in this cohort, they were not significantly associated with ROP at extremes of birth weight. This suggests that other clinical, maternal, or genetic factors may protect from or predispose to ROP.

Recombinant canine adenovirus type-2 expressing TgROP16 provides partial protection against acute Toxoplasma gondii infection in mice.

PubMed

Li, Xiu-Zhen; Lv, Lin; Zhang, Xu; Anchang, Kenneth Yongabi; Abdullahi, Auwalu Yusuf; Tu, Liqing; Wang, Xiaohu; Xia, Lijun; Zhang, Xiu-Xiang; Feng, Weili; Lu, Chunxia; Li, Shoujun; Yuan, Zi-Guo

2016-11-01

We previously demonstrated that the survival time of BALB/c mice challenged with Toxoplasma gondii RH strain was prolonged by immunising the mice with a eukaryotic vector expressing the protein ROP16 of T. gondii. Building upon previous findings, we are exploring improved vaccination strategies to enhance protection. In this work, a novel recombinant canine adenovirus type 2 expressing ROP16 (CAV-2-ROP16) of T. gondii was constructed and identified to express ROP16 in Madin-Darby canine kidney cells (MDCK) cells by western blot (WB) and indirect immunofluorescence (IFA) assays. Intramuscular immunisation of BALB/c mice with CAV-2-ROP16 was performed to evaluate the humoral and cellular immune responses. This vaccination triggered significant humoral and cellular responses, including ROP16-stimulated lymphoproliferation (P<0.05). Compared to control groups, the CAV-2-ROP16 immunised mice had high production of IFN-γ, IL-2 and IL-12 (P<0.05), with a predominance of IgG2a production, but not IL-10 (P>0.05), revealing that a predominant Th1-type response had developed. The cell-mediated cytotoxic activity with high levels of IFN-γ and TNF-α was significantly increased in both CD4 + and CD8 + T-cell compartments in the mice immunised with CAV-2-ROP16 (P<0.05), compared to three control groups. In addition, when immunised mice were challenged with the RH strain of T. gondii, they showed a significantly increased survival rate (25%) 80days post infection compared with control mice that all died within seven days (P<0.05). The 25% protection rate elicited by the recombinant virus CAV-2-ROP16 has not been achieved in the field of anti-T. gondii vaccination until now. Our work presents the successful use of recombinant virus CAV-2-ROP16 in vaccination protocols to protect against intraperitoneal challenge with the virulent RH strain of T. gondii. This system was shown to be extremely efficient in eliciting humoral and cellular immune responses that led to a significant improvement in survival time in mice. Copyright © 2016 Elsevier B.V. All rights reserved.

Novel structural and regulatory features of rhoptry secretory kinases in Toxoplasma gondii

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qiu, Wei; Wernimont, Amy; Tang, Keliang

2009-09-29

Serine/threonine kinases secreted from rhoptry organelles constitute important virulence factors of Toxoplasma gondii. Rhoptry kinases are highly divergent and their structures and regulatory mechanism are hitherto unknown. Here, we report the X-ray crystal structures of two related pseudokinases named ROP2 and ROP8, which differ primarily in their substrate-binding site. ROP kinases contain a typical bilobate kinase fold and a novel N-terminal extension that both stabilizes the N-lobe and provides a unique means of regulation. Although ROP2 and ROP8 were catalytically inactive, they provided a template for homology modelling of the active kinase ROP18, a major virulence determinant of T. gondii.more » Autophosphorylation of key residues in the N-terminal extension resulted in ROP18 activation, which in turn phosphorylated ROP2 and ROP8. Mutagenesis and mass spectrometry experiments revealed that ROP18 was maximally activated when this phosphorylated N-terminus relieved autoinhibition resulting from extension of aliphatic side chains into the ATP-binding pocket. This novel means of regulation governs ROP kinases implicated in parasite virulence.« less

MVA ROP2 vaccinia virus recombinant as a vaccine candidate for toxoplasmosis.

PubMed

Roque-Reséndiz, J L; Rosales, R; Herion, P

2004-04-01

Toxoplasma gondii is the aetiological agent of toxoplasmosis and is the most frequent and best known of the parasitic diseases. In the United States, a serological survey from the Third National Health and Nutrition Examination Survey found that an estimated 23% of adolescents and adults have laboratory evidence of infection with T. gondii. Although toxoplasmosis is asymptomatic or shows self-limited symptoms in adults, in pregnant women infections can cause severe health problems to the fetus if the parasites are transmitted. Also, in immunodeficient patients, chronic infection with T. gondii can reactivate and produce encephalitis, which is frequently lethal. In addition, in veterinary medicine, T. gondii infection is of economic importance due to abortion and neonatal loss in sheep and goats. Recently, the development of vaccines against toxoplasmosis has progressed considerably. The live attenuated S48 strain of Toxoplasma has been broadly used for veterinary purposes. DNA vaccines containing the full-length of SAG1/P30, ROP2 or ROP1 genes have proved to be a promising candidate to induce protection against toxoplasmosis. Viral vectors have proved to be the best candidates for vaccination in different diseases. A recombinant Herpes virus carrying the ROP2 gene is able to induce protective immunity in cats. In the present work we describe the potential of the MVA ROP2 recombinant vaccinia virus as a vaccine against toxoplasmosis. MVA ROP2 induces antibodies against the ROP2 protein in similar amount and types as the thermo-sensible strain ts-4 of T. gondii, which is able to fully protect mice against challenge with the virulent RH strain of T. gondii. Also, the life-span of mice is increased in MVA ROP2 vaccinated animals. We conclude that MVA ROP2 vaccine can possibly generate an immune response, which could be useful in protection against toxoplasmosis.

Induction of Protective Immunity against Toxoplasmosis in BALB/c Mice Vaccinated with Toxoplasma gondii Rhoptry-1

PubMed Central

Sonaimuthu, Parthasarathy; Ching, Xiao T.; Fong, Mun Y.; Kalyanasundaram, Ramaswamy; Lau, Yee L.

2016-01-01

Toxoplasma gondii is the causative agent for toxoplasmosis. The rhoptry protein 1 (ROP1) is secreted by rhoptry, an apical secretory organelle of the parasite. ROP1 plays an important role in host cell invasion. In this study, the efficacy of ROP1 as a vaccine candidate against toxoplasmosis was evaluated through intramuscular or subcutaneous injection of BALB/c mice followed by immunological characterization (humoral- and cellular-mediated) and lethal challenge against virulent T. gondii RH strain in BALB/c mice. Briefly, a recombinant DNA plasmid (pVAX1-GFP-ROP1) was expressed in CHO cells while expression of recombinant ROP1 protein (rROP1) was carried out in Escherichia coli expression system. Immunization study involved injection of the recombinant pVAX1-ROP1 and purified rROP1 into different group of mice. Empty vector and PBS served as two different types of negative controls. Results obtained demonstrated that ROP1 is an immunogenic antigen that induced humoral immune response whereby detection of a protein band with expected size of 43 kDa was observed against vaccinated mice sera through western blot analysis. ROP1 antigen was shown to elicit cellular-mediated immunity as well whereby stimulated splenocytes with total lysate antigen (TLA) and rROP1 from pVAX1-ROP1 and rROP1-immunized mice, respectively, readily proliferated and secreted large amount of IFN-γ (712 ± 28.1 pg/ml and 1457 ± 31.19 pg/ml, respectively) and relatively low IL-4 level (94 ± 14.5 pg/ml and 186 ± 14.17 pg/ml, respectively). These phenomena suggested that Th1-favored immunity was being induced. Vaccination with ROP1 antigen was able to provide partial protection in the vaccinated mice against lethal challenge with virulent RH strain of tachyzoites. These findings proposed that the ROP1 antigen is a potential candidate for the development of vaccine against toxoplasmosis. PMID:27303390

Vaccination with a DNA vaccine encoding Toxoplasma gondii ROP54 induces protective immunity against toxoplasmosis in mice.

PubMed

Yang, Wen-Bin; Zhou, Dong-Hui; Zou, Yang; Chen, Kai; Liu, Qing; Wang, Jin-Lei; Zhu, Xing-Quan; Zhao, Guang-Hui

2017-12-01

Toxoplasma gondii is an obligatory intracellular protozoan, which infects most of the warm-blooded animals, causing serious public health problems and enormous economic losses worldwide. The rhoptry effector protein 54 (ROP54) has been indicated as a virulence factor that promotes Toxoplasma infection by modulating GBP2 loading onto parasite-containing vacuoles, which can modulate some aspects of the host immune response. In order to evaluate the immuno-protective value of ROP54, we constructed a eukaryotic recombinant plasmid expressing T. gondii ROP54 and intramuscularly immunized Kunming mice with this recombinant plasmid against acute and chronic toxoplasmosis. All mice immunized with pVAX-ROP54 elicited a high level of specific antibody responses, a significant increase of lymphocyte proliferation, and a significant level of Th1-type cytokines (IFN-γ, IL-2 and IL-12p70), in addition to an increased production of Th2-type cytokines (IL-4 and IL-10). These results demonstrated that pVAX-ROP54 induced significant cellular and humoral (Th1/Th2) immune responses, which extended the survival time (13.0±1.15days for pVAX-ROP54 vs 6.7±0.48days for pVAX I, 6.8±0.42days for PBS and 6.5±0.53 for blank control) and significantly reduced cyst burden (35.9% for pVAX-ROP54, 1% for pVAX I and 2% for PBS, compared with blank control) of immunized mice. These results indicate that the recombinant ROP54 plasmid can provide partial protection and might be a potential vaccine candidate against acute and chronic toxoplasmosis. Copyright © 2017 Elsevier B.V. All rights reserved.

The Molecular Characterization and Immunity Identification of Rhoptry protein 22 (ROP22) of Toxoplasma gondii as a DNA Vaccine Candidate Against Toxoplasmosis.

PubMed

Zhang, Zhenchao; Li, Yuhua; Xie, Qing; Li, Pengju; Nan, Xiaoxu; Kong, Lingmin; Zeng, Dapeng; Ding, Zhifang; Wang, Shuai

2018-06-02

Toxoplasma gondii (T. gondii) rhoptry proteins (TgROPs) have been considered main targets and indicator molecules for immune diagnosis and prophylaxis since they initially present during the process of invasion. In this study, the effect of intramuscularly injecting the genetic vaccine pVAX-ROP22 was evaluated, made by inserting the TgROP22 sequence into the eukaryotic expression vector of pVAX I, into BALB/c mice. The levels of IgG, IgG1 and IgG2a in pVAX-ROP22 vaccinated animals were integrally increased. It was uncovered by cytokine profile analyses that the levels of IFN-γ and IL-2 were significantly increased, while no significant changes were detected in IL-4 and IL-10 levels. Additionally, we found that immunization with pVAX-ROP22 significantly prolonged the survival time (13.80 ± 1.75 days) of mice after challenge infection with the virulent T. gondii RH strain, in comparison to those of control animals (died within 10 days). Moreover, the number of brain cysts (1406 ± 277) in the animals subjected to pVAX-TgROP22 vaccination decreased remarkably (P < 0.05) compared to the blank control mice (2333 ± 473), and the size of brain cysts in pVAX-TgROP22 group was significantly smaller than the groups of blank, PBS and pVAXI. These results suggested that TgROP22 as DNA vaccine could trigger strong humoral and cellular responses and induce partial protection against toxoplasmosis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Finite element modeling of ROPS in static testing and rear overturns.

PubMed

Harris, J R; Mucino, V H; Etherton, J R; Snyder, K A; Means, K H

2000-08-01

Even with the technological advances of the last several decades, agricultural production remains one of the most hazardous occupations in the United States. Death due to tractor rollover is a prime contributor to this hazard. Standards for rollover protective structures (ROPS) performance and certification have been developed by groups such as the Society of Automotive Engineers (SAE) and the American Society of Agricultural Engineers (ASAE) to combat these problems. The current ROPS certification standard, SAE J2194, requires either a dynamic or static testing sequence or both. Although some ROPS manufacturers perform both the dynamic and static phases of SAE J2194 testing, it is possible for a ROPS to be certified for field operation using static testing alone. This research compared ROPS deformation response from a simulated SAE J2194 static loading sequence to ROPS deformation response as a result of a simulated rearward tractor rollover. Finite element analysis techniques for plastic deformation were used to simulate both the static and dynamic rear rollover scenarios. Stress results from the rear rollover model were compared to results from simulated static testing per SAE J2194. Maximum stress values from simulated rear rollovers exceeded maximum stress values recorded during simulated static testing for half of the elements comprising the uprights. In the worst case, the static model underpredicts dynamic model results by approximately 7%. In the best case, the static model overpredicts dynamic model results by approximately 32%. These results suggest the need for additional experimental work to characterize ROPS stress levels during staged overturns and during testing according to the SAE standard.

Cost-effectiveness of a ROPS social marketing campaign.

PubMed

Sorensen, J A; Jenkins, P; Bayes, B; Clark, S; May, J J

2010-01-01

Tractor rollovers are the most frequent cause of death in the farm community. Rollover protection structures (ROPS) can prevent the injuries and fatalities associated with these events; however, almost half of U.S. farms lack these essential devices. One promising strategy for increasing ROPS use is social marketing. The purpose of this study was to assess the costs associated with the New York ROPS Social Marketing Campaign in relation to the cost of fatalities and injuries averted as a result of the campaign to determine whether cost savings could be demonstrated in the initial years of program implementation. A total of 524 farmers who had retrofitted a tractor through the program were mailed a survey to assess the number of rollovers or close calls that occurred since ROPS installation. Responses were obtained from 382 farmers, two of whom indicated that they had a potential fatality/injury scenario since retrofitting their tractor through the program. The cost savings associated with the intervention was estimated using a decision-tree analysis adapted from Myers and Pana-Cryan with appropriate consumer price index adjustments. The data were compared to the cost of the New York ROPS Social Marketing Campaign to arrive at an associated cost-savings estimate relative to the intervention. This study indicates that a net savings will likely be demonstrated within the third year of the New York ROPS Social Marketing initiative. These data may provide evidence for researchers hoping to generate support from state and private agencies for similar initiatives.

Structural and functional analysis of RopB: A major virulence regulator in Streptococcus pyogenes

DOE PAGES

Makthal, Nishanth; Gavagan, Maire; Do, Hackwon; ...

2016-02-19

Group A Streptococcus (GAS) is an exclusive human pathogen that causes significant disease burden. Global regulator RopB of GAS controls the expression of several major virulence factors including secreted protease SpeB during high cell density. However, the molecular mechanism for RopB-dependent speB expression remains unclear. To understand the mechanism of transcription activation by RopB, we determined the crystal structure of the C-terminal domain of RopB. RopB-CTD has the TPR motif, a signature motif involved in protein-peptide interactions and shares significant structural homology with the quorum sensing RRNPP family regulators. Characterization of the high cell density-specific cell-free growth medium demonstrated themore » presence of a low molecular weight proteinaceous secreted factor that upregulates RopB-dependent speB expression. Together, these results suggest that RopB and its cognate peptide signals constitute an intercellular signalling machinery that controls the virulence gene expression in concert with population density. Structure-guided mutational analyses of RopB dimer interface demonstrated that single alanine substitutions at this critical interface significantly altered RopB-dependent speB expression and attenuated GAS virulence. Finally, results presented here suggested that a properly aligned RopB dimer interface is important for GAS pathogenesis and highlighted the dimerization interactions as a plausible therapeutic target for the development of novel antimicrobials.« less

Structural and functional analysis of RopB: A major virulence regulator in Streptococcus pyogenes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Makthal, Nishanth; Gavagan, Maire; Do, Hackwon

Group A Streptococcus (GAS) is an exclusive human pathogen that causes significant disease burden. Global regulator RopB of GAS controls the expression of several major virulence factors including secreted protease SpeB during high cell density. However, the molecular mechanism for RopB-dependent speB expression remains unclear. To understand the mechanism of transcription activation by RopB, we determined the crystal structure of the C-terminal domain of RopB. RopB-CTD has the TPR motif, a signature motif involved in protein-peptide interactions and shares significant structural homology with the quorum sensing RRNPP family regulators. Characterization of the high cell density-specific cell-free growth medium demonstrated themore » presence of a low molecular weight proteinaceous secreted factor that upregulates RopB-dependent speB expression. Together, these results suggest that RopB and its cognate peptide signals constitute an intercellular signalling machinery that controls the virulence gene expression in concert with population density. Structure-guided mutational analyses of RopB dimer interface demonstrated that single alanine substitutions at this critical interface significantly altered RopB-dependent speB expression and attenuated GAS virulence. Finally, results presented here suggested that a properly aligned RopB dimer interface is important for GAS pathogenesis and highlighted the dimerization interactions as a plausible therapeutic target for the development of novel antimicrobials.« less

A stochastic analysis of tractor overturn costs on catfish farms.

PubMed

Ibendahl, G A; Stephens, W B; Myers, M L

2012-10-01

An area of health and safety risk in agriculture that can be especially dangerous is catfish farming. One of the potential sources of injuries on catfish farms is tractor overturns that often result in crushing injuries. There is likely a higher probability of tractor overturns on a catfish farm than on a traditional crop farm due to the conditions that prevail on catfish farms. A catfish farm requires tractor movement near pond levees and water, and these levees have steep banks. Many of the activities on a catfish farm, such as mowing, feeding, and pond maintenance, require operating a tractor near a pond levee. Rollover protection structures (ROPS) on tractors can help to minimize the injuries caused by tractor overturns. ROPS do not lessen the probability of overturns, but ROPS mitigate the expected injury severity and lower the associated costs of an overturn. Despite the benefits of ROPS, not every tractor is so equipped. Some earlier work indicated that the cost to retrofit older tractors might outweigh the expected benefits. This article uses stochastic (i.e., randomly determined) analysis to determine if risk-averse farmers are more likely than risk-neutral farmers to retrofit tractors with ROPS. For this analysis, a distribution function of injury costs should an overturn occur was developed for both ROPS and non-ROPS tractors, and a Monte Carlo simulation was conducted. Results indicate that many risk-averse producers would be willing to retrofit older tractors with ROPS. However producers who are risk-neutral probably will not retrofit. These results might explain why not all tractors have been retrofitted despite the long-term availability of retrofit kits.

Stories or statistics? Farmers' attitudes toward messages in an agricultural safety campaign.

PubMed

Morgan, S E; Cole, H P; Struttmann, T; Piercy, L

2002-05-01

Farming is the second most hazardous occupation in the U.S. The high mortality rate is due in large part to farm equipment hazards, particularly tractor overturns. Injuries and deaths associated with tractor overturns could be prevented with the use of a rollover protective structure (ROPS). In spite of the known dangers associated with overturn incidents, farmers are reluctant to retrofit ROPS on older tractors. Few agricultural safety campaigns target the issue of ROPS retrofits, and none have been evaluated systematically. This article reports a study that examines a set of messages that were central to the Community Partners for Healthy Farming project. This study indicates that narrative-based messages and messages incorporating fear appeals are more favorably evaluated by farmers than messages that simply inform farmers or messages that rely on statistics.

Towards vaccine against toxoplasmosis: evaluation of the immunogenic and protective activity of recombinant ROP5 and ROP18 Toxoplasma gondii proteins.

PubMed

Grzybowski, Marcin M; Dziadek, Bożena; Gatkowska, Justyna M; Dzitko, Katarzyna; Długońska, Henryka

2015-12-01

Toxoplasmosis is one of the most common parasitic infections worldwide. An effective vaccine against human and animal toxoplasmosis is still needed to control this parasitosis. The polymorphic rhoptry proteins, ROP5 and ROP18, secreted by Toxoplasma gondii during the invasion of the host cell have been recently considered as promising vaccine antigens, as they appear to be the major determinants of T. gondii virulence in mice. The goal of this study was to evaluate their immunogenic and immunoprotective activity after their administration (separately or both recombinant proteins together) with the poly I:C as an adjuvant. Immunization of BALB/c and C3H/HeOuJ mice generated both cellular and humoral specific immune responses with some predominance of IgG1 antibodies. The spleen cells derived from vaccinated animals reacted to the parasite's native antigens. Furthermore, the immunization led to a partial protection against acute and chronic toxoplasmosis. These findings confirm the previous assumptions about ROP5 and ROP18 antigens as valuable components of a subunit vaccine against toxoplasmosis.

Evaluation of protective effect of multiantigenic DNA vaccine encoding MIC3 and ROP18 antigen segments of Toxoplasma gondii in mice.

PubMed

Qu, Daofeng; Han, Jianzhong; Du, Aifang

2013-07-01

The high incidence and severe damage caused by Toxoplasma gondii infection clearly indicates the need for the development of a vaccine. In this study, we evaluated the immune responses and protection against toxoplasmosis by immunizing ICR mice with a multiantigenic DNA vaccine. To develop the multiantigenic vaccine, two T. gondii antigens, MIC3 and ROP18, selected on the basis of previous studies were chosen. ICR mice were immunized subcutaneously with PBS, empty pcDNA3.1 vector, pMIC3, pROP18, and pROP18-MIC3, respectively. The results of lymphocyte proliferation assay, cytokine, and antibody determinations showed that mice immunized with pROP18-MIC3 elicited stronger humoral and Th1-type cellular immune responses than those immunized with single-gene plasmids, empty plasmid, or phosphate-buffered saline. After a lethal challenge with the highly virulent T. gondii RH strain, a prolonged survival time in pROP18-MIC3-immunized mice was observed in comparison to control groups. Our study indicates that the introduction of multiantigenic DNA vaccine is more powerful and efficient than single-gene vaccine, and deserves further evaluation and development.

29 CFR 1926.1000 - Rollover protective structures (ROPS) for material handling equipment.

Code of Federal Regulations, 2013 CFR

2013-07-01

... two times the weight of the prime mover applied at the point of impact. (i) The design objective shall..., if any; (3) Machine make, model, or series number that the structure is designed to fit. (f) Machines... performance criteria detailed in §§ 1926.1001 and 1926.1002, as applicable or shall be designed, fabricated...

29 CFR 1926.1000 - Rollover protective structures (ROPS) for material handling equipment.

Code of Federal Regulations, 2010 CFR

2010-07-01

... two times the weight of the prime mover applied at the point of impact. (i) The design objective shall..., if any; (3) Machine make, model, or series number that the structure is designed to fit. (f) Machines... performance criteria detailed in §§ 1926.1001 and 1926.1002, as applicable or shall be designed, fabricated...

29 CFR 1926.1000 - Rollover protective structures (ROPS) for material handling equipment.

Code of Federal Regulations, 2014 CFR

2014-07-01

... two times the weight of the prime mover applied at the point of impact. (i) The design objective shall..., if any; (3) Machine make, model, or series number that the structure is designed to fit. (f) Machines... performance criteria detailed in §§ 1926.1001 and 1926.1002, as applicable or shall be designed, fabricated...

29 CFR 1926.1000 - Rollover protective structures (ROPS) for material handling equipment.

Code of Federal Regulations, 2011 CFR

2011-07-01

... two times the weight of the prime mover applied at the point of impact. (i) The design objective shall..., if any; (3) Machine make, model, or series number that the structure is designed to fit. (f) Machines... performance criteria detailed in §§ 1926.1001 and 1926.1002, as applicable or shall be designed, fabricated...

29 CFR 1926.1000 - Rollover protective structures (ROPS) for material handling equipment.

Code of Federal Regulations, 2012 CFR

2012-07-01

... two times the weight of the prime mover applied at the point of impact. (i) The design objective shall..., if any; (3) Machine make, model, or series number that the structure is designed to fit. (f) Machines... performance criteria detailed in §§ 1926.1001 and 1926.1002, as applicable or shall be designed, fabricated...

Cost-effectiveness of a ROPS retrofit education campaign.

PubMed

Myers, M L; Cole, H P; Westneat, S C

2004-05-01

A community educational campaign implemented in two Kentucky counties was effective in influencing farmers to retrofit their tractors with rollover protective structures (ROPS) to protect tractor operators from injury in the event of an overturn. This article reports on the cost-effectiveness of this program in the two counties when compared to no program in a control county. A decision analysis indicated that it would be effective at averting 0.27 fatal and 1.53 nonfatal injuries over a 20-year period, and when this analysis was extended statewide, 7.0 fatal and 40 nonfatal injuries would be averted in Kentucky. Over the 20-year period, the cost-per-injury averted was calculated to be $172,657 at a 4% annual discount rate. This cost compared favorably with a national cost of $489,373 per injury averted despite the additional program cost in Kentucky. The principle reason for the increased cost-effectiveness of the Kentucky program was the three-fold higher propensity for tractors to overturn in Kentucky. The cost-per-injury averted in one of the two counties was $112,535. This lower cost was attributed principally to incentive awards financed locally for farmers to retrofit their tractors with ROPS.

Correlation of interactions between NOS3 polymorphisms and oxygen therapy with retinopathy of prematurity susceptibility

PubMed Central

Yu, Chunhong; Yi, Jinglin; Yin, Xiaolong; Deng, Yan; Liao, Yujun; Li, Xiaobing

2015-01-01

Aim: This study was aimed to detect the correlation of nitric oxide synthase 3 (NOS3) gene polymorphisms (T-786C and G894T) and retinopathy of prematurity (ROP) susceptibility. Interaction between NOS3 gene polymorphisms and the duration of oxygen therapy was also explored in ROP babies. Methods: Genotypes of NOS3 gene polymorphisms were genotyped by MassArray method. Hardy-Weinberg equilibrium (HWE) was used to calculate the representativeness of the cases and controls. Crossover analysis was utilized to explore the gene environment interactions. Relative risk of ROP was presented by odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs). Results: Among the subject features, oxygen therapy had obvious difference between case and control groups (P<0.05). There existed significant association between-786C allele and ROP susceptibility (P=0.049, OR=0.669, 95% CI=0.447-0.999). Genotypes of T-786C polymorphism and genotypes and alleles of G894T polymorphism did not related to the susceptibility of ROP. Interactions were existed between NOS3 gene polymorphisms and oxygen therapy duration. When the duration of oxygen therapy was less than 17 days, both -786CC genotype and 894GT genotype were correlated with ROP susceptibility (P=0.020, OR=0.115, 95% CI=0.014-0.960; P=0.011, OR=0.294, 95% CI=0.100-0.784). Conclusion: -786C allele might have a protective effect for ROP. Interactions of -786CC and 894GT genotype with oxygen therapy duration (less than 17 days) were both protection factors of ROP. PMID:26823875

Vaccine potential of antigen cocktails composed of recombinant Toxoplasma gondii TgPI-1, ROP2 and GRA4 proteins against chronic toxoplasmosis in C3H mice.

PubMed

Picchio, Mariano S; Sánchez, Vanesa R; Arcon, Nadia; Soto, Ariadna S; Perrone Sibilia, Matías; Aldirico, María de Los Angeles; Urrutia, Mariela; Moretta, Rosalía; Fenoy, Ignacio M; Goldman, Alejandra; Martin, Valentina

2018-02-01

The development of an effective and safe vaccine to prevent Toxoplasma gondii infection is an important aim due to the great clinical and economic impact of this parasitosis. We have previously demonstrated that immunization with the serine protease inhibitor-1 (TgPI-1) confers partial protection to C3H/HeN and C57BL/6 mice. In order to improve the level of protection, in this work, we combined this novel antigen with ROP2 and/or GRA4 recombinant proteins (rTgPI-1+rROP2, rTgPI-1+rGRA4, rTgPI-1+rROP2+rGRA4) to explore the best combination against chronic toxoplasmosis in C3H/HeN mice. All tested vaccine formulations, administered following a homologous prime-boost protocol that combines intradermal and intranasal routes, conferred partial protection as measured by the reduction of brain cyst burden following oral challenge with tissue cysts of Me49 T. gondii strain. The highest level of protection was achieved by the mixture of rTgPI-1 and rROP2 proteins with an average parasite burden reduction of 50% compared to the unvaccinated control group. The vaccine-induced protective effect was related to the elicitation of systemic cellular and humoral immune responses that included antigen-specific spleen cell proliferation, the release of Th1/Th2 cytokines, and the generation of antigen-specific antibodies in serum. Additionally, mucosal immune responses were also induced, characterized by secretion of antigen-specific IgA antibodies in intestinal lavages and specific mesenteric lymph node cell proliferation. Our results demonstrate that rTgPI-1+rROP2 antigens seem a promising mixture to be combined with other immunogenic proteins in a multiantigenic vaccine formulation against toxoplasmosis. Copyright © 2018 Elsevier Inc. All rights reserved.

Immuno-efficacy of DNA vaccines encoding PLP1 and ROP18 against experimental Toxoplasma gondii infection in mice.

PubMed

Chen, Yajun; Yu, Miao; Hemandez, J A; Li, Jiexi; Yuan, Zi-Guo; Yan, Haikuo

2018-05-01

We constructed a new plasmid pIRESneo/ROP18/PLP1 that was injected intramuscularly into Kunming mice to evaluate its immune efficacy. The immunized mice exhibited significantly increased serum IgG2a levels, lymphocyte counts and Th1-type cytokine (IL-2, IL-12 and IFN-γ) levels. Moreover, the immunized mice exhibited longer survival times (44.7 ± 2.1 days for ROP18/PLP1 and 47.2 ± 2.9 days for ROP18/PLP1 + IL-18) and lower brain cyst burden (68.9% for ROP18/PLP1 and 72.4% for ROP18/PLP1 + IL-18) than control mice after T. gondii challenge. Our results demonstrate that the multiple-gene DNA vaccine including both ROP18 and PLP1 elicits greater protection against T. gondii challenge and stronger immunogenicity than single-gene vaccines. Copyright © 2018 Elsevier Inc. All rights reserved.

29 CFR 1926.1002 - Protective frames (roll-over protective structures, known as ROPS) for wheel-type agricultural...

Code of Federal Regulations, 2012 CFR

2012-07-01

... produced by using a 4,410-lb (2,000-kg) weight acting as a pendulum. The impact face of the weight shall be... the center of gravity of the pendulum will swing, or more than one restraining cable shall give a... to the side on the same frame. The pendulum dropped from the height (see the definition of “H” in...

29 CFR 1926.1002 - Protective frames (roll-over protective structures, known as ROPS) for wheel-type agricultural...

Code of Federal Regulations, 2011 CFR

2011-07-01

... produced by using a 4,410-lb (2,000-kg) weight acting as a pendulum. The impact face of the weight shall be... the center of gravity of the pendulum will swing, or more than one restraining cable shall give a... to the side on the same frame. The pendulum dropped from the height (see the definition of “H” in...

29 CFR 1926.1002 - Protective frames (roll-over protective structures, known as ROPS) for wheel-type agricultural...

Code of Federal Regulations, 2010 CFR

2010-07-01

... produced by using a 4,410-lb (2,000-kg) weight acting as a pendulum. The impact face of the weight shall be... the center of gravity of the pendulum will swing, or more than one restraining cable shall give a... to the side on the same frame. The pendulum dropped from the height (see the definition of “H” in...

29 CFR 1926.1002 - Protective frames (roll-over protective structures, known as ROPS) for wheel-type agricultural...

Code of Federal Regulations, 2013 CFR

2013-07-01

... produced by using a 4,410-lb (2,000-kg) weight acting as a pendulum. The impact face of the weight shall be... the center of gravity of the pendulum will swing, or more than one restraining cable shall give a... to the side on the same frame. The pendulum dropped from the height (see the definition of “H” in...

29 CFR 1926.1002 - Protective frames (roll-over protective structures, known as ROPS) for wheel-type agricultural...

Code of Federal Regulations, 2014 CFR

2014-07-01

... produced by using a 4,410-lb (2,000-kg) weight acting as a pendulum. The impact face of the weight shall be... the center of gravity of the pendulum will swing, or more than one restraining cable shall give a... to the side on the same frame. The pendulum dropped from the height (see the definition of “H” in...

Integrating Cost-effective Rollover Protective Structure Installation in High School Agricultural Mechanics: A Feasibility Study.

PubMed

Mazur, Joan; Vincent, Stacy; Watson, Jennifer; Westneat, Susan

2015-01-01

This study with three Appalachian county agricultural education programs examined the feasibility, effectiveness, and impact of integrating a cost-effective rollover protective structure (CROPS) project into high school agricultural mechanics classes. The project aimed to (1) reduce the exposure to tractor overturn hazards in three rural counties through the installation of CROPS on seven tractors within the Cumberland Plateau in the east region; (2) increase awareness in the targeted rural communities of cost-effective ROPS designs developed by the National Institution for Occupational Safety and Health (NIOSH) to encourage ROPS installations that decrease the costs of a retrofit; (3) test the feasibility of integration of CROPS construction and installations procedures into the required agricultural mechanics classes in these agricultural education programs; and (4) explore barriers to the implementation of this project in high school agricultural education programs. Eighty-two rural students and three agricultural educators participated in assembly and installation instruction. Data included hazard exposure demographic data, knowledge and awareness of CROPS plans, and pre-post knowledge of construction and assessment of final CROPS installation. Findings demonstrated the feasibility and utility of a CROPS education program in a professionally supervised secondary educational setting. The project promoted farm safety and awareness of availability and interest in the NIOSH Cost-effective ROPS plans. Seven CROPS were constructed and installed. New curriculum and knowledge measures also resulted from the work. Lessons learned and recommendations for a phase 2 implementation and further research are included.

A histological and immunohistochemical study of the effects of N-acetyl cysteine on retinopathy of prematurity by modifying insulin-like growth factor-1.

PubMed

El-Hadidy, A R; El-Mohandes, E M; Asker, S A; Ghonaim, F M

2016-08-01

Retinopathy of prematurity (ROP) is a vasoproliferative disorder that occurs in premature infants and may lead to permanent visual impairment. We investigated both the possible protective role of N-acetyl cysteine (NAC) for preventing ROP and the role of IGF-1 in the disorder. Forty-five newborn rats were divided into three groups. Group 1 was raised in room air as controls. Group 2 was exposed to 60% oxygen for 14 days after birth, then transferred to room air. Group 3 was exposed to the same conditions as group 2, but received intraperitoneal injections of NAC on postnatal days 7-17. After 35 days, both eyes of all rats were processed for histology. Some sections were stained with hematoxylin and eosin to assess structural changes and other sections were immunostained to determine the location of IGF-1. Frozen sections also were prepared and stained for adenosine triphosphatase to detect retinal blood vessels. Compared to the controls, more blood vessels, many of which were abnormal, and increased IGF-1 expression were observed in group 2. In group 3, abnormal blood vessels and IGF-1 expression were less evident. NAC appeared to be an effective vascular-protective agent for ROP by decreasing IGF-1 expression.

Human milk feeding protects very low-birth-weight infants from retinopathy of prematurity: a pre-post cohort analysis.

PubMed

Ginovart, Gemma; Gich, Ignasi; Verd, Sergio

2016-12-01

To examine the effect of early human milk (HM) feeding on the incidence of retinopathy of prematurity (ROP) among very low-birth-weight (VLBW) infants. Observational cohort research in a Level III neonatal intensive care unit. A total of 186 infants were enrolled in this pre-post cohort study (114 infants were included in the HM-fed group and 72 in the formula-fed group). ROP, type of feeding (early exclusive HM versus any formula), and potential confounding variables were measured. Differences between groups were explored. The clinical characteristics of the neonates did not differ between the two groups. By bivariate analysis, HM feeding was associated with 75% lower odds of Stage 2 or 3 ROP (OR = 0.25, 95% CI: 0.091 to 0.705; p = 0.009) At multivariate logistic regression, type of milk feeding retained significance, exclusive HM being protective with p = 0.002. This study found an association between early exposure to formula in VLBW infants and ROP. An initial HM diet, devoid of cow milk-containing products before achieving full enteral feeding, may help prevent ROP.

Anthropometric Procedures for Protective Equipment Sizing and Design

PubMed Central

Hsiao, Hongwei

2015-01-01

Objectives This article presented four anthropometric theories (univariate, bivariate/probability distribution, multivariate, and shape-based methods) for protective equipment design decisions. Background While the significance of anthropometric information for product design is well recognized, designers continue to face challenges in selecting efficient anthropometric data processing methods and translating the acquired information into effective product designs. Methods For this study, 100 farm tractor operators, 3,718 respirator users, 951 firefighters, and 816 civilian workers participated in four studies on the design of tractor roll-over protective structures (ROPS), respirator test panels, fire truck cabs, and fall-arrest harnesses, respectively. Their anthropometry and participant-equipment interfaces were evaluated. Results Study 1 showed a need to extend the 90-cm vertical clearance for tractor ROPS in the current industrial standards to 98.3 to 101.3 cm. Study 2 indicated that current respirator test panel would have excluded 10% of the male firefighter population; a systematic adjustment to the boundaries of test panel cells was suggested. Study 3 provided 24 principal component analysis-based firefighter body models to facilitate fire truck cab design. Study 4 developed an improved gender-based fall-arrest harness sizing scheme to supplant the current unisex system. Conclusions This article presented four anthropometric approaches and a six-step design paradigm for ROPS, respirator test panel, fire truck cab, and fall-arrest harness applications, which demonstrated anthropometric theories and practices for defining protective equipment fit and sizing schemes. Applications The study provided a basis for equipment designers, standards writers, and industry manufacturers to advance anthropometric applications for product design and improve product efficacy. PMID:23516791

30 CFR 77.403-1 - Mobile equipment; rollover protective structures (ROPS).

Code of Federal Regulations, 2010 CFR

2010-07-01

... WORK AREAS OF UNDERGROUND COAL MINES Safeguards for Mechanical Equipment § 77.403-1 Mobile equipment... surface coal mines or the surface work areas of underground coal mines shall be provided with rollover... complying with paragraph (d) (1) (iii) (A) of this section. Stresses shall not exceed the ultimate strength...

30 CFR 77.403-1 - Mobile equipment; rollover protective structures (ROPS).

Code of Federal Regulations, 2011 CFR

2011-07-01

... WORK AREAS OF UNDERGROUND COAL MINES Safeguards for Mechanical Equipment § 77.403-1 Mobile equipment... surface coal mines or the surface work areas of underground coal mines shall be provided with rollover... complying with paragraph (d) (1) (iii) (A) of this section. Stresses shall not exceed the ultimate strength...

Release of GTP Exchange Factor Mediated Down-Regulation of Abscisic Acid Signal Transduction through ABA-Induced Rapid Degradation of RopGEFs

PubMed Central

Waadt, Rainer; Schroeder, Julian I.

2016-01-01

The phytohormone abscisic acid (ABA) is critical to plant development and stress responses. Abiotic stress triggers an ABA signal transduction cascade, which is comprised of the core components PYL/RCAR ABA receptors, PP2C-type protein phosphatases, and protein kinases. Small GTPases of the ROP/RAC family act as negative regulators of ABA signal transduction. However, the mechanisms by which ABA controls the behavior of ROP/RACs have remained unclear. Here, we show that an Arabidopsis guanine nucleotide exchange factor protein RopGEF1 is rapidly sequestered to intracellular particles in response to ABA. GFP-RopGEF1 is sequestered via the endosome-prevacuolar compartment pathway and is degraded. RopGEF1 directly interacts with several clade A PP2C protein phosphatases, including ABI1. Interestingly, RopGEF1 undergoes constitutive degradation in pp2c quadruple abi1/abi2/hab1/pp2ca mutant plants, revealing that active PP2C protein phosphatases protect and stabilize RopGEF1 from ABA-mediated degradation. Interestingly, ABA-mediated degradation of RopGEF1 also plays an important role in ABA-mediated inhibition of lateral root growth. The presented findings point to a PP2C-RopGEF-ROP/RAC control loop model that is proposed to aid in shutting off ABA signal transduction, to counteract leaky ABA signal transduction caused by “monomeric” PYL/RCAR ABA receptors in the absence of stress, and facilitate signaling in response to ABA. PMID:27192441

The influence of early postnatal nutrition on retinopathy of prematurity in extremely low birth weight infants.

PubMed

Porcelli, Peter J; Weaver, R Grey

2010-06-01

Retinopathy of prematurity(ROP) is the most common serious ophthalmic disease in preterm infants. Human milk may provide a protective effect for ROP; however, beneficial effects of human milk preclude randomized trials. Therefore, we conducted a retrospective analysis comparing early postnatal nutrition with ROP development. Evaluate relationship between early postnatal nutriture and ROP surgery. Nutrition data was collected for inborn AGA infants, BW 700-1000 g. ROP surgery was the primary outcome variable. A single pediatric ophthalmologist supervised examinations. All infants received triweekly IM vitamin A as chronic lung disease prophylaxis (Tyson: NEJM, 1999). BW and gestational age were 867+/-85 g and 26.3+/-1.2 weeks (n=77, mean+/-1SD). ROP surgery infants(n=11) received more parenteral nutrition, 1648 mL, and less human milk, 13.8 mL/kg-day, and vitamin E, 1.4 mg/kg-day, during the second postnatal week. Human milk was a negative predictor for ROP surgery, odds ratio=0.94. Both groups met vitamin A recommendations; however, 74% was administered via IM injections. Neither group met vitamin E recommendations. Human milk feeding, parenteral nutrition volume and vitamin E intake were predictors for ROP surgery. IM vitamin A injections provided the majority of vitamin A; vitamin E administration was insufficient. Improving human milk feeding rates and vitamin dosing options may affect ROP surgery rates. Copyright 2010 Elsevier Ltd. All rights reserved.

Foveal fine structure in retinopathy of prematurity: an adaptive optics Fourier domain optical coherence tomography study.

PubMed

Hammer, Daniel X; Iftimia, Nicusor V; Ferguson, R Daniel; Bigelow, Chad E; Ustun, Teoman E; Barnaby, Amber M; Fulton, Anne B

2008-05-01

To describe the fine structure of the fovea in subjects with a history of mild retinopathy of prematurity (ROP) using adaptive optics-Fourier domain optical coherence tomography (AO-FDOCT). High-speed, high-resolution AO-FDOCT videos were recorded in subjects with a history of ROP (n = 5; age range, 14-26 years) and in control subjects (n = 5; age range, 18-25 years). Custom software was used to extract foveal pit depth and volume from three-dimensional (3-D) retinal maps. The thickness of retinal layers as a function of retinal eccentricity was measured manually. The retinal vasculature in the parafoveal region was assessed. The foveal pit was wider and shallower in ROP than in control subjects. Mean pit depth, defined from the base to the level at which the pit reaches a lateral radius of 728 microm, was 121 microm compared with 53 microm. Intact, contiguous inner retinal layers overlay the fovea in ROP subjects but were absent in the control subjects. Mean full retinal thickness at the fovea was greater in the subjects with ROP (279.0 microm vs. 190.2 microm). The photoreceptor layer thickness did not differ between ROP and control subjects. An avascular zone was not identified in the subjects with ROP but was present in all the control subjects. The foveas of subjects with a history of mild ROP have significant structural abnormalities that are probably a consequence of perturbations of neurovascular development.

A vaccine formulation combining rhoptry proteins NcROP40 and NcROP2 improves pup survival in a pregnant mouse model of neosporosis.

PubMed

Pastor-Fernández, Iván; Arranz-Solís, David; Regidor-Cerrillo, Javier; Álvarez-García, Gema; Hemphill, Andrew; García-Culebras, Alicia; Cuevas-Martín, Carmen; Ortega-Mora, Luis M

2015-01-30

Currently there are no effective vaccines for the control of bovine neosporosis. During the last years several subunit vaccines based on immunodominant antigens and other proteins involved in adhesion, invasion and intracellular proliferation of Neospora caninum have been evaluated as targets for vaccine development in experimental mouse infection models. Among them, the rhoptry antigen NcROP2 and the immunodominant NcGRA7 protein have been assessed with varying results. Recent studies have shown that another rhoptry component, NcROP40, and NcNTPase, a putative dense granule antigen, exhibit higher expression levels in tachyzoites of virulent N. caninum isolates, suggesting that these could be potential vaccine candidates to limit the effects of infection. In the present work, the safety and efficacy of these recombinant antigens formulated in Quil-A adjuvant as monovalent vaccines or pair-wise combinations (rNcROP40+rNcROP2 and rNcGRA7+rNcNTPase) were evaluated in a pregnant mouse model of neosporosis. All the vaccine formulations elicited a specific immune response against their respective native proteins after immunization. Mice vaccinated with rNcROP40 and rNcROP2 alone or in combination produced the highest levels of IFN-γ and exhibited low parasite burdens and low IgG antibody levels after the challenge. In addition, most of the vaccine formulations were able to increase the median survival time in the offspring. However, pup survival only ensued in the groups vaccinated with rNcROP40+rNcROP2 (16.2%) and rNcROP2 (6.3%). Interestingly, vertical transmission was not observed in those survivor pups immunized with rNcROP40+rNcROP2, as shown by PCR analyses. These results show a partial protection against N. caninum infection after vaccination with rNcROP40+rNcROP2, suggesting a synergistic effect of the two recombinant rhoptry antigens. Copyright © 2014 Elsevier B.V. All rights reserved.

29 CFR 1928.51 - Roll-over protective structures (ROPS) for tractors used in agricultural operations.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., designed to furnish the power to pull, carry, propel, or drive implements that are designed for agriculture... point of the hood does not exceed 60 inches, and (4) The tractor is designed so that the operator.... The seat mounting shall be capable of withstanding this load plus a load equal to four times the...

29 CFR 1928.51 - Roll-over protective structures (ROPS) for tractors used in agricultural operations.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., designed to furnish the power to pull, carry, propel, or drive implements that are designed for agriculture... point of the hood does not exceed 60 inches, and (4) The tractor is designed so that the operator.... The seat mounting shall be capable of withstanding this load plus a load equal to four times the...

29 CFR 1928.51 - Roll-over protective structures (ROPS) for tractors used in agricultural operations.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., designed to furnish the power to pull, carry, propel, or drive implements that are designed for agriculture... point of the hood does not exceed 60 inches, and (4) The tractor is designed so that the operator.... The seat mounting shall be capable of withstanding this load plus a load equal to four times the...

29 CFR 1928.51 - Roll-over protective structures (ROPS) for tractors used in agricultural operations.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., designed to furnish the power to pull, carry, propel, or drive implements that are designed for agriculture... point of the hood does not exceed 60 inches, and (4) The tractor is designed so that the operator.... The seat mounting shall be capable of withstanding this load plus a load equal to four times the...

Incidence of retinopathy of prematurity in the United States: 1997 through 2005.

PubMed

Lad, Eleonora M; Hernandez-Boussard, Tina; Morton, John M; Moshfeghi, Darius M

2009-09-01

To determine the incidence of retinopathy of prematurity (ROP) based on a national database and to identify baseline characteristics, demographic information, comorbidities, and surgical interventions. Retrospective study based on the National Inpatient Sample from 1997 through 2005. The National Inpatient Sample was queried for all newborn infants with and without ROP. Multivariate logistic regression was used to predict risk factors for ROP. Thirty-four million live births were recorded during the study period. The total ROP incidence was 0.17% overall and 15.58% for premature infants with length of stay of more than 28 days. Our results conclusively demonstrated the importance of low birth weight as a risk for ROP development in infants with length of stay of more than 28 days, as well as association with respiratory conditions, fetal hemorrhage, intraventricular hemorrhage, and blood transfer. An interesting finding was the protective effect conferred by hypoxia, necrotizing enterocolitis, and hemolytic disease of the newborn. Infants with ROP had a higher incidence of undergoing laser photocoagulation therapy, pars plana vitrectomy, and scleral buckle surgery. The current study represents a large, retrospective analysis of newborns with ROP. The multivariate analysis emphasizes the role of birth weight in extended-stay infants, as well as respiratory conditions, fetal hemorrhage, intraventricular hemorrhage, and blood transfer.

Bioinformatics analysis of ROP8 protein to improve vaccine design against Toxoplasma gondii.

PubMed

Foroutan, Masoud; Ghaffarifar, Fatemeh; Sharifi, Zohreh; Dalimi, Abdolhosein; Pirestani, Majid

2018-04-26

Rhoptry proteins (ROPs) are involved in the different stages of Toxoplasma gondii (T. gondii) invasion and are also critical for survival within host cells. ROP8 is expressed in the early stages of infection and have a key role in the parasitophorous vacuole (PV) formation. In this paper, we have combined several bioinformatics online servers for immunogenicity prediction of ROP8 protein. In this study, several bioinformatics approaches were used to analyze the different aspects of ROP8 protein, including the physico-chemical properties, transmembrane domain, subcellular localization, secondary and tertiary structure, B and T-cell potential epitopes, and other important characteristics of this protein. The findings showed that ROP8 protein had 60 potential post-translational modification sites. Also, only one transmembrane domain was recognized for this protein. The secondary structure of ROP8 protein comprises 33.04% alpha-helix, 18.26% extended strand, and 48.70% random coil. Moreover, several potential B and T-cell epitopes were identified for ROP8. In addition, the obtained findings from antigenicity and allergenicity evaluation remarked that this protein is immunogenic and non-allergen. Based on the results of Ramachandran plot, 94.8%, 4.1%, and 1.1% of amino acid residues were incorporated in the favored, allowed, and outlier regions, respectively. This paper provides a foundation for further investigations, and laid a theoretical basis for the development of an appropriate vaccine against toxoplasmosis. More studies are needed experimentally using the ROP8 alone or in combination with other antigens in the future. Copyright © 2018 Elsevier B.V. All rights reserved.

Visual acuity at 10 years in Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) study eyes: effect of retinal residua of retinopathy of prematurity.

PubMed

Dobson, Velma; Quinn, Graham E; Summers, C Gail; Hardy, Robert J; Tung, Betty

2006-02-01

To describe recognition (letter) acuity at age 10 years in eyes with and without retinal residua of retinopathy of prematurity (ROP). Presence and severity of ROP residua were documented by a study ophthalmologist. Masked testers measured monocular recognition visual acuity (Early Treatment of Diabetic Retinopathy Study) when the children were 10 years old. Two hundred forty-seven of 255 surviving Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) randomized trial patients participated. A reference group of 102 of 104 Philadelphia-based CRYO-ROP study participants who did not develop ROP was also tested. More severe retinal residua were associated with worse visual acuity, regardless of whether retinal ablation was performed to treat the severe acute-phase ROP. However, within each ROP residua category, there was a wide range of visual acuity results. This is the first report of the relation between visual acuity (Early Treatment of Diabetic Retinopathy Study charts) and structural abnormalities related to ROP in a large group of eyes that developed threshold ROP in the perinatal period. Visual deficits are greater in eyes with more severe retinal residua than in eyes with mild or no residua. However, severity of ROP residua does not predict the visual acuity of an individual eye because within a single residua category, acuity may range from near normal to blind.

Retinopathy of prematurity and brain damage in the very preterm newborn.

PubMed

Allred, Elizabeth N; Capone, Antonio; Fraioli, Anthony; Dammann, Olaf; Droste, Patrick; Duker, Jay; Gise, Robert; Kuban, Karl; Leviton, Alan; O'Shea, T Michael; Paneth, Nigel; Petersen, Robert; Trese, Michael; Stoessel, Kathleen; Vanderveen, Deborah; Wallace, David K; Weaver, Grey

2014-06-01

To explain why very preterm newborns who develop retinopathy of prematurity (ROP) appear to be at increased risk of abnormalities of both brain structure and function. A total of 1,085 children born at <28 weeks' gestation had clinically indicated retinal examinations and had a developmental assessment at 2 years corrected age. Relationships between ROP categories and brain abnormalities were explored using logistic regression models with adjustment for potential confounders. The 173 children who had severe ROP, defined as prethreshold ROP (n = 146) or worse (n = 27) were somewhat more likely than their peers without ROP to have brain ultrasound lesions or cerebral palsy. They were approximately twice as likely to have very low Bayley Scales scores. After adjusting for risk factors common to both ROP and brain disorders, infants who developed severe ROP were at increased risk of low Bayley Scales only. Among children with prethreshold ROP, exposure to anesthesia was not associated with low Bayley Scales. Some but not all of the association of ROP with brain disorders can be explained by common risk factors. Most of the increased risks of very low Bayley Scales associated with ROP are probably not a consequence of exposure to anesthetic agents. Copyright © 2014 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.

Involving fathers in teaching youth about farm tractor seatbelt safety--a randomized control study.

PubMed

Jinnah, Hamida Amirali; Stoneman, Zolinda; Rains, Glen

2014-03-01

Farm youth continue to experience high rates of injury and deaths as a result of agricultural activities. Farm machinery, especially tractors, is the most common cause of casualties to youth. A Roll-Over Protection Structure (ROPS) along with a fastened seatbelt can prevent almost all injuries and fatalities from tractor overturns. Despite this knowledge, the use of seatbelts by farmers on ROPS tractors remains low. This study treats farm safety as a family issue and builds on the central role of parents as teachers and role models of farm safety for youth. This research study used a longitudinal, repeated-measures, randomized-control design in which youth 10-19 years of age were randomly assigned to either of two intervention groups (parent-led group and staff-led group) or the control group. Fathers in the parent-led group were less likely to operate ROPS tractors without a seatbelt compared with other groups. They were more likely to have communicated with youth about the importance of wearing seatbelts on ROPS tractors. Consequently, youth in the parent-led group were less likely to operate a ROPS tractor without a seatbelt than the control group at post-test. This randomized control trial supports the effectiveness of a home-based, father-led farm safety intervention as a promising strategy for reducing youth as well as father-unsafe behaviors (related to tractor seatbelts) on the farm. This intervention appealed to fathers' strong motivation to practice tractor safety for the sake of their youth. Involving fathers helped change both father as well as youth unsafe tractor-seatbelt behaviors. Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Protective efficacy of a Toxoplasma gondii rhoptry protein 13 plasmid DNA vaccine in mice.

PubMed

Wang, Pei-Yuan; Yuan, Zi-Guo; Petersen, Eskild; Li, Jie; Zhang, Xiu-Xiang; Li, Xiu-Zhen; Li, Hao-Xin; Lv, Zhi-Cheng; Cheng, Tian; Ren, Di; Yang, Gui-Lian; Lin, Rui-Qing; Zhu, Xing-Quan

2012-12-01

Toxoplasma gondii is an obligate intracellular parasite infecting humans and other warm-blooded animals, resulting in serious public health problems and economic losses worldwide. Rhoptries are involved in T. gondii invasion and host cell interaction and have been implicated as important virulence factors. In the present study, a DNA vaccine expressing rhoptry protein 13 (ROP13) of T. gondii inserted into eukaryotic expression vector pVAX I was constructed, and the immune protection it induced in Kunming mice was evaluated. Kunming mice were immunized intramuscularly with pVAX-ROP13 and/or with interleukin-18 (IL-18). Then, we evaluated the immune response using a lymphoproliferative assay, cytokine and antibody measurements, and the survival times of mice challenged with the virulent T. gondii RH strain (type I) and the cyst-forming PRU strain (type II). The results showed that pVAX-ROP13 alone or with pVAX/IL-18 induced a high level of specific anti-T. gondii antibodies and specific lymphocyte proliferative responses. Coinjection of pVAX/IL-18 significantly increased the production of gamma interferon (IFN-γ), IL-2, IL-4, and IL-10. Further, challenge experiments showed that coimmunization of pVAX-ROP13 with pVAX/IL-18 significantly (P < 0.05) increased survival time (32.3 ± 2.7 days) compared with pVAX-ROP13 alone (24.9 ± 2.3 days). Immunized mice challenged with T. gondii cysts (strain PRU) had a significant reduction in the number of brain cysts, suggesting that ROP13 could trigger a strong humoral and cellular response against T. gondii cyst infection and that it is a potential vaccine candidate against toxoplasmosis, which provided the foundation for further development of effective vaccines against T. gondii.

Role of Retinopathy of Prematurity (ROP) Tertiary Centers of Excellence in Capacity-building.

PubMed

Rani, Padmaja Kumari; Balakrishnanan, D; Padhi, T R; Jalali, Subhadra

2016-11-07

Tertiary Centres of Excellence in India have been at the forefront of the efforts against Retinopathy of Prematurity (ROP) - associated blindness. The epidemic of blindness from ROP; however, has now spread rapidly into large parts of interiors of developing countries due to improved newborn care facilities. Due to their knowledge and experience of more than a decade, these centres of excellence, both from child care and Ophthalmology care, now need to come forward in substantial measures and need to be supported by funds and programs so that concerns of neonatal eye-health, training, screening, prevention and treatment can get integrated and embedded into newborn critical care and health programs. This will protect newborn preterm survivors from losing the potentially good vision that they are born with, reduce the rapidly rising blindness epidemic, and also protect staff from potential high-value litigations.

Practice Patterns in Retinopathy of Prematurity Treatment for Disease Milder than Recommended by Guidelines

PubMed Central

Gupta, Mrinali Patel; Chan, RV. Paul; Anzures, Rachelle; Ostmo, Susan; Jonas, Karyn; Chiang, Michael F.

2015-01-01

Purpose To characterize the frequency of and clinical indications for which experts treat retinopathy of prematurity (ROP) milder than Type 1 disease, the recommended threshold for treatment from established consensus guidelines. Design Descriptive analysis Methods Setting: Multicenter. Study Population: A database of 1444 eyes generated prospectively from all babies screened for ROP at one of 6 major ROP centers whose parents provided informed consent. Intervention: Retrospective review of the database and charts to identify all patients treated for ROP milder than Type 1. Main Outcome Measure: Indication(s) for treatment. Results 137 eyes of 70 infants were treated for ROP. Of these 137 eyes, 13 (9.5%) were treated despite a clinical diagnosis milder than Type 1 ROP. Indications for treatment included: active ROP with the fellow eye being treated for Type 1 ROP (2 eyes, 15.4%); concerning structural changes (9 eyes, 69.2%), including tangential traction with temporal vessel straightening concerning for macular dragging (8 eyes, 61.5%) and thick stage 3 membranes with anteroposterior traction concerning for progression to stage 4 ROP (3 eyes, 23.1%); persistent ROP at an advanced postmenstrual age (4 eyes, 30.8%); and/or vitreous hemorrhage (3 eyes, 23.1%). Conclusion Experts in this study occasionally recommended treatment in eyes with disease less than Type 1 ROP. This study has important clinical implications and highlights the role of individual clinical judgment in situations not covered by evidence-based treatment guidelines. PMID:26705094

Mononuclear salen-gallium complexes for iso-selective ring-opening polymerization (ROP) of rac-lactide.

PubMed

Specklin, David; Fliedel, Christophe; Hild, Frédéric; Mameri, Samir; Karmazin, Lydia; Bailly, Corinne; Dagorne, Samuel

2017-10-03

A series of mononuclear salen-supported gallium amido/alkoxide derivatives were prepared and structurally characterized and subsequently used as initiators in rac-lactide ring-opening polymerisation (ROP). The reaction of variously substituted salen ligands (1a-1f) with 0.5 equiv. of Ga 2 (NMe 2 ) 6 allowed the isolation of the corresponding (salen)Ga-NMe 2 chelates (2b-2d, 2f) via an amine elimination route, as poorly soluble compounds in common solvents. The (salen)Ga-OBn derivatives (3a-3e) may be readily accessed by an amine-elimination/alcoholysis sequence and the molecular structures of 3a, 3d and 3e were confirmed through X-ray crystallography diffraction analysis. The present (salen)Ga-X species may effectively mediate the iso-selective ROP of rac-LA in a controlled manner (P m up to 0.77 using a 1/1 2f/BnOH mixture as ROP initiator), with a ROP activity greatly dependent upon steric hindrance and geometrical constraints imposed by the variously substituted salen ligands. Based on the present study, salen ligands with limited steric hindrance and a certain degree of flexibility appear best suited for iso-selective ROP by (salen)Ga chelates. The salen-gallium complex 3a is also effective for the controlled ROP of ε-caprolactone (CL) and the production of PCL-b-PLA copolymers.

Rho proteins of plants--functional cycle and regulation of cytoskeletal dynamics.

PubMed

Mucha, Elena; Fricke, Inka; Schaefer, Antje; Wittinghofer, Alfred; Berken, Antje

2011-11-01

Rho-related ROP proteins are molecular switches that essentially regulate a wide variety of processes. Of central interest is their influence on the plant cytoskeleton by which they affect vital processes like cell division, growth, morphogenesis, and pathogen defense. ROPs switch between GTP- and GDP-bound conformations by strictly regulated nucleotide exchange and GTP-hydrolysis, and only the active GTP-form interacts with downstream effectors to ultimately provoke a biological response. However, the mode of action of the engaged regulators and effectors as well as their upstream and downstream interaction partners have long been largely unknown. As opposed to analogous systems in animals and fungi, plants use specific GTPase activating proteins (RopGAPs) with a unique domain composition and novel guanine nucleotide exchange factors (RopGEFs) with a probable link to cell surface receptors. Moreover, plants comprise novel effector molecules and adapters connecting ROPs to mostly unknown downstream targets on the route to the cytoskeleton. This review aims to summarize recent knowledge on the molecular mechanisms and reaction cascades involved in ROP dependent cytoskeletal rearrangements, addressing the structure and function of the unusual RopGAPs, RopGEFs and effectors, and the upstream and downstream pathways linking ROPs to cell receptor-like kinases, actin filaments, and microtubules. Copyright © 2010 Elsevier GmbH. All rights reserved.

Retinopathy of Prematurity: Therapeutic Strategies Based on Pathophysiology.

PubMed

Cayabyab, Rowena; Ramanathan, Rangasamy

2016-01-01

Retinopathy of prematurity (ROP) continues to be a major preventable cause of blindness and visual handicaps globally. With improved perinatal care, improved survival of moderately preterm infants, and limited resources for oxygen delivery and monitoring, more mature preterm infants are developing severe ROP in developing countries. The pathophysiology of ROP is characterized by two phases. Phase I ROP is due to vaso-obliteration beginning immediately after birth secondary to a marked decrease in vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1). Phase II begins around 33 weeks' postmenstrual age (PMA). During this phase, VEGF levels increase, especially if there is retinal hypoxia with increasing retinal metabolism and demand for oxygen leading to abnormal vasoproliferation. Since the original description of ROP in 1942 by Terry et al. [Am J Ophthalmol 1942;25:203-204], four epidemics of ROP have been observed. Prevention or early treatment of ROP involves careful titration of oxygen saturation by pulse oximeter (SpO2). Optimal SpO2 target remains elusive. Most of the large trials have focused on either a low SpO2 (85-89%) or a high SpO2 (91-95%) from the first day of birth to 36 weeks' PMA. Although the incidence of severe ROP and bronchopulmonary dysplasia decreased significantly, predischarge mortality was higher in these studies. Use of graded SpO2 during the 2 different phases of ROP (early, low SpO2 during phase I vs. late, high SpO2 during phase II) may be the best approach to prevent this disabling condition. Further trials should focus on this strategy. Other biological agents that are currently being studied include IGF-1 with IGF-binding protein-3 (rhIGF-1 + rhIGFBP-3) and propranolol. For advanced stages of ROP, laser ablation of avascular retina, early treatment of ROP (ETROP) protocol, intravitreal injection of anti-VEGF antibodies (e.g. bevacizumab) and vitrectomy are used to protect central vision and prevent retinal detachment. Long-term complications such as refractory errors, recurrence of ROP and risk of retinal detachment require continued follow-up with an ophthalmologist through adolescence and beyond. Optimal nutrition including adequate intake of omega-3 polyunsaturated fatty acids and decreasing infection/inflammation to promote normal vascularization are important strategies. Screening guidelines for ROP based on local incidence of ROP in different regions of the world are very important. Oxygen therapy is clearly a modifiable risk factor to decrease ROP that needs further study. Understanding the two phases of ROP will help to identify appropriate therapeutic strategies and improve visual outcomes in many preterm infants globally. © 2016 S. Karger AG, Basel.

Trisomy 21 and Risk of Retinopathy of Prematurity.

PubMed

Movsas, Tammy Z; Spitzer, Alan R; Gewolb, Ira H

2015-08-01

Trisomy 21 is known to decrease the risk of several (nonocular) angiogenic-mediated diseases. The objective of this study was to determine whether trisomy 21 can also be shown to be significantly protective against ocular angiogenic-mediated disorders such as retinopathy of prematurity (ROP). A retrospective analysis of deidentified data from the Pediatrix BabySteps Clinical Warehouse. This large repository of neonatal data is approved for use in research studies by the Western Institutional Review Board. The study population consisted of 99,080 infants with very low birth weights (BWs; BW <1500 g), born between 1996 and 2013, cared for at >300 US NICUs, and who had been discharged alive from hospital. Statistical significance for unadjusted comparisons between groups was determined with Pearson's χ(2) test or Student's t test. Logistic regression models were used to calculate the odds of ROP (of any stage) and advanced ROP (stage 3 or greater) for infants with trisomy 21 compared with all other infants. The prevalence of trisomy 21 was 0.3% in the study population (321 of 99,080). After adjustment for BW, gestational age, oxygen exposure, and other potential confounders, there was an odds ratio of 0.6 (95% confidence interval: 0.5-0.8) for ROP in infants with trisomy 21compared with other infants and an odds ratio of 0.4 (95% confidence interval: 0.1-0.9) for advanced-stage ROP. Trisomy 21 significantly decreases the odds for ROP in very low BW infant survivors. This study unmasks a potentially identifiable genetic component to ROP risk, paving the way for the development of a laboratory-based ROP screening tool. Copyright © 2015 by the American Academy of Pediatrics.

Comparative systems pharmacology of HIF stabilization in the prevention of retinopathy of prematurity

PubMed Central

Hoppe, George; Yoon, Suzy; Gopalan, Banu; Savage, Alexandria R.; Brown, Rebecca; Case, Kelsey; Vasanji, Amit; Chan, E. Ricky; Silver, Randi B.; Sears, Jonathan E.

2016-01-01

Retinopathy of prematurity (ROP) causes 100,000 new cases of childhood blindness each year. ROP is initiated by oxygen supplementation necessary to prevent neonatal death. We used organ systems pharmacology to define the transcriptomes of mice that were cured of oxygen-induced retinopathy (OIR, ROP model) by hypoxia-inducible factor (HIF) stabilization via HIF prolyl hydroxylase inhibition using the isoquinolone Roxadustat or the 2-oxoglutarate analog dimethyloxalylglycine (DMOG). Although both molecules conferred a protective phenotype, gene expression analysis by RNA sequencing found that Roxadustat can prevent OIR by two pathways: direct retinal HIF stabilization and induction of aerobic glycolysis or indirect hepatic HIF-1 stabilization and increased serum angiokines. As predicted by pathway analysis, Roxadustat rescued the hepatic HIF-1 knockout mouse from retinal oxygen toxicity, whereas DMOG could not. The simplicity of systemic treatment that targets both the liver and the eye provides a rationale for protecting the severely premature infant from oxygen toxicity. PMID:27091985

Investigating the effects of PDC cutters geometry on ROP using the Taguchi technique

NASA Astrophysics Data System (ADS)

Jamaludin, A. A.; Mehat, N. M.; Kamaruddin, S.

2017-10-01

At times, the polycrystalline diamond compact (PDC) bit’s performance dropped and affects the rate of penetration (ROP). The objective of this project is to investigate the effect of PDC cutter geometry and optimize them. An intensive study in cutter geometry would further enhance the ROP performance. The relatively extended analysis was carried out and four significant geometry factors have been identified that directly improved the ROP. Cutter size, back rake angle, side rake angle and chamfer angle are the stated geometry factors. An appropriate optimization technique that effectively controls all influential geometry factors during cutters manufacturing is introduced and adopted in this project. By adopting L9 Taguchi OA, simulation experiment is conducted by using explicit dynamics finite element analysis. Through a structure Taguchi analysis, ANOVA confirms that the most significant geometry to improve ROP is cutter size (99.16% percentage contribution). The optimized cutter is expected to drill with high ROP that can reduce the rig time, which in its turn, may reduce the total drilling cost.

Impact of regulated secretion on anti-parasitic CD8 T cell responses

PubMed Central

Grover, Harshita Satija; Chu, H. Hamlet; Kelly, Felice D.; Yang, Soo Jung; Reese, Michael L.; Blanchard, Nicolas; Gonzalez, Federico; Chan, Shiao Wei; Boothroyd, John C.; Shastri, Nilabh; Robey, Ellen A.

2014-01-01

Summary CD8 T cells play a key role in defense against the intracellular parasite Toxoplasma but why certain CD8 responses are more potent than others is not well understood. Here, we describe a parasite antigen ROP5 that elicits a modest CD8 T cell response in genetically susceptible mice. ROP5 is secreted via parasite organelles termed rhoptries that are injected directly into host cells during invasion, whereas the protective, dense granule antigen, GRA6, is constitutively secreted into the parasitophorous vacuole. Transgenic parasites in which the ROP5 antigenic epitope was targeted for secretion through dense granules led to enhanced CD8 T cell responses, whereas targeting the GRA6 epitope to rhoptries led to reduced CD8 responses. CD8 T cell responses to the dense granule-targeted ROP5 epitope resulted in reduced parasite load in the brain. These data suggest that the mode of secretion impacts the efficacy of parasite-specific CD8 T cell responses. PMID:24857659

Mechanistic Studies of ε-Caprolactone Polymerization by (salen)AlOR Complexes and a Predictive Model for Cyclic Ester Polymerizations

PubMed Central

2016-01-01

Aluminum alkoxide complexes (2) of salen ligands with a three-carbon linker and para substituents having variable electron-withdrawing capabilities (X = NO2, Br, OMe) were prepared, and the kinetics of their ring-opening polymerization (ROP) of ε-caprolactone (CL) were investigated as a function of temperature, with the aim of drawing comparisons to similar systems with two-carbon linkers investigated previously (1). While 1 and 2 exhibit saturation kinetics and similar dependences of their ROP rates on substituents X (invariant Keq, similar Hammett ρ = +1.4(1) and 1.2(1) for k2, respectively), ROP by 2 was significantly faster than for 1. Theoretical calculations confirm that, while the reactant structures differ, the transition state geometries are quite similar, and by analyzing the energetics of the involved distortions accompanying the structural changes, a significant contribution to the basis for the rate differences was identified. Using this knowledge, a simplified computational method for evaluating ligand structural influences on cyclic ester ROP rates is proposed that may have utility for future catalyst design. PMID:26900488

Investigation of Variations in the Human Urine Metabolome Amongst European Populations. An Exploratory Search for Biomarkers of People at Risk-of-Poverty.

PubMed

Trimigno, Alessia; Khakimov, Bekzod; Savorani, Francesco; Tenori, Leonardo; Hendrixson, Vaiva; Čivilis, Alminas; Glibetic, Marija; Gurinovic, Mirjana; Pentikäinen, Saara; Sallinen, Janne; Garduno Diaz, Sara; Pasqui, Francesca; Khokhar, Santosh; Luchinat, Claudio; Bordoni, Alessandra; Capozzi, Francesco; Balling Engelsen, Søren

2018-05-14

According to Eurostat 2016, approximately 119 million European citizens live at-risk-of-poverty (ROP). This subpopulation is highly diverse by ethnicity, age and culture in the different EU states, but they all have in common a low income, that could represent an increased risk of nutrients deficiencies due to poor nutritional habits. This study aims to investigate the human urine metabolome in the search of common biomarkers representing dietary deficiencies amongst European populations at ROP. 2732 urine samples were collected from 1391 subjects across five different European countries including the United Kingdom, Finland, Italy, Lithuania and Serbia, and analysed using 1 H-NMR spectroscopy. The resulting urine metabolome data were explored according to study design factors including economic status, country and gender. Partitioning of the effects derived from the study design factors using ANOVA-Simultaneous Component Analysis (ASCA) revealed that country and gender effects were responsible for most of the systematic variation. The effect of economic status was as expected much weaker than country and gender, but more pronounced in Lithuania than in other countries. Citrate and hippurate were among the most powerful ROP biomarkers. The possible relationship between these markers and nutritional deficiencies amongst the ROP population is discussed. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

rROP2 from Toxoplasma gondii as a potential vaccine against oocyst shedding in domestic cats.

PubMed

Zulpo, Dauton Luiz; Igarashi, Michelle; Sammi, Ana Sue; Santos, Joeleni Rosa Dos; Sasse, João Pedro; Cunha, Ivo Alexandre Leme da; Taroda, Alessandra; Barros, Luiz Daniel de; Almeida, Jonatas Campos de; Jenkins, Mark Christopher; Navarro, Italmar Teodorico; Garcia, João Luis

2017-01-01

The aim of the present study was to evaluate oocyst shedding in cats immunized by nasal route with T. gondii proteins ROP2. Twelve short hair cats (Felis catus) were divided in three groups G1, G2 and G3 (n=4). Animals from G1 received 100 μg of rROP2 proteins plus 20 μg of Quil-A, G2 received 100 μg of BSA plus 20 μg of Quil-A, and the G3 only saline solution (control group). All treatments were done by intranasal route at days 0, 21, 42, and 63. The challenge was performed in all groups on day 70 with ≅ 800 tissue cysts of ME-49 strain by oral route. Animals from G1 shed less oocysts (86.7%) than control groups. ELISA was used to detect anti-rROP2 IgG and IgA, however, there were no correlation between number of oocyst shedding by either IgG or IgA antibody levels. In the present work, in spite of lesser oocysts production in immunized group than control groups, it was not possible to associate the use of rROP2 via nostrils with protection against oocyst shedding. For the future, the use of either other recombinant proteins or DNA vaccine, in combination with rROP2 could be tested to try improving the efficacy of this kind of vaccine.

Astigmatism in the Early Treatment for Retinopathy of Prematurity Study: findings to 3 years of age

PubMed Central

Davitt, Bradley V.; Dobson, Velma; Quinn, Graham E.; Hardy, Robert J.; Tung, Betty; Good, William V.

2009-01-01

Purpose To examine the prevalence of astigmatism (≥ 1.00 diopter (D)) and high astigmatism (≥ 2.00 D) at 6 and 9 months post-term and 2 and 3 years postnatal, in preterm children with birth weight < 1251g who developed high-risk prethreshold retinopathy of prematurity (ROP) and participated in the Early Treatment for ROP (ETROP) Study. Design Randomized controlled clinical trial Participants 401 infants who developed prethreshold ROP in one or both eyes and were randomized after they were determined to have a high risk (≥ 15%) of poor structural outcome without treatment, using the RM-ROP2 risk management program. Refractive error was measured by cycloplegic retinoscopy. Eyes with additional retinal, glaucoma, or cataract surgery were excluded. Intervention Eyes were randomized to receive laser photocoagulation at high-risk prethreshold ROP (early treated (ET)) or to be conventionally managed (CM), receiving treatment only if threshold ROP developed. Main Outcome Measures Astigmatism and high astigmatism at each visit. Astigmatism was classified as “with-the rule” (75° – 105° (WTR)), “against-the-rule” (0° – 15° and 165° – 180° (ATR), or “oblique” (16° – 74° and 106° – 164° (OBL)). Results The prevalence of astigmatism in ET and CM eyes was similar at each test age. For both groups, there was an increase in prevalence of astigmatism from approximately 32% at 6 months to approximately 42% by 3 years, mostly occurring between 6 and 9 months. Among eyes that could be refracted, astigmatism was not influenced by zone of acute-phase ROP, presence of plus disease, or retinal residua of ROP. Eyes with astigmatism and high astigmatism most often had WTR astigmatism. Conclusions By age 3 years, nearly 43% of eyes treated at high-risk prethreshold ROP developed astigmatism ≥ 1.00 D and nearly 20% had astigmatism ≥ 2.00 D. Presence of astigmatism was not influenced by timing of treatment of acute-phase ROP, characteristics of acute-phase or cicatricial ROP. These findings reinforce the need for follow-up eye examinations in infants with high risk prethreshold ROP. PMID:19091409

[Study on construction and immune protective effect of recombinant nucleic acid vaccine of Toxoplasma gondii].

PubMed

Wei, Qing-Kuan

2012-04-01

To construct the polyvalent recombinant nucleic acid vaccine of Toxoplasma gondii and measure its protective immune effect. The gene of heat shock protein (HSP70) was amplified by PCR and inserted into the recombinant plasmid of pcDNA3-ROP2-p30 to construct recombinant polyvalent nucleic vaccine (pcDNA3-ROP2-p30-Hsp70). BALB/c mice were immunized with the constructed recombinant nucleic vaccine. CD4+ and CD8+ in the splenic lymphocytes and the lymphocytes in anticoagulant whole blood, the immune indices such as antibodies (IgG, IgM and IgA) and IFN-gamma, TNF, IL-2, IL-4, IL-12 in serum and splenic lymphocytes culture medium were detected, along with the challenge experiment. The protective immune responses that caused by the vaccine was measured by detecting the changes of immune indices of mice and the challenge experiment. 916 bp fragment of HSP70 gene was amplified by PCR. The recombinant polyvalent nucleic vaccine pcDNA3-ROP2-p30-HSP70 that included the whole open reading frame sequence of HSP gene was successfully constructed. The immunization results also showed this polyvalent nucleic vaccine could induce strong cellular and humoral responses by the detection of higher antibody titer in the experimental mice group, the increasing proliferation of CD4+ and CD8+ cells with significant deviations among the groups (F(CD4+) = 45.00, F(CD8+) = 15.01, all P < 0.01) and the apparent up-regulated levels of several cytokines IFN-gamma, IL-2 and IL-12 in serum and cultural supernatant of spleen cells, with more striking effect in serum. As a result of the challenge experiment, the immunized mice showed a longer survival time. The recombinant nucleic acid vaccine pcDNA3-ROP2-p30-HSP70 possesses a strong immunogenicity and is able to induce an immune protection.

Structural plasticity of 4-α-helical bundles exemplified by the puzzle-like molecular assembly of the Rop protein

PubMed Central

Amprazi, Maria; Kotsifaki, Dina; Providaki, Mary; Kapetaniou, Evangelia G.; Fellas, Georgios; Kyriazidis, Ioannis; Pérez, Javier; Kokkinidis, Michael

2014-01-01

The dimeric Repressor of Primer (Rop) protein, a widely used model system for the study of coiled-coil 4-α-helical bundles, is characterized by a remarkable structural plasticity. Loop region mutations lead to a wide range of topologies, folding states, and altered physicochemical properties. A protein-folding study of Rop and several loop variants has identified specific residues and sequences that are linked to the observed structural plasticity. Apart from the native state, native-like and molten-globule states have been identified; these states are sensitive to reducing agents due to the formation of nonnative disulfide bridges. Pro residues in the loop are critical for the establishment of new topologies and molten globule states; their effects, however, can be in part compensated by Gly residues. The extreme plasticity in the assembly of 4-α-helical bundles reflects the capacity of the Rop sequence to combine a specific set of hydrophobic residues into strikingly different hydrophobic cores. These cores include highly hydrated ones that are consistent with the formation of interchain, nonnative disulfide bridges and the establishment of molten globules. Potential applications of this structural plasticity are among others in the engineering of bio-inspired materials. PMID:25024213

Optimal design of earth-moving machine elements with cusp catastrophe theory application

NASA Astrophysics Data System (ADS)

Pitukhin, A. V.; Skobtsov, I. G.

2017-10-01

This paper deals with the optimal design problem solution for the operator of an earth-moving machine with a roll-over protective structure (ROPS) in terms of the catastrophe theory. A brief description of the catastrophe theory is presented, the cusp catastrophe is considered, control parameters are viewed as Gaussian stochastic quantities in the first part of the paper. The statement of optimal design problem is given in the second part of the paper. It includes the choice of the objective function and independent design variables, establishment of system limits. The objective function is determined as mean total cost that includes initial cost and cost of failure according to the cusp catastrophe probability. Algorithm of random search method with an interval reduction subject to side and functional constraints is given in the last part of the paper. The way of optimal design problem solution can be applied to choose rational ROPS parameters, which will increase safety and reduce production and exploitation expenses.

"Oxygen with love" and diode laser treatment decreases comorbidity and avoidable blindness due to retinopathy of prematurity: results achieved in the past 12 years.

PubMed

Garcia-Serrano, Jose Luis; Uberos Fernández, José; Anaya-Alaminos, Roberto; Jerez-Calero, Antonio; Padilla-Torres, José Francisco; Ramírez-Garcia, Maria Carmen; Piñar-Molina, Raquel

2013-12-01

To determine whether the "Oxygen with Love" (OWL) and diode laser treatment provided in a neonatal intensive care unit has reduced the risk of avoidable blindness caused by retinopathy of prematurity (ROP) over the past decade. A prospective observational cohort study was performed, in which 351 infants were examined for ROP. The inclusion conditions were as follows: preterm infants, birthweight <1500 g or <32 weeks' gestational age, and birth between 1 Jan 2000 to 31 August 2012. From mid-2009, the OWL program was implemented and the ventilation protocols for such infants were amended. We tested whether the incidence of unfavorable structural outcomes of ROP had decreased following these changes. From 2004 to 2012, the survival rates of younger children increased (p < 0.003). From 2005 to 2012, laser treatment rather than cryotherapy was applied, and the incidence of unfavorable structural outcomes of ROP fell from 13% to 5.6% (not significant). From 2009 to 2012, the incidence of ROP decreased from 55% to 29% (p < 0.002). From 1 August 2009 to 31 August 2012, there was less need for ablative treatment for premature infants, with the rate falling from 11.81% to 3.9% (p < 0.03). This improvement was significantly associated with a reduction in the number of days of intubation (p < 0.0017), lower rates of sepsis (p < 0.003), and improvements in postnatal weight gain (p < 0.0002). The introduction of the OWL program, together with lower rates of sepsis, improvements in postnatal weight gain, and the use of diode laser treatment, has reduced the incidence of unfavorable structural outcomes of ROP. Copyright © 2013. Published by Elsevier B.V.

A Domain-Specific Terminology for Retinopathy of Prematurity and Its Applications in Clinical Settings.

PubMed

Zhang, Yinsheng; Zhang, Guoming

2018-01-01

A terminology (or coding system) is a formal set of controlled vocabulary in a specific domain. With a well-defined terminology, each concept in the target domain is assigned with a unique code, which can be identified and processed across different medical systems in an unambiguous way. Though there are lots of well-known biomedical terminologies, there is currently no domain-specific terminology for ROP (retinopathy of prematurity). Based on a collection of historical ROP patients' data in the electronic medical record system, we extracted the most frequent terms in the domain and organized them into a hierarchical coding system-ROP Minimal Standard Terminology, which contains 62 core concepts in 4 categories. This terminology has been successfully used to provide highly structured and semantic-rich clinical data in several ROP-related applications.

Encouraging farmers to retrofit tractors: a qualitative analysis of risk perceptions among a group of high-risk farmers in New York.

PubMed

Sorensen, J A; May, J J; Paap, K; Purschwitz, M A; Emmelin, M

2008-01-01

Tractor rollovers continue to be one of the most frequent causes of agricultural fatalities. Despite knowledge of rollovers and the efficacy of rollover protective structures (ROPS), few New York farmers have considered installing ROPS on their unprotected tractors. Qualitative interviews conducted with an "at-risk" segment of the New York farming community indicate that there are a number of barriers to safety in general and to retrofitting, in particular. The following themes and categories emerged in relation to safety and risk taking: constant exposures to risk with positive outcomes normalizes risk; the modeling of risk by significant others positions risk as part of a farming identity; and the pressure to reduce costs, save time, and accept risk frames risk-taking as the cost-effective option (especially in regard to retrofitting, which farmers believe is both expensive and time-consuming). Recommendations for researchers planning retrofitting interventions would be to focus safety messages on the risk to significant others or on the financial impact of rollovers, and to provide financial incentives and assistance to farmers considering retrofitting.

The Neural Retina in Retinopathy of Prematurity

PubMed Central

Hansen, Ronald M.; Moskowitz, Anne; Akula, James D.; Fulton, Anne B.

2016-01-01

Retinopathy of prematurity (ROP) is a neurovascular disease that affects prematurely born infants and is known to have significant long term effects on vision. We conducted the studies described herein not only to learn more about vision but also about the pathogenesis of ROP. The coincidence of ROP onset and rapid developmental elongation of the rod photoreceptor outer segments motivated us to consider the role of the rods in this disease. We used noninvasive electroretinographic (ERG), psychophysical, and retinal imaging procedures to study the function and structure of the neurosensory retina. Rod photoreceptor and post-receptor responses are significantly altered years after the preterm days during which ROP is an active disease. The alterations include persistent rod dysfunction, and evidence of compensatory remodeling of the post-receptor retina is found in ERG responses to full-field stimuli and in psychophysical thresholds that probe small retinal regions. In the central retina, both Mild and Severe ROP delay maturation of parafoveal scotopic thresholds and are associated with attenuation of cone mediated multifocal ERG responses, significant thickening of post-receptor retinal laminae, and dysmorphic cone photoreceptors. These results have implications for vision and control of eye growth and refractive development and suggest future research directions. These results also lead to a proposal for noninvasive management using light that may add to the currently invasive therapeutic armamentarium against ROP. PMID:27671171

Structural and evolutionary adaptation of rhoptry kinases and pseudokinases, a family of coccidian virulence factors

PubMed Central

2013-01-01

Background The widespread protozoan parasite Toxoplasma gondii interferes with host cell functions by exporting the contents of a unique apical organelle, the rhoptry. Among the mix of secreted proteins are an expanded, lineage-specific family of protein kinases termed rhoptry kinases (ROPKs), several of which have been shown to be key virulence factors, including the pseudokinase ROP5. The extent and details of the diversification of this protein family are poorly understood. Results In this study, we comprehensively catalogued the ROPK family in the genomes of Toxoplasma gondii, Neospora caninum and Eimeria tenella, as well as portions of the unfinished genome of Sarcocystis neurona, and classified the identified genes into 42 distinct subfamilies. We systematically compared the rhoptry kinase protein sequences and structures to each other and to the broader superfamily of eukaryotic protein kinases to study the patterns of diversification and neofunctionalization in the ROPK family and its subfamilies. We identified three ROPK sub-clades of particular interest: those bearing a structurally conserved N-terminal extension to the kinase domain (NTE), an E. tenella-specific expansion, and a basal cluster including ROP35 and BPK1 that we term ROPKL. Structural analysis in light of the solved structures ROP2, ROP5, ROP8 and in comparison to typical eukaryotic protein kinases revealed ROPK-specific conservation patterns in two key regions of the kinase domain, surrounding a ROPK-conserved insert in the kinase hinge region and a disulfide bridge in the kinase substrate-binding lobe. We also examined conservation patterns specific to the NTE-bearing clade. We discuss the possible functional consequences of each. Conclusions Our work sheds light on several important but previously unrecognized features shared among rhoptry kinases, as well as the essential differences between active and degenerate protein kinases. We identify the most distinctive ROPK-specific features conserved across both active kinases and pseudokinases, and discuss these in terms of sequence motifs, evolutionary context, structural impact and potential functional relevance. By characterizing the proteins that enable these parasites to invade the host cell and co-opt its signaling mechanisms, we provide guidance on potential therapeutic targets for the diseases caused by coccidian parasites. PMID:23742205

A Comparison of Strategies for Retinopathy of Prematurity Detection

PubMed Central

Prosser, Lisa A.; Wade, Kelly C.; Repka, Michael X.; Ying, Gui-shuang; Baumritter, Agnieshka; Quinn, Graham E.

2016-01-01

BACKGROUND AND OBJECTIVES: Delayed detection of type 1 retinopathy of prematurity (ROP) can lead to permanent visual impairment. Providing ROP examinations is challenging because of the limited ophthalmology workforce. This study compares digital imaging–based ROP detection strategies versus serial ROP examinations. METHODS: We conducted an individual-level microsimulation studyof a hypothetical cohort of 650 infants with gestational age from 23 to 30 weeks. Infants were evaluated by using strategies based on indirect ophthalmoscopy or digital imaging beginning at 32 weeks’ postmenstrual age (PMA) and continuing to discharge, transfer, or 40 weeks’ PMA. ROP status and the accuracy of digital imaging were based on the e-ROP (Telemedicine Approaches to Evaluating Acute-Phase ROP) study, which enrolled high-risk infants. RESULTS: Within the hypothetical NICU, the strategy of ROP examinations identified an average of 45.8 cases of type 1 ROP by discharge, transfer, or 40 weeks’ PMA, and another 1.9 cases were included in the group of infants recommended to have later follow-up. Digital imaging with an ROP examination at discharge identified all 47.7 cases of type 1 ROP. On average, the ROP examination–only strategy required 1745.7 ROP examinations, whereas digital imaging with a discharge examination required 1065.5 ROP examinations and 1786.2 digital imaging sessions. CONCLUSIONS: Although digital imaging decreased the number of ROP examinations per infant, there was an increase in the total number of interventions (ie, ROP examinations and imaging sessions). Providing an ROP examination at the time of NICU discharge can significantly reduce the number of infants who require follow-up. PMID:26672022

A Dosing Study of Bevacizumab for Retinopathy of Prematurity: Late Recurrences and Additional Treatments.

PubMed

Wallace, David K; Dean, Trevano W; Hartnett, Mary Elizabeth; Kong, Lingkun; Smith, Lois E; Hubbard, G Baker; McGregor, Mary Lou; Jordan, Catherine O; Mantagos, Iason S; Bell, Edward F; Kraker, Raymond T

2018-06-07

Intravitreal bevacizumab is increasingly used to treat severe retinopathy of prematurity (ROP), but it enters the bloodstream, and there is concern that it may alter development of other organs. Previously we reported short-term outcomes of 61 infants enrolled in a dose de-escalation study, and we report the late recurrences and additional treatments. Masked, multicenter, dose de-escalation study. A total of 61 premature infants with type 1 ROP. If type 1 ROP was bilateral at enrollment, then the study eye was randomly selected. In the study eye, bevacizumab intravitreal injections were given at de-escalating doses of 0.25 mg, 0.125 mg, 0.063 mg, or 0.031 mg; if needed, fellow eyes received 1 dose level higher: 0.625 mg, 0.25 mg, 0.125 mg, or 0.063 mg, respectively. After 4 weeks, additional treatment was at the discretion of the investigator. Early and late ROP recurrences, additional treatments, and structural outcomes after 6 months. Of 61 study eyes, 25 (41%; 95% confidence interval [CI], 29%-54%) received additional treatment: 3 (5%; 95% CI, 1%-14%) for early failure (within 4 weeks), 11 (18%; 95% CI, 9%-30%) for late recurrence of ROP (after 4 weeks), and 11 (18%; 95% CI, 9%-30%) for persistent avascular retina. Re-treatment for early failure or late recurrence occurred in 2 of 11 eyes (18%; 95% CI, 2%-52%) treated with 0.25 mg, 4 of 16 eyes (25%; 95% CI, 7%-52%) treated with 0.125 mg, 8 of 24 eyes (33%; 95% CI, 16%-55%) treated with 0.063 mg, and 0 (0%; 95% CI, 0%-31%) of 10 eyes treated with 0.031 mg. By 6 months corrected age, 56 of 61 study eyes had regression of ROP with normal posterior poles, 1 study eye had developed a Stage 5 retinal detachment, and 4 infants had died of preexisting medical conditions. Retinal structural outcomes are very good after low-dose bevacizumab treatment for ROP, although many eyes received additional treatment. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Detection of Potentially Severe Retinopathy of Prematurity by Remote Image Grading.

PubMed

Quinn, Graham E; Ying, Gui-Shuang; Pan, Wei; Baumritter, Agnieshka; Daniel, Ebenezer

2017-09-01

Telemedicine in retinopathy of prematurity (ROP) has the potential for delivering timely care to premature infants at risk for serious ROP. To describe the characteristics of eyes at risk for ROP to provide insights into what types of ROP are most easily detected early by image grading. Secondary analysis of eyes with referral-warranted (RW) ROP (stage 3 ROP, zone I ROP, plus disease) on diagnostic examination from the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity (e-ROP) study was conducted from May 1, 2011, to October 31, 2013, in 1257 premature infants with birth weights less than 1251 g in 13 neonatal units in North America. Data analysis was performed between February 1, 2016, and June 5, 2017. Serial imaging sessions with concurrent diagnostic examinations for ROP. Time of detecting RW-ROP on image evaluation compared with clinical examination. In the e-ROP study, 246 infants (492 eyes) were included in the analysis; 138 (56.1%) were male. A total of 447 eyes had RW-ROP on diagnostic examination. Image grading in 123 infants (mean [SD] gestational age, 24.8 [1.4] weeks) detected RW-ROP earlier than diagnostic examination (early) in 191 (42.7%) eyes by about 15 days and detected RW-ROP in 123 infants (mean [SD] gestational age, 24.6 [1.5] weeks) at the same time (same) in 200 (44.7%) eyes. Most of the early eyes (153 [80.1%]) interpreted as being RW-ROP positive on imaging evaluation agreed with examination findings when the examination subsequently documented RW-ROP. At the sessions in which RW-ROP was first found by examination, stage 3 or more in 123 infants (mean [SD] gestational age, 24.8 [1.4] weeks) ROP was noted earlier on image evaluation in 151 of 191 early eyes (79.1%) and in 172 of 200 of same eyes (86.0%) (P = .08); the presence of zone I ROP was detected in 57 of 191 (29.8%) early eyes vs 64 of 200 (32.0%) same eyes (P = .90); and plus disease was noted in 30 of 191 (15.7%) early eyes and 45 of 200 (22.5%) same eyes (P = .08). In both early and same eyes, zone I and/or stage 3 ROP determined a significant proportion of RW-ROP; plus disease played a relatively minor role. In most early RW-ROP eyes, the findings were consistent with clinical examination and/or image grading at the next session. Because ROP telemedicine is used more widely, development of standard approaches and protocols is essential.

Predictive algorithms for early detection of retinopathy of prematurity.

PubMed

Piermarocchi, Stefano; Bini, Silvia; Martini, Ferdinando; Berton, Marianna; Lavini, Anna; Gusson, Elena; Marchini, Giorgio; Padovani, Ezio Maria; Macor, Sara; Pignatto, Silvia; Lanzetta, Paolo; Cattarossi, Luigi; Baraldi, Eugenio; Lago, Paola

2017-03-01

To evaluate sensitivity, specificity and the safest cut-offs of three predictive algorithms (WINROP, ROPScore and CHOP ROP) for retinopathy of prematurity (ROP). A retrospective study was conducted in three centres from 2012 to 2014; 445 preterms with gestational age (GA) ≤ 30 weeks and/or birthweight (BW) ≤ 1500 g, and additional unstable cases, were included. No-ROP, mild and type 1 ROP were categorized. The algorithms were analysed for infants with all parameters (GA, BW, weight gain, oxygen therapy, blood transfusion) needed for calculation (399 babies). Retinopathy of prematurity (ROP) was identified in both eyes in 116 patients (26.1%), and 44 (9.9%) had type 1 ROP. Gestational age and BW were significantly lower in ROP group compared with no-ROP subjects (GA: 26.7 ± 2.2 and 30.2 ± 1.9, respectively, p < 0.0001; BW: 839.8 ± 287.0 and 1288.1 ± 321.5 g, respectively, p = 0.0016). Customized alarms of ROPScore and CHOP ROP correctly identified all infants having any ROP or type 1 ROP. WINROP missed 19 cases of ROP, including three type 1 ROP. ROPScore and CHOP ROP provided the best performances with an area under the receiver operating characteristic curve for the detection of severe ROP of 0.93 (95% CI, 0.90-0.96, and 95% CI, 0.89-0.96, respectively), and WINROP obtained 0.83 (95% CI, 0.77-0.87). Median time from alarm to treatment was 11.1, 5.1 and 9.1 weeks, for WINROP, ROPScore and CHOP ROP, respectively. ROPScore and CHOP ROP showed 100% sensitivity to identify sight-threatening ROP. Predictive algorithms are a reliable tool for early identification of infants requiring referral to an ophthalmologist, for reorganizing resources and reducing stressful procedures to preterm babies. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Validated System for Centralized Grading of Retinopathy of Prematurity: Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity (e-ROP) Study.

PubMed

Daniel, Ebenezer; Quinn, Graham E; Hildebrand, P Lloyd; Ells, Anna; Hubbard, G Baker; Capone, Antonio; Martin, E Revell; Ostroff, Candace P; Smith, Eli; Pistilli, Maxwell; Ying, Gui-Shuang

2015-06-01

Measurable competence derived from comprehensive and advanced training in grading digital images is critical in studies using a reading center to evaluate retinal fundus images from infants at risk for retinopathy of prematurity (ROP). Details of certification for nonphysician trained readers (TRs) have not yet been described. To describe a centralized system for grading ROP digital images by TRs in the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity (e-ROP) Study. Multicenter observational cohort study conducted from July 1, 2010, to June 30, 2014. The TRs were trained by experienced ROP specialists and certified to detect ROP morphology in digital retinal images under supervision of an ophthalmologist reading center director. An ROP reading center was developed with standard hardware, secure Internet access, and customized image viewing software with an electronic grading form. A detailed protocol for grading was developed. Based on results of TR gradings, a computerized algorithm determined whether referral-warranted ROP (RW-ROP; defined as presence of plus disease, zone I ROP, and stage 3 or worse ROP) was present in digital images from infants with birth weight less than 1251 g enrolled from May 25, 2011, through October 31, 2013. Independent double grading was done by the TRs with adjudication of discrepant fields performed by the reading center director. Digital retinal images. Intragrader and intergrader variability and monitoring for temporal drift. Four TRs underwent rigorous training and certification. A total of 5520 image sets were double graded, with 24.5% requiring adjudication for at least 1 component of RW-ROP. For individual RW-ROP components, the adjudication rate was 3.9% for plus disease, 12.4% for zone I ROP, and 16.9% for stage 3 or worse ROP. The weighted κ for intergrader agreement (n = 80 image sets) was 0.72 (95% CI, 0.52-0.93) for RW-ROP, 0.57 (95% CI, 0.37-0.77) for plus disease, 0.43 (95% CI, 0.24-0.63) for zone I ROP, and 0.67 (95% CI, 0.47-0.88) for stage 3 or worse ROP. The weighted κ for grade-regrade agreement was 0.77 (95% CI, 0.57-0.97) for RW-ROP, 0.87 (95% CI, 0.67-1.00) for plus disease, 0.70 (95% CI, 0.51-0.90) for zone I ROP, and 0.77 (95% CI, 0.57-0.97) for stage 3 or worse ROP. These data suggest that the e-ROP system for training and certifying nonphysicians to grade ROP images under the supervision of a reading center director reliably detects potentially serious ROP with good intragrader and intergrader consistency and minimal temporal drift.

Development of population structure and spatial distribution patterns of a restored forest during 17-year succession (1993-2010) in Pingshuo opencast mine spoil, China.

PubMed

Zhao, Zhongqiu; Wang, Lianhua; Bai, Zhongke; Pan, Ziguan; Wang, Yun

2015-07-01

Afforestation of native tree species is often recommended for ecological restoration in mining areas, but the understanding of the ecological processes of restored vegetation is quite limited. In order to provide insight of the ecological processes of restored vegetation, in this study, we investigate the development of the population structure and spatial distribution patterns of restored Robinia pseudoacacia (ROPS) and Pinus tabuliformis (PITA) mixed forests during the 17 years of the mine spoil period of the Pingshuo opencast mine, Shanxi Province, China. After a 17-year succession, apart from the two planted species, Ulmus pumila (ULPU), as an invasive species, settled in the plot along with a large number of small diameter at breast height (DBH) size. In total, there are 10,062 living individual plants, much more than that at the plantation (5105), and ROPS had become the dominant species with a section area with a breast height of 9.40 m(2) hm(-2) and a mean DBH of 6.72 cm, much higher than both PITA and ULPU. The DBH size classes of all the total species showed inverted J-shaped distributions, which may have been a result of the large number of small regenerated ULPU trees. The DBH size classes of both ROPS and PITA showed peak-type structures with individuals mainly gathering in the moderate DBH size class, indicating a relatively healthy DBH size class structure. Meanwhile, invasive ULPU were distributed in a clear L shape, concentrating on the small DBH size class, indicating a relatively low survival rate for adult trees. Both ROPS and PITA species survival in the plantation showed uniform and aggregated distribution at small scales and random with scales increasing. ULPU showed a strong aggregation at small scales as well as random with scales increasing. Both the population structure and spatial distribution indicated that ROPS dominates and will continue to dominate the community in the future succession, which should be continuously monitored.

Evaluation of the WinROP system for identifying retinopathy of prematurity in Czech preterm infants.

PubMed

Timkovic, Juraj; Pokryvkova, Martina; Janurova, Katerina; Barinova, Denisa; Polackova, Renata; Masek, Petr

2017-03-01

Retinopathy of Prematurity (ROP) is a potentially serious condition that can afflict preterm infants. Timely and correct identification of individuals at risk of developing a serious form of ROP is therefore of paramount importance. WinROP is an online system for predicting ROP based on birth weight and weight increments. However, the results vary significantly for various populations. It has not been evaluated in the Czech population. This study evaluates the test characteristics (specificity, sensitivity, positive and negative predictive values) of the WinROP system in Czech preterm infants. Data on 445 prematurely born infants included in the ROP screening program at the University Hospital Ostrava, Czech Republic, were retrospectively entered into the WinROP system and the outcomes of the WinROP and regular screening were compared. All 24 infants who developed high-risk (Type 1 or Type 2) ROP were correctly identified by the system. The sensitivity and negative predictive values for this group were 100%. However, the specificity and positive predictive values were substantially lower, resulting in a large number of false positives. Extending the analysis to low risk ROP, the system did not provide such reliable results. The system is a valuable tool for identifying infants who are not likely to develop high-risk ROP and this could help to substantially reduce the number of preterm infants in need of regular ROP screening. It is not suitable for predicting the development of less serious forms of ROP which is however in accordance with the declared aims of the WinROP system.

Validation of the Colorado Retinopathy of Prematurity Screening Model.

PubMed

McCourt, Emily A; Ying, Gui-Shuang; Lynch, Anne M; Palestine, Alan G; Wagner, Brandie D; Wymore, Erica; Tomlinson, Lauren A; Binenbaum, Gil

2018-04-01

The Colorado Retinopathy of Prematurity (CO-ROP) model uses birth weight, gestational age, and weight gain at the first month of life (WG-28) to predict risk of severe retinopathy of prematurity (ROP). In previous validation studies, the model performed very well, predicting virtually all cases of severe ROP and potentially reducing the number of infants who need ROP examinations, warranting validation in a larger, more diverse population. To validate the performance of the CO-ROP model in a large multicenter cohort. This study is a secondary analysis of data from the Postnatal Growth and Retinopathy of Prematurity (G-ROP) Study, a retrospective multicenter cohort study conducted in 29 hospitals in the United States and Canada between January 2006 and June 2012 of 6351 premature infants who received ROP examinations. Sensitivity and specificity for severe (early treatment of ROP [ETROP] type 1 or 2) ROP, and reduction in infants receiving examinations. The CO-ROP model was applied to the infants in the G-ROP data set with all 3 data points (infants would have received examinations if they met all 3 criteria: birth weight, <1501 g; gestational age, <30 weeks; and WG-28, <650 g). Infants missing WG-28 information were included in a secondary analysis in which WG-28 was considered fewer than 650 g. Of 7438 infants in the G-ROP study, 3575 (48.1%) were girls, and maternal race/ethnicity was 2310 (31.1%) African American, 3615 (48.6%) white, 233 (3.1%) Asian, 40 (0.52%) American Indian/Alaskan Native, and 93 (1.3%) Pacific Islander. In the study cohort, 747 infants (11.8%) had type 1 or 2 ROP, 2068 (32.6%) had lower-grade ROP, and 3536 (55.6%) had no ROP. The CO-ROP model had a sensitivity of 96.9% (95% CI, 95.4%-97.9%) and a specificity of 40.9% (95% CI, 39.3%-42.5%). It missed 23 (3.1%) infants who developed severe ROP. The CO-ROP model would have reduced the number of infants who received examinations by 26.1% (95% CI, 25.0%-27.2%). The CO-ROP model demonstrated high but not 100% sensitivity for severe ROP and missed infants who might require treatment in this large validation cohort. The model requires all 3 criteria to be met to signal a need for examinations, but some infants with a birth weight or gestational age above the thresholds developed severe ROP. Most of these infants who were not detected by the CO-ROP model had obvious deviation in expected weight trajectories or nonphysiologic weight gain. These findings suggest that the CO-ROP model needs to be revised before considering implementation into clinical practice.

Social and Individual Influences on Tractor Operating Practices of Young Adult Agricultural Workers.

PubMed

Rudolphi, Josie M; Campo, Shelly; Gerr, Fred; Rohlman, Diane S

2018-05-01

Tractor-related incidents are the leading cause of agricultural-related fatalities in the United States. Injuries from rollovers can be prevented by equipping tractors with rollover protective structures (ROPS, an engineering approach) and by using seatbelts (a behavior-based approach). While adult farmers report low seatbelt use and frequent use of tractors without ROPS, it is unknown whether the young adult population has adopted similar tractor driving practices. This study was designed to identify tractor operating practices among young adult agricultural workers and the influence of supervisors, peers, and parents on their safety behaviors. An online survey was conducted among college students enrolled in agricultural science classes in four Midwestern colleges and universities. Participants answered questions about their tractor operating practices, the influence of supervisors, peers, parents, and individual risk taking tendencies on their workplace practices. A tractor operation safety score was estimated from participants' responses. Linear regression was used to examine the association of these influences and the tractor operation safety score. Of the 193 respondents, most (78.8%) reported that they never or rarely wear a seatbelt when operating a tractor with a ROPS. Supervisory influences, such as being negatively evaluated by a supervisor, were found to be more strongly associated with tractor operating behaviors than peer or parent influence. Young adult agricultural workers frequently reported unsafe tractor operating behaviors. Supervisors were found to have the most influence over reported behaviors of young adult agricultural workers. Copyright © 2017 The Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

78 FR 34677 - Agency Information Collection Activities: Submission for the Office of Management and Budget (OMB...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-10

... ensure adequate protection of public health and safety, to promote the common defense and security, and to protect the environment. One way to support this mission is through the implementation of the Reactor Oversight Process (ROP), which is the agency's program to inspect, measure, and assess the safety...

The Microtubule-Associated Protein MAP18 Affects ROP2 GTPase Activity during Root Hair Growth1[OPEN

PubMed Central

Kang, Erfang; Zheng, Mingzhi; Zhang, Yan; Yuan, Ming; Fu, Ying

2017-01-01

Establishment and maintenance of the polar site are important for root hair tip growth. We previously reported that Arabidopsis (Arabidopsis thaliana) MICROTUBULE-ASSOCIATED PROTEIN18 (MAP18) functions in controlling the direction of pollen tube growth and root hair elongation. Additionally, the Rop GTPase ROP2 was reported as a positive regulator of both root hair initiation and tip growth in Arabidopsis. Both loss of function of ROP2 and knockdown of MAP18 lead to a decrease in root hair length, whereas overexpression of either MAP18 or ROP2 causes multiple tips or a branching hair phenotype. However, it is unclear whether MAP18 and ROP2 coordinately regulate root hair growth. In this study, we demonstrate that MAP18 and ROP2 interact genetically and functionally. MAP18 interacts physically with ROP2 in vitro and in vivo and preferentially binds to the inactive form of the ROP2 protein. MAP18 promotes ROP2 activity during root hair tip growth. Further investigation revealed that MAP18 competes with RhoGTPase GDP DISSOCIATION INHIBITOR1/SUPERCENTIPEDE1 for binding to ROP2, in turn affecting the localization of active ROP2 in the plasma membrane of the root hair tip. These results reveal a novel function of MAP18 in the regulation of ROP2 activation during root hair growth. PMID:28314794

Maize ROP2 GTPase provides a competitive advantage to the male gametophyte.

PubMed

Arthur, K M; Vejlupkova, Z; Meeley, R B; Fowler, J E

2003-12-01

Rop GTPases have been implicated in the regulation of plant signal transduction and cell morphogenesis. To explore ROP2 function in maize, we isolated five Mutator transposon insertions (rop2::Mu alleles). Transmission frequency through the male gametophyte, but not the female, was lower than expected in three of the rop2::Mu mutants. These three alleles formed an allelic series on the basis of the relative transmission rate of each when crossed as trans-heterozygotes. A dramatic reduction in the level of ROP2-mRNA in pollen was associated with the three alleles causing a transmission defect, whereas a rop2::Mu allele that did not result in a defect had wild-type transcript levels, thus confirming that mutation of rop2 causes the mutant phenotype. These data strongly support a role for rop2 in male gametophyte function, perhaps surprisingly, given the expression in pollen of the nearly identical duplicate gene rop9. However, the transmission defect was apparent only when a rop2::Mu heterozygote was used as the pollen donor or when a mixture of wild-type and homozygous mutant pollen was used. Thus, mutant pollen is at a competitive disadvantage compared to wild-type pollen, although mutant pollen grains lacked an obvious cellular defect. Our data demonstrate the importance in vivo of a specific Rop, rop2, in the male gametophyte.

Assessment of a Tele-education System to Enhance Retinopathy of Prematurity Training by International Ophthalmologists-in-Training in Mexico.

PubMed

Patel, Samir N; Martinez-Castellanos, Maria Ana; Berrones-Medina, David; Swan, Ryan; Ryan, Michael C; Jonas, Karyn E; Ostmo, Susan; Campbell, J Peter; Chiang, Michael F; Chan, R V Paul

2017-07-01

To evaluate a tele-education system developed to improve diagnostic competency in retinopathy of prematurity (ROP) by ophthalmologists-in-training in Mexico. Prospective, randomized cohort study. Fifty-eight ophthalmology residents and fellows from a training program in Mexico consented to participate. Twenty-nine of 58 trainees (50%) were randomized to the educational intervention (pretest, ROP tutorial, ROP educational chapters, and posttest), and 29 of 58 trainees (50%) were randomized to a control group (pretest and posttest only). A secure web-based educational system was created using clinical cases (20 pretest, 20 posttest, and 25 training chapter-based) developed from a repository of over 2500 unique image sets of ROP. For each image set used, a reference standard ROP diagnosis was established by combining the clinical diagnosis by indirect ophthalmoscope examination and image-based diagnosis by multiple experts. Trainees were presented with image-based clinical cases of ROP during a pretest, posttest, and training chapters. The accuracy of ROP diagnosis (e.g., plus disease, zone, stage, category) was determined using sensitivity and specificity calculations from the pretest and posttest results of the educational intervention group versus control group. The unweighted kappa statistic was used to analyze the intragrader agreement for ROP diagnosis by the ophthalmologists-in-training during the pretest and posttest for both groups. Trainees completing the tele-education system had statistically significant improvements (P < 0.01) in the accuracy of ROP diagnosis for plus disease, zone, stage, category, and aggressive posterior ROP (AP-ROP). Compared with the control group, trainees who completed the ROP tele-education system performed better on the posttest for accurately diagnosing plus disease (67% vs. 48%; P = 0.04) and the presence of ROP (96% vs. 91%; P < 0.01). The specificity for diagnosing AP-ROP (94% vs. 78%; P < 0.01), type 2 ROP or worse (92% vs. 84%; P = 0.04), and ROP requiring treatment (89% vs. 79%; P < 0.01) was better for the trainees completing the tele-education system compared with the control group. Intragrader agreement improved for identification of plus disease, zone, stage, and category of ROP after completion of the educational intervention. A tele-education system for ROP education was effective in improving the diagnostic accuracy of ROP by ophthalmologists-in-training in Mexico. This system has the potential to increase competency in ROP diagnosis and management for ophthalmologists-in-training from middle-income nations. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

A Tiered Approach to Retinopathy of Prematurity Screening (TARP) Using a Weight Gain Predictive Model and a Telemedicine System.

PubMed

Gurwin, Jaclyn; Tomlinson, Lauren A; Quinn, Graham E; Ying, Gui-Shuang; Baumritter, Agnieshka; Binenbaum, Gil

2017-01-05

The Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity (e-ROP) Study telemedicine system of remote fundus image grading and The Children's Hospital of Philadelphia Retinopathy of Prematurity (CHOP-ROP) postnatal weight gain predictive model are 2 approaches for improving ROP screening efficiency. Current screening has low specificity for severe ROP. To describe a tiered approach to ROP screening (TARP) for identifying children who develop severe ROP using telemedicine and a predictive model synergistically. This investigation was a post hoc analysis of a cohort in the e-ROP Study (a multicenter prospective telemedicine study) and the Postnatal Growth and Retinopathy of Prematurity (G-ROP) Study (a multicenter retrospective cohort study). The setting was neonatal intensive care units at The Children's Hospital of Philadelphia and the Hospital of the University of Pennsylvania. Participants in the e-ROP Study were premature infants with a birth weight less than 1251 g and a known ROP outcome enrolled between May 25, 2011, and October 31, 2013. The G-ROP Study enrolled all infants undergoing ROP examinations with a known ROP outcome who were born between January 1, 2006, and December 31, 2011. The mean outcomes were the sensitivity for type 1 ROP, reductions in infants requiring imaging or examinations, numbers of imaging sessions and examinations, and total clinical encounters (imaging sessions and examinations combined). The following 4 screening approaches were evaluated: ROUTINE (only diagnostic examinations by an ophthalmologist), CHOP-ROP (birth weight and gestational age, with weekly weight gain initiating examinations when the risk cut point is surpassed), e-ROP IMAGING (trained reader grading of type 1 or 2 ROP initiates diagnostic examinations), and TARP (CHOP-ROP alarm initiates imaging, and imaging finding of severe ROP initiates diagnostic examinations). A total of 242 infants were included in the study, with a median birth weight of 858 g (range, 690-1035 g). The median gestational age was 27 weeks (range, 25-29 weeks). Fifty-one percent (124 of 242) were female, and 49% (118 of 242) were male. The race/ethnicity was 27.3% (66 of 242) white, 56.2% (136 of 242) black, 2.1% (5 of 242) Native American, 1.7% (4 of 242) Asian, and 12.8% (31 of 242) other. The sensitivity for detecting type 1 ROP (32 infants) was 100% (95% CI, 89.3%-100%) with each approach. With ROUTINE, 242 infants had 877 examinations; with CHOP-ROP, 184 infants had 730 examinations; with e-ROP IMAGING, 242 infants had 532 imaging sessions, and 94 infants had 345 examinations (877 patient encounters); and with TARP, 182 infants had 412 imaging sessions, and 87 infants had 322 examinations (734 patient encounters). The tiered approach to ROP screening was associated with a reduced number of examinations and imaging sessions compared with the other approaches. Applying a postnatal growth model and telemedicine system in a tiered approach may reduce the number of clinical ROP interventions more than either approach alone.

Toxoplasma's arms race with the host interferon response: a ménage à trois of ROPs.

PubMed

Zhao, Yanlin; Yap, George S

2014-05-14

The Toxoplasma gondii virulence factors ROP5 and ROP18 both target immunity-related GTPases (IRGs) to evade immunity. In this issue of Cell Host & Microbe, Etheridge et al. (2014) identify a third virulence factor, ROP17, which forms a complex and synergizes with ROP5/ROP18 to fully disable the IRG system of antiparasite defense. Copyright © 2014 Elsevier Inc. All rights reserved.

Retinopathy of prematurity: Risk factors and variability in Canadian neonatal intensive care units.

PubMed

Thomas, K; Shah, P S; Canning, R; Harrison, A; Lee, S K; Dow, K E

2015-01-01

To identify predictors of severe retinopathy of prematurity (ROP) in a large population-based cohort and to examine risk-adjusted variations across units. Retrospective analysis of Canadian Neonatal Network data on neonates with birth weight <1500 g who were screened for ROP between 2003 and 2010. Characteristics of infants with and without ROP were compared and a risk-adjusted model for severe ROP was developed. Rates of severe ROP were compared between sites. 1163 of 9187 (12.7%) infants developed severe ROP. Lower gestational age, male sex, small for gestational age, patent ductus arteriosus, late onset sepsis, more than two blood transfusions, inotrope use, and outborn status were associated with an increased risk of severe ROP. Severe ROP rates varied significantly between units. Younger, smaller and sicker male infants had higher adjusted risks of severe ROP and rates varied significantly among sites.

Characterization of ROP18 alleles in human toxoplasmosis.

PubMed

Sánchez, Víctor; de-la-Torre, Alejandra; Gómez-Marín, Jorge Enrique

2014-04-01

The role of the virulent gene ROP18 polymorphisms is not known in human toxoplasmosis. A total of 320 clinical samples were analyzed. In samples positive for ROP18 gene, we determined by an allele specific PCR, if patients got the upstream insertion positive ROP18 sequence Toxoplasma strain (mouse avirulent strain) or the upstream insertion negative ROP18 sequence Toxoplasma strain (mouse virulent strain). We designed an ELISA assay for antibodies against ROP18 derived peptides from the three major clonal lineages of Toxoplasma. 20 clinical samples were of quality for ROP18 allele analysis. In patients with ocular toxoplasmosis, a higher inflammatory reaction on eye was associated to a PCR negative result for the upstream region of ROP18. 23.3%, 33% and 16.6% of serums from individuals with ocular toxoplasmosis were positive for type I, type II and type III ROP18 derived peptides, respectively but this assay was affected by cross reaction. The absence of Toxoplasma ROP18 promoter insertion sequence in ocular toxoplasmosis was correlated with severe ocular inflammatory response. Determination of antibodies against ROP18 protein was not useful for serotyping in human toxoplasmosis. © 2013.

Final visual acuity results in the early treatment for retinopathy of prematurity study.

PubMed

Good, William V; Hardy, Robert J; Dobson, Velma; Palmer, Earl A; Phelps, Dale L; Tung, Betty; Redford, Maryann

2010-06-01

To compare visual acuity at 6 years of age in eyes that received early treatment for high-risk prethreshold retinopathy of prematurity (ROP) with conventionally managed eyes. Infants with symmetrical, high-risk prethreshold ROP (n = 317) had one eye randomized to earlier treatment at high-risk prethreshold disease and the other eye managed conventionally, treated if ROP progressed to threshold severity. For asymmetric cases (n = 84), the high-risk prethreshold eye was randomized to either early treatment or conventional management. The main outcome measure was ETDRS visual acuity measured at 6 years of age by masked testers. Retinal structure was assessed as a secondary outcome. Analysis of all subjects with high-risk prethreshold ROP showed no statistically significant benefit for early treatment (24.3% vs 28.6% [corrected] unfavorable outcome; P = .15). Analysis of 6-year visual acuity results according to the Type 1 and 2 clinical algorithm showed a benefit for Type 1 eyes (25.1% vs 32.8%; P = .02) treated early but not Type 2 eyes (23.6% vs 19.4%; P = .37). Early-treated eyes showed a significantly better structural outcome compared with conventionally managed eyes (8.9% vs 15.2% unfavorable outcome; P < .001), with no greater risk of ocular complications. Early treatment for Type 1 high-risk prethreshold eyes improved visual acuity outcomes at 6 years of age. Early treatment for Type 2 high-risk prethreshold eyes did not. Application to Clinical Practice Type 1 eyes, not Type 2 eyes, should be treated early. These results are particularly important considering that 52% of Type 2 high-risk prethreshold eyes underwent regression of ROP without requiring treatment. Trial Registration clinicaltrials.gov Identifier: NCT00027222.

Postnatal Growth and Retinopathy of Prematurity Study: Rationale, Design, and Subject Characteristics.

PubMed

Binenbaum, Gil; Tomlinson, Lauren A

2017-02-01

Postnatal-growth-based predictive models demonstrate strong potential for improving the low specificity of retinopathy of prematurity (ROP) screening. Prior studies are limited by inadequate sample size. We sought to study a sufficiently large cohort of at-risk infants to enable development of a model with highly precise estimates of sensitivity for severe ROP. The Postnatal Growth and ROP (G-ROP) Study was a multicenter retrospective cohort study of infants at 30 North American hospitals during 2006-2012. A total of 65 G-ROP-certified abstractors submitted data to a secure, web-based database. Data included ROP examination findings, treatments, complications, daily weight measurements, daily oxygen supplementation, maternal/infant demographics, medical comorbidities, surgical events, and weekly nutrition. Data quality was monitored with system validation rules, data audits, and discrepancy algorithms. Of 11,261 screened infants, 8334 were enrolled, and 2927 had insufficient data due to transfer, discharge, or death. Of the enrolled infants, 90% (7483) had a known ROP outcome and were included in the study. Median birth weight was 1070 g (range 310-3000g) and mean gestational age 28 weeks (range 22-35 weeks). Severe ROP (Early Treatment of Retinopathy type 1 or 2) developed in 931 infants (12.5%). Successful incorporation of a predictive model into ROP screening requires confidence that it will capture cases of severe ROP. This dataset provides power to estimate sensitivity with half-confidence interval width of less than 0.5%, determined by the high number of severe ROP cases. The G-ROP Study represents a large, diverse cohort of at-risk infants undergoing ROP screening. It will facilitate evaluation of growth-based algorithms to improve efficiency of ROP screening.

The Rhoptry Proteins ROP18 and ROP5 Mediate Toxoplasma gondii Evasion of the Murine, But Not the Human, Interferon-Gamma Response

PubMed Central

Niedelman, Wendy; Gold, Daniel A.; Rosowski, Emily E.; Sprokholt, Joris K.; Lim, Daniel; Farid Arenas, Ailan; Melo, Mariane B.; Spooner, Eric; Yaffe, Michael B.; Saeij, Jeroen P. J.

2012-01-01

The obligate intracellular parasite Toxoplasma gondii secretes effector proteins into the host cell that manipulate the immune response allowing it to establish a chronic infection. Crosses between the types I, II and III strains, which are prevalent in North America and Europe, have identified several secreted effectors that determine strain differences in mouse virulence. The polymorphic rhoptry protein kinase ROP18 was recently shown to determine the difference in virulence between type I and III strains by phosphorylating and inactivating the interferon-γ (IFNγ)-induced immunity-related GTPases (IRGs) that promote killing by disrupting the parasitophorous vacuole membrane (PVM) in murine cells. The polymorphic pseudokinase ROP5 determines strain differences in virulence through an unknown mechanism. Here we report that ROP18 can only inhibit accumulation of the IRGs on the PVM of strains that also express virulent ROP5 alleles. In contrast, specific ROP5 alleles can reduce IRG coating even in the absence of ROP18 expression and can directly interact with one or more IRGs. We further show that the allelic combination of ROP18 and ROP5 also determines IRG evasion and virulence of strains belonging to other lineages besides types I, II and III. However, neither ROP18 nor ROP5 markedly affect survival in IFNγ-activated human cells, which lack the multitude of IRGs present in murine cells. These findings suggest that ROP18 and ROP5 have specifically evolved to block the IRGs and are unlikely to have effects in species that do not have the IRG system, such as humans. PMID:22761577

Type 1 Retinopathy of Prematurity and Its Laser Treatment of Large Preterm Infants in East China.

PubMed

Shan, Haidong; Ni, Yinqing; Xue, Kang; Yu, Jia; Huang, Xin

2015-01-01

To describe Type 1 retinopathy of prematurity (ROP) and its laser treatment outcomes in premature infants with birth weight > 1250 g in Eastern China. A retrospective review of 3175 ROP records was conducted at Shanghai Eye & ENT Hospital of Fudan University. The records were collected at the ROP clinic from 2006 to 2014, including their demographic and medical information such as gestational age, birth weight, supplemental oxygen therapy, systemic complications, ROP stage, location, presence of plus disease. All infants were examined by RetCam fundus camera. Those with Type 1 ROP were also examined by indirect ophthalmoscope before undergoing transpupillary laser treatment. A total of 12 infants (24 eyes) with Type 1 ROP and birth weight > 1250 g were enrolled. All infants enrolled had plus disease and ROP in zone II retina. Specifically, 16 eyes (67%) had stage 2 ROP. 8 eyes (33%) had stage 3 ROP. ROP regressed in 23 eyes (96%) following laser treatment. Partial retinal detachment developed in one eye (4%). No severe involution sequelaes or laser-related complications were recorded. Mean follow-up was 30±6 weeks. Type 1 ROP may occur in large premature infants who have undergone supplemental oxygen therapy. This Type 1 ROP is mainly located in zone II retina. Laser treatment is a safe and effective intervention for these infants.

Validation of the Children's Hospital of Philadelphia Retinopathy of Prematurity (CHOP ROP) Model.

PubMed

Binenbaum, Gil; Ying, Gui-Shuang; Tomlinson, Lauren A

2017-08-01

The Children's Hospital of Philadelphia Retinopathy of Prematurity (CHOP ROP) model uses birth weight (BW), gestational age at birth (GA), and weight gain rate to predict the risk of severe retinopathy of prematurity (ROP). In a model development study, it predicted all infants requiring treatment, while greatly reducing the number of examinations compared with current screening guidelines. To validate the CHOP ROP model in a multicenter cohort that is large enough to obtain a precise estimate of the model's sensitivity for treatment-requiring ROP. This investigation was a secondary analysis of data from the Postnatal Growth and Retinopathy of Prematurity (G-ROP) Study. The setting was 30 hospitals in the United States and Canada between January 1, 2006, and June 30, 2012. The dates of analysis were September 28 to October 5, 2015. Participants were premature infants at risk for ROP with a known ROP outcome. Sensitivity for Early Treatment of Retinopathy of Prematurity type 1 ROP and potential reduction in the number of infants requiring examinations. In the primary analysis, the CHOP ROP model was applied weekly to predict the risk of ROP. If the risk was above a cut-point level (high risk), examinations were indicated, while low-risk infants received no examinations. In a secondary analysis, low-risk infants received fewer examinations rather than no examinations. Participants included 7483 premature infants at risk for ROP with a known ROP outcome. Their median BW was 1070 g (range, 310-3000 g), and their median GA was 28 weeks (range, 22-35 weeks). Among them, 3575 (47.8%) were female, and their race/ethnicity was 3615 white (48.3%), 2310 black (30.9%), 233 Asian (3.1%), 93 Pacific Islander (1.2%), and 40 American Indian/Alaskan native (0.5%). The original CHOP ROP model correctly predicted 452 of 459 infants who developed type 1 ROP (sensitivity, 98.5%; 95% CI, 96.9%-99.3%), reducing the number of infants requiring examinations by 34.3% if only high-risk infants received examinations. Lowering the cut point to capture all type 1 ROP cases (sensitivity, 100%; 95% CI, 99.2%-100%) resulted in only 6.8% of infants not requiring examinations. However, if low-risk infants were examined at 37 weeks' postmenstrual age and followed up only if ROP was present at that examination, all type 1 ROP cases would be captured, and the number of examinations performed among infants with GA exceeding 27 weeks would be reduced by 28.4%. The CHOP ROP model demonstrated high but not 100% sensitivity and may be better used to reduce examination frequency. The model might be used reliably to guide a modified ROP screening schedule and decrease the number of examinations performed.

The trend of retinopathy of prematurity in Malaysia from 1992 to 2001 based on a nationwide blind schools study.

PubMed

Chang, Khai Meng; Patel, Dinesh Kumar; Tajunisah, Iqbal; Subrayan, Visvaraja

2015-03-01

Retinopathy of prematurity (ROP) is one of the most important causes of childhood blindness worldwide. The trend of ROP in Malaysia was unclear because there was no national registry before 2002. The purpose of this study is to analyze ROP students of different ages in the schools for the blind in Malaysia in order to evaluate the trend of ROP from 1992 to 2001. Data were obtained from a previous survey of 24 blind schools. It was found that 78 students or 17.4% were blind/severely visual impaired as a result of ROP. There was a significant surge in the number of ROP students who were born in 1994 when the use of synthetic surfactants was first introduced in Malaysia; otherwise there was no increasing trend in the number of students with ROP. However, the percentage of ROP in total was increasing, which indicates that ROP is becoming a more important cause of childhood blindness in this country. © 2012 APJPH.

The ropAe gene encodes a porin-like protein involved in copper transit in Rhizobium etli CFN42.

PubMed

González-Sánchez, Antonio; Cubillas, Ciro A; Miranda, Fabiola; Dávalos, Araceli; García-de Los Santos, Alejandro

2017-12-27

Copper (Cu) is an essential micronutrient for all aerobic forms of life. Its oxidation states (Cu + /Cu 2+ ) make this metal an important cofactor of enzymes catalyzing redox reactions in essential biological processes. In gram-negative bacteria, Cu uptake is an unexplored component of a finely regulated trafficking network, mediated by protein-protein interactions that deliver Cu to target proteins and efflux surplus metal to avoid toxicity. Rhizobium etliCFN42 is a facultative symbiotic diazotroph that must ensure its appropriate Cu supply for living either free in the soil or as an intracellular symbiont of leguminous plants. In crop fields, rhizobia have to contend with copper-based fungicides. A detailed deletion analysis of the pRet42e (505 kb) plasmid from an R. etli mutant with enhanced CuCl 2 tolerance led us to the identification of the ropAe gene, predicted to encode an outer membrane protein (OMP) with a β-barrel channel structure that may be involved in Cu transport. In support of this hypothesis, the functional characterization of ropAe revealed that: (I) gene disruption increased copper tolerance of the mutant, and its complementation with the wild-type gene restored its wild-type copper sensitivity; (II) the ropAe gene maintains a low basal transcription level in copper overload, but is upregulated when copper is scarce; (III) disruption of ropAe in an actP (copA) mutant background, defective in copper efflux, partially reduced its copper sensitivity phenotype. Finally, BLASTP comparisons and a maximum likelihood phylogenetic analysis highlight the diversification of four RopA paralogs in members of the Rhizobiaceae family. Orthologs of RopAe are highly conserved in the Rhizobiales order, poorly conserved in other alpha proteobacteria and phylogenetically unrelated to characterized porins involved in Cu or Mn uptake. © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

Retinopathy of prematurity and serum level of insulin-like growth factor-1.

PubMed

Banjac, Lidija; Bokan, Vesna

2012-06-01

The aim of our study was to measure and compare serum insulin-like growth factor-1 (IGF-1) levels at postmenstrual age of 33 weeks between preterm infants with and without retinopathy of prematurity (ROP). ROP occurs in two phases. Low serum levels of IGF-1 during ROP phase 1 have been found to correlate with the severity of ROP. ROP phase 2 begins around postmenstrual week 33. We conducted a prospective cohort study to measure serum IGF-1 levels in premature infants at postmenstrual age of 33 weeks. The study included all premature infants (N = 74), gestational age < or = 33 weeks, hospitalized at Department of Neonatology, Clinical Center of Montenegro, from April 2008 to July 2009. The incidence of ROP in the study cohort was 50.7%. Infants with ROP had a significantly lower birth weight and significantly shorter gestational age. The mean level of IGF-1 at postmenstrual age of 33 weeks was 23.7 mcg/L. Study results showed that there was no significant difference in serum IGF-1 level between newborns with and without ROP at postmenstrual age of 33 weeks (in newborns with ROP, it was the beginning of ROP phase 2). A large controlled study with repeated measurement of IGF-1 level in the neonatal period is needed to confirm that restoration of IGF-I level occurs in ROP phase 2, i.e. that the low level of IGF-1 is only a feature of ROP phase 1.

Corrected and Republished from: Activation Status-Coupled Transient S-Acylation Determines Membrane Partitioning of a Plant Rho-Related GTPase.

PubMed

Sorek, Nadav; Poraty, Limor; Sternberg, Hasana; Buriakovsky, Ella; Bar, Einat; Lewinsohn, Efraim; Yalovsky, Shaul

2017-12-01

ROPs or RACs are plant Rho-related GTPases implicated in the regulation of a multitude of signaling pathways that function at the plasma membrane via posttranslational lipid modifications. The relationships between ROP activation status and membrane localization has not been established. Here, we show that endogenous ROPs, as well as a transgenic His 6 -green fluorescent protein (GFP)- Arabidopsis thaliana ROP6 (AtROP6) fusion protein, were partitioned between Triton X-100-soluble and -insoluble membranes. In contrast, the His 6 -GFP-Atrop6 CA activated mutant accumulated exclusively in detergent-resistant membranes. GDP induced accumulation of ROPs in Triton-soluble membranes, whereas GTPγS induced accumulation of ROPs in detergent-resistant membranes. Recombinant wild-type and constitutively active AtROP6 proteins were purified from Arabidopsis plants, and in turn, their lipids were cleaved and analyzed by gas chromatography-coupled mass spectrometry. In Triton-soluble membranes, the wild-type AtROP6 was only prenylated, primarily by geranylgeranyl. The activated AtROP6 that accumulated in detergent-resistant membranes was modified by prenyl and acyl lipids, identified as palmitic and stearic acids. Consistently, activated His 6 -GFP-Atrop6 CA mS 156 , in which C156 was mutated into serine, accumulated in Triton-soluble membranes. These findings show that upon GTP binding and activation, AtROP6, and possibly other ROPs, are transiently S-acylated, inducing their partitioning into detergent-resistant membranes. Copyright © 2017 American Society for Microbiology.

Corrected and Republished from: Activation Status-Coupled Transient S-Acylation Determines Membrane Partitioning of a Plant Rho-Related GTPase

PubMed Central

Sorek, Nadav; Poraty, Limor; Sternberg, Hasana; Buriakovsky, Ella; Bar, Einat; Lewinsohn, Efraim

2017-01-01

ABSTRACT ROPs or RACs are plant Rho-related GTPases implicated in the regulation of a multitude of signaling pathways that function at the plasma membrane via posttranslational lipid modifications. The relationships between ROP activation status and membrane localization has not been established. Here, we show that endogenous ROPs, as well as a transgenic His6-green fluorescent protein (GFP)-Arabidopsis thaliana ROP6 (AtROP6) fusion protein, were partitioned between Triton X-100-soluble and -insoluble membranes. In contrast, the His6-GFP-Atrop6CA activated mutant accumulated exclusively in detergent-resistant membranes. GDP induced accumulation of ROPs in Triton-soluble membranes, whereas GTPγS induced accumulation of ROPs in detergent-resistant membranes. Recombinant wild-type and constitutively active AtROP6 proteins were purified from Arabidopsis plants, and in turn, their lipids were cleaved and analyzed by gas chromatography-coupled mass spectrometry. In Triton-soluble membranes, the wild-type AtROP6 was only prenylated, primarily by geranylgeranyl. The activated AtROP6 that accumulated in detergent-resistant membranes was modified by prenyl and acyl lipids, identified as palmitic and stearic acids. Consistently, activated His6-GFP-Atrop6CAmS156, in which C156 was mutated into serine, accumulated in Triton-soluble membranes. These findings show that upon GTP binding and activation, AtROP6, and possibly other ROPs, are transiently S-acylated, inducing their partitioning into detergent-resistant membranes. PMID:28894027

Beta-blockers for prevention and treatment of retinopathy of prematurity in preterm infants.

PubMed

Kaempfen, Siree; Neumann, Roland P; Jost, Kerstin; Schulzke, Sven M

2018-03-02

Retinopathy of prematurity (ROP) is a vision-threatening disease of preterm neonates. The use of beta-adrenergic blocking agents (beta-blockers), which modulate the vasoproliferative retinal process, may reduce the progression of ROP or even reverse established ROP. To determine the effect of beta-blockers on short-term structural outcomes, long-term functional outcomes, and the need for additional treatment, when used either as prophylaxis in preterm infants without ROP, stage 1 ROP (zone I), or stage 2 ROP (zone II) without plus disease or as treatment in preterm infants with at least prethreshold ROP. We searched the Cochrane Neonatal Review Group Specialized Register; CENTRAL (in the Cochrane Library Issue 7, 2017); Embase (January 1974 to 7 August 2017); PubMed (January 1966 to 7 August 2017); and CINAHL (January 1982 to 7 August 2017). We checked references and cross-references and handsearched abstracts from the proceedings of the Pediatric Academic Societies Meetings. We considered for inclusion randomised or quasi-randomised clinical trials that used beta-blockers for prevention or treatment of ROP in preterm neonates of less than 37 weeks' gestational age. We used the standard methods of Cochrane and the Cochrane Neonatal Review Group. We used the GRADE approach to assess the quality of evidence. We included three randomised trials (N = 366) in this review. Two of these studies were at high risk of bias. All studies reported on prevention of ROP and compared oral propranolol with placebo or no treatment. We found no trials assessing beta-blockers in infants with established stage 2 or higher ROP with plus disease.In one trial, study medication was started after one week of life, i.e. prior to the first ROP screening. The other two trials included preterm infants if they had stage 2 or lower ROP without plus disease. Based on the GRADE assessment, we considered evidence to be of low quality for the following outcomes: rescue treatment with anti-VEGF or laser therapy; and arterial hypotension or bradycardia requiring inotropic support. Evidence was of moderate quality for the following outcomes: progression to stage 2 with plus disease; progression to stage 3 ROP; and progression to stage 4 or 5 ROP.Meta-analysis of three trials (N = 366) suggested beneficial effects of oral beta-blockers on the risk of requiring anti-VEGF agents (typical risk ratio (RR) 0.32, 95% confidence interval (CI) 0.12 to 0.86; I² = 0%; typical risk difference (RD) -0.06, 95% CI -0.10 to -0.01; I² = 75%; number needed to treat for an additional beneficial outcome (NNTB) 18, 95% CI 14 to 84) and laser therapy (typical RR 0.54, 95% CI 0.32 to 0.89; typical RD -0.09, 95% CI -0.16 to -0.02; I² = 31%; NNTB 12, 95% CI 8 to 47). Meta-analysis of two trials (N = 161) demonstrated a beneficial effect of oral beta-blockers on progression to stage 3 ROP (typical RR 0.60, 95% CI 0.37 to 0.96; I² = 0%; typical RD -0.15, 95% CI -0.28 to -0.02; I² = 73%; NNTB 7, 95% CI 5 to 67). There was no significant effect of oral beta-blockers on progression to stage 2 ROP with plus disease or to stage 4 or 5 ROP. Although meta-analysis did not indicate a significant effect of beta-blockers on arterial hypotension or bradycardia, propranolol dosage in one study was reduced by 50% in infants of less than 26 weeks' gestational age due to severe hypotension, bradycardia, and apnoea in several participants. Analyses did not indicate significant effects of beta-blockers on complications of prematurity or mortality. None of the trials reported on long-term visual impairment. Limited evidence of low-to-moderate quality suggests that prophylactic administration of oral beta-blockers might reduce progression towards stage 3 ROP and decrease the need for anti-VEGF agents or laser therapy. The clinical relevance of those findings is unclear as no data on long-term visual impairment were reported. Adverse events attributed to oral propranolol at a dose of 2 mg/kg/d raise concerns regarding systemic administration of this drug for prevention of ROP at the given dose. There is insufficient evidence to determine the efficacy and safety of beta-blockers for prevention of ROP due to high risk of bias in two included trials and the lack of long-term functional outcomes. We would encourage researchers to conduct large, well-designed trials to confirm or refute the role of beta-blockers for prevention and treatment of ROP in preterm infants. Trials should report on long-term visual impairment. Researchers should consider dose-finding studies of systemic beta-blockers and topical administration of beta-blockers, in order to optimise drug delivery and minimise adverse events.

Incidence and Risk Factors of Retinopathy of Prematurity in Two Neonatal Intensive Care Units in North and South China

PubMed Central

Chen, Yi; Xun, Deng; Wang, Ya-Cong; Wang, Bin; Geng, Shao-Hui; Chen, Hui; Li, Yan-Tao; Li, Xiao-Xin

2015-01-01

Background: To investigate the incidence and risk factors of retinopathy of prematurity (ROP) in two Neonatal Intensive Care Units in North and South of China, respectively. Methods: We studied data concerning 472 infants with gestational age (GA) ≤34 weeks or birth weight (BW) ≤2000 g who were admitted to the Zhujiang Hospital of Southern Medical University and the Fourth Hospital of Shijiazhuang between January 1, 2011 and December 31, 2011. Clinical information about perinatal neonates was collected and was confirmed by reviewing medical charts. The incidence and severity of ROP were assessed in the screened population. Main outcome measures are the incidence and severity of ROP. The relationship of clinical risk factors and the development of ROP were analyzed. Results: The overall incidence of ROP was 12.7%, and the overall incidence of type 1 ROP was 2.3%; 9.4% of infants in Zhujiang Hospital had ROP compared to 15.0% infants in the Fourth Hospital of Shijiazhuang developed ROP, and the difference is statistically significant. ROP was significantly associated with GA (odds ratio [OR]: 0.77 [0.62–0.95], P = 0.015), BW (OR: 0.998 [0.996–0.999], P = 0.008), maternal supplemental oxygen administration before and during delivery (OR: 4.27 [1.21–15.10], P = 0.024) and preeclampsia (OR: 6.07 [1.73–21.36] P = 0.005). The risk factors for ROP are different in two hospitals. In Zhujiang Hospital, BW is the independent risk factors for ROP while GA, BW and preeclampsia in the Fourth Hospital in Shijiazhuang Conclusions: Retinopathy of prematurity incidence is different based on area. Incidence of ROP is still high in China. More efforts need to prevent ROP. PMID:25836612

Research on offense and defense technology for iOS kernel security mechanism

NASA Astrophysics Data System (ADS)

Chu, Sijun; Wu, Hao

2018-04-01

iOS is a strong and widely used mobile device system. It's annual profits make up about 90% of the total profits of all mobile phone brands. Though it is famous for its security, there have been many attacks on the iOS operating system, such as the Trident apt attack in 2016. So it is important to research the iOS security mechanism and understand its weaknesses and put forward targeted protection and security check framework. By studying these attacks and previous jailbreak tools, we can see that an attacker could only run a ROP code and gain kernel read and write permissions based on the ROP after exploiting kernel and user layer vulnerabilities. However, the iOS operating system is still protected by the code signing mechanism, the sandbox mechanism, and the not-writable mechanism of the system's disk area. This is far from the steady, long-lasting control that attackers expect. Before iOS 9, breaking these security mechanisms was usually done by modifying the kernel's important data structures and security mechanism code logic. However, after iOS 9, the kernel integrity protection mechanism was added to the 64-bit operating system and none of the previous methods were adapted to the new versions of iOS [1]. But this does not mean that attackers can not break through. Therefore, based on the analysis of the vulnerability of KPP security mechanism, this paper implements two possible breakthrough methods for kernel security mechanism for iOS9 and iOS10. Meanwhile, we propose a defense method based on kernel integrity detection and sensitive API call detection to defense breakthrough method mentioned above. And we make experiments to prove that this method can prevent and detect attack attempts or invaders effectively and timely.

Risk Score for Predicting Treatment-Requiring Retinopathy of Prematurity (ROP) in the Telemedicine Approaches to Evaluating Acute-Phase ROP Study.

PubMed

Ying, Gui-Shuang; VanderVeen, Deborah; Daniel, Ebenezer; Quinn, Graham E; Baumritter, Agnieshka

2016-10-01

To develop a risk score for predicting treatment-requiring retinopathy of prematurity (TR-ROP) in the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity (e-ROP) study. Second analyses of an observational cohort study. Infants with birth weight (BW) <1251 g who had ≥1 imaging session by 34 weeks of postmenstrual age (PMA) and ≥1 subsequent retinopathy of prematurity (ROP) examination for determining TR-ROP by study-certified ophthalmologists. Nonphysician trained readers evaluated wide-field retinal image sets for characteristics of ROP, pre-plus/plus disease, and retinal hemorrhage. Risk score points for predicting TR-ROP were derived from the regression coefficients of significant predictors in a multivariate logistic regression model. TR-ROP. Eighty-five of 771 infants (11.0%) developed TR-ROP. In a multivariate model, significant predictors for TR-ROP were gestational age (GA) (odds ratio [OR], 5.7; 95% confidence interval [CI], 1.7-18.9 for ≤25 vs. ≥28 weeks), need for respiratory support (OR, 7.0; 95% CI, 1.3-37.1 for high-frequency oscillatory ventilation vs. no respiratory support), slow weight gain (OR, 2.4; 95% CI, 1.2-4.6 for weight gain ≤12 g/day vs. >15 g/day), and image findings at the first image session including number of quadrants with pre-plus (OR, 3.8; 95% CI, 1.5-9.7 for 4 pre-plus quadrants vs. no pre-plus), stage and zone of ROP (OR, 4.7; 95% CI, 2.1-11.8 for stage 1-2 zone I, OR, 5.9; 95% CI, 2.1-16.6 for stage 3 zone I vs. no ROP), and presence of blot hemorrhage (OR, 3.1; 95% CI, 1.4-6.7). Image findings predicted TR-ROP better than GA (area under receiver operating characteristic curve [AUC] = 0.82 vs. 0.75, P = 0.03). The risk of TR-ROP steadily increased with higher risk score and predicted TR-ROP well (AUC = 0.88; 95% CI, 0.85-0.92). Risk score ≥3 points for predicting TR-ROP had a sensitivity of 98.8%, specificity of 40.1%, and positive and negative predictive values of 17.0% and 99.6%, respectively. Image characteristics at 34 PMA weeks or earlier independently predict TR-ROP. If externally validated in other infants, risk score, calculated from image findings, GA, weight gain, and respiratory support, enables early identification of infants in need of increased surveillance for TR-ROP. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

The C-terminal hypervariable domain targets Aradopsis ROP9 to the invaginated pollen tube plasma membrane

USDA-ARS?s Scientific Manuscript database

Rop9 is a small GTPase of the Type II class, whereas the often studied type I Rops play roles during pollen tube growth. In pollen, Rop9 is located at the invaginated plasma membrane that surrounds the sperm cells, whereas type I Rops are located at the apical membrane of the pollen tube. The C-ter...

Does observer bias contribute to variations in the rate of retinopathy of prematurity between centres?

PubMed

Darlow, Brian A; Elder, Mark J; Horwood, L John; Donoghue, Deborah A; Henderson-Smart, David J

2008-01-01

We aimed to indirectly assess the contribution from observer bias to between centre variability in the incidence of acute retinopathy of prematurity (ROP). The Australian and New Zealand Neonatal Network (ANZNN) collected data on the highest stage of acute ROP in either eye in 2286 infants born at less than 29 weeks in 1998-1999 and cared for in one of 25 neonatal intensive care units (NICUs). Chi-squared analysis was used to detect differences in the proportion of stages of ROP for each neonatal intensive care unit. These proportions were compared with those reported in two large studies of treatment for ROP. The incidence of acute ROP in the ANZNN cohort was 42% and the ratio of stage 1:2:3 ROP was 1.5:1.9:1. There was considerable variation in both the incidence of acute ROP and the proportions with stage 1:2:3 ROP between centres. A chi-squared test determined that the assignment of stages 1, 2 and 3/4 ROP was not independent of centre (chi(2)(48) = 165.2; P < 0.0001). Treatment of stage 3 ROP varied between 15% and 120%, indicating some eyes were treated at less than stage 3. The data are highly suggestive of observer bias contributing to the observed between centre variation in the incidence of acute ROP. In neonatal intervention studies where acute ROP is an outcome it would seem important to have an accreditation process for examining ophthalmologists, and there are similar arguments for neonatal networks which collect these data.

Surface modification of hydroxyapatite nanoparticles by poly( L-phenylalanine) via ROP of L-phenylalanine N-carboxyanhydride (Pha-NCA)

NASA Astrophysics Data System (ADS)

Dai, Yanfeng; Xu, Min; Wei, Junchao; Zhang, Haobin; Chen, Yiwang

2012-01-01

The surface of hydroxyapatite nanoparticles was modified by poly(L-phenylalanine) via the ring opening polymerization (ROP) of L-phenylalanine N-carboxyanhydride. The preparation procedure was monitored by Fourier transform infrared spectroscopy (FTIR), and the modified hydroxyapatite was characterized by thermal gravimetric analysis (TGA) and X-ray diffraction (XRD). The results showed that the surface grafting amounts of poly(L-phenylalanine) on HA ranging from 20.26% to 38.92% can be achieved by tuning the reaction condition. The XRD patterns demonstrated that the crystalline structure of the modified hydroxyapatite was nearly the same with that of HA, implying that the ROP was an efficient surface modification method. The MTT assay proved that the biocompatibility of modified HA was very good, which showed the potential application of modified HA in bone tissue engineering.

Can We Stop the Current Epidemic of Blindness From Retinopathy of Prematurity?

PubMed

Dutta, Sourabh; Raghuveer, Talkad; Vinekar, Anand; Dogra, Mangat Ram

2016-11-07

Retinopathy of Prematurity (ROP) is a retinal vascular disease of the premature infant. There have been significant advances in the understanding of the pathogenesis, prevention, detection and treatment of severe ROP. In developed countries, all premature infants at risk for ROP are screened routinely based on national guidelines and treatment is prompt, resulting in good visual outcomes. Blindness from ROP is a rare event in these countries. However, there is an ongoing epidemic of ROP- induced blindness in India. The reasons for this epidemic of ROP blindness are many and include increasing survival of premature infants, lack of equipment such as oxygen-blenders and pulse oximeters that are necessary for safe use of supplemental oxygen in premature infants, lack of routine screening for ROP, lack of trained personnel for ROP screening, and lack of Ophthalmologists to promptly initiate treatment when infants develop severe ROP. All the identified causes can be resolved with a concerted national co-operative effort of Pediatricians, Neonatologists, Ophthalmologists, Indian Academy of Pediatrics, National Neonatology Forum, Indian Academy of Ophthalmologists, Government of India, and parents of premature infants. We feel that tt is possible to stop the current epidemic of preventable childhood blindness from ROP with concerted action by all stakeholders.

Incidence of Retinopathy of Prematurity in Extremely Premature Infants

PubMed Central

Şahin, Alparslan; Şahin, Muhammed; Türkcü, Fatih Mehmet; Cingü, Abdullah Kürşat; Yüksel, Harun; Çınar, Yasin; Arı, Şeyhmus; Çaça, İhsan

2014-01-01

Purpose. To investigate the incidence and the severity of retinopathy of prematurity (ROP) in extremely preterm infants born before 28 weeks of gestation in southeastern Turkey. Methods. A retrospective chart review was performed for infants born before 28 weeks of gestation. The following data were reviewed: gender, gestational age (GA), birth weight (BW), zone and stage of ROP, presence of plus disease, and treatment for ROP if needed. Infants were divided into 2 groups according to GA as follows: group 1 included infants of GAs 25 weeks and under; group 2 included infants of GAs less than 28 weeks and over 25 weeks. Results. The incidence of any ROP in the whole cohort, in group 1, and in group 2, was 66.0%, 95.5%, and 58.6%, respectively. Incidence of any ROP was significantly associated with BW and GA (P = 0.014 and P = 0.002, resp.). The overall incidence of type 1 ROP was 35.8% (59.1% in group 1 and 29.9% in group 2). Development of type 1 ROP was independently associated with GA. Conclusion. Any ROP was significantly associated with BW and GA. Extremely premature infants with lower GA were found to be more likely to develop type 1 ROP. BW cannot predict the development of type 1 ROP. PMID:24734191

Incidence of retinopathy of prematurity in extremely premature infants.

PubMed

Sahin, Alparslan; Sahin, Muhammed; Türkcü, Fatih Mehmet; Cingü, Abdullah Kürşat; Yüksel, Harun; Cınar, Yasin; Arı, Seyhmus; Caça, Ihsan

2014-01-01

Purpose. To investigate the incidence and the severity of retinopathy of prematurity (ROP) in extremely preterm infants born before 28 weeks of gestation in southeastern Turkey. Methods. A retrospective chart review was performed for infants born before 28 weeks of gestation. The following data were reviewed: gender, gestational age (GA), birth weight (BW), zone and stage of ROP, presence of plus disease, and treatment for ROP if needed. Infants were divided into 2 groups according to GA as follows: group 1 included infants of GAs 25 weeks and under; group 2 included infants of GAs less than 28 weeks and over 25 weeks. Results. The incidence of any ROP in the whole cohort, in group 1, and in group 2, was 66.0%, 95.5%, and 58.6%, respectively. Incidence of any ROP was significantly associated with BW and GA (P = 0.014 and P = 0.002, resp.). The overall incidence of type 1 ROP was 35.8% (59.1% in group 1 and 29.9% in group 2). Development of type 1 ROP was independently associated with GA. Conclusion. Any ROP was significantly associated with BW and GA. Extremely premature infants with lower GA were found to be more likely to develop type 1 ROP. BW cannot predict the development of type 1 ROP.

Pollen-tube tip growth requires a balance of lateral propagation and global inhibition of Rho-family GTPase activity

PubMed Central

Hwang, Jae-Ung; Wu, Guang; Yan, An; Lee, Yong-Jik; Grierson, Claire S.; Yang, Zhenbiao

2010-01-01

Rapid tip growth allows for efficient development of highly elongated cells (e.g. neuronal axons, fungal hyphae and pollen tubes) and requires an elaborate spatiotemporal regulation of the growing region. Here, we use the pollen tube as a model to investigate the mechanism regulating the growing region. ROPs (Rho-related GTPases from plants) are essential for pollen tip growth and display oscillatory activity changes in the apical plasma membrane (PM). By manipulating the ROP activity level, we showed that the PM distribution of ROP activity as an apical cap determines the tip growth region and that efficient tip growth requires an optimum level of the apical ROP1 activity. Excessive ROP activation induced the enlargement of the tip growth region, causing growth depolarization and reduced tube elongation. Time-lapse analysis suggests that the apical ROP1 cap is generated by lateral propagation of a localized ROP activity. Subcellular localization and gain- and loss-of-function analyses suggest that RhoGDI- and RhoGAP-mediated global inhibition limits the lateral propagation of apical ROP1 activity. We propose that the balance between the lateral propagation and the global inhibition maintains an optimal apical ROP1 cap and generates the apical ROP1 activity oscillation required for efficient pollen-tube elongation. PMID:20053639

Activation status-coupled transient S acylation determines membrane partitioning of a plant Rho-related GTPase.

PubMed

Sorek, Nadav; Poraty, Limor; Sternberg, Hasana; Bar, Enat; Lewinsohn, Efraim; Yalovsky, Shaul

2007-03-01

ROPs or RACs are plant Rho-related GTPases implicated in the regulation of a multitude of signaling pathways that function at the plasma membrane by virtue of posttranslational lipid modifications. The relationship between ROP activation status and membrane localization has not been established. Here we demonstrate that endogenous ROPs, as well as a transgenic His(6)-green fluorescent protein (GFP)-AtROP6 fusion protein, were partitioned between Triton X-100-soluble and -insoluble membranes. In contrast, an activated His(6)-GFP-Atrop6(CA) mutant protein accumulated exclusively in detergent-resistant membranes. GDP induced accumulation of ROPs in Triton-soluble membranes, whereas GTPgammaS induced accumulation of ROPs in detergent-resistant membranes. Recombinant wild-type and constitutively active AtROP6 isoforms were purified from Arabidopsis plants, and their lipids were cleaved and analyzed by gas chromatography-coupled mass spectrometry. In Triton-soluble membranes, wild-type AtROP6 was only prenylated, primarily by geranylgeranyl. The activated AtROP6 that accumulated in detergent-resistant membranes was modified by prenyl and acyl lipids. The acyl lipids were identified as palmitic and stearic acids. In agreement, activated His(6)-GFP-Atrop6(CA)mS(156) in which cysteine(156) was mutated into serine accumulated in Triton-soluble membranes. These findings show that upon GTP binding and activation, AtROP6 and possibly other ROPs are transiently S acylated, which induces their partitioning into detergent-resistant membranes.

Ethylene negatively regulates transcript abundance of ROP-GAP rheostat-encoding genes and affects apoplastic reactive oxygen species homeostasis in epicarps of cold stored apple fruits

PubMed Central

Zermiani, Monica; Zonin, Elisabetta; Nonis, Alberto; Begheldo, Maura; Ceccato, Luca; Vezzaro, Alice; Baldan, Barbara; Trentin, Annarita; Masi, Antonio; Pegoraro, Marco; Fadanelli, Livio; Teale, William; Palme, Klaus; Quintieri, Luigi; Ruperti, Benedetto

2015-01-01

Apple (Malus×domestica Borkh) fruits are stored for long periods of time at low temperatures (1 °C) leading to the occurrence of physiological disorders. ‘Superficial scald’ of Granny Smith apples, an economically important ethylene-dependent disorder, was used as a model to study relationships among ethylene action, the regulation of the ROP-GAP rheostat, and maintenance of H2O2 homeostasis in fruits during prolonged cold exposure. The ROP-GAP rheostat is a key module for adaptation to low oxygen in Arabidopsis through Respiratory Burst NADPH Oxidase Homologs (RBOH)-mediated and ROP GTPase-dependent regulation of reactive oxygen species (ROS) homeostasis. Here, it was shown that the transcriptional expression of several components of the apple ROP-GAP machinery, including genes encoding RBOHs, ROPs, and their ancillary proteins ROP-GEFs and ROP-GAPs, is coordinately and negatively regulated by ethylene in conjunction with the progressive impairment of apoplastic H2O2 homeostatic levels. RNA sequencing analyses showed that several components of the known ROP- and ROS-associated transcriptional networks are regulated along with the ROP-GAP rheostat in response to ethylene perception. These findings may extend the role of the ROP-GAP rheostat beyond hypoxic responses and suggest that it may be a functional regulatory node involved in the integration of ethylene and ROS signalling pathways in abiotic stress. PMID:26428066

Increased frequency of retinopathy of prematurity over the last decade and significant regional differences.

PubMed

Holmström, Gerd; Tornqvist, Kristina; Al-Hawasi, Abbas; Nilsson, Åsa; Wallin, Agneta; Hellström, Ann

2018-03-01

Retinopathy of prematurity (ROP) causes childhood blindness globally in prematurely born infants. Although increased levels of oxygen supply lead to increased survival and reduced frequency of cerebral palsy, increased incidence of ROP is reported. With the help of a Swedish register for ROP, SWEDROP, national and regional incidences of ROP and frequencies of treatment were evaluated from 2008 to 2015 (n = 5734), as well as before and after targets of provided oxygen changed from 85-89% to 91-95% in 2014. Retinopathy of prematurity (ROP) was found in 31.9% (1829/5734) of all infants with a gestational age (GA) of <31 weeks at birth and 5.7% of the infants (329/5734) had been treated for ROP. Analyses of the national data revealed an increased incidence of ROP during the 8-year study period (p = 0.003), but there was no significant increase in the frequency of treatment. There were significant differences between the seven health regions of Sweden, regarding both incidence of ROP and frequency of treatment (p < 0.001). Comparison of regional data before and after the new oxygen targets revealed a significant increase in treated ROP in one region [OR: 2.24 (CI: 1.11-4.49), p = 0.024] and a borderline increase in one other [OR: 3.08 (CI: 0.99-9.60), p = 0.052]. The Swedish national ROP register revealed an increased incidence of ROP during an 8-year period and significant regional differences regarding the incidence of ROP and frequency of treatment. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Screening Tool for Early Postnatal Prediction of Retinopathy of Prematurity in Preterm Newborns (STEP-ROP).

PubMed

Ricard, Caroline A; Dammann, Christiane E L; Dammann, Olaf

2017-01-01

Retinopathy of prematurity (ROP) is a disorder of the preterm newborn characterized by neurovascular disruption in the immature retina that may cause visual impairment and blindness. To develop a clinical screening tool for early postnatal prediction of ROP in preterm newborns based on risk information available within the first 48 h of postnatal life. Using data submitted to the Vermont Oxford Network (VON) between 1995 and 2015, we created logistic regression models based on infants born <28 completed weeks gestational age. We developed a model with 60% of the data and identified birth weight, gestational age, respiratory distress syndrome, non-Hispanic ethnicity, and multiple gestation as predictors of ROP. We tested the model in the remaining 40%, performed tenfold cross-validation, and tested the score in ELGAN study data. Of the 1,052 newborns in the VON database, 627 recorded an ROP status. Forty percent had no ROP, 40% had mild ROP (stages 1 and 2), and 20% had severe ROP (stages 3-5). We created a weighted score to predict any ROP based on the multivariable regression model. A cutoff score of 5 had the best sensitivity (95%, 95% CI 93-97), while maintaining a strong positive predictive value (63%, 95% CI 57-68). When applied to the ELGAN data, sensitivity was lower (72%, 95% CI 69-75), but PPV was higher (80%, 95% CI 77-83). STEP-ROP is a promising screening tool. It is easy to calculate, does not rely on extensive postnatal data collection, and can be calculated early after birth. Early ROP screening may help physicians limit patient exposure to additional risk factors, and may be useful for risk stratification in clinical trials aimed at reducing ROP. © 2017 S. Karger AG, Basel.

Retinopathy of prematurity: Revisiting incidence and risk factors from Oman compared to other countries.

PubMed

Reyes, Zenaida Soriano; Al-Mulaabed, Sharef Waadallah; Bataclan, Flordeliz; Montemayor, Cheryl; Ganesh, Anuradha; Al-Zuhaibi, Sanaa; Al-Waili, Huda; Al-Wahibi, Fatma

2017-01-01

The purpose of this study is to determine the incidence of retinopathy of prematurity (ROP) and the maternal/neonatal risk factors at a tertiary care hospital in Oman, compared to other countries. A retrospective analysis of premature neonates born with gestational age (GA) 24-32 weeks at Sultan Qaboos University Hospital, Oman, from January 2007 to December 2010. Maternal and neonatal in-hospital course was retrieved. The incidence of ROP was reported. Risk factors analyses were performed using univariate and multivariate statistics. A total of 171 neonates (57% males, 43% females) were included for analysis. The incidence of ROP (any stage) was 69/171 (40.4%). Infants with ROP had significantly lower GA (27.7±2 weeks) compared to non-ROP group (30.2±1.7 weeks), P < 0.001),P < 0.001) and significantly lower birth weight (BW) (948 ± 242 g in ROP group vs. 1348 ± 283 g in non-ROP group;P < 0.001). Other significant risk factors associated with ROP were: small for GA, respiratory distress syndrome, requirement for ventilation, duration of ventilation or oxygen therapy, bronchopulmonary dysplasia, hyperglycemia, late onset sepsis (clinical or proven), necrotizing enterocolitis, patent ductus arteriosus, seizures, and number of blood transfusions. There was no significant difference in maternal characteristics between the ROP and non-ROP groups except that mothers of infants with ROP were found to be significantly younger. Logistic regression analysis revealed early GA, low BW, duration of Oxygen therapy, and late-onset clinical or proven sepsis as independent risk factors. ROP is still commonly encountered in neonatal practice in Oman and other countries. Early GA, low BW, and prolonged oxygen therapy continue to be the main risk factors associated with the occurrence of ROP in our setting. In addition, an important preventable risk factor identified in our cohort includes clinical or proven late-onset sepsis.

Retinopathy of prematurity: Revisiting incidence and risk factors from Oman compared to other countries

PubMed Central

Reyes, Zenaida Soriano; Al-Mulaabed, Sharef Waadallah; Bataclan, Flordeliz; Montemayor, Cheryl; Ganesh, Anuradha; Al-Zuhaibi, Sanaa; Al-Waili, Huda; Al-Wahibi, Fatma

2017-01-01

Purpose: The purpose of this study is to determine the incidence of retinopathy of prematurity (ROP) and the maternal/neonatal risk factors at a tertiary care hospital in Oman, compared to other countries. Patients and Methods: A retrospective analysis of premature neonates born with gestational age (GA) 24–32 weeks at Sultan Qaboos University Hospital, Oman, from January 2007 to December 2010. Maternal and neonatal in-hospital course was retrieved. The incidence of ROP was reported. Risk factors analyses were performed using univariate and multivariate statistics. Results: A total of 171 neonates (57% males, 43% females) were included for analysis. The incidence of ROP (any stage) was 69/171 (40.4%). Infants with ROP had significantly lower GA (27.7±2 weeks) compared to non-ROP group (30.2±1.7 weeks), P < 0.001),P < 0.001) and significantly lower birth weight (BW) (948 ± 242 g in ROP group vs. 1348 ± 283 g in non-ROP group;P < 0.001). Other significant risk factors associated with ROP were: small for GA, respiratory distress syndrome, requirement for ventilation, duration of ventilation or oxygen therapy, bronchopulmonary dysplasia, hyperglycemia, late onset sepsis (clinical or proven), necrotizing enterocolitis, patent ductus arteriosus, seizures, and number of blood transfusions. There was no significant difference in maternal characteristics between the ROP and non-ROP groups except that mothers of infants with ROP were found to be significantly younger. Logistic regression analysis revealed early GA, low BW, duration of Oxygen therapy, and late-onset clinical or proven sepsis as independent risk factors. Conclusion: ROP is still commonly encountered in neonatal practice in Oman and other countries. Early GA, low BW, and prolonged oxygen therapy continue to be the main risk factors associated with the occurrence of ROP in our setting. In addition, an important preventable risk factor identified in our cohort includes clinical or proven late-onset sepsis. PMID:28298861

Retinopathy of prematurity screening criteria in Iran: new screening guidelines.

PubMed

Roohipoor, Ramak; Karkhaneh, Reza; Farahani, Afsar; Ebrahimiadib, Nazanin; Modjtahedi, Bobeck; Fotouhi, Akbar; Yaseri, Mehdi; Khodabande, Alireza; Zarei, Mohammad; Imani Fuladi, Marjan; Taheri, Arash; Riazi Esfahani, Mohammad; Loewenstein, John

2016-07-01

To test the applicability of existing retinopathy of prematurity (ROP) guidelines on Iranian patients and to develop novel ROP screening criteria in Iran. Both eyes of 1932 infants born ≤37 weeks of gestation and/or weighting ≤3000 g were included in this prospective cohort study that was conducted across nine neonatal intensive care units and a tertiary eye hospital ROP clinic. The patients were examined for ROP and the need for treatment (type 1 ROP or worse). All the patients were screened 4 weeks after birth or at 31 weeks of postmenstrual age, whichever was later. The patients were followed until retinal vascularisation was completed or the patients reached 50 weeks of gestational age (GA) without prethreshold ROP. A receiver operating characteristic curve was used to determine the best screening criteria for ROP. Screening criteria from other countries were applied to our patient data to determine their ability to appropriately detect ROP. Patients with ROP requiring treatment. The mean GA±SD and birth weight (BW)±SD of the screened patients were 32±2.7 weeks and 1713±516 g, respectively. Using criteria of GA≤32 weeks or BW ≤2000 yielded sensitivity and specificity of 100% and 26.7%, respectively, for treatment requiring ROP regardless of clinical comorbidities. Using screening recommendations of American Academy of Pediatrics would miss 25.4% of ROP and 8.4%ROP requiring treatment in our cohort. Other countries screening recommendations would result in a significant amount of missed cases of treatment requiring ROP when applied to Iran. As a result, we have proposed new guidelines for premature babies in Iran. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The Arabidopsis Rho of Plants GTPase AtROP6 Functions in Developmental and Pathogen Response Pathways1[C][W][OA

PubMed Central

Poraty-Gavra, Limor; Zimmermann, Philip; Haigis, Sabine; Bednarek, Paweł; Hazak, Ora; Stelmakh, Oksana Rogovoy; Sadot, Einat; Schulze-Lefert, Paul; Gruissem, Wilhelm; Yalovsky, Shaul

2013-01-01

How plants coordinate developmental processes and environmental stress responses is a pressing question. Here, we show that Arabidopsis (Arabidopsis thaliana) Rho of Plants6 (AtROP6) integrates developmental and pathogen response signaling. AtROP6 expression is induced by auxin and detected in the root meristem, lateral root initials, and leaf hydathodes. Plants expressing a dominant negative AtROP6 (rop6DN) under the regulation of its endogenous promoter are small and have multiple inflorescence stems, twisted leaves, deformed leaf epidermis pavement cells, and differentially organized cytoskeleton. Microarray analyses of rop6DN plants revealed that major changes in gene expression are associated with constitutive salicylic acid (SA)-mediated defense responses. In agreement, their free and total SA levels resembled those of wild-type plants inoculated with a virulent powdery mildew pathogen. The constitutive SA-associated response in rop6DN was suppressed in mutant backgrounds defective in SA signaling (nonexpresser of PR genes1 [npr1]) or biosynthesis (salicylic acid induction deficient2 [sid2]). However, the rop6DN npr1 and rop6DN sid2 double mutants retained the aberrant developmental phenotypes, indicating that the constitutive SA response can be uncoupled from ROP function(s) in development. rop6DN plants exhibited enhanced preinvasive defense responses to a host-adapted virulent powdery mildew fungus but were impaired in preinvasive defenses upon inoculation with a nonadapted powdery mildew. The host-adapted powdery mildew had a reduced reproductive fitness on rop6DN plants, which was retained in mutant backgrounds defective in SA biosynthesis or signaling. Our findings indicate that both the morphological aberrations and altered sensitivity to powdery mildews of rop6DN plants result from perturbations that are independent from the SA-associated response. These perturbations uncouple SA-dependent defense signaling from disease resistance execution. PMID:23319551

Preterm-associated visual impairment and estimates of retinopathy of prematurity at regional and global levels for 2010

PubMed Central

Blencowe, Hannah; Lawn, Joy E.; Vazquez, Thomas; Fielder, Alistair; Gilbert, Clare

2013-01-01

Background: Retinopathy of prematurity (ROP) is a leading cause of potentially avoidable childhood blindness worldwide. We estimated ROP burden at the global and regional levels to inform screening and treatment programs, research, and data priorities. Methods: Systematic reviews and meta-analyses were undertaken to estimate the risk of ROP and subsequent visual impairment for surviving preterm babies by level of neonatal care, access to ROP screening, and treatment. A compartmental model was used to estimate ROP cases and numbers of visually impaired survivors. Results: In 2010, an estimated 184,700 (uncertainty range: 169,600–214,500) preterm babies developed any stage of ROP, 20,000 (15,500–27,200) of whom became blind or severely visually impaired from ROP, and a further 12,300 (8,300–18,400) developed mild/moderate visual impairment. Sixty-five percent of those visually impaired from ROP were born in middle-income regions; 6.2% (4.3–8.9%) of all ROP visually impaired infants were born at >32-wk gestation. Visual impairment from other conditions associated with preterm birth will affect larger numbers of survivors. Conclusion: Improved care, including oxygen delivery and monitoring, for preterm babies in all facility settings would reduce the number of babies affected with ROP. Improved data tracking and coverage of locally adapted screening/treatment programs are urgently required. PMID:24366462

Refractive status and optical components of premature babies with or without retinopathy of prematurity at 3-4 years old.

PubMed

Ouyang, Li-Juan; Yin, Zheng-Qin; Ke, Ning; Chen, Xin-Ke; Liu, Qin; Fang, Jing; Chen, Lin; Chen, Xiu-Rong; Shi, Hui; Tang, Ling; Pi, Lian-Hong

2015-01-01

To investigate the refractive status and optical components of premature babies with or without retinopathy of prematurity (ROP) at 3-4 years old, and to explore the influence of prematurity and ROP on the refractive status and optical components. Premature babies receiving fundus examination were recruited into ROP group and non-ROP group, with age-matched full-term babies as controls. The incidence of myopia was the highest in ROP (3/59, 5.08%). The incidence of astigmatism was significantly different between ROP (37.29%, 22/59) and controls (17.86%, 15/84). The corneal refractive power in ROP and non-ROP was more potent compared with controls (P<0.05); corneal curvature was steeper (P<0.05); lens thickness was thinner (P<0.05); ocular axial length was shorter P<0.05). The gestational age was negatively related to corneal astigmatism and astigmatism, positively associated with vitreous thickness and axial length. The birth-weight was negatively associated with corneal astigmatism, astigmatism and corneal refractive power, positively related to corneal radius of curvature, vitreous thickness and ocular axial length. Premature babies with or without ROP are susceptible to myopia and astigmatism. ROP, prematurity and low birth-weight synergistically influence the development of refractive status and optical components, of which the prematurity and low birth-weight are more important.

Retrospective cohort study shows that the risks for retinopathy of prematurity included birth age and weight, medical conditions and treatment.

PubMed

Ali, Aliaa A; Gomaa, Nancy A S; Awadein, Ahmed R; Al-Hayouti, Huda H; Hegazy, Ahmed I

2017-12-01

This study described the characteristics and risk factors of neonates who developed retinopathy of prematurity (ROP) and severe treatable ROP in two Egyptian neonatal intensive care units (NICUs). This retrospective cohort study comprised 108 preterm neonates who were screened for ROP after being admitted to the two NICUs run by Cairo University Hospital from June 2014 to May 2015. Patients were examined using digital fundus photography and indirect ophthalmoscopy was performed if ROP was detected. Retinopathy of prematurity occurred in 75 patients. Late-onset sepsis, ventilation and hypercapnia were independently associated with ROP. Patients who developed severe treatable ROP had a younger gestational age (GA) than patients who did not develop ROP or developed mild or moderate ROP (29 weeks, range 27-33 weeks versus 32 weeks, range 28-36 weeks, p = 0.002) and a lower birthweight (1200 g, range 980-1590 g versus 1460 g, range 770-2475 g, p = 0.029). The risk factors associated with severe treatable ROP included the duration of admission, the duration of incubator oxygen, late-onset sepsis, intraventricular haemorrhage, total parenteral nutrition and the duration of caffeine citrate therapy. This study showed that the risks for ROP were wide-ranging and included GA and weight, medical conditions and treatment. ©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Retinopathy of prematurity in Indonesia: Incidence and risk factors.

PubMed

Edy Siswanto, J; Sauer, Pieter Jj

2017-01-01

Retinopathy of prematurity (ROP) is a vaso-proliferative disease of the eye, which mainly affects preterm newborn infants with an incompletely vascularized retina. The incidence of ROP has increased in industrialized countries due to the increased survival of extremely low birth weight (ELBW) infants. ROP is also increasing in developing countries like Indonesia, where it is most likely due to the improved survival of ELBW infants. To ascertain the incidence of ROP and possible risk factors associated with the development of ROP in preterm infants in Indonesia. We reviewed the literature on the incidence and potential risk factors for the development of ROP in Indonesia, obtained data from three referral eye clinics and added data from our institution. The reported incidence of all stages of ROP in infants with a gestational age of <32 weeks ranged from 18-30%. One study showed that ROP also occurred at older gestational ages. Blindness due to ROP was seen in infants up to 35 weeks and with a birth weight of 2000 g. Retinopathy of prematurity is an important cause of ocular morbidity and blindness in Indonesia. The overall incidence of ROP in infants born below 32 weeks in Indonesia is higher than in developed countries, and it is seen in infants with older gestational ages. This might be due to a less strict monitoring during the use of oxygen in Indonesia compared to industrialized countries.

Screening for retinopathy of prematurity in a large tertiary neonatal intensive care unit in Turkey: frequency and risk factors.

PubMed

Sarikabadayi, Yusuf Unal; Aydemir, Ozge; Ozen, Zuhal Tunay; Aydemir, Cumhur; Tok, Levent; Oguz, Serife Suna; Erdeve, Omer; Uras, Nurdan; Dilmen, Ugur

2011-12-01

We aimed to determine applicable guidelines for screening of retinopathy of prematurity (ROP), and evaluate the contribution of risk factors for severe ROP. A prospective cohort study of neonates with a gestational age (GA) < 34 weeks or birth weight < 2000g who were admitted to the Neonatal Intensive Care Unit (NICU) of a tertiary level hospital was conducted. The study group was classified into three groups according to eye examination findings as no ROP, mild ROP and severe ROP. Of the 700 neonates screened, the frequencies of ROP for any stage and severe ROP were 32.7% and 3.1%, respectively. Laser photocoagulation was needed in 9.6% of neonates with ROP. None of the neonates with a GA ≥ 31 weeks required treatment. Any ROP was detected in 199 (53.6%) of the babies < 32 weeks (n = 371), 22 (5.9%) of whom were treated with laser photocoagulation. Independent risk factors for severe ROP in babies < 32 weeks GA were birth weight, duration of mechanical ventilation and patent ductus arteriosus (PDA). This is the largest prospective cohort study including infants younger than 34 weeks GA from Turkey. Our data which belongs to the last 1-year period shows lower incidence of severe ROP when compared to previous reports from Turkey. According to our data, screening babies smaller than 32 weeks GA or 1500g birth weight seems reasonable. In the presence of long duration of mechanical ventilation and PDA, screening should be intensified.

Long-term effects of retinopathy of prematurity (ROP) on rod and rod-driven function.

PubMed

Harris, Maureen E; Moskowitz, Anne; Fulton, Anne B; Hansen, Ronald M

2011-02-01

The purpose of this study was to determine whether recovery of scotopic sensitivity occurs in human ROP, as it does in the rat models of ROP. Following a cross-sectional design, scotopic electroretinographic (ERG) responses to full-field stimuli were recorded from 85 subjects with a history of preterm birth. In 39 of these subjects, dark adapted visual threshold was also measured. Subjects were tested post-term as infants (median age 2.5 months) or at older ages (median age 10.5 years) and stratified by severity of ROP: severe, mild, or none. Rod photoreceptor sensitivity, S (ROD), was derived from the a-wave, and post-receptor sensitivity, log σ, was calculated from the b-wave stimulus-response function. Dark adapted visual threshold was measured using a forced-choice preferential procedure. For S (ROD), the deficit from normal for age varied significantly with ROP severity but not with age group. For log σ, in mild ROP, the deficit was smaller in older subjects than in infants, while in severe ROP, the deficit was quite large in both age groups. In subjects who never had ROP, S (ROD) and log σ in both age groups were similar to those in term born controls. Deficits in dark adapted threshold and log σ were correlated in mild but not in severe ROP. The data are evidence that sensitivity of the post-receptor retina improves in those with a history of mild ROP. We speculate that beneficial reorganization of the post-receptor neural circuitry occurs in mild but not in severe ROP.

Ethylene negatively regulates transcript abundance of ROP-GAP rheostat-encoding genes and affects apoplastic reactive oxygen species homeostasis in epicarps of cold stored apple fruits.

PubMed

Zermiani, Monica; Zonin, Elisabetta; Nonis, Alberto; Begheldo, Maura; Ceccato, Luca; Vezzaro, Alice; Baldan, Barbara; Trentin, Annarita; Masi, Antonio; Pegoraro, Marco; Fadanelli, Livio; Teale, William; Palme, Klaus; Quintieri, Luigi; Ruperti, Benedetto

2015-12-01

Apple (Malus×domestica Borkh) fruits are stored for long periods of time at low temperatures (1 °C) leading to the occurrence of physiological disorders. 'Superficial scald' of Granny Smith apples, an economically important ethylene-dependent disorder, was used as a model to study relationships among ethylene action, the regulation of the ROP-GAP rheostat, and maintenance of H2O2 homeostasis in fruits during prolonged cold exposure. The ROP-GAP rheostat is a key module for adaptation to low oxygen in Arabidopsis through Respiratory Burst NADPH Oxidase Homologs (RBOH)-mediated and ROP GTPase-dependent regulation of reactive oxygen species (ROS) homeostasis. Here, it was shown that the transcriptional expression of several components of the apple ROP-GAP machinery, including genes encoding RBOHs, ROPs, and their ancillary proteins ROP-GEFs and ROP-GAPs, is coordinately and negatively regulated by ethylene in conjunction with the progressive impairment of apoplastic H2O2 homeostatic levels. RNA sequencing analyses showed that several components of the known ROP- and ROS-associated transcriptional networks are regulated along with the ROP-GAP rheostat in response to ethylene perception. These findings may extend the role of the ROP-GAP rheostat beyond hypoxic responses and suggest that it may be a functional regulatory node involved in the integration of ethylene and ROS signalling pathways in abiotic stress. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

The Global Education Network for Retinopathy of Prematurity (Gen-Rop): Development, Implementation, and Evaluation of A Novel Tele-Education System (An American Ophthalmological Society Thesis).

PubMed

Chan, R V Paul; Patel, Samir N; Ryan, Michael C; Jonas, Karyn E; Ostmo, Susan; Port, Alexander D; Sun, Grace I; Lauer, Andreas K; Chiang, Michael F

2015-01-01

To describe the design, implementation, and evaluation of a tele-education system developed to improve diagnostic competency in retinopathy of prematurity (ROP) by ophthalmology residents. A secure Web-based tele-education system was developed utilizing a repository of over 2,500 unique image sets of ROP. For each image set used in the system, a reference standard ROP diagnosis was established. Performance by ophthalmology residents (postgraduate years 2 to 4) from the United States and Canada in taking the ROP tele-education program was prospectively evaluated. Residents were presented with image-based clinical cases of ROP during a pretest, posttest, and training chapters. Accuracy and reliability of ROP diagnosis (eg, plus disease, zone, stage, category) were determined using sensitivity, specificity, and the kappa statistic calculations of the results from the pretest and posttest. Fifty-five ophthalmology residents were provided access to the ROP tele-education program. Thirty-one ophthalmology residents completed the program. When all training levels were analyzed together, a statistically significant increase was observed in sensitivity for the diagnosis of plus disease, zone, stage, category, and aggressive posterior ROP (P<.05). Statistically significant changes in specificity for identification of stage 2 or worse (P=.027) and pre-plus (P=.028) were observed. A tele-education system for ROP education is effective in improving diagnostic accuracy of ROP by ophthalmology residents. This system may have utility in the setting of both healthcare and medical education reform by creating a validated method to certify telemedicine providers and educate the next generation of ophthalmologists.

75 FR 11184 - Agency Forms Undergoing Paperwork Reduction Act Review

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-10

... ROPS. To overcome these barriers, NIOSH designed a prototype of a cost-effective roll over protective... installation complexity is significantly reduced. NIOSH has CROPS prototype designs for five tractors: Ford 3000 series, Ford 4000 series, Ford 8N, Ford 4600 and Massey-Ferguson 135. However, this technology has...

Foveal Depression and Related Factors in Patients with a History of Retinopathy of Prematurity.

PubMed

Miki, Akiko; Honda, Shigeru; Inoue, Yukako; Yamada, Yuko; Nakamura, Makoto

2018-05-09

This study evaluates optical coherence tomography (OCT) findings of the macula in patients with a history of retinopathy of prematurity (ROP). We enrolled 112 patients (age: 6-15 years) and categorized them into 3 groups: gestational age (GA) < 36 weeks with or without a history of ROP (ROP group, preterm group) and GA ≥37 weeks. We included 1 eye of each patient and measured the retinal thickness of the macula by OCT. The ROP group demonstrated the worst VA and the shallowest foveal depression. Furthermore, foveal depression significantly correlated with birth weight, GA, ganglion cell layer/inner plexiform layer (GCL-IPL) thickness, and a history of ROP. This study established a correlation of fovea formation with premature birth, damage of GCL-IPL, and a history of ROP. The retention of the inner retina possibly contributes to abnormal foveal morphology in patients with a history of ROP. © 2018 S. Karger AG, Basel.

The Juxtamembrane and carboxy-terminal domains of Arabidopsis PRK2 are critical for ROP-induced growth in pollen tubes

USDA-ARS?s Scientific Manuscript database

Polarized growth of pollen tubes is a critical step for successful reproduction in angiosperms and is controlled by ROP GTPases. Spatiotemporal activation of ROP (Rho GTPases of plants) necessitates a complex and sophisticated regulatory system, in which guanine nucleotide exchange factors (RopGEFs)...

Role of cytokines and treatment algorithms in retinopathy of prematurity.

PubMed

Hartnett, M Elizabeth

2017-05-01

Currently, severe retinopathy of prematurity (ROP) is diagnosed by clinical evaluation and not a laboratory test. Laser is still considered standard care. However, anti-vascular endothelial growth factor (VEGF) agents are being used and there are questions whether and/or if to use them, what dose or type of agent should be considered and what agent may be most beneficial in specific cases. Also unclear are the effects of laser or anti-VEGF on severe ROP, refractive outcomes or infant development. This article reviews recent studies related to these questions and other trials for severe ROP. Imaging studies identify biomarkers of risk (plus disease, stage 3 ROP, and ROP in zone I). Intravitreal bevacizumab or ranibizumab are reported effective in treating aggressive posterior ROP in small series. Recurrences and effects on myopia vary among studies. Use of anti-VEGF agents affects cytokines in the infant blood and reduces systemic VEGF for up to 2 months, raising potential safety concerns. The effects of treatment vary based on infant size and are not comparable. Evidence for most studies is not high. Studies support experimental evidence that inhibiting VEGF reduces stage 3 ROP and peripheral avascular retina. Ongoing large-scale clinical trials may provide clarity for best treatments of severe ROP. Current guidelines hold for screening and treatment for type 1 ROP.

A Human Proteome Array Approach to Identifying Key Host Proteins Targeted by Toxoplasma Kinase ROP18*

PubMed Central

Yang, Zhaoshou; Hou, Yongheng; Hao, Taofang; Rho, Hee-Sool; Wan, Jun; Luan, Yizhao; Gao, Xin; Yao, Jianping; Pan, Aihua; Xie, Zhi; Qian, Jiang; Liao, Wanqin; Zhu, Heng; Zhou, Xingwang

2017-01-01

Toxoplasma kinase ROP18 is a key molecule responsible for the virulence of Toxoplasma gondii; however, the mechanisms by which ROP18 exerts parasite virulence via interaction with host proteins remain limited to a small number of identified substrates. To identify a broader array of ROP18 substrates, we successfully purified bioactive mature ROP18 and used it to probe a human proteome array. Sixty eight new putative host targets were identified. Functional annotation analysis suggested that these proteins have a variety of functions, including metabolic process, kinase activity and phosphorylation, cell growth, apoptosis and cell death, and immunity, indicating a pleiotropic role of ROP18 kinase. Among these proteins, four candidates, p53, p38, UBE2N, and Smad1, were further validated. We demonstrated that ROP18 targets p53, p38, UBE2N, and Smad1 for degradation. Importantly, we demonstrated that ROP18 phosphorylates Smad1 Ser-187 to trigger its proteasome-dependent degradation. Further functional characterization of the substrates of ROP18 may enhance understanding of the pathogenesis of Toxoplasma infection and provide new therapeutic targets. Similar strategies could be used to identify novel host targets for other microbial kinases functioning at the pathogen-host interface. PMID:28087594

Preeclampsia and Retinopathy of Prematurity in Very-Low-Birth-Weight Infants: A Population-Based Study.

PubMed

Huang, Hsin-Chung; Yang, Hwai-I; Chou, Hung-Chieh; Chen, Chien-Yi; Hsieh, Wu-Shiun; Tsou, Kuo-Inn; Tsao, Po-Nien

2015-01-01

Preeclampsia and retinopathy of prematurity (ROP) are associated with impaired angiogenesis. Previous studies on the relationship between preeclampsia and ROP have produced conflicting results. The goal of this study was to evaluate the association between maternal preeclampsia and ROP using a large population-based cohort of very-low-birth-weight (VLBW) infants from 21 neonatal departments registered in the database of the Premature Baby Foundation of Taiwan. Multivariable logistic regression analysis was used to estimate the adjusted odds ratios (OR) and 95% confidence intervals (CI) for preeclampsia with reference to ROP and severe ROP. A total of 5,718 VLBW infants (844 cases with maternal preeclampsia) were included for analysis. The overall incidences of mild and severe ROP were 36.0% and 12.2%, respectively. Univariable analysis showed lower GA and lower birth weight, vaginal delivery, non-SGA, RDS, PDA, sepsis, transfusion, and absence of maternal preeclampsia to be associated with mild and severe ROP development. However, OR (95% CI) adjusted for the variables that were significant according to univariable analysis showed the risks of developing any-stage ROP and severe ROP for maternal preeclampsia to be 1.00 (0.84-1.20) and 0.89 (0.63-1.25), respectively. The results remained unchanged in stratified analyses according to SGA status. Our data showed that maternal preeclampsia was not associated with the subsequent development of any stage or severe ROP in VLBW infants.

Incidence of Retinopathy of Prematurity in Bahrain, 2002–2011

PubMed Central

Al Alawi, Ebtisam K.; Al Omran, Mohamed Shaker; Al Bahrana, Ebtihal H.

2015-01-01

Purpose: The purpose was to determine the incidence of retinopathy of prematurity (ROP) in Bahrain. Designs and Methods: premature infants (gestation age ≤32 weeks, birth weight ≤1500 g) admitted to the Neonatal Intensive Care Unit at Salmaniya Medical Complex were examined based on a predetermined screening protocol. The first examination was performed at 4–6 weeks of age, from January 1, 2002 to December 3, 2011. Data were collected on the type and incidence of each of ROP, birth weight, and age. Odds ratios and 95% confidence intervals (CI) were calculated. Results: A total of 1795 premature infants comprised the study population. Group 1 (<1000 g), and Group II (1000–1500 g), included 700 (39%) and 1095 (61%) infants. ROP was detected in 367 (20.4%) infants (95% CI = 18.6–22.3). The proportions of stage III ROP, stage III threshold disease requiring laser retinal photocoagulation and stage IV were 19%, 6%, and 1%, respectively. There were 68 (18.5%) infants with stage III ROP, 21 infants with Stage III ROP with threshold, and 5 infants with stage IV ROP requiring vitreoretinal surgery. There were 203 (80%) infants with a birth weight <1000 g. Birth weight of <1000 g was significantly associated to ROP [OR = 2.3 (95% CI = 1.8–2.9)]. Conclusion: One-fifth of premature infants had ROP in Bahrain. Birth weight <1000 g was a risk factor for ROP. PMID:26180473

The Global Education Network for Retinopathy of Prematurity (Gen-Rop): Development, Implementation, and Evaluation of A Novel Tele-Education System (An American Ophthalmological Society Thesis)

PubMed Central

Chan, R.V. Paul; Patel, Samir N.; Ryan, Michael C.; Jonas, Karyn E.; Ostmo, Susan; Port, Alexander D.; Sun, Grace I.; Lauer, Andreas K.; Chiang, Michael F.

2015-01-01

Purpose: To describe the design, implementation, and evaluation of a tele-education system developed to improve diagnostic competency in retinopathy of prematurity (ROP) by ophthalmology residents. Methods: A secure Web-based tele-education system was developed utilizing a repository of over 2,500 unique image sets of ROP. For each image set used in the system, a reference standard ROP diagnosis was established. Performance by ophthalmology residents (postgraduate years 2 to 4) from the United States and Canada in taking the ROP tele-education program was prospectively evaluated. Residents were presented with image-based clinical cases of ROP during a pretest, posttest, and training chapters. Accuracy and reliability of ROP diagnosis (eg, plus disease, zone, stage, category) were determined using sensitivity, specificity, and the kappa statistic calculations of the results from the pretest and posttest. Results: Fifty-five ophthalmology residents were provided access to the ROP tele-education program. Thirty-one ophthalmology residents completed the program. When all training levels were analyzed together, a statistically significant increase was observed in sensitivity for the diagnosis of plus disease, zone, stage, category, and aggressive posterior ROP (P<.05). Statistically significant changes in specificity for identification of stage 2 or worse (P=.027) and pre-plus (P=.028) were observed. Conclusions: A tele-education system for ROP education is effective in improving diagnostic accuracy of ROP by ophthalmology residents. This system may have utility in the setting of both healthcare and medical education reform by creating a validated method to certify telemedicine providers and educate the next generation of ophthalmologists. PMID:26538772

A C597-->A polymorphism in the Norrie disease gene is associated with advanced retinopathy of prematurity in premature Kuwaiti infants.

PubMed

Haider, M Z; Devarajan, L V; Al-Essa, M; Kumar, H

2002-01-01

Retinopathy of prematurity (ROP) is a retinal vascular disease which occurs in infants with a short gestational age and low birth weight and may lead to retinal detachment and blindness. In some premature infants, ROP progresses to advanced stages despite rigorous intervention, but in the majority, it spontaneously regresses before the threshold stage. Genetic factors, e.g. mutations in the Norrie disease (ND) gene, have been implicated in determining the progression of ROP to advanced stages. We have identified a novel C597A polymorphism of the ND gene; we screened this and another mutation in the ND gene, C110G, in 210 premature Kuwaiti infants using PCR-RFLP, DNA sequence analysis and DNA enzyme immunoassay hybridization to investigate their association with advanced-stage ROP. In this cohort of premature Kuwaiti newborns, 115 of 210 babies had no eye problems and served as controls, while 95 were found to have ROP. In 71 of the 95 ROP cases, the disease spontaneously regressed at or before stage 3, while in 24 of 95 ROP cases, the disease progressed to advanced stages 4 or 5. The incidence of the AA genotype of the C597A polymorphism was considerably higher in advanced-stage ROP cases (83.3%) compared to spontaneously regressing ROP cases (0%) and the normal controls (10.4%) (p < 0.0001). For the other genotypes, no significant difference was detected between the controls and ROP cases. In the case of the C110G mutation in the ND gene, no significant differences were detected between the controls and ROP cases, and the majority of subjects had a CC genotype in all three groups. Copyright 2002 National Science Council, ROC and S. Karger AG, Basel

Results of screening for retinopathy of prematurity in a large nursery in Kuwait: Incidence and risk factors.

PubMed

Wani, Vivek B; Kumar, Niranjan; Sabti, Khalid; Raizada, Seemant; Rashwan, Nabeel; Shukkur, Mumtaz M; Harbi, Mohammed

2010-01-01

The aim of the study was to report the incidence of retinopathy of prematurity (ROP) and severe ROP and identify the risk factors for their development in a large nursery in Kuwait. This was a retrospective, interventional, non-comparative, hospital-based study. Retrospective review of ROP records of premature babies having either birth weight of less than 1501 g or gestational age at birth of 34 weeks or less and born between January 2001 and August 2003. By univariate and multivariate logistic regression analysis. Out of the 599 babies studied, 38.9% developed ROP and 7.8% needed treatment for severe ROP. Multivariate analysis showed low birth weight (OR 13.753, 95% CI 3.66-51.54; ( P < 0.001), gestational age (OR 13.75, 95% CI 3.66-51.54; P < 0.001), surfactant (OR 1.72, 95% CI 1.04-2.83; P = 0.032) and stay in the intensive care unit for longer than 15 days (OR 2.25, 95% CI 1.05-4.85; P = 0.033) to be significant for the development of any ROP. Low birth weight (OR 22.86, 95% CI 3.86-134.82; P = 0.001), bacterial sepsis (OR 3.27, 95% CI 1.51-7.05; P = 0.002) and need for surfactant (OR 4.41, 95% CI 0.94 -20.56; P = 0.059) were found to be the risk factors for severe ROP needing laser treatment. The incidence of both any ROP and ROP needing treatment are comparable to other studies. Low birth weight is the most important risk factor for both any ROP and severe ROP.

The German ROP Registry: data from 90 infants treated for retinopathy of prematurity.

PubMed

Walz, Johanna M; Bemme, Sebastian; Pielen, Amelie; Aisenbrey, Sabine; Breuß, Helge; Alex, Anne F; Wagenfeld, Lars; Schiedel, Susanne; Krohne, Tim U; Stahl, Andreas

2016-12-01

The German retinopathy of prematurity (ROP) Registry collects data on treated ROP in a multicentre approach to analyse epidemiology and treatment patterns of severe ROP. Nine centres entered data from 90 treated ROP infants (born between January 2011 and December 2013) into a central database. Analysis included incidence rate of severe ROP, demographic data, stage of ROP, treatment patterns, recurrence rates, relevant comorbidities and ophthalmological or systemic complications associated with treatment. Treatment rate for ROP was 3.2% of the screened population. The most frequent ROP stage at time of treatment was zone II, stage 3 +  (137 eyes). Treatment was bilateral in 97% of infants. Treatment patterns changed over time from 7% anti-vascular endothelial growth factor (VEGF) monotherapy in 2011 to 32% in 2014. Overall, laser treatment was the predominant treatment. However, all infants with zone I disease received anti-VEGF treatment. About 19% of infants required retreatment (16% of laser-treated and 21% of anti-VEGF treated infants). Mean time between first and second treatment was 3.8 weeks (± 11 days) for laser-treated and 10.4 weeks (± 60 days) for anti-VEGF-treated infants. This study is the first multicentre analysis of severe ROP in Germany. The identified treatment patterns find laser as the most prevalent form of therapy, with an increasing use of anti-VEGF therapy over recent years. Recurrence rates were relatively high overall with slightly higher recurrence rates and later recurrence times in the anti-VEGF group. Anti-VEGF was predominantly used for high-risk stages like AP-ROP and zone I disease. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Alterations of the tunica vasculosa lentis in the rat model of retinopathy of prematurity.

PubMed

Favazza, Tara L; Tanimoto, Naoyuki; Munro, Robert J; Beck, Susanne C; Garcia Garrido, Marina; Seide, Christina; Sothilingam, Vithiyanjali; Hansen, Ronald M; Fulton, Anne B; Seeliger, Mathias W; Akula, James D

2013-08-01

To study the relationship between retinal and tunica vasculosa lentis (TVL) disease in retinopathy of prematurity (ROP). Although the clinical hallmark of ROP is abnormal retinal blood vessels, the vessels of the anterior segment, including the TVL, are also altered. ROP was induced in Long-Evans pigmented and Sprague Dawley albino rats; room-air-reared (RAR) rats served as controls. Then, fluorescein angiographic images of the TVL and retinal vessels were serially obtained with a scanning laser ophthalmoscope near the height of retinal vascular disease, ~20 days of age, and again at 30 and 64 days of age. Additionally, electroretinograms (ERGs) were obtained prior to the first imaging session. The TVL images were analyzed for percent coverage of the posterior lens. The tortuosity of the retinal arterioles was determined using Retinal Image multiScale Analysis (Gelman et al. in Invest Ophthalmol Vis Sci 46:4734-4738, 2005). In the youngest ROP rats, the TVL was dense, while in RAR rats, it was relatively sparse. By 30 days, the TVL in RAR rats had almost fully regressed, while in ROP rats, it was still pronounced. By the final test age, the TVL had completely regressed in both ROP and RAR rats. In parallel, the tortuous retinal arterioles in ROP rats resolved with increasing age. ERG components indicating postreceptoral dysfunction, the b-wave, and oscillatory potentials were attenuated in ROP rats. These findings underscore the retinal vascular abnormalities and, for the first time, show abnormal anterior segment vasculature in the rat model of ROP. There is delayed regression of the TVL in the rat model of ROP. This demonstrates that ROP is a disease of the whole eye.

Alterations of the Tunica Vasculosa Lentis in the Rat Model of Retinopathy of Prematurity

PubMed Central

Favazza, Tara L; Tanimoto, Naoyuki; Munro, Robert J.; Beck, Susanne C.; Garrido, Marina G.; Seide, Christina; Sothilingam, Vithiyanjali; Hansen, Ronald M.; Fulton, Anne B.; Seeliger, Mathias W.; Akula, James D

2013-01-01

Purpose To study the relation between retinal and tunica vasculosa lentis (TVL) disease in ROP. Although the clinical hallmark of retinopathy of prematurity (ROP) is abnormal retinal blood vessels, the vessels of the anterior segment, including the TVL, are also altered. Methods ROP was induced in Long Evans pigmented and Sprague-Dawley albino rats; room-air-reared (RAR) rats served as controls. Then, fluorescein angiographic images of the TVL and retinal vessels were serially obtained with a scanning laser ophthalmoscope (SLO) near the height of retinal vascular disease, ∼20 days-of-age, and again at 30 and 64 days-of-age. Additionally, electroretinograms (ERGs) were obtained prior to the first imaging session. The TVL images were analyzed for percent coverage of the posterior lens. The tortuosity of the retinal arterioles was determined using Retinal Image multiScale Analysis (RISA; Gelman et al., 2005). Results In the youngest ROP rats, the TVL was dense, while in RAR rats, it was relatively sparse. By 30 days, the TVL in RAR rats had almost fully regressed, while in ROP rats it was still pronounced. By the final test age, the TVL had completely regressed in both ROP and RAR rats. In parallel, the tortuous retinal arterioles in ROP rats resolved with increasing age. ERG components indicating postreceptoral dysfunction, the b-wave and oscillatory potentials (OPs), were attenuated in ROP rats. Conclusions These findings underscore the retinal vascular abnormalities and, for the first time, show abnormal anterior segment vasculature in the rat model of ROP. There is delayed regression of the TVL in the rat model of ROP. This demonstrates that ROP is a disease of the whole eye. PMID:23748796

The Relationship of Novel Plasma Proteins in the Early Neonatal Period With Retinopathy of Prematurity

PubMed Central

Lynch, Anne M.; Wagner, Brandie D.; Mandava, Naresh; Palestine, Alan G.; Mourani, Peter M.; McCourt, Emily A.; Oliver, Scott C. N.; Abman, Steven H.

2016-01-01

Purpose Retinopathy of prematurity (ROP) is a vision-threatening disease associated with abnormal retinal vascular development. Proteins from the insulin-like growth factor pathway are related to ROP. However, there is a paucity of research on the role of other proteins in ROP. The aim of this study was to identify plasma proteins related to clinically significant ROP. Methods We measured 1121 plasma proteins in the early neonatal period in infants at risk for ROP using an aptamer-based proteomic technology. The primary aim of the study was to compare plasma protein concentrations in infants who did (n = 12) and did not (n = 23) subsequently develop clinically significant ROP using logistic regression. As a secondary aim, we examined patterns in the proteins across categories of clinically significant, low-grade, and no ROP groups. Results Lower levels of 16 proteins were associated with an increased risk of clinically significant ROP. In this group, superoxide dismutase (Mn), mitochondrial (MnSOD), and chordin-like protein 1 (CRDL1) were highly ranked. Other proteins in this group included: C-C motif chemokine 14 (HCC-1), prolactin, insulin-like growth factor-binding protein 7 (IGFBP-7), and eotaxin. Higher levels of 12 proteins were associated with a higher risk for ROP. Fibroblast growth factor 19 (FGF-19) was the top-ranked protein target followed by hepatocyte growth factor-like protein (MSP), luteinizing hormone (LH), cystatin M, plasminogen, and proprotein convertase subtilisin/kexin type 9 (PCSK9). We also noted different patterns in the trend of concentrations of proteins across the clinically significant, low-grade, and no ROP groups. Conclusions We discovered plasma proteins with novel associations with clinically significant ROP (MnSOD, CRDL1, PCSK9), proteins with links to established ROP signaling pathways (IGFBP-7), and proteins such as MnSOD that may be a target for future therapeutic interventions. PMID:27679852

Genetic variants associated with severe retinopathy of prematurity in extremely low birth weight infants.

PubMed

Hartnett, M Elizabeth; Morrison, Margaux A; Smith, Silvia; Yanovitch, Tammy L; Young, Terri L; Colaizy, Tarah; Momany, Allison; Dagle, John; Carlo, Waldemar A; Clark, Erin A S; Page, Grier; Murray, Jeff; DeAngelis, Margaret M; Cotten, C Michael

2014-08-12

To determine genetic variants associated with severe retinopathy of prematurity (ROP) in a candidate gene cohort study of US preterm infants. Preterm infants in the discovery cohort were enrolled through the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, and those in the replication cohort were from the University of Iowa. All infants were phenotyped for ROP severity. Because of differences in the durations of enrollment between cohorts, severe ROP was defined as threshold disease in the discovery cohort and as threshold disease or type 1 ROP in the replication cohort. Whole genome amplified DNA from stored blood spot samples from the Neonatal Research Network biorepository was genotyped using an Illumina GoldenGate platform for candidate gene single nucleotide polymorphisms (SNPs) involving angiogenic, developmental, inflammatory, and oxidative pathways. Three analyses were performed to determine significant epidemiologic variables and SNPs associated with levels of ROP severity. Analyses controlled for multiple comparisons, ancestral eigenvalues, family relatedness, and significant epidemiologic variables. Single nucleotide polymorphisms significantly associated with ROP severity from the discovery cohort were analyzed in the replication cohort and in meta-analysis. Eight hundred seventeen infants in the discovery cohort and 543 in the replication cohort were analyzed. Severe ROP occurred in 126 infants in the discovery and in 14 in the replication cohort. In both cohorts, ventilation days and seizure occurrence were associated with severe ROP. After controlling for significant factors and multiple comparisons, two intronic SNPs in the gene BDNF (rs7934165 and rs2049046, P < 3.1 × 10(-5)) were associated with severe ROP in the discovery cohort and were not associated with severe ROP in the replication cohort. However, when the cohorts were analyzed together in an exploratory meta-analysis, rs7934165 increased in associated significance with severe ROP (P = 2.9 × 10(-7)). Variants in BDNF encoding brain-derived neurotrophic factor were associated with severe ROP in a large candidate gene study of infants with threshold ROP. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Influence of Fluorescein Angiography on the Diagnosis and Management of Retinopathy of Prematurity

PubMed Central

Klufas, Michael A.; Patel, Samir N.; Ryan, Michael C.; Gupta, Mrinali Patel; Jonas, Karyn E.; Ostmo, Susan; Martinez-Castellanos, Maria Ana; Berrocal, Audina M.; Chiang, Michael F.; Chan, R.V. Paul

2016-01-01

Purpose To examine the influence of fluorescein angiography (FA) on the diagnosis and management of retinopathy of prematurity (ROP). Design Prospective cohort study. Participants Nine recognized ROP experts (3 pediatric ophthalmologists; 6 retina specialists) interpreted 32 sets (16 color fundus photographs; 16 color fundus photographs paired with the corresponding FAs) of wide-angle retinal images from infants with ROP. Methods All experts independently reviewed the 32 image sets on a secure web site and provided a diagnosis and management plan for the case presented, first based on color fundus photographs alone, and then by color fundus photographs and corresponding FA. Main Outcome Measures Sensitivity and specificity of the ROP diagnosis (zone, stage, plus disease, and category – i.e. no ROP, mild ROP, type-2 ROP, and treatment-requiring ROP) was calculated using a consensus reference standard diagnosis, determined from the diagnosis of the color fundus photographs by three experienced readers in combination with the clinical diagnosis based on ophthalmoscopic examination. The kappa statistic was used to analyze the average intergrader agreement among experts for the diagnosis of zone, stage, plus disease, and category. Results Addition of FA to color fundus photographs resulted in a significant improvement in sensitivity for diagnosis of stage 3 or worse disease (39.8% vs. 74.1%, P = 0.008), type-2 or worse ROP (69.4% vs. 86.8%, P = 0.013), and pre-plus or worse disease (50.5 vs. 62.6%, P = 0.031). There was a nonsignificant trend towards improved sensitivity for diagnosis of treatment-requiring ROP (22.2% vs. 40.3%, P = 0.063). Using the kappa statistic, addition of FA to color fundus photographs significantly improved intergrader agreement for diagnosis of treatment-requiring ROP. Addition of FA to color fundus photographs did not significantly affect intergrader agreement for the diagnosis of stage, zone, or plus disease. Conclusions Compared to color fundus photographs alone, fluorescein angiography may improve the sensitivity of diagnosis of ROP by experts, particularly for stage 3 disease. In addition, intergrader agreement for diagnosis of treatment-requiring ROP may improve with FA interpretation. PMID:26028345

Predictors for the Development of Referral-Warranted Retinopathy of Prematurity in the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity (e-ROP) Study

PubMed Central

Ying, Gui-Shuang; Quinn, Graham E.; Wade, Kelly C.; Repka, Michael X.; Baumritter, Agnieshka; Daniel, Ebenezer

2015-01-01

Importance Detection of treatment-requiring retinopathy of prematurity (ROP) involves serial eye examinations. An ROP prediction model using predictive factors could identify high-risk infants and reduce required eye examinations. Objective To determine predictive factors for the development of referral-warranted (RW) ROP. Design, Setting, and Participants This multicenter observational cohort study included secondary analysis of data from the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity Study. Infants included in the study had a birth weight (BW) of less than 1251 g. Exposures Serial ROP examinations of premature infants who had 2 or more ROP examinations. Main Outcomes and Measures Incidence of RW-ROP (defined as the presence of plus disease, zone I ROP, or ROP stage 3 or greater in either eye) and associations with predictive factors. Results Among 979 infants without RW-ROP at first study-related eye examination (median postmenstrual age, 33 weeks; range, 29-40 weeks) who underwent at least 2 eye examinations, 149 (15.2%) developed RW-ROP. In a multivariate model, significant predictors for RW-ROP were male sex (odds ratio [OR], 1.80; 95% CI, 1.13-2.86 vs female), nonblack race (OR, 2.76; 95% CI, 1.50-5.08 for white vs black race and OR, 4.81; 95% CI, 2.19-10.6 for other vs black race), low BW (OR, 5.16; 95% CI, 1.12-7.20 for ≤500 g vs >1100 g), younger gestational age (OR, 9.79; 95% CI, 3.49-27.5 for ≤24 weeks vs ≥28 weeks), number of quadrants with preplus disease (OR, 7.12; 95% CI, 2.53-20.1 for 1-2 quadrants and OR, 18.4; 95% CI, 4.28-79.4 for 3-4 quadrants vs no preplus disease), stage 2 ROP (OR, 4.13; 95% CI, 2.13-8.00 vs no ROP), the presence of retinal hemorrhage (OR, 4.36; 95% CI, 1.57-12.1 vs absence), the need for respiratory support (OR, 4.99; 95% CI, 1.89-13.2 for the need for controlled mechanical ventilator; OR, 11.0; 95% CI, 2.26-53.8 for the need for high-frequency oscillatory ventilation vs no respiratory support), and slow weight gain (OR, 2.44; 95% CI, 1.22-4.89 for weight gain ≤12 g/d vs >18 g/d). These characteristics predicted the development of RW-ROP significantly better than BW and gestational age (area under receiver operating characteristic curve, 0.88 vs 0.78; P < .001). Conclusions and Relevance When controlling for very low BW and prematurity, the presence of preplus disease, stage 2 ROP, retinal hemorrhage, and the need for ventilation at time of first study-related eye examination were strong independent predictors for RW-ROP. These predictors may help identify infants in need of timely eye examinations. PMID:25521746

Predictors for the development of referral-warranted retinopathy of prematurity in the telemedicine approaches to evaluating acute-phase retinopathy of prematurity (e-ROP) study.

PubMed

Ying, Gui-Shuang; Quinn, Graham E; Wade, Kelly C; Repka, Michael X; Baumritter, Agnieshka; Daniel, Ebenezer

2015-03-01

Detection of treatment-requiring retinopathy of prematurity (ROP) involves serial eye examinations. An ROP prediction model using predictive factors could identify high-risk infants and reduce required eye examinations. To determine predictive factors for the development of referral-warranted (RW) ROP. This multicenter observational cohort study included secondary analysis of data from the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity Study. Infants included in the study had a birth weight (BW) of less than 1251 g. Serial ROP examinations of premature infants who had 2 or more ROP examinations. Incidence of RW-ROP (defined as the presence of plus disease, zone I ROP, or ROP stage 3 or greater in either eye) and associations with predictive factors. Among 979 infants without RW-ROP at first study-related eye examination (median postmenstrual age, 33 weeks; range, 29-40 weeks) who underwent at least 2 eye examinations, 149 (15.2%) developed RW-ROP. In a multivariate model, significant predictors for RW-ROP were male sex (odds ratio [OR], 1.80; 95% CI, 1.13-2.86 vs female), nonblack race (OR, 2.76; 95% CI, 1.50-5.08 for white vs black race and OR, 4.81; 95% CI, 2.19-10.6 for other vs black race), low BW (OR, 5.16; 95% CI, 1.12-7.20 for ≤500 g vs >1100 g), younger gestational age (OR, 9.79; 95% CI, 3.49-27.5 for ≤24 weeks vs ≥28 weeks), number of quadrants with preplus disease (OR, 7.12; 95% CI, 2.53-20.1 for 1-2 quadrants and OR, 18.4; 95% CI, 4.28-79.4 for 3-4 quadrants vs no preplus disease), stage 2 ROP (OR, 4.13; 95% CI, 2.13-8.00 vs no ROP), the presence of retinal hemorrhage (OR, 4.36; 95% CI, 1.57-12.1 vs absence), the need for respiratory support (OR, 4.99; 95% CI, 1.89-13.2 for the need for controlled mechanical ventilator; OR, 11.0; 95% CI, 2.26-53.8 for the need for high-frequency oscillatory ventilation vs no respiratory support), and slow weight gain (OR, 2.44; 95% CI, 1.22-4.89 for weight gain ≤12 g/d vs >18 g/d). These characteristics predicted the development of RW-ROP significantly better than BW and gestational age (area under receiver operating characteristic curve, 0.88 vs 0.78; P < .001). When controlling for very low BW and prematurity, the presence of preplus disease, stage 2 ROP, retinal hemorrhage, and the need for ventilation at time of first study-related eye examination were strong independent predictors for RW-ROP. These predictors may help identify infants in need of timely eye examinations.

Anti-Vascular Endothelial Growth Factor Therapy for Primary Treatment of Type 1 Retinopathy of Prematurity: A Report by the American Academy of Ophthalmology.

PubMed

VanderVeen, Deborah K; Melia, Michele; Yang, Michael B; Hutchinson, Amy K; Wilson, Lorri B; Lambert, Scott R

2017-05-01

To review the available evidence on the ocular safety and efficacy of anti-vascular endothelial growth factor (VEGF) agents for the treatment of retinopathy of prematurity (ROP) compared with laser photocoagulation therapy. A literature search of the PubMed and Cochrane Library databases was conducted last on September 6, 2016, with no date restrictions and limited to articles published in English. This search yielded 311 citations, of which 37 were deemed clinically relevant for full-text review. Thirteen of these were selected for inclusion in this assessment. The panel methodologist assigned ratings to the selected articles according to the level of evidence. Of the 13 citations, 6 articles on 5 randomized clinical trials provided level II evidence supporting the use of anti-VEGF agents, either as monotherapy or in combination with laser therapy. The primary outcome for these articles included recurrence of ROP and the need for retreatment (3 articles), retinal structure (2 articles), and refractive outcome (1 article). Seven articles were comparative case series that provided level III evidence. The primary outcomes included the effects of anti-VEGF treatment on development of peripheral retinal vessels (1 article), refractive outcomes (1 article), or both structural and refractive or visual outcomes (5 articles). Current level II and III evidence indicates that intravitreal anti-VEGF therapy is as effective as laser photocoagulation for achieving regression of acute ROP. Although there are distinct ocular advantages to anti-VEGF pharmacotherapy for some cases (such as eyes with zone I disease or aggressive posterior ROP), the disadvantages are that the ROP recurrence rate is higher, and vigilant and extended follow-up is needed because retinal vascularization is usually incomplete. After intravitreal injection, bevacizumab can be detected in serum within 1 day, and serum VEGF levels are suppressed for at least 8 to 12 weeks. The effects of lowering systemic VEGF levels on the developing organ systems of premature infants are unknown, and there are limited long-term data on potential systemic and neurodevelopmental effects after anti-VEGF use for ROP treatment. Anti-VEGF agents should be used judiciously and with awareness of the known and unknown or potential side effects. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Clinical relevance of retinal structure in children with laser-treated retinopathy of prematurity versus controls - using optical coherence tomography.

PubMed

Stoica, Florina; Chirita-Emandi, Adela; Andreescu, Nicoleta; Stanciu, Alina; Zimbru, Cristian G; Puiu, Maria

2018-03-01

We aimed to assess the macular anatomy using spectral domain optical coherence tomography (SD-OCT), in children born preterm who had laser-treated retinopathy of prematurity (ROP), and to investigate the relationship between structural changes in macula and visual function. Thirty-seven 3-8 years old children were included in the study in two groups: 20 children born preterm [(<34 weeks of gestation, birthweight (BW) <2000 g)] who had laser-treated ROP in the Neonatology Department, Municipal Clinical Emergency Hospital of Timisoara, Romania; and 17 controls (children born at term, without eye disease, matched for age and gender). Spectral domain optical coherence tomography (SD-OCT) imaging (Spectralis OCT) was performed at central fovea and 1 mm nasally. In the ROP group (total 34 eyes), we included both eyes in 14 children, and on one eye in six other children. In the control group, both eyes for all 17 children were included. Central fovea thickness (CFT) was significantly higher in children born preterm and with laser-treated ROP as compared to controls (275 ± 34.8 μm versus 224 ± 27.2 μm; p < 0.001). The laser-treated eyes with ROP had mean best-corrected visual acuity (BCVA) = 0.19 logMAR (20/31 Snellen); 35% had BCVA ≥0.3 logMAR (20/40 Snellen). In receiver operating characteristic curve (ROC) analysis, with BCVA as static variable (category 0 = BCVA ≤0.3 logMAR), the CFT cut-off was 257 μm (sensitivity: 0.917; specificity: 0.661; area under the curve: 0.810, p = 0.001). Years after the laser intervention, central fovea was significantly thicker in ROP laser-treated children born preterm when compared to controls. Central fovea thickness (CFT) correlated strongly and inversely with BW and gestational age (GA) at birth, while a CFT value above 257 μm was suggestive for suboptimal visual acuity. The proposed cut-off value needs to be validated in future larger studies. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Serum Ropivacaine Concentrations and Systemic Local Anesthetic Toxicity in Trauma Patients Receiving Long-Term Continuous Peripheral Nerve Block Catheters

DTIC Science & Technology

2010-02-01

concentrations were calculated from the following 2 methods: 1. Using peak area ratio of ropivacaine/ bupivacaine of samples versus peak area ratio of...ropivacaine/ bupivacaine of standards (0–3000 ng/mL) using the following formula: RopS (PA of Rop)/(PA of Bup)S /(PA of Rop)/(PA of Bup)STD Bup...1/mL serum used) where Rop ropivacaine, Bup bupivacaine , PA peak area, S sample, and STD standard. 2. Samples of ropivacaine concentrations

Refractive and ocular biometric profile of children with a history of laser treatment for retinopathy of prematurity.

PubMed

Kaur, Savleen; Sukhija, Jaspreet; Katoch, Deeksha; Sharma, Mansi; Samanta, Ramanuj; Dogra, Mangat R

2017-09-01

Indian children belong to a diverse socioeconomic strata with retinopathy of prematurity (ROP) developing in mature, higher birth weight babies as well. The purpose of our study is to analyze the long-term status of refractive errors and its relationship with ocular biometry in children with ROP who were laser treated at a tertiary center in North India. Cross sectional study. Children (<16 years) enrolled from January 2014 to December 2014 with a history of laser treatment for ROP and examined for refractive and biometric status. Thirty-six children presenting to us at the mean age of 7.37 ± 3.07 years (6-15 years) were included. Mean spherical equivalent (SE) was -4.05 D ± 5.10. 75% were myopic, with high astigmatism in 31%. Higher lens thickness (P = 0.03) and higher SE (P = 0.002) at 1 year postnatal age were predictors of larger SE. 79.4% achieved a favorable functional outcome (visual acuity ≥20/40). 5.88% achieved unsatisfactory outcome (<20/200) despite having a favorable structural outcome. There are a substantial number of children who develop myopia and high astigmatism while undergoing laser treatment for ROP. We found myopia in our cohort to be lenticular and greater axial length contributing to the development of high myopia. An initial large refractive error predicts the future development of myopia in these children. Nearly 6% of patients with good structural outcome have unexplained subnormal vision. Our threshold for prescribing glasses in these children should be low.

Refractive and ocular biometric profile of children with a history of laser treatment for retinopathy of prematurity

PubMed Central

Kaur, Savleen; Sukhija, Jaspreet; Katoch, Deeksha; Sharma, Mansi; Samanta, Ramanuj; Dogra, Mangat R

2017-01-01

Purpose: Indian children belong to a diverse socioeconomic strata with retinopathy of prematurity (ROP) developing in mature, higher birth weight babies as well. The purpose of our study is to analyze the long-term status of refractive errors and its relationship with ocular biometry in children with ROP who were laser treated at a tertiary center in North India. Methods: Cross sectional study. Children (<16 years) enrolled from January 2014 to December 2014 with a history of laser treatment for ROP and examined for refractive and biometric status. Results: Thirty-six children presenting to us at the mean age of 7.37 ± 3.07 years (6–15 years) were included. Mean spherical equivalent (SE) was −4.05 D ± 5.10. 75% were myopic, with high astigmatism in 31%. Higher lens thickness (P = 0.03) and higher SE (P = 0.002) at 1 year postnatal age were predictors of larger SE. 79.4% achieved a favorable functional outcome (visual acuity ≥20/40). 5.88% achieved unsatisfactory outcome (<20/200) despite having a favorable structural outcome. Conclusion: There are a substantial number of children who develop myopia and high astigmatism while undergoing laser treatment for ROP. We found myopia in our cohort to be lenticular and greater axial length contributing to the development of high myopia. An initial large refractive error predicts the future development of myopia in these children. Nearly 6% of patients with good structural outcome have unexplained subnormal vision. Our threshold for prescribing glasses in these children should be low. PMID:28905827

Retinopathy of prematurity: applicability and compliance of guidelines in Hong Kong.

PubMed

Luk, Abbie S W; Yip, Wilson W K; Lok, Julie Y C; Lau, Henry H W; Young, Alvin L

2017-04-01

To analyse the incidence, application and compliance to Royal College of Ophthalmologists retinopathy of prematurity (ROP) screening recommendations and subsequent treatment of ROP in a neonatal intensive care unit of a large tertiary referral centre in Hong Kong. A retrospective review was performed for all eligible premature neonates screened for ROP over a 7-year period from June 2008 to December 2015 in our local tertiary neonatal intensive care unit in Prince of Wales Hospital, Hong Kong, using the Royal College of Ophthalmologists ROP screening guideline (2008). Comparison between established UK and American screening guidelines were analysed for their applicability in our locality. A total of 602 infants were screened, with the incidence of ROP in 28.2% and type 1 ROP in 3.8%, and indirect diode laser performed in all type 1 ROP cases. Overall, adherence for screening criteria was 99.7%, with the average time to commence first screening at 4 weeks postnatal age. Of the 602 cases, 94 (15.6%) were early and 35 (5.8%) were later than the guidelines, of which only 5 (0.8%) of late-screened cases developed ROP requiring treatment. Subsequent treatment of ROP for all the late-screened cases was not delayed. Current ROP screening using the UK guidelines (2008) is applicable, effective and safe to our predominantly Asian population in Hong Kong, with a low rate of delayed screening. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Intravitreal bevacizumab monotherapy for retinopathy of prematurity.

PubMed

Şahin, Alparslan; Şahin, Muhammed; Cingü, Abdullah Kürşat; Çınar, Yasin; Türkcü, Fatih Mehmet; Yüksel, Harun; Kaya, Savaş; Arı, Şeyhmus; Caça, İhsan

2013-10-01

The aim of this study was to evaluate the treatment outcomes of intravitreal bevacizumab (IVB) injections, used as a monotherapy in type 1 retinopathy of prematurity (ROP). A retrospective chart review was performed for 17 type 1 ROP patients (34 eyes), who had IVB injection between July 2011 and June 2012. Birthweight, gestational age at birth, stage and location of ROP, IVB injection time, time of complete retinal vascularization, and additional treatments if needed, were noted. A total of 0.625 mg (0.025 mL) bevacizumab was injected intravitreally. Thirty eyes of 17 patients with type 1 ROP enrolled in the study were treated with IVB injection. Of them seven had aggressive posterior-ROP, six had stage 2 ROP, and four had stage 3 ROP. The mean gestational age was 28.44 weeks (range, 26-31 weeks); and the mean birthweight was 1151.88 g (range, 600-1600 g). The mean age for IVB injection was 35.47 weeks. The mean full retinal vascularization time was 136.6 ± 26.6 days. The mean follow-up time was 285.3 ± 70 days. ROP was regressed and retinal vascularization was completed in all cases except one eye, which had threshold disease. IVB injection, used as a monotherapy, is an effective treatment approach in patients with type 1 ROP. Timely treatment of stage 2 and early stage 3 ROP in which disease progression was observed, prevents vitreoretinal membrane formation in posterior disease. Further studies need to be performed to determine the safety of IVB injection. © 2013 The Authors. Pediatrics International © 2013 Japan Pediatric Society.

[Telemedicine correlation in retinopathy of prematurity between experts and non-expert observers].

PubMed

Ossandón, D; Zanolli, M; López, J P; Stevenson, R; Agurto, R; Cartes, C

2015-01-01

To study the correlation between expert and non-expert observers in the reporting images for the diagnosis of retinopathy of prematurity (ROP) in a telemedicine setting. A cross-sectional, multicenter study, consisting of 25 sets of images of patients screened for ROP. They were evaluated by two experts in ROP and 1 non-expert and classified according to telemedicine classification, zone, stage, plus disease and Ells referral criteria. The telemedicine classification was: no ROP, mild ROP, type 2 ROP, or ROP that requires treatment. Ells referral criteria is defined as the presence at least one of the following: ROP in zone I, Stage 3 in zone I or II, or plus+ For statistical analysis, SPSS 16.0 was used. For correlation, Kappa value was performed. There was a high correlation between observers for the assessment of ROP stage (0.75; 0.54-0.88) plus disease (0.85; 0.71-0.92), and Ells criteria (0.89; 0.83-1.0). However, inter-observer values were low for zone (0.41; 0.27-0.54) and telemedicine classification (0.43; 0.33-0.6). When evaluating telemedicine images by examiners with different levels of expertise in ROP, the Ells criteria gave the best correlation. In addition, stage of disease and plus disease have good correlation among observers. In contrast, the correlation between observers was low for zone and telemedicine classification. Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

Retinopathy of prematurity: inflammation, choroidal degeneration, and novel promising therapeutic strategies.

PubMed

Rivera, José Carlos; Holm, Mari; Austeng, Dordi; Morken, Tora Sund; Zhou, Tianwei Ellen; Beaudry-Richard, Alexandra; Sierra, Estefania Marin; Dammann, Olaf; Chemtob, Sylvain

2017-08-22

Retinopathy of prematurity (ROP) is an important cause of childhood blindness globally, and the incidence is rising. The disease is characterized by initial arrested retinal vascularization followed by neovascularization and ensuing retinal detachment causing permanent visual loss. Although neovascularization can be effectively treated via retinal laser ablation, it is unknown which children are at risk of entering this vision-threatening phase of the disease. Laser ablation may itself induce visual field deficits, and there is therefore a need to identify targets for novel and less destructive treatments of ROP. Inflammation is considered a key contributor to the pathogenesis of ROP. A large proportion of preterm infants with ROP will have residual visual loss linked to loss of photoreceptor (PR) and the integrity of the retinal pigment epithelium (RPE) in the macular region. Recent studies using animal models of ROP suggest that choroidal degeneration may be associated with a loss of integrity of the outer retina, a phenomenon so far largely undescribed in ROP pathogenesis. In this review, we highlight inflammatory and neuron-derived factors related to ROP progression, as well, potential targets for new treatment strategies. We also introduce choroidal degeneration as a significant cause of residual visual loss following ROP. We propose that ROP should no longer be considered an inner retinal vasculopathy only, but also a disease of choroidal degeneration affecting both retinal pigment epithelium and photoreceptor integrity.

The progress of prophylactic treatment in retinopathy of prematurity

PubMed Central

Zhang, Hong-Bing; Wang, Xiao-Dong; Xu, Kun; Li, Xiao-Gang

2018-01-01

Retinopathy of prematurity (ROP) is a retinal vascular disorder frequently found in premature infants. Different therapeutic strategies have been developed to treat ROP. However, there are still many children with ROP suffering by severe limitations in vision or even blindness. Recently, ROP has been suggested to be caused by abnormal development of the retinal vasculature, but not simply resulted by retinal neovascularization which takes about 4 to 6wk after birth in premature infants. Thus, instead of focusing on how to reduce retinal neovascularization, understanding the pathological changes and mechanisms that occur prior to retinal neovascularization is meaningful, which may lead to identify novel target(s) for the development of novel strategy to promote the healthy growth of retinal blood vessels rather than passively waiting for the appearance of retinal neovascularization and removing it by force. In this review, we discussed recent studies about, 1) the pathogenesis prior to retinal neovascularization in oxygen-induced retinopathy (OIR; a ROP in animal model) and in premature infants with ROP; 2) the preclinical and clinical research on preventive treatment of early OIR and ROP. We will not only highlight the importance of the mechanisms and signalling pathways in regulating early stage of ROP but also will provide guidance for actively exploring novel mechanisms and discovering novel treatments for early phase OIR and ROP prior to retinal neovascularization in the future. PMID:29862189

Satellite Navigation Backup Study

DTIC Science & Technology

2007-09-19

uro pe Eu rop...nd s To tal E uro pe Eu rop e A C Eu rop e G A Eu rop e G ov /St nd s D/D/I GPS/INS eLORAN Figure 6-14: Assessment Results – Solution Preference...LORAN for RNP 0.3 Approach: The Preliminary Conclusions of LORAN Integrity Performance Panel (LORIPP); Sherman Lo , Per Enge, Ben Peterson,

Preeclampsia and retinopathy of prematurity in preterm births.

PubMed

Yu, Xiao Dan; Branch, D Ware; Karumanchi, S Ananth; Zhang, Jun

2012-07-01

The relationship between gestational hypertension, preeclampsia, and the risk of retinopathy of prematurity (ROP) remains unclear. Thus, we used a large cohort database to study the influence of maternal gestational hypertension and preeclampsia on the occurrence of ROP in preterm infants. We used data from a previous retrospective cohort study that includes 25,473 eligible preterm neonates. We examined the association between gestational hypertension, preeclampsia, and ROP while controlling for potential confounders by multiple logistic regression analysis. Of the 8758 early preterm infants (gestational age <34 weeks), 1024 (11.69%) had ROP, while of the 16,715 late preterm infants, only 29 (0.17%) had ROP. After adjusting for confounders, preeclampsia was associated with a significantly reduced risk of ROP (adjusted odds ratio [aOR], 0.65; 95% confidence interval [CI], 0.49-0.86 for early preterm birth; aOR, 0.10; 95% CI, 0.01-0.93 for late preterm birth; aOR, 0.66; 95% CI, 0.50-0.87 for all preterm births). Gestational hypertension was not significantly associated with ROP at early or late preterm births. Preeclampsia, but not gestational hypertension, was associated with a reduced risk of ROP in preterm births.

Retinopathy of prematurity and neurodevelopmental disabilities in premature infants.

PubMed

Beligere, Nagamani; Perumalswamy, Vijayalaksmi; Tandon, Manish; Mittal, Amit; Floora, Jayasheele; Vijayakumar, B; Miller, Marilyn T

2015-10-01

Prematurity is a major global health issue leading to high mortality and morbidity among the survivors. Neurodevelopmental disability (NDD) and retinopathy of prematurity (ROP) are the most common complications of prematurity. In fact, ROP is the second leading cause of childhood blindness in the world. Although there is much information regarding the occurrence of ROP and of NDD in premature infants, there have been few studies on ROP and its association with NDD. The objectives of this article are to review the current literature on the subject and to publish our own findings concerning the association between ROP and NDD in premature infants. The review suggests that although NDDs are related to degree of prematurity, NDD could also be the result of visual impairments resulting from ROP. Our own study shows a close association between NDD and zonal involvement of ROP: higher NDD if zone 1 is involved and less if zone 3 is involved. Copyright © 2015 Elsevier Ltd. All rights reserved.

Reduced utility of serum IGF-1 levels in predicting retinopathy of prematurity reflects maternal ethnicity.

PubMed

Reddy, M Ashwin; Patel, Himanshu I; Karim, Shah M; Lock, Helen; Perry, Leslie; Bunce, Catey; Kempley, Steve; Sinha, Ajay K

2016-04-01

To validate known risk factors and identify a threshold level for serum insulin-like growth factor 1 (IGF-1) in the development of severe retinopathy of prematurity (ROP) in an ethnically diverse population at a tertiary neonatal unit, 2011-2013. A prospective cohort masked study was conducted. Serum IGF-1 levels at 31, 32 and 33 weeks were measured and risk factor data collected including gestational age (GA), birth weight (BW), absolute weight gain (AWG) and maternal ethnicity. The eventual ROP outcome was divided into two groups: minimal ROP (Stages 0 and 1) and severe ROP (Stage 2 or worse including Type 1 ROP). 36 patients were recruited: 14 had minimal ROP and 22 severe ROP. Significant differences between the groups were found in GA, BW, AWG and IGF-1 at 32 and 33 weeks. There was minimal rise in IGF-1 in Stage 2 patients and/or black patients (p=0.0013) between 32 and 33 weeks but no pragmatic threshold level of IGF-1 that could distinguish between minimal or severe ROP. There were significant differences in GA, BW, AWG and IGF-1 at 32 and 33 weeks between those babies with severe ROP and those with minimal ROP. However, there was no threshold level of IGF-1 at a time point between 31 and 33 weeks that can be used to exclude a large proportion of babies from screening. We also found ethnic differences in IGF-1 levels with infants born to black mothers having significantly lower IGF-1 levels at 32 and 33 weeks gestation. The determination of ROP risk using IGF-1 is a race-specific phenomenon. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Impact of improved neonatal care on the profile of retinopathy of prematurity in rural neonatal centers in India over a 4-year period.

PubMed

Vinekar, Anand; Jayadev, Chaitra; Kumar, Siddesh; Mangalesh, Shwetha; Dogra, Mangat Ram; Bauer, Noel J; Shetty, Bhujang

2016-01-01

To report the reduction in the incidence and severity of retinopathy of prematurity (ROP) in rural India over a 4-year period following the introduction of improved neonatal care practices. The Karnataka Internet Diagnosis of Retinopathy of Prematurity program (KIDROP), is a tele-medicine network that screens for ROP in different zones of Karnataka state in rural India. North Karnataka is the most underdeveloped and remote zone of this program and did not have any ROP screening programs before the intervention of the KIDROP in 2011. Six government and eleven private neonatal centers in this zone were screened weekly. Specific neonatal guidelines for ROP were developed and introduced in these centers. They included awareness about risk factors, oxygen regulation protocols, use of pulse oxymetry, monitoring postnatal weight gain, nutritional best practices, and management of sepsis. The incidence and severity of ROP were compared before the guidelines were introduced (Jan 2011 to Dec 2012) and after the guidelines were introduced (July 2013 to June 2015). During this 4-year period, 4,167 infants were screened over 11,390 imaging sessions. The number of enrolled infants increased from 1,825 to 2,342 between the two periods ( P <0.001). The overall incidence of any stage ROP reduced significantly from 26.8% to 22.4% ( P <0.001). The incidence of treatment-requiring ROP reduced from 20.7% to 16% ( P =0.06), and of the treated disease, aggressive posterior ROP reduced from 20.8% to 13.1% ( P =0.23) following introduction of the guidelines. Rural neonatal centers in middle-income countries have a large, unscreened burden of ROP. Improving neonatal care in these centers can positively impact the incidence and severity of ROP even in a relatively short period. A combined approach of a robust ROP screening program and improved neonatal care practices is required to address the challenge.

Impact of improved neonatal care on the profile of retinopathy of prematurity in rural neonatal centers in India over a 4-year period

PubMed Central

Vinekar, Anand; Jayadev, Chaitra; Kumar, Siddesh; Mangalesh, Shwetha; Dogra, Mangat Ram; Bauer, Noel J; Shetty, Bhujang

2016-01-01

Purpose To report the reduction in the incidence and severity of retinopathy of prematurity (ROP) in rural India over a 4-year period following the introduction of improved neonatal care practices. Methods The Karnataka Internet Diagnosis of Retinopathy of Prematurity program (KIDROP), is a tele-medicine network that screens for ROP in different zones of Karnataka state in rural India. North Karnataka is the most underdeveloped and remote zone of this program and did not have any ROP screening programs before the intervention of the KIDROP in 2011. Six government and eleven private neonatal centers in this zone were screened weekly. Specific neonatal guidelines for ROP were developed and introduced in these centers. They included awareness about risk factors, oxygen regulation protocols, use of pulse oxymetry, monitoring postnatal weight gain, nutritional best practices, and management of sepsis. The incidence and severity of ROP were compared before the guidelines were introduced (Jan 2011 to Dec 2012) and after the guidelines were introduced (July 2013 to June 2015). Results During this 4-year period, 4,167 infants were screened over 11,390 imaging sessions. The number of enrolled infants increased from 1,825 to 2,342 between the two periods (P<0.001). The overall incidence of any stage ROP reduced significantly from 26.8% to 22.4% (P<0.001). The incidence of treatment-requiring ROP reduced from 20.7% to 16% (P=0.06), and of the treated disease, aggressive posterior ROP reduced from 20.8% to 13.1% (P=0.23) following introduction of the guidelines. Discussion Rural neonatal centers in middle-income countries have a large, unscreened burden of ROP. Improving neonatal care in these centers can positively impact the incidence and severity of ROP even in a relatively short period. A combined approach of a robust ROP screening program and improved neonatal care practices is required to address the challenge. PMID:28539801

The Zinc Finger Proteins Mxr1p and Repressor of Phosphoenolpyruvate Carboxykinase (ROP) Have the Same DNA Binding Specificity but Regulate Methanol Metabolism Antagonistically in Pichia pastoris*

PubMed Central

Kumar, Nallani Vijay; Rangarajan, Pundi N.

2012-01-01

The methanol-inducible alcohol oxidase I (AOXI) promoter of the methylotrophic yeast, Pichia pastoris, is used widely for the production of recombinant proteins. AOXI transcription is regulated by the zinc finger protein Mxr1p (methanol expression regulator 1). ROP (repressor of phosphoenolpyruvate carboxykinase, PEPCK) is a methanol- and biotin starvation-inducible zinc finger protein that acts as a negative regulator of PEPCK in P. pastoris cultured in biotin-deficient, glucose-ammonium medium. The function of ROP during methanol metabolism is not known. In this study, we demonstrate that ROP represses methanol-inducible expression of AOXI when P. pastoris is cultured in a nutrient-rich medium containing yeast extract, peptone, and methanol (YPM). Deletion of the gene encoding ROP results in enhanced expression of AOXI and growth promotion whereas overexpression of ROP results in repression of AOXI and growth retardation of P. pastoris cultured in YPM medium. Surprisingly, deletion or overexpression of ROP has no effect on AOXI gene expression and growth of P. pastoris cultured in a minimal medium containing yeast nitrogen base and methanol (YNBM). Subcellular localization studies indicate that ROP translocates from cytosol to nucleus of cells cultured in YPM but not YNBM. In vitro DNA binding studies indicate that AOXI promoter sequences containing 5′ CYCCNY 3′ motifs serve as binding sites for Mxr1p as well as ROP. Thus, Mxr1p and ROP exhibit the same DNA binding specificity but regulate methanol metabolism antagonistically in P. pastoris. This is the first report on the identification of a transcriptional repressor of methanol metabolism in any yeast species. PMID:22888024

Retinopathy of prematurity: mutations in the Norrie disease gene and the risk of progression to advanced stages.

PubMed

Haider, M Z; Devarajan, L V; Al-Essa, M; Srivastva, B S; Kumar, H; Azad, R; Rashwan, N

2001-04-01

Retinopathy of prematurity (ROP) is a retinal vascular disease that occurs in infants with short gestational age and low birth weight and may lead to retinal detachment and blindness. Missense mutations in the Norrie disease (ND) gene have been associated with the risk of progression to advanced stages in cases of ROP from the US and also in clinically similar ND and familial exudative vitreoretinopathy. We have screened two ND gene mutations, namely A105T and Val60Glu, by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele-specific PCR methods, respectively, in 210 Kuwaiti premature newborns to replicate these findings in a different ethnic group. In the Kuwaiti premature newborn cohort, 115 of 210 babies had no eye problems and served as controls, while 95 were cases of ROP. In 71 of 95 ROP cases, the disease regressed spontaneously on or before stage 3, while in 24 of 95 ROP cases the disease progressed to advanced stages 4 and 5. In case of missense mutation (A105T), the AA genotype was detected in 96% of controls compared with 87% of ROP cases (NS); similarly no significant difference was found between spontaneously regressed ROP cases and those who progressed to advanced stages. For the Val60Glu mutation, no significant association was detected between the genotype and progression of ROP to advanced stages. Unlike data from the US, our findings from a Kuwaiti cohort of ROP cases and controls suggest a lack of association between the two ND gene mutations (A105T and Val60Glu) and ROP and the risk of progression of the disease to advanced stages.

The CHOP postnatal weight gain, birth weight, and gestational age retinopathy of prematurity risk model.

PubMed

Binenbaum, Gil; Ying, Gui-Shuang; Quinn, Graham E; Huang, Jiayan; Dreiseitl, Stephan; Antigua, Jules; Foroughi, Negar; Abbasi, Soraya

2012-12-01

To develop a birth weight (BW), gestational age (GA), and postnatal-weight gain retinopathy of prematurity (ROP) prediction model in a cohort of infants meeting current screening guidelines. Multivariate logistic regression was applied retrospectively to data from infants born with BW less than 1501 g or GA of 30 weeks or less at a single Philadelphia hospital between January 1, 2004, and December 31, 2009. In the model, BW, GA, and daily weight gain rate were used repeatedly each week to predict risk of Early Treatment of Retinopathy of Prematurity type 1 or 2 ROP. If risk was above a cut-point level, examinations would be indicated. Of 524 infants, 20 (4%) had type 1 ROP and received laser treatment; 28 (5%) had type 2 ROP. The model (Children's Hospital of Philadelphia [CHOP]) accurately predicted all infants with type 1 ROP; missed 1 infant with type 2 ROP, who did not require laser treatment; and would have reduced the number of infants requiring examinations by 49%. Raising the cut point to miss one type 1 ROP case would have reduced the need for examinations by 79%. Using daily weight measurements to calculate weight gain rate resulted in slightly higher examination reduction than weekly measurements. The BW-GA-weight gain CHOP ROP model demonstrated accurate ROP risk assessment and a large reduction in the number of ROP examinations compared with current screening guidelines. As a simple logistic equation, it can be calculated by hand or represented as a nomogram for easy clinical use. However, larger studies are needed to achieve a highly precise estimate of sensitivity prior to clinical application.

Educational paper: Retinopathy of prematurity.

PubMed

Casteels, Ingele; Cassiman, Catherine; Van Calster, Joachim; Allegaert, Karel

2012-06-01

Retinopathy of prematurity (ROP) is a proliferative retinal vascular disease affecting the premature infant with an incompletely vascularized retina. The spectrum of ophthalmological findings in ROP exists from minimal sequelae, which do not affect vision, to bilateral retinal detachment and total blindness. With the increased survival of very small infants, retinopathy of prematurity has become one of the leading causes of childhood blindness. Over the past two decades, major advances have been made in understanding the pathogenesis of ROP, to a large extent as a result of changes in clinical risk factors (oxygen and non-oxygen related) and characteristics observed in ROP cases. This article provides a literature review on the evolution in clinical characteristics, classification and treatment modalities and indications of ROP. Special attention is hereby paid to the neonatal factors influencing the development of ROP and to the necessity for everyone caring for premature babies to have a well-defined screening and treatment protocol for ROP. Such screening protocol needs to be based on a unit-specific ROP risk profile and, consequently, may vary between different European regions. Retinopathy of prematurity is an important cause of ocular morbidity and blindness in children. With better understanding of the pathogenesis, screening and treatment guidelines have changed over time and are unit specific.

Differences in risk factors for retinopathy of prematurity development in paired twins: a Chinese population study.

PubMed

Yau, Gordon S K; Lee, Jacky W Y; Tam, Victor T Y; Yip, Stan; Cheng, Edith; Liu, Catherine C L; Chu, Benjamin C Y; Yuen, Can Y F

2014-01-01

To determine the differences in risk factors for retinopathy of prematurity (ROP) in paired twins. A retrospective medical record review was performed for all paired twins screened for ROP between 2007 and 2012. Screening was offered to very low birth weight (≤ 1500 grams) and preterm (≤ 32 weeks) neonates. Twins 1 and 2 were categorized based on the order of delivery. Maternal and neonatal covariates were analyzed using univariate and multivariate regression analyses for both ROP and Type 1 ROP. In 34 pairs of Chinese twins, the mean gestational age (GA) was 30.2 ± 2.0 weeks. In Twin 1, smaller GA (OR = 0.44, P = 0.02), higher mean oxygen concentration (OR = 1.34, P = 0.03), presence of thrombocytopenia (OR = 1429.60, P < 0.0001), and intraventricular hemorrhage (OR = 18.67, P = 0.03) were significant risk factors for ROP. For Twin 2, a smaller GA (OR = 0.45, P = 0.03) was the only risk factor. There were no significant risk factors for ROP in Twin 1 or Twin 2 on multivariate analysis. In Chinese twin pairs, smaller GA was the only common risk factor for ROP while Twin 1 was more susceptible to the postnatal risks for ROP.

Association between hyperglycemia and retinopathy of prematurity: a systemic review and meta-analysis

PubMed Central

Au, Sunny C. L.; Tang, Shu-Min; Rong, Shi-Song; Chen, Li-Jia; Yam, Jason C. S.

2015-01-01

As the role of hyperglycemia in the development of retinopathy of prematurity (ROP) has not been well established, a meta-analysis of the association between hyperglycemia and ROP was conducted. Studies were identified through literature search in MEDLINE and EMBASE up to June 20, 2014 with keywords related to “hyperglycaemia” and “ROP”. Nine eligible studies involving 1939 neonates with 509 cases of ROP were included. Unadjusted analyses showed that hyperglycemia was significantly associated with ROP (Odds ratio [OR] = 4.16, P<0.0001). Comparing with the control, subjects in the ROP group had a significantly longer duration of hyperglycemia (Standardized mean difference [SMD] = 1.21, P< 0.0001), and higher mean glucose level. (SMD = 0.88, P = 0.0004) However, when combining the adjusted OR (after adjustment for birth weight, gestational age and other factors) provided from individual studies, only borderline significant association were observed on duration of hyperglycemia with ROP (adjusted OR 1.08, P = 0.03); and no significant association on mean glucose level with ROP (adjusted OR = 1.08, P = 0.15). Hence, hyperglycemia cannot be definitely considered as a risk factor for ROP, and further studies should adjust for potential confounding factors to clarify this association. PMID:25766465

Limitations in ROP Programs in 32 Neonatal Intensive Care Units in Five States in Mexico

PubMed Central

Zepeda-Romero, L. Consuelo; Gilbert, Clare

2015-01-01

Retinopathy of prematurity (ROP) is the main cause of avoidable blindness in children in Mexico despite National ROP Guidelines and examination of preterm infants being a legal requirement. Objective. To assess coverage of ROP programs and their compliance with national guidelines. Study Design. Thirty-two neonatal intensive care units (NICUs) in five of the largest states were visited. Staff were interviewed to collect information on their ROP programs which were defined as (1) compliant, if National Guidelines for screening and treatment were followed, (2) noncompliant, if other approaches were used, or (3) no program. Results. Only 10 (31.2%) had fully compliant programs and 11 (34.4%) had no program. In the remaining 11 (34.4%) different screening criteria were used (7 units): screening was undertaken by an ophthalmologist in unsalaried time (4), was not undertaken in the NICU (2), and was undertaken by a neonatologist (1) and/or Avastin was used as first-line treatment (7). Poorer states had poorer programs. Conclusions. Despite legislation mandating eye examination of preterm births, many ROP programs in the largest cities in Mexico require improvement or need to be established. Prevention of blindness due to ROP needs to be prioritized in Mexico to control the epidemic of ROP blindness. PMID:26167494

ROP GTPase-mediated auxin signaling regulates pavement cell interdigitation in Arabidopsis thaliana.

PubMed

Lin, Deshu; Ren, Huibo; Fu, Ying

2015-01-01

In multicellular plant organs, cell shape formation depends on molecular switches to transduce developmental or environmental signals and to coordinate cell-to-cell communication. Plants have a specific subfamily of the Rho GTPase family, usually called Rho of Plants (ROP), which serve as a critical signal transducer involved in many cellular processes. In the last decade, important advances in the ROP-mediated regulation of plant cell morphogenesis have been made by using Arabidopsis thaliana leaf and cotyledon pavement cells. Especially, the auxin-ROP signaling networks have been demonstrated to control interdigitated growth of pavement cells to form jigsaw-puzzle shapes. Here, we review findings related to the discovery of this novel auxin-signaling mechanism at the cell surface. This signaling pathway is to a large extent independent of the well-known Transport Inhibitor Response (TIR)-Auxin Signaling F-Box (AFB) pathway, and instead requires Auxin Binding Protein 1 (ABP1) interaction with the plasma membrane-localized, transmembrane kinase (TMK) receptor-like kinase to regulate ROP proteins. Once activated, ROP influences cytoskeletal organization and inhibits endocytosis of the auxin transporter PIN1. The present review focuses on ROP signaling and its self-organizing feature allowing ROP proteins to serve as a bustling signal decoder and integrator for plant cell morphogenesis. © 2014 Institute of Botany, Chinese Academy of Sciences.

Volume reduction of the corpus callosum and its relationship with deficits in interhemispheric transfer of information in recent-onset psychosis.

PubMed

Chaim, Tiffany M; Schaufelberger, Maristela S; Ferreira, Luiz K; Duran, Fábio L S; Ayres, Adriana M; Scazufca, Marcia; Menezes, Paulo R; Amaro, Edson; Leite, Claudia C; Murray, Robin M; McGuire, Philip K; Rushe, Teresa M; Busatto, Geraldo F

2010-10-30

The present study aimed to investigate the presence of corpus callosum (CC) volume deficits in a population-based recent-onset psychosis (ROP) sample, and whether CC volume relates to interhemispheric communication deficits. For this purpose, we used voxel-based morphometry comparisons of magnetic resonance imaging data between ROP (n =122) and healthy control (n = 94) subjects. Subgroups (38 ROP and 39 controls) were investigated for correlations between CC volumes and performance on the Crossed Finger Localization Test (CFLT). Significant CC volume reductions in ROP subjects versus controls emerged after excluding substance misuse and non-right-handedness. CC reductions retained significance in the schizophrenia subgroup but not in affective psychoses subjects. There were significant positive correlations between CC volumes and CFLT scores in ROP subjects, specifically in subtasks involving interhemispheric communication. From these results, we can conclude that CC volume reductions are present in association with ROP. The relationship between such deficits and CFLT performance suggests that interhemispheric communication impairments are directly linked to CC abnormalities in ROP. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Effect of Rock Properties on ROP Modeling Using Statistical and Intelligent Methods: A Case Study of an Oil Well in Southwest of Iran

NASA Astrophysics Data System (ADS)

Bezminabadi, Sina Norouzi; Ramezanzadeh, Ahmad; Esmaeil Jalali, Seyed-Mohammad; Tokhmechi, Behzad; Roustaei, Abbas

2017-03-01

Rate of penetration (ROP) is one of the key indicators of drilling operation performance. The estimation of ROP in drilling engineering is very important in terms of more accurate assessment of drilling time which affects operation costs. Hence, estimation of a ROP model using operational and environmental parameters is crucial. For this purpose, firstly physical and mechanical properties of rock were derived from well logs. Correlation between the pair data were determined to find influential parameters on ROP. A new ROP model has been developed in one of the Azadegan oil field wells in southwest of Iran. The model has been simulated using Multiple Nonlinear Regression (MNR) and Artificial Neural Network (ANN). By adding the rock properties, the estimation of the models were precisely improved. The results of simulation using MNR and ANN methods showed correlation coefficients of 0.62 and 0.87, respectively. It was concluded that the performance of ANN model in ROP prediction is fairly better than MNR method.

Fluorescein angiography and retinal vascular development in premature infants.

PubMed

Purcaro, Velia; Velia, Purcaro; Baldascino, Antonio; Antonio, Baldascino; Papacci, Patrizia; Patrizia, Papacci; Giannantonio, Carmen; Carmen, Giannantonio; Molisso, Anna; Anna, Molisso; Molle, Fernando; Fernando, Molle; Lepore, Domenico; Domenico, Lepore; Romagnoli, Costantino; Costantino, Romagnoli

2012-10-01

To investigate the role of fluorescein angiography (FA) in the management of retinopathy of prematurity (ROP) in preterm newborns. An observational case series of 13 extremely low birth weight infants. From September 2009 to March 2010, 13 newborn infants with a gestational age <29 weeks end/or birth weight <1000 g underwent serial fluorescein angiography with RetCam (Clarity, Pleasanton, CA) every 2 weeks. The fluorescein angiograms were examined to optimize the timing of diagnosis of ROP and to investigate development of retinal and choroidal vascularization. There were no side effects related to FA. Variable features of retinal and choroidal circulation in preterm infants with a high risk of developing ROP were noted. FA allows vessels branching at the junction between vascular and avascular retina (V-Av junction) to be viewed easily and shows the ROP findings that sometimes cannot be seen by indirect ophthalmoscopy. Dye leakage is the most significant sign of progression to severe ROP or the need for surgery in newborn babies with ROP. RetCam-assisted intravenous FA is safe and allows a more objective assessment of the ROP stage and zone.

A Comparison of Breast Milk and Sucrose in Reducing Neonatal Pain During Eye Exam for Retinopathy of Prematurity.

PubMed

Şener Taplak, Ayşe; Erdem, Emine

2017-06-01

This double-blind randomized controlled experimental study aimed to determine the effects of breast milk and sucrose in reducing pain in preterm infants during retinopathy of prematurity (ROP) examination. This study was conducted with 60 preterm infants (breast milk group = 20, sucrose group = 20, and control/distilled water group = 20) meeting the inclusion criteria. The data were collected with the use of an Infant Evaluation Form, Procedure Monitoring Form, and Premature Infant Pain Profile (PIPP). The preterm infants were provided with 1 mL of breast milk, sucrose, and distilled water before the ROP examination. The pain level in preterm infants was measured by the PIPP 5 minutes before, during, and 5 minutes after the ROP examination. The ROP examinations were video recorded, and videos were evaluated by three observers blinded to the study. No significant difference was determined between the three groups in terms of their postconceptional and postnatal ages, their body weights at birth and during the ROP examination. The PIPP scores of the preterm infants in the three groups were higher during the ROP examination and were not significantly different. The PIPP scores of the control group were significantly higher than those in the breast milk and sucrose groups after the ROP examination (p < 0.001). The preterm infants in the breast milk group recovered and returned to their initial values more quickly after the ROP examination than the infants in the sucrose group. To reduce pain in preterm infants during ROP examination, breast milk is recommended.

Risk factors and rate of progression for zone I versus zone II type 1 retinopathy of prematurity.

PubMed

Shin, Dong Hoon; Kong, Mingui; Kim, Sang Jin; Ham, Don Il; Kang, Se Woong; Chang, Yun Sil; Park, Won Soon

2014-04-01

To compare the risk factors and rate of progression of zone I versus zone II type 1 retinopathy of prematurity (ROP). The medical records of consecutive preterm infants with bilateral type 1 ROP in zone I and age-matched control infants with type 1 ROP in zone II were retrospectively analyzed. Fundus findings at each screening examination and systemic parameters were compared between groups. Univariate and conditional multivariate regression analyses were employed to identify variables significantly associated with zone I ROP. A total of 30 cases and 30 controls were included. The mean gestational age of included infants was 24.6 weeks in both groups, and the mean birth weights were 685 g in the zone I group and 667 g in the zone II group. The postmenstrual age (PMA) at the time of initial ROP detection did not differ between groups, but the PMA at the time of type 1 ROP detection was significantly earlier in the zone I group (mean, 34.9 vs 37.6 weeks). Conditional multiple logistic regression revealed that mechanical ventilation for 30 days or more was significantly associated with the type 1 ROP in zone I compared with zone II (OR, 3.5; 95% CI, 1.2-10.0). Zone I ROP exhibited rapid progression, necessitating close monitoring and prompt treatment. Compromised pulmonary function with associated mechanical ventilation in early life may restrict retinal vascular growth and increase the likelihood of zone I type 1 ROP. Copyright © 2014 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.

75 FR 66725 - National Fire Protection Association (NFPA) Proposes To Revise Codes and Standards

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-29

... Technical Committee by a formal written ballot. If the ROP does not receive approval by a two-thirds vote.... Following the completion of the Proposal and Comment periods, there is a further opportunity for debate and... the debate and consideration of motions to amend the Report. Before making an allowable motion at an...

Outcomes after Intravitreal Bevacizumab versus Laser Photocoagulation for Retinopathy of Prematurity: A 5-Year Retrospective Analysis

PubMed Central

Hwang, Christopher K.; Hubbard, G. Baker; Hutchinson, Amy K.; Lambert, Scott R.

2014-01-01

Purpose To determine the relative effectiveness, major complications, and refractive errors associated with intravitreal bevacizumab (IVB) versus panretinal photocoagulation (PRP) to treat Type 1 retinopathy of prematurity (ROP). Subjects Consecutive infants with Type 1 ROP who received either IVB or PRP between January 2008 and December 2012 and had at least six months of follow-up. Design Retrospective case series. Methods The data from infants treated with either IVB or PRP for Type 1 ROP between January 2008 and December 2012 were recorded from two medical centers in Atlanta, Georgia. Main Outcome Measures Recurrence rate, complication rate, refractive error. Results A total of 54 eyes (28 patients) with Type 1 ROP were evaluated: 22 eyes (11 patients) received IVB, and 32 eyes (17 patients) received PRP. Among the 22 eyes treated with IVB, 16 eyes had Zone I ROP and 6 eyes had posterior Zone II ROP. The number of Zone I and Zone II ROP eyes treated with PRP were 5 and 27 eyes, respectively. Mean gestational age, birth weight, postmenstrual age at the initial treatment, and follow-up period for the infants receiving IVB were 24.2 weeks, 668.1 grams, 35.1 weeks, and 21.7 weeks, respectively, and for the infants receiving PRP were 24.8, 701.4 grams, 36.1 weeks, and 34.5 weeks, respectively. ROP recurred in 3/22 (14%) IVB-treated eyes and in 1/32 (3%) PRP-treated eyes. None of IVB-treated eyes progressed to retinal detachment or developed macular ectopia. Only one eye went on to retinal detachment and five eyes developed macular ectopia in PRP-treated eyes. Mean spherical equivalent and postgestational age at the last refraction for IVB-treated eyes were −2.4 D and 22.4 months, respectively, and for PRP-treated eyes were −5.3 D and 37.1 months, respectively. Mean spherical equivalent for Zone I ROP eyes treated with IVB and PRP were −3.7 D and −10.1 D, respectively, and for Zone II ROP eyes were 0.6 D and −4.7 D, respectively. Conclusions Both IVB and PRP are effective treatment options for Type 1 ROP with low complication rates. Zone I ROP was associated with high minus refractive errors in eyes treated with either IVB or PRP. PMID:25687024

Algorithms for the prediction of retinopathy of prematurity based on postnatal weight gain.

PubMed

Binenbaum, Gil

2013-06-01

Current ROP screening guidelines represent a simple risk model with two dichotomized factors, birth weight and gestational age at birth. Pioneering work has shown that tracking postnatal weight gain, a surrogate for low insulin-like growth factor 1, may capture the influence of many other ROP risk factors and improve risk prediction. Models including weight gain, such as WINROP, ROPScore, and CHOP ROP, have demonstrated accurate ROP risk assessment and a potentially large reduction in ROP examinations, compared to current guidelines. However, there is a need for larger studies, and generalizability is limited in countries with developing neonatal care systems. Copyright © 2013 Elsevier Inc. All rights reserved.

Plant Rho-type (Rop) GTPase-dependent activation of receptor-like cytoplasmic kinases in vitro.

PubMed

Dorjgotov, Dulguun; Jurca, Manuela E; Fodor-Dunai, Csilla; Szucs, Attila; Otvös, Krisztina; Klement, Eva; Bíró, Judit; Fehér, Attila

2009-04-02

Plants have evolved distinct mechanisms to link Rho-type (Rop) GTPases to downstream signaling pathways as compared to other eukaryotes. Here, experimental data are provided that members of the Medicago, as well as Arabidopsis, receptor-like cytoplasmic kinase family (RLCK Class VI) were strongly and specifically activated by GTP-bound Rop GTPases in vitro. Deletion analysis indicated that the residues implicated in the interaction might be distributed on various parts of the kinases. Using a chimaeric Rop GTPase protein, the importance of the Rho-insert region in kinase activation could also be verified. These data strengthen the possibility that RLCKs may serve as Rop GTPase effectors in planta.

Parenteral Fish-Oil Lipid Emulsions in the Prevention of Severe Retinopathy of Prematurity: A Systematic Review and Meta-Analysis.

PubMed

Vayalthrikkovil, Sakeer; Bashir, Rani A; Rabi, Yacov; Amin, Harish; Spence, Jill-Marie; Robertson, Helen Lee; Lodha, Abhay

2017-06-01

Objective  Omega-3 fatty acids are vital for brain and retinal maturation. It is not clear if early use of ω-3 fatty acids in the form of fish-oil lipid emulsions (FLEs) prevents retinopathy of prematurity (ROP) in preterm infants. The aim of this meta-analysis is to evaluate whether early administration of parenteral FLEs reduces ROP requiring laser therapy or severe ROP ≥stage 3 in preterm infants. Methods  A literature search was performed to identify studies comparing parenteral FLEs with soybean-based lipid emulsions (SLEs) in preventing ROP. The main outcome was incidence of severe ROP or ROP requiring laser therapy. Results  Studies met the inclusion criteria (four RCTs and two observational studies). The pooled relative risk of ROP requiring laser therapy or severe ROP ≥ stage 3 in FLEs group was 0.47 [95% CI: 0.24-0.90] and 0.40 [95% CI: 0.22-0.76] in RCTs and observational studies, respectively. FLEs also reduced cholestasis; however, other secondary outcomes of bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), sepsis, intraventricular hemorrhage (IVH), and mortality were similar. Conclusion  The use of FLEs may reduce the incidence of severe ROP or need for laser therapy in preterm infants. A large multicenter RCT is required to confirm this. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Prevalence of retinopathy of prematurity in Latin America

PubMed Central

Carrion, Juliana Zimmermann; Filho, João Borges Fortes; Tartarella, Marcia Beatriz; Zin, Andrea; Jornada, Ignozy Dorneles

2011-01-01

The purpose of this work was to review the studies published over the last 10 years concerning the prevalence of retinopathy of prematurity (ROP) in Latin American countries, to determine if there was an improvement in ROP prevalence rates in that period, and to identify the inclusion criteria for patients at risk of developing ROP in the screening programs. A total of 33 studies from ten countries published between 2000 and 2010 were reviewed. Prevalence of any ROP stage in the regions considered ranged from 6.6% to 82%; ROP severe enough to require treatment ranged from 1.2% to 23.8%. There was no routine screening for ROP, and there was a lack of services for treatment of the disease in many countries. Inclusion criteria for patients in the studies ranged between birth weight ≤1500 g and ≤2000 g and gestational age ≤32 and <37 weeks. Use of different inclusion criteria regarding birth weight and gestational age in several Latin American studies hindered comparative analysis of the published data. Highly restrictive selection criteria for ROP screening in relation to birth weight and gestational age should not be used throughout most Latin American countries because of their different social characteristics and variable neonatal care procedures. The studies included in this review failed to provide adequate information to determine if the prevalence of ROP has decreased in Latin America. PMID:22174577

Prevalence of retinopathy of prematurity in Latin America.

PubMed

Carrion, Juliana Zimmermann; Fortes Filho, João Borges; Tartarella, Marcia Beatriz; Zin, Andrea; Jornada, Ignozy Dorneles

2011-01-01

The purpose of this work was to review the studies published over the last 10 years concerning the prevalence of retinopathy of prematurity (ROP) in Latin American countries, to determine if there was an improvement in ROP prevalence rates in that period, and to identify the inclusion criteria for patients at risk of developing ROP in the screening programs. A total of 33 studies from ten countries published between 2000 and 2010 were reviewed. Prevalence of any ROP stage in the regions considered ranged from 6.6% to 82%; ROP severe enough to require treatment ranged from 1.2% to 23.8%. There was no routine screening for ROP, and there was a lack of services for treatment of the disease in many countries. Inclusion criteria for patients in the studies ranged between birth weight ≤ 1500 g and ≤ 2000 g and gestational age ≤ 32 and <37 weeks. Use of different inclusion criteria regarding birth weight and gestational age in several Latin American studies hindered comparative analysis of the published data. Highly restrictive selection criteria for ROP screening in relation to birth weight and gestational age should not be used throughout most Latin American countries because of their different social characteristics and variable neonatal care procedures. The studies included in this review failed to provide adequate information to determine if the prevalence of ROP has decreased in Latin America.

Nucleophilically assisted and cationic ring-opening polymerization of tin-bridged [1]ferrocenophanes.

PubMed

Baumgartner, Thomas; Jäkle, Frieder; Rulkens, Ron; Zech, Gernot; Lough, Alan J; Manners, Ian

2002-08-28

To obtain mechanistic insight, detailed studies of the intriguing "spontaneous" ambient temperature ring-opening polymerization (ROP) of tin-bridged [1]ferrocenophanes Fe(eta-C(5)H(4))(2)SnR(2) 3a (R = t-Bu) and 3b (R = Mes) in solution have been performed. The investigations explored the influence of non-nucleophilic additives such as radicals and radical traps, neutral and anionic nucleophiles, Lewis acids, protic species, and other cationic electrophiles. Significantly, two novel methodologies and mechanisms for the ROP of strained [1]ferrocenophanes are proposed based on this study. First, as the addition of amine nucleophiles such as pyridine was found to strongly accelerate the polymerization rate in solution, a new nucleophilicallyassisted ROP methodology was proposed. This operates at ambient temperature in solution even in the presence of chlorosilanes but, unlike the anionic polymerization of ferrocenophanes, does not involve cyclopentadienyl anions. Second, the addition of small quantities of the electrophilic species H(+) and Bu(3)Sn(+) was found to lead to a cationic ROP process. These studies suggest that the "spontaneous" ROP of tin-bridged [1]ferrocenophanes may be a consequence of the presence of spurious, trace quantities of Lewis basic or acidic impurities. The new ROP mechanisms reported are likely to be of general significance for the ROP of other metallocenophanes (e.g., for thermal ROP in the melt) and for other metallacycles containing group 14 elements.

Retinopathy of prematurity: an epidemic in the making.

PubMed

Quinn, Graham E; Gilbert, Clare; Darlow, Brian A; Zin, Andrea

2010-10-01

To explore the etiology, incidence and methods to prevent and treat severe retinopathy of prematurity (ROP), which is rapidly becoming a threat to the vision of babies in areas of the world where increasing numbers of premature babies are surviving. The data used in this review were mainly from Medline and PubMed published in English. The search term was "retinopathy of prematurity and premature birth". We discuss the historical perspectives, prevalence and incidence, classification and treatment methods of ROP in premature babies. Peripheral retinal ablation for eyes with severe ROP can help prevent progression to blindness and several large clinical trials have shown the effectiveness of this treatment in high risk eyes. As a greater proportion of VLBW and ELBW babies survive, the population of babies at risk increases. In various regions of the world, different identification criteria are used to determine which babies are at risk of blindness in order to provide timely diagnostic examinations and treatment as needed. Methods for preventing ROP include better ante-natal and obstetric care leading to a reduction in the rate of prematurity, the use of ante-natal corticosteroids, and better neonatal care practices. Recent developments have indicated that management of oxygen supplementation is important for the prevention of severe ROP; however, there is not yet known what oxygen saturation target should be adopted. Sepsis increases severe ROP in very preterm infants. Genetic associations and a telemedicine approach may be explored to detect ROP. Treatment of anti-VEGF therapy are potentially useful in eyes with severe ROP, but long term effects are not yet known and such treatment should be used with great caution. ROP is a potentially binding disease for premature babies which is becoming more prevalent with the development improving neonatal services in many countries in recent years. High priority should be placed on developing approaches to prevent ROP blindness by reducing preterm birth, improving care of premature babies in neonatal care units, and providing adequate ophthalmological services in those regions.

Comparison of Bevacizumab, Ranibizumab, and Laser Photocoagulation in the Treatment of Retinopathy of Prematurity in Turkey.

PubMed

Gunay, Murat; Sukgen, Emine Alyamac; Celik, Gokhan; Kocluk, Yusuf

2017-03-01

To evaluate the efficacies and treatment outcomes following intravitreal bevacizumab (IVB), intravitreal ranibizumab (IVR), and laser photocoagulation (LPC) in retinopathy of prematurity (ROP). This was a retrospective interventional case series study including the data of 134 infants (264 eyes) who were treated with IVB, IVR, or LPC for ROP. The data were collected from two major ROP treatment centers in Turkey without any randomization or masking. Regression of ROP, recurrence profile, complications after each treatment modality, and indications for retreatment were evaluated. The main outcome measures included the total inactivation of ROP with anatomic and refractive outcomes at 1.5 years of adjusted age. There were 55 infants (41.1%) in the IVB group, 22 infants (16.4%) in the IVR group, and 57 infants (42.5%) in the LPC group. All but 3 infants (5.5%) in the IVB group and 11 infants (50%) in the IVR group showed recurrence to stage 1 and 2 ROP following IVB and IVR (p < 0.001). Retreatment was performed in three infants in both IVB and IVR groups (p = 0.098). At 1.5 years of adjusted age, all infants showed favorable anatomic outcome except one infant in the LPC group. No significant difference of the mean spherical equivalent (SE) was observed between the groups (p = 0.131). In Zone I ROP, laser treated infants had significantly higher rates of myopia and high myopia than IVB and IVR treated infants (p = 0.040 and p = 0.019, respectively). Both IVB and IVR treated infants had significantly better refractive outcomes in Zone I ROP as compared to LPC treated infants at 1.5 years of adjusted age. The higher rate of disease recurrence was associated with IVR. Gestational age (GA) and the zone of ROP were also predictive factors for recurrence of ROP in the study.

One-year experience in the retinopathy of prematurity: frequency and risk factors, short-term results and follow-up.

PubMed

Mehmet, Sariaydin; Fusun, Atlihan; Sebnem, Calkavur; Ozgur, Olukman; Gulten, Ercan; Taylan, Ozturk Arif; Fatma, Kaya Kilic; Filiz, Gokaslan; Derya, Altinyaprak; Rana, Malatyali

2011-01-01

As a result of the increase in premature births and the advances in neonatal intensive care, retinopathy of prematurity (ROP) remains one of the most important causes of childhood blindness worldwide. The main factors in the development of ROP are gestational age, birth weight and oxygen therapy. ROP continues to gain importance due to the increasing survival rates of more immature babies. Between January 2007 and October 2008, 203 premature infants treated at the Neonatal Intensive Care Unit (NNICU) were prospectively enrolled and the relationship between known risk factors and the occurance of ROP was studied. ROP in various stages developed in 86 cases (42.4%). Statistically significant correlations were found between the development of ROP and birth weight (P<0.0001) gestational age (P<0.0001), oxygen treatment and its duration (P<0.0001 and P=0.002), mechanical ventilation (MV) and its duration (P=0,0001 and P=0.0001), apnea (P=0.001), intraventricular hemorrhage (IVH) (P=0.046), sepsis (P=0.0001), use of erythropoietin (EPO) (P=0.003), the number of blood transfusions and frequency (P=0.0001 and P=0.0001), surfactant application (P=0.0001), the presence of patent ductus arteriosus (PDA) (P=0.001) or bronchopulmonary dysplasia (BPD) (P=0.0001). No significant correlations were found between the occurance of ROP and maternal pre-eclampsia (P=0.293), multiple pregnancy (P=0.218), or hyperbilirubinemia (P=0.494). Severity of ROP was related significantly with birth weight (P=0.0001), but no significant correlation between severity of ROP and gestational age was present. Early description and reduction of the risk factors related with the occurance of ROP with the help of routine screening programs may warrant the prevention of visual loss, however early ophthalmic diagnosis and treatment are still mandatory to provide better visual rehabilitation.

One-year experience in the retinopathy of prematurity: frequency and risk factors, short-term results and follow-up

PubMed Central

Mehmet, Sariaydin; Fusun, Atlihan; Sebnem, Calkavur; Ozgur, Olukman; Gulten, Ercan; Taylan, Ozturk Arif; Fatma, Kaya Kilic; Filiz, Gokaslan; Derya, Altinyaprak; Rana, Malatyali

2011-01-01

AIM As a result of the increase in premature births and the advances in neonatal intensive care, retinopathy of prematurity (ROP) remains one of the most important causes of childhood blindness worldwide. The main factors in the development of ROP are gestational age, birth weight and oxygen therapy. ROP continues to gain importance due to the increasing survival rates of more immature babies. METHODS Between January 2007 and October 2008, 203 premature infants treated at the Neonatal Intensive Care Unit (NNICU) were prospectively enrolled and the relationship between known risk factors and the occurance of ROP was studied. RESULTS ROP in various stages developed in 86 cases (42.4%). Statistically significant correlations were found between the development of ROP and birth weight (P<0.0001) gestational age (P<0.0001), oxygen treatment and its duration (P<0.0001 and P=0.002), mechanical ventilation (MV) and its duration (P=0,0001 and P=0.0001), apnea (P=0.001), intraventricular hemorrhage (IVH) (P=0.046), sepsis (P=0.0001), use of erythropoietin (EPO) (P=0.003), the number of blood transfusions and frequency (P=0.0001 and P=0.0001), surfactant application (P=0.0001), the presence of patent ductus arteriosus (PDA) (P=0.001) or bronchopulmonary dysplasia (BPD) (P=0.0001). No significant correlations were found between the occurance of ROP and maternal pre-eclampsia (P=0.293), multiple pregnancy (P=0.218), or hyperbilirubinemia (P=0.494). Severity of ROP was related significantly with birth weight (P=0.0001), but no significant correlation between severity of ROP and gestational age was present. CONCLUSION Early description and reduction of the risk factors related with the occurance of ROP with the help of routine screening programs may warrant the prevention of visual loss, however early ophthalmic diagnosis and treatment are still mandatory to provide better visual rehabilitation. PMID:22553735

Comparison of digital imaging screening and indirect ophthalmoscopy for retinopathy of prematurity.

PubMed

Ezz El Din, Zahraa Mohamed; El Sada, Mohamed Ahmed; Ali, Aliaa Adel; Al Husseiny, Khalid; Yousef, Aly Abdel Rahman

2015-01-01

The aims of this study were to determine the incidence and severity of retinopathy of prematurity (ROP) using digital imaging screening, confirm findings by indirect opthalmoscopy, and document risk factors of ROP in the neonatal intensive care unit (NICU) of a large tertiary hospital in a developing country. This prospective cohort study included infants with gestational age (GA) ≤ 32 wk, birth weight (BW) ≤ 1,500 g, or older and heavier neonates who were critically ill. Two hundred twenty two eyes (111 infants) were screened with digital imaging (Ret-Cam) and indirect ophthalmoscopy until retinal vascularization was complete or the disease regressed. Perinatal risk factors for ROP were analyzed. The overall incidence of ROP was 18.9 %. The incidence of ROP requiring treatment was 5.4 % (12/222) of the total eyes screened. Lower GA and blood transfusion were independent risk factors associated with ROP by multivariate analysis (p = 0.001, OR = 0.562, 95 % CI = 0.395-0.802, and p = 0.027, OR = 6.11, 95 % CI = 1.22-30.44, respectively). Digital imaging facilitated timely screening and detection of ROP, and enabled transfer of images, allowing early intervention for patients who required treatment.

New insights in diagnosis and treatment for Retinopathy of Prematurity.

PubMed

Cernichiaro-Espinosa, Linda A; Olguin-Manriquez, Francisco J; Henaine-Berra, Andree; Garcia-Aguirre, Gerardo; Quiroz-Mercado, Hugo; Martinez-Castellanos, Maria A

2016-10-01

The purpose of this study was to review current perspectives on diagnosis and treatment of Retinopathy of Prematurity (ROP). We performed a systematic review of how much has been produced in research published online and on print regarding ROP in different settings around the world. Early Treatment for ROP (ETROP) classification is the currently accepted classification of ROP. Fluorescein angiography and spectral domain optical coherence tomography (SD-OCT) may eventually lead to changes in the definition of ROP, and as a consequence, they will serve as a guide for treatment. Intravitreal anti-VEGF therapy has proven to be more effective in terms of lowering recurrence, allowing growth of the peripheral retina, and diminishing the incidence of retinal detachment when proliferative ROP is diagnosed. Whether anti-VEGF plus laser are better than any of these therapies separately remains a subject of discussion. Telemedicine is evolving everyday to allow access to remote areas that do not count with a retina specialist for treatment. A management algorithm is proposed according to our reference center experience. ROP is an evolving subject, with a vulnerable population of study that, once treated with good results, leads to a reduction in visual disability and in consequence, in a lifetime improvement.

The KIDROP model of combining strategies for providing retinopathy of prematurity screening in underserved areas in India using wide-field imaging, tele-medicine, non-physician graders and smart phone reporting

PubMed Central

Vinekar, Anand; Gilbert, Clare; Dogra, Mangat; Kurian, Mathew; Shainesh, Gangadharan; Shetty, Bhujang; Bauer, Noel

2014-01-01

Aim: To report the Karnataka Internet Assisted Diagnosis of Retinopathy of Prematurity (KIDROP) program for retinopathy of prematurity (ROP) screening in underserved rural areas using an indigenously developed tele-ROP model. Materials and Methods: KIDROP currently provides ROP screening and treatment services in three zones and 81 neonatal units in Karnataka, India. Technicians were trained to use a portable Retcam Shuttle (Clarity, USA) and validated against ROP experts performing indirect ophthalmoscopy. An indigenously developed 20-point score (STAT score) graded their ability (Level I to III) to image and decide follow-up based on a three-way algorithm. Images were also uploaded on a secure tele-ROP platform and accessed and reported by remote experts on their smart phones (iPhone, Apple). Results: 6339 imaging sessions of 1601 infants were analyzed. A level III technician agreed with 94.3% of all expert decisions. The sensitivity, specificity, positive predictive value and negative predictive value for treatment grade disease were 95.7, 93.2, 81.5 and 98.6 respectively. The kappa for technicians to decide discharge of babies was 0.94 (P < 0.001). Only 0.4% of infants needing treatment were missed. The kappa agreement of experts reporting on the iPhone vs Retcam for treatment requiring and mild ROP were 0.96 and 0.94 (P < 0.001) respectively. Conclusions: This is the first and largest real-world program to employ accredited non-physicians to grade and report ROP. The KIDROP tele-ROP model demonstrates that ROP services can be delivered to the outreach despite lack of specialists and may be useful in other middle-income countries with similar demographics. PMID:24492500

Comparison of UK and US screening criteria for detection of retinopathy of prematurity in a developing nation.

PubMed

Ugurbas, Silay Canturk; Gulcan, Hande; Canan, Handan; Ankarali, Handan; Torer, Birgin; Akova, Yonca Aydın

2010-12-01

To determine the incidence, risk factors, and appropriateness of differing guidelines in developed nations for screening for retinopathy of prematurity (ROP) in a single nursery in a large urban city in southern Turkey. The records of 260 premature infants born ≤34 weeks in a single tertiary unit were retrospectively reviewed for ROP risk factors and diagnosis. Applicability of UK and US criteria were assessed by the use of receiver operating characteristic curves. ROP of any stage was present in 60 infants (23%); ROP requiring treatment was seen in 30 (11.5%). Univariate analysis showed a significant relationship among the following factors: gestational age, birth weight, total duration of supplemental oxygen, duration of mechanical ventilation, respiratory distress syndrome, anemia, and intraventricular hemorrhage (p < 0.0001). Multiple logistic regression analysis showed gestational age (p = 0.039), birth weight (p = 0.05), respiratory distress syndrome (p = 0.05), and anemia (p = 0.004) as independent predictors of ROP requiring treatment. Area under curve for gestational age alone for diagnosing stage 2 or greater ROP was 0.824 ± 0.03 (p = 0.0001) and for birth weight alone was 0.808 ± 0.03 (p = 0.0001). UK screening criteria detected all stage 2 and greater ROP; US screening criteria missed 2 infants with stage 2 ROP but detected all treatment-requiring disease. Adoption of these screening criteria would have reduced unnecessary examinations by either 21% (UK) or 37% (US). UK and US criteria improved the detection accuracy for ROP requiring treatment in Turkey and should be studied for other developing nations. Copyright © 2010 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.

Severe retinopathy of prematurity predicts delayed white matter maturation and poorer neurodevelopment.

PubMed

Glass, Torin J A; Chau, Vann; Gardiner, Jane; Foong, Justin; Vinall, Jillian; Zwicker, Jill G; Grunau, Ruth E; Synnes, Anne; Poskitt, Kenneth J; Miller, Steven P

2017-11-01

To determine whether severe retinopathy of prematurity (ROP) is associated with (1) abnormal white matter maturation and (2) neurodevelopmental outcomes at 18 months' corrected age (CA) compared with neonates without severe ROP. We conducted a prospective longitudinal cohort of extremely preterm neonates born 24-28 weeks' gestational age recruited between 2006 and 2013 with brain MRIs obtained both early in life and at term-equivalent age. Severe ROP was defined as ROP treated with retinal laser photocoagulation. Using diffusion tensor imaging and tract-based spatial statistics (TBSS), white matter maturation was assessed by mean fractional anisotropy (FA) in seven predefined regions of interest. Neurodevelopmental outcomes were assessed with Bayley Scales of Infant and Toddler Development-III (Bayley-III) composite scores at 18 months' CA. Subjects were compared using Fisher's exact, Kruskal-Wallis and generalised estimating equations. Families were recruited from the neonatal intensive care unit at BC Women's Hospital. Of 98 extremely preterm neonates (median: 26.0 weeks) assessed locally for ROP, 19 (19%) had severe ROP and 83 (85%) were assessed at 18 months' CA. Severe ROP was associated with lower FA in the posterior white matter, and with decreased measures of brain maturation in the optic radiations, posterior limb of the internal capsule (PLIC) and external capsule on TBSS. Bayley-III cognitive and motor scores were lower in infants with severe ROP. Severe ROP is associated with maturational delay in the optic radiations, PLIC, external capsule and posterior white matter, housing the primary visual and motor pathways, and is associated with poorer cognitive and motor outcomes at 18 months' CA. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Validation of WINROP for detecting retinopathy of prematurity in a North American cohort of preterm infants.

PubMed

Jung, Jennifer L; Wagner, Brandie D; McCourt, Emily A; Palestine, Alan G; Cerda, Ashlee; Cao, Jennifer H; Enzenauer, Robert W; Singh, Jasleen K; Braverman, Rebecca S; Wymore, Erica; Lynch, Anne M

2017-06-01

WINROP (weight, insulin-like growth factor 1, neonatal, retinopathy of prematurity) is a web-based retinopathy of prematurity (ROP) risk algorithm that uses postnatal weight gain as a surrogate of insulin-like growth factor-1 (IGF-1) to predict the risk of severe ROP in premature infants. The purpose of this study was to validate the web-based algorithm WINROP in detecting severe (type 1 or type 2) ROP in a North American cohort of infants. The records of consecutive infants who underwent ROP examinations between 2008 and 2011 were reviewed retrospectively. Infants were classified into categories of "alarm" (at risk for developing severe ROP) and "no alarm" (minimal risk for severe ROP). A total of 483 were included. Alarm occurred in 241 neonates (50%), with the median time from birth to alarm of 2 weeks. WINROP had a sensitivity of 81.8% (95% CI, 67.3%-91.8%) and specificity of 53.3% (95% CI, 48.5%-58.0%) for identifying infants with severe ROP. Eight of the 44 infants with severe ROP were not detected (5 with type 1 and 3 with type 2). Of these 8 infants, 7 (88%) had birth weight in excess of the 70 th pecentile. With additional weight data entry, sensitivity of WINROP rose to 88.6%. Very preterm infants (gestational age of ≤27 weeks) with relatively high birth weight for gestational age may not be detected by WINROP as high risk for developing severe ROP. Copyright © 2017 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

Adjusted poor weight gain for birth weight and gestational age as a predictor of severe ROP in VLBW infants.

PubMed

Aydemir, O; Sarikabadayi, Y U; Aydemir, C; Tunay, Z O; Tok, L; Erdeve, O; Oguz, S S; Uras, N; Dilmen, U

2011-06-01

To analyze relative weight gain by 2-week intervals up to 6 weeks after birth in order to predict the development of retinopathy of prematurity (ROP) requiring treatment among very low birth weight (BW) infants. A prospective study including infants with BW ≤1500 g born in a single tertiary intensive care unit over 1-year period was conducted. Body weight measurements were recorded weekly and relative weight gains (g/kg/day) were calculated. The main outcome was development of ROP requiring treatment. Mean BW and gestational age (GA) of the whole cohort were 1165±223 g and 29.3±2.3 weeks, respectively. Relative weight gain at 2 weeks and 4 weeks postnatal age were significantly lower in infants with severe ROP (P=0.041 and P=0.017, respectively). Relative weight gain at 6 weeks was not different between groups. Infants with severe ROP gained 6.7±4 g/kg/day in the first 4 weeks of life, compared with 9.3±4.5 g/kg/day for those with mild or no ROP. After adjusted for BW and GA in logistic regression poor relative weight gain in the first 4 weeks was found to be related to severe ROP (P=0.015). When all the other risk factors significant for severe ROP were included in the logistic regression poor weight gain did not arise as an independent risk factor. Poor postnatal weight gain in the first 4 weeks of life is the end result of several comorbidities rather than being an independent risk factor. Poor weight gain can be an additional predictor of severe ROP in very low BW infants.

The Arabidopsis ROP-activated receptor-like cytoplasmic kinase RLCK VI_A3 is involved in control of basal resistance to powdery mildew and trichome branching.

PubMed

Reiner, Tina; Hoefle, Caroline; Huesmann, Christina; Ménesi, Dalma; Fehér, Attila; Hückelhoven, Ralph

2015-03-01

The Arabidopsis receptor-like cytoplasmic kinase AtRLCK VI_A3 is activated by AtROPs and is involved in trichome branching and pathogen interaction. Receptor-like cytoplasmic kinases (RLCKs) belong to the large superfamily of receptor-like kinases, which are involved in a variety of cellular processes like plant growth, development and immune responses. Recent studies suggest that RLCKs of the VI_A subfamily are possible downstream effectors of the small monomeric G proteins of the plant-specific Rho family, called 'Rho of plants' (RAC/ROPs). Here, we describe Arabidopsis thaliana AtRLCK VI_A3 as a molecular interactor of AtROPs. In Arabidopsis epidermal cells, transient co-expression of plasma membrane located constitutively activated (CA) AtROP4 or CA AtROP6 resulting in the recruitment of green fluorescent protein-tagged AtRLCK VI_A3 to the cell periphery. Intrinsic kinase activity of AtRLCK VI_A3 was enhanced in the presence of CA AtROP6 in vitro and further suggested a functional interaction between the proteins. In the interaction of the biotrophic powdery mildew fungus Erysiphe cruciferarum (E. cruciferarum) and its host plant Arabidopsis, Atrlck VI_A3 mutant lines supported enhanced fungal reproduction. Furthermore Atrlck VI_A3 mutant lines showed slightly reduced size and an increase in trichome branch number compared to wild-type plants. In summary, our data suggest a role of the AtROP-regulated AtRLCK VI_A3 in basal resistance to E. cruciferarum as well as in plant growth and cellular differentiation during trichome morphogenesis. Results are discussed in the context of literature suggesting a function of RAC/ROPs in both resistance and susceptibility to pathogen infection.

DROP: Detecting Return-Oriented Programming Malicious Code

NASA Astrophysics Data System (ADS)

Chen, Ping; Xiao, Hai; Shen, Xiaobin; Yin, Xinchun; Mao, Bing; Xie, Li

Return-Oriented Programming (ROP) is a new technique that helps the attacker construct malicious code mounted on x86/SPARC executables without any function call at all. Such technique makes the ROP malicious code contain no instruction, which is different from existing attacks. Moreover, it hides the malicious code in benign code. Thus, it circumvents the approaches that prevent control flow diversion outside legitimate regions (such as W ⊕ X ) and most malicious code scanning techniques (such as anti-virus scanners). However, ROP has its own intrinsic feature which is different from normal program design: (1) uses short instruction sequence ending in "ret", which is called gadget, and (2) executes the gadgets contiguously in specific memory space, such as standard GNU libc. Based on the features of the ROP malicious code, in this paper, we present a tool DROP, which is focused on dynamically detecting ROP malicious code. Preliminary experimental results show that DROP can efficiently detect ROP malicious code, and have no false positives and negatives.

Comparative study of RetCamRetCam II vs. binocular ophthalmoscopy in a screening program for retinopathy of prematurity.

PubMed

Tejada-Palacios, P; Zarratea, L; Moral, M; de la Cruz-Bértolo, J

2015-08-01

To determine the performance of RetCam vs. binocular ophthalmoscopy (BIO) in a screening program for retinopathy of prematurity (ROP). Observational comparative study with prospective data collection. Examinations with RetCam (n=169) were performed on 83 infants included in a screening program for ROP and stored for analysis at a later stage. An experienced ophthalmologist examined the ocular fundus with binocular indirect ophthalmoscopy (BIO). The RetCam images were assessed for the presence of ROP, zone, grade, and presence of plus disease. RetCam and BIO data were compared by visually to estimate sensitivity, specificity, positive (VPP) and negative (VPN) predictive values. ROP disease was detected in 108 eyes with BIO, and in 74 with RetCam. Out of 306 eyes examined with RetCam, false negative results were found in 34 eyes, with no false positives. Sensitivity of RetCam exam vs. BIO was 0.68, and specificity was 0.99. Positive predictive value was 0.93 and negative predictive value was 0.85. All 34 ROP cases not detected with RetCam were in zone III or outer zone II. They were all mild and regressed spontaneously. No threshold ROP was missed with RetCam. Binocular indirect ophthalmoscopy is the reference method for the diagnosis of ROP. RetCam may be used as an alternative for ROP screening. Copyright © 2010 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

[Reliability of retinal imaging screening in retinopathy of prematurity].

PubMed

Navarro-Blanco, C; Peralta-Calvo, J; Pastora-Salvador, N; Alvarez-Rementería, L; Chamorro, E; Sánchez-Ramos, C

2014-09-01

The retinopathy of prematurity (ROP) is a potentially avoidable cause of blindness in children. The advances in neonatal care make the survival of extremely premature infants, who show a greater incidence of the disease, possible. The aim of the study is to evaluate the reliability of ROP screening using retinography imaging with the RetCam 3 wide-angle camera and also study the variability of ROP diagnosis depending on the evaluator. The indirect ophthalmoscopy exam was performed by a Pediatric ROP-Expert Ophthalmologist. The same ophthalmologist and a technician specialized in digital image capture took retinal images using the RetCam 3 wide-angle camera. A total of 30 image sets were analyzed by 3 masked groups: group A (8 ophthalmologists), group B (5 experts in vision), and group C (2 ROP-expert ophthalmologists). According to the diagnosis using indirect ophthalmoscopy, the sensitivity (26-93), Kappa (0.24-0.80), and the percent agreement were statistically significant in group C for the diagnosis of ROP Type 1. In the diagnosis of ROP Type 1+Type 2, Kappa (0.17-0.33) and the percent agreement (58-90) were statistically significant, with higher values in group C. The diagnosis, carried out by ROP-expert ophthalmologists, using the wide-angle camera RetCam 3 has proved to be a reliable method. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Association of Maternal Preeclampsia With Infant Risk of Premature Birth and Retinopathy of Prematurity.

PubMed

Shulman, Julia P; Weng, Cindy; Wilkes, Jacob; Greene, Tom; Hartnett, M Elizabeth

2017-09-01

Studies report conflicting associations between preeclampsia and retinopathy of prematurity (ROP). This study provides explanations for the discrepancies to clarify the relationship between preeclampsia and ROP. To evaluate the association of maternal preeclampsia and risk of ROP among infants in an unrestricted birth cohort and a restricted subcohort of preterm, very low birth weight (P-VLBW) infants. A retrospective review of 290 992 live births within the Intermountain Healthcare System in Utah from January 1, 2001, through December 31, 2010, was performed. Generalized estimating equations for logistic regressions with covariate adjustment were applied to relate ROP to preeclampsia among the full cohort and in a subcohort of P-VLBW infants born at younger than 31 weeks' gestation and weighing less than 1500 g. The occurrence of ROP was related to maternal preeclampsia in the full cohort and in a subcohort of P-VLBW infants. In the full cohort, 51% of the infants were male and the mean (SD) gestational age was 38.38 (1.87) weeks. In the P-VLBW cohort, 55% were male and the mean (SD) gestational age was 26.87 (2.40) weeks. In the full cohort, preeclampsia was associated with an increased risk of all ROP (adjusted odds ratio [aOR], 2.46; 95% CI, 2.17-2.79; P < .001), severe ROP (aOR, 5.21; 95% CI, 3.44-7.91; P < .001), infant death (aOR, 1.66; 95% CI, 1.16-2.38; P = .006), and giving birth to a P-VLBW infant (aOR, 7.74; 95% CI, 6.92-8.67; P < .001). In the P-VLBW subcohort, preeclampsia was inversely associated with the development of all ROP (aOR, 0.79; 95% CI, 0.68-0.92; P = .003), severe ROP (aOR, 0.62; 95% CI, 0.36-1.06; P = .08), and infant death (aOR, 0.19; 95% CI, 0.11-0.32; P < .001). Preeclampsia was associated with an increased risk of developing ROP among an unrestricted cohort but with a reduced risk of ROP among a restricted subcohort of P-VLBW infants. Although the conflicting associations in the full and P-VLBW cohorts may reflect true differences, the association of a reduced risk of ROP among the P-VLBW subcohort also may reflect biases from restricting the cohort to prematurity, because prematurity is an outcome of preeclampsia.

14 CFR Appendix B to Part 417 - Flight Hazard Area Analysis for Aircraft and Ship Protection

Code of Federal Regulations, 2010 CFR

2010-01-01

... location that is the farthest left-hand crossrange, the location that is the farthest right-hand crossrange... trajectory dispersion that are the farthest uprange, downrange, right crossrange, and left crossrange... · (NEW)1/3 Where: Rop is the over pressure distance in feet. NEW = WE · C (pounds). WE is the weight of...

Genetic association of single nucleotide polymorphisms of FZD4 and BDNF genes with retinopathy of prematurity.

PubMed

Lasabova, Zora; Stanclova, Andrea; Grendar, Marian; Mikolajcikova, Silvia; Calkovska, Andrea; Lenhartova, Nina; Ziak, Peter; Matasova, Katarina; Caprnda, Martin; Kruzliak, Peter; Zibolen, Mirko

2018-06-01

Retinopathy of prematurity (ROP) is a multifactorial disease occurring in preterm neonates, caused by incorrect development of retinal blood vessels. It has been suggested that, in addition to gestational age, weight, and oxygen supplementation, genetic factors can play a role in the pathogenesis of ROP. In the present prospective study, 97 neonates were enrolled based on the gestational age and weight, and genomic DNA from patients diagnosed with ROP and premature newborns without ROP was collected. The DNA sequence of protein coding and 5´and 3´ untranslated regions (UTRs) of the frizzled-4 (FZD4) gene and the genotype of the locus rs7934165:G˃A (NM_170731.4: c.3 + 10976 C˃T) within the brain-derived neurotrophic factor gene (BDNF) were determined. We detected a significant association between rs61749246:C˃A (NM_012193.3: c.*2G˃T) and ROP in a general genetic model as well as in a multiplicative model and by the Cochran-Armitage test for trend. Moreover, rs61749246 was strongly associated with ROP, requiring surgical intervention. We suggest that rs61749246:C˃A of the FZD4 gene is likely associated with the development of ROP. It is necessary to confirm this suggestion in larger studies.

Early postnatal weight gain as a predictor for the development of retinopathy of prematurity.

PubMed

Biniwale, Manoj; Weiner, Angela; Sardesai, Smeeta; Cayabyab, Rowena; Barton, Lorayne; Ramanathan, Rangasamy

2017-10-01

The objective of this study is to validate the reliability of early postnatal weight gain as an accurate predictor of type 1 retinopathy of prematurity (ROP) requiring treatment in a large predominantly Hispanic US cohort with the use of an online tool called WINROP (weight, neonatal retinopathy of prematurity (IGF-1), neonatal retinopathy of prematurity). Retrospective cohort study consisted of preterm infants <32 weeks gestation and birth weight <1500 g. Weekly weights to 36 weeks post-menstrual age or discharge if earlier were entered into the WINROP tool. This tool generated alarm and risk indicator for developing ROP. The infants with type 1 ROP requiring treatment as well as all stages of ROP were compared with the alarms and risks generated by WINROP tool. A total of 492 infants were entered into the WINROP tool. The infants who developed type 1 ROP requiring treatment, the WINROP tool detected 80/89 (90%) at less than 32 weeks gestation. Nine infants developed type 1 ROP were classified as low risk and did not alarm. Postnatal weight gain alone, in predominantly Hispanic US population, predicted type 1 ROP requiring treatment before 32 weeks of gestation in infants with a sensitivity of 90%. The tool appeared to identify majority of affected infants much earlier than the scheduled screening.

Asociación de la hemorragia prerretiniana con la presencia y la gravedad de la retinopatía del prematuro en pacientes de alto riesgo.

PubMed

Garza-Cantú, Daniel; Sánchez-Álvarez, Saria; Palacios-Barragán, David Ramón; Palacios-Saucedo, Gerardo Del Carmen

2017-01-01

To assess whether preretinal hemorrhage (PRH) is associated with the presence and severity of retinopathy of prematurity (ROP) in high-risk patients. Prospective cohort study, patients referred to the Department of Ophthalmology for ROP screening during October-November 2016 were evaluated weekly on 4 occasions to assess the relationship with PRH and the development of ROP as well as degree of severity associated. We used absolute, median frequencies with minimum and maximum values, χ 2 test and Mann-Whitney U-test, as well as relative risk with 95% confidence interval. A total of 30 patients, in the first week 11 females (36%) and 4 males (13%) had PRH; in the 2 nd week 13 patients (43%) presented PRH and 14 (46%) developed ROP; on the 3 rd week there were no changes; in the last week 8 presented HPR (26%) and 11 patients (36%) with ROP. Stage I severity occurred more frequently. Statistical significance (p = 0.040) was found in the presence of PRH and the development of ROP in the first week with. HPR is a risk factor for the development of ROP during the first weeks of life and is associated with stages of mild severity. Copyright: © 2017 SecretarÍa de Salud

The importance of oxygen control reaffirmed: experience of ROP reduction at a single tertiary care center.

PubMed

Nobile, Stefano; Gnocchini, Francesco; Pantanetti, Marco; Battistini, Paola; Carnielli, Virgilio P

2014-01-01

To report the impact of the adoption of a low oxygen saturation policy on retinopathy of prematurity (ROP) incidence at a single tertiary care center. ROP incidence, procedures for ROP, and neonatal outcome among very low birth weight infants were compared before and after the adoption of a low saturation policy, which took place in 2004. The Mann– Whitney test was performed to look for differences. The incidence of severe ROP significantly decreased from 5.3% of live very low birth weight infants between 1999 and 2004 to 1% of live very low birth weight infants between 2005 and 2012 (P = .003). The use of laser therapy for severe ROP between the same periods significantly decreased from 6.4% of live very low birth weight infants between 1999 and 2004 to 0.6% of live very low birth weight infants between 2005 and 2012 (P = .002). There was also a significant reduction of death or bronchopulmonary dysplasia from 33.8% between 1999 and 2004 to 24.2% between 2005 and 2012 (P = .02). Trained personnel and low and tailored oxygen saturation intervals for very low birth weight infants could play a pivotal role in reducing the incidence of severe ROP without increasing mortality.

Patent ductus arteriosus and indomethacin treatment as independent risk factors for plus disease in retinopathy of prematurity.

PubMed

Tsui, Irena; Ebani, Edward; Rosenberg, Jamie B; Lin, Juan; Angert, Robert M; Mian, Umar

2013-01-01

To examine whether clinically significant patent ductus arteriosus (PDA) or indomethacin treatment are associated with plus disease or retinopathy of prematurity (ROP) requiring treatment. Retrospective, cross-sectional study. Charts were reviewed for gestational age, birth weight, birth head circumference, birth length, maternal characteristics, gender, bronchopulmonary dysplasia, neurologic comorbidities, PDA and its treatments, gastrointestinal comorbidities, blood transfusions, and sepsis. Main outcome measures were increased rates of plus disease or ROP requiring treatment. A total of 450 premature infants screened for ROP in a mid-sized, urban neonatal intensive care unit were included. On univariate analysis, gestational age, birth weight, birth head circumference, birth length, bronchopulmonary dysplasia, neurologic comorbidities, PDA and its treatments, gastrointestinal comorbidities, and sepsis were significantly correlated to plus disease and ROP requiring treatment. PDA was significantly associated with bronchopulmonary dysplasia, neurologic comorbidities, sepsis, and blood transfusions (P < .0001). With type 3 multivariate analysis, only gestational age and bronchopulmonary dysplasia were independent risk factors for ROP. PDA and indomethacin were associated with plus disease and ROP requiring treatment on univariate analysis but this was not significant after adjusting for other risk factors. PDA was also strongly related to bronchopulmonary dysplasia and blood transfusions, which may explain its effect on ROP. Copyright 2013, SLACK Incorporated.

Plus disease in retinopathy of prematurity: a continuous spectrum of vascular abnormality as basis of diagnostic variability

PubMed Central

Campbell, J. Peter; Kalpathy-Cramer, Jayashree; Erdogmus, Deniz; Tian, Peng; Kedarisetti, Dharanish; Moleta, Chace; Reynolds, James D.; Hutcheson, Kelly; Shapiro, Michael J.; Repka, Michael X.; Ferrone, Philip; Drenser, Kimberly; Horowitz, Jason; Sonmez, Kemal; Swan, Ryan; Ostmo, Susan; Jonas, Karyn E.; Chan, R.V. Paul; Chiang, Michael F.

2016-01-01

Objective To identify patterns of inter-expert discrepancy in plus disease diagnosis in retinopathy of prematurity (ROP). Design We developed two datasets of clinical images of varying disease severity (100 images and 34 images) as part of the Imaging and Informatics in ROP study, and determined a consensus reference standard diagnosis (RSD) for each image, based on 3 independent image graders and the clinical exam. We recruited 8 expert ROP clinicians to classify these images and compared the distribution of classifications between experts and the RSD. Subjects, Participants, and/or Controls Images obtained during routine ROP screening in neonatal intensive care units. 8 participating experts with >10 years of clinical ROP experience and >5 peer-reviewed ROP publications. Methods, Intervention, or Testing Expert classification of images of plus disease in ROP. Main Outcome Measures Inter-expert agreement (weighted kappa statistic), and agreement and bias on ordinal classification between experts (ANOVA) and the RSD (percent agreement). Results There was variable inter-expert agreement on diagnostic classifications between the 8 experts and the RSD (weighted kappa 0 – 0.75, mean 0.30). RSD agreement ranged from 80 – 94% agreement for the dataset of 100 images, and 29 – 79% for the dataset of 34 images. However, when images were ranked in order of disease severity (by average expert classification), the pattern of expert classification revealed a consistent systematic bias for each expert consistent with unique cut points for the diagnosis of plus disease and pre-plus disease. The two-way ANOVA model suggested a highly significant effect of both image and user on the average score (P<0.05, adjusted R2=0.82 for dataset A, and P< 0.05 and adjusted R2 =0.6615 for dataset B). Conclusions and Relevance There is wide variability in the classification of plus disease by ROP experts, which occurs because experts have different “cut-points” for the amounts of vascular abnormality required for presence of plus and pre-plus disease. This has important implications for research, teaching and patient care for ROP, and suggests that a continuous ROP plus disease severity score may more accurately reflect the behavior of expert ROP clinicians, and may better standardize classification in the future. PMID:27591053

Expert diagnosis of plus disease in retinopathy of prematurity from computer-based image analysis

PubMed Central

Campbell, J. Peter; Ataer-Cansizoglu, Esra; Bolon-Canedo, Veronica; Bozkurt, Alican; Erdogmus, Deniz; Kalpathy-Cramer, Jayashree; Patel, Samir N.; Reynolds, James D.; Horowitz, Jason; Hutcheson, Kelly; Shapiro, Michael; Repka, Michael X.; Ferrone, Phillip; Drenser, Kimberly; Martinez-Castellanos, Maria Ana; Ostmo, Susan; Jonas, Karyn; Chan, R.V. Paul; Chiang, Michael F.

2016-01-01

Importance Published definitions of “plus disease” in retinopathy of prematurity (ROP) reference arterial tortuosity and venous dilation within the posterior pole based on a standard published photograph. One possible explanation for limited inter-expert reliability for plus disease diagnosis is that experts deviate from the published definitions. Objective To identify vascular features used by experts for diagnosis of plus disease through quantitative image analysis. Design We developed a computer-based image analysis system (Imaging and Informatics in ROP, i-ROP), and trained the system to classify images compared to a reference standard diagnosis (RSD). System performance was analyzed as a function of the field of view (circular crops 1–6 disc diameters [DD] radius) and vessel subtype (arteries only, veins only, or all vessels). The RSD was compared to the majority diagnosis of experts. Setting Routine ROP screening in neonatal intensive care units at 8 academic institutions. Participants A set of 77 digital fundus images was used to develop the i-ROP system. A subset of 73 images was independently classified by 11 ROP experts for validation. Main Outcome Measures The primary outcome measure was the percentage accuracy of i-ROP system classification of plus disease with the RSD as a function of field-of-view and vessel type. Secondary outcome measures included the accuracy of the 11 experts compared to the RSD. Results Accuracy of plus disease diagnosis by the i-ROP computer based system was highest (95%, confidence interval [CI] 94 – 95%) when it incorporated vascular tortuosity from both arteries and veins, and with the widest field of view (6 disc diameter radius). Accuracy was ≤90% when using only arterial tortuosity (P<0.001), and ≤85% using a 2–3 disc diameter view similar to the standard published photograph (p<0.001). Diagnostic accuracy of the i-ROP system (95%) was comparable to that of 11 expert clinicians (79–99%). Conclusions and Relevance ROP experts appear to consider findings from beyond the posterior retina when diagnosing plus disease, and consider tortuosity of both arteries and veins, in contrast to published definitions. It is feasible for a computer-based image analysis system to perform comparably to ROP experts, using manually segmented images. PMID:27077667

Intraocular Hemorrhages and Retinopathy of Prematurity in the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity (e-ROP) Study.

PubMed

Daniel, Ebenezer; Ying, Gui-Shuang; Siatkowski, R Michael; Pan, Wei; Smith, Eli; Quinn, Graham E

2017-03-01

To describe the clinical characteristics of intraocular hemorrhages (IOHs) in infants in the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity (e-ROP) Study and to evaluate their potential use for prediction of disease severity. Secondary data analysis from a prospective study. Preterm infants with birth weight (BW) ≤1250 g. Infants underwent serial digital retinal imaging in both eyes starting at 32 weeks' postmenstrual age. Nonphysician trained readers (TRs) evaluated all image sets from eyes that ever had IOHs documented on image evaluation or eye examination for the presence, location, type, area, and relation of the IOH to the junction between vascularized and avascular retina. Associations of IOH with demographic and neonatal factors, and with the presence and severity of retinopathy of prematurity (ROP) were investigated by univariate and multivariate analyses. Sensitivity and specificity of the telemedicine system for detecting referral-warranted ROP (RW-ROP) were calculated with and without incorporating hemorrhage into the standardized grading protocol. Retinal and vitreous hemorrhage. Among 1239 infants (mean [standard deviation] BW = 864 [212] g; gestational age [GA] = 27 [2.2] weeks) who underwent an average of 3.2 imaging sessions, 22% had an IOH in an eye on at least 1 of the e-ROP visits. Classification of IOH was preretinal (57%), blot (57%), dot (38%), flame-shaped (16%), and vitreous (8%); most IOHs were unilateral (70%). The IOH resolved in 35% of eyes by the next imaging session and in the majority (76%) of cases by 8 weeks after initial detection. Presence of IOH was inversely associated with BW and GA and significantly associated (P < 0.0001) with the presence and severity of ROP (BW and GA adjusted odds ratios [ORs] of 2.46 for any ROP, 2.88 for stage 3, and 3.19 for RW-ROP). Incorporating IOH into the grading protocol minimally altered the sensitivity of the system (94% vs. 95%). Approximately 1 in 5 preterm infants examined had IOHs, generally unilateral. The presence of hemorrhage was directly correlated with both presence and severity of ROP and inversely correlated with BW and GA, although including hemorrhage in the grading algorithm only minimally improved the sensitivity of the telemedicine system to detect RW-ROP. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Plus Disease in Retinopathy of Prematurity: Improving Diagnosis by Ranking Disease Severity and Using Quantitative Image Analysis.

PubMed

Kalpathy-Cramer, Jayashree; Campbell, J Peter; Erdogmus, Deniz; Tian, Peng; Kedarisetti, Dharanish; Moleta, Chace; Reynolds, James D; Hutcheson, Kelly; Shapiro, Michael J; Repka, Michael X; Ferrone, Philip; Drenser, Kimberly; Horowitz, Jason; Sonmez, Kemal; Swan, Ryan; Ostmo, Susan; Jonas, Karyn E; Chan, R V Paul; Chiang, Michael F

2016-11-01

To determine expert agreement on relative retinopathy of prematurity (ROP) disease severity and whether computer-based image analysis can model relative disease severity, and to propose consideration of a more continuous severity score for ROP. We developed 2 databases of clinical images of varying disease severity (100 images and 34 images) as part of the Imaging and Informatics in ROP (i-ROP) cohort study and recruited expert physician, nonexpert physician, and nonphysician graders to classify and perform pairwise comparisons on both databases. Six participating expert ROP clinician-scientists, each with a minimum of 10 years of clinical ROP experience and 5 ROP publications, and 5 image graders (3 physicians and 2 nonphysician graders) who analyzed images that were obtained during routine ROP screening in neonatal intensive care units. Images in both databases were ranked by average disease classification (classification ranking), by pairwise comparison using the Elo rating method (comparison ranking), and by correlation with the i-ROP computer-based image analysis system. Interexpert agreement (weighted κ statistic) compared with the correlation coefficient (CC) between experts on pairwise comparisons and correlation between expert rankings and computer-based image analysis modeling. There was variable interexpert agreement on diagnostic classification of disease (plus, preplus, or normal) among the 6 experts (mean weighted κ, 0.27; range, 0.06-0.63), but good correlation between experts on comparison ranking of disease severity (mean CC, 0.84; range, 0.74-0.93) on the set of 34 images. Comparison ranking provided a severity ranking that was in good agreement with ranking obtained by classification ranking (CC, 0.92). Comparison ranking on the larger dataset by both expert and nonexpert graders demonstrated good correlation (mean CC, 0.97; range, 0.95-0.98). The i-ROP system was able to model this continuous severity with good correlation (CC, 0.86). Experts diagnose plus disease on a continuum, with poor absolute agreement on classification but good relative agreement on disease severity. These results suggest that the use of pairwise rankings and a continuous severity score, such as that provided by the i-ROP system, may improve agreement on disease severity in the future. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Plus Disease in Retinopathy of Prematurity: A Continuous Spectrum of Vascular Abnormality as a Basis of Diagnostic Variability.

PubMed

Campbell, J Peter; Kalpathy-Cramer, Jayashree; Erdogmus, Deniz; Tian, Peng; Kedarisetti, Dharanish; Moleta, Chace; Reynolds, James D; Hutcheson, Kelly; Shapiro, Michael J; Repka, Michael X; Ferrone, Philip; Drenser, Kimberly; Horowitz, Jason; Sonmez, Kemal; Swan, Ryan; Ostmo, Susan; Jonas, Karyn E; Chan, R V Paul; Chiang, Michael F

2016-11-01

To identify patterns of interexpert discrepancy in plus disease diagnosis in retinopathy of prematurity (ROP). We developed 2 datasets of clinical images as part of the Imaging and Informatics in ROP study and determined a consensus reference standard diagnosis (RSD) for each image based on 3 independent image graders and the clinical examination results. We recruited 8 expert ROP clinicians to classify these images and compared the distribution of classifications between experts and the RSD. Eight participating experts with more than 10 years of clinical ROP experience and more than 5 peer-reviewed ROP publications who analyzed images obtained during routine ROP screening in neonatal intensive care units. Expert classification of images of plus disease in ROP. Interexpert agreement (weighted κ statistic) and agreement and bias on ordinal classification between experts (analysis of variance [ANOVA]) and the RSD (percent agreement). There was variable interexpert agreement on diagnostic classifications between the 8 experts and the RSD (weighted κ, 0-0.75; mean, 0.30). The RSD agreement ranged from 80% to 94% for the dataset of 100 images and from 29% to 79% for the dataset of 34 images. However, when images were ranked in order of disease severity (by average expert classification), the pattern of expert classification revealed a consistent systematic bias for each expert consistent with unique cut points for the diagnosis of plus disease and preplus disease. The 2-way ANOVA model suggested a highly significant effect of both image and user on the average score (dataset A: P < 0.05 and adjusted R 2  = 0.82; and dataset B: P < 0.05 and adjusted R 2  = 0.6615). There is wide variability in the classification of plus disease by ROP experts, which occurs because experts have different cut points for the amounts of vascular abnormality required for presence of plus and preplus disease. This has important implications for research, teaching, and patient care for ROP and suggests that a continuous ROP plus disease severity score may reflect more accurately the behavior of expert ROP clinicians and may better standardize classification in the future. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Lack of Screening Underlies Most Stage-5 Retinopathy of Prematurity among Cases Presenting to a Tertiary Eye Center in India.

PubMed

Azad, Rajvardhan; Chandra, Parijat; Gangwe, Anil; Kumar, Vivek

2016-11-07

To study the barriers to effective screening, early detection and treatment of Retinopathy of Prematurity leading to advanced disease. Cross-sectional study. Tertiary eye care hospital in northern India. 115 babies with bilateral stage 5 ROP identified amongst 354 preterm infants examined over a one year period. Information regarding gestational age, birthweight, duration of stay in nursery, duration of supplemental oxygen therapy and treatment details were obtained from discharge summary when available, and by interviewing carers.28 stage 5 ROP eyes underwent pars plana lensectomy and vitrectomy. Among the 354 infants (708 eyes) examined, 115 had stage 5 ROP in both eyes. The mean post conceptional age (PCA) at first visit to an ophthalmologist was 54.6 (7.6) weeks (Median 52.9 ± 4.2). The mean overall delay in first examination for Retinopathy of Prematurity was 24.7 (3.9) weeks. Most common risk factor was oxygen therapy in 103 babies (89.6%). 109 (89.8%) babies had never been screened for ROP; four babies fell outside the NNF guidelines (i.e. they had a birth weight of 1750 gms or more and were born at 34 weeks gestational age or more). Another important finding is that only 4.3% of babies were given the correct diagnosis. While 99 babies (86.1%) were referred by ophthalmologists, only 10 babies (8.7%) were referred by pediatricians. A large number were from the capital city of Delhi (21 babies, 18.2%). 28 stage 5 ROP eyes (12.1%) underwent surgery, and at 6 months follow up, only 20 operated eyes had visible attached posterior pole. 210 (91.3%) stage 5 eyes were irreversibly blind. ROP is an increasingly important cause of leucocoria. There were notable gaps in timely ROP screening, referral and treatment and much needs to be done to improve awareness amongst ophthalmologists about ROP. Measures are needed to improve the coverage of initiatives for the detection and timely treatment of sight threatening ROP in India as well as improving neonatal care to reduce sight threatening ROP in bigger, more mature infants.

Study protocol: safety and efficacy of propranolol 0.2% eye drops in newborns with a precocious stage of retinopathy of prematurity (DROP-ROP-0.2%): a multicenter, open-label, single arm, phase II trial.

PubMed

Filippi, Luca; Cavallaro, Giacomo; Berti, Elettra; Padrini, Letizia; Araimo, Gabriella; Regiroli, Giulia; Bozzetti, Valentina; De Angelis, Chiara; Tagliabue, Paolo; Tomasini, Barbara; Buonocore, Giuseppe; Agosti, Massimo; Bossi, Angela; Chirico, Gaetano; Aversa, Salvatore; Pasqualetti, Roberta; Fortunato, Pina; Osnaghi, Silvia; Cavallotti, Barbara; Vanni, Maurizio; Borsari, Giulia; Donati, Simone; Nascimbeni, Giuseppe; la Marca, Giancarlo; Forni, Giulia; Milani, Silvano; Cortinovis, Ivan; Bagnoli, Paola; Dal Monte, Massimo; Calvani, Anna Maria; Pugi, Alessandra; Villamor, Eduardo; Donzelli, Gianpaolo; Mosca, Fabio

2017-07-14

Retinopathy of prematurity (ROP) still represents one of the leading causes of visual impairment in childhood. Systemic propranolol has proven to be effective in reducing ROP progression in preterm newborns, although safety was not sufficiently guaranteed. On the contrary, topical treatment with propranolol eye micro-drops at a concentration of 0.1% had an optimal safety profile in preterm newborns with ROP, but was not sufficiently effective in reducing the disease progression if administered at an advanced stage (during stage 2). The aim of the present protocol is to evaluate the safety and efficacy of propranolol 0.2% eye micro-drops in preterm newborns at a more precocious stage of ROP (stage 1). A multicenter, open-label, phase II, clinical trial, planned according to the Simon optimal two-stage design, will be performed to analyze the safety and efficacy of propranolol 0.2% eye micro-drops in preterm newborns with stage 1 ROP. Preterm newborns with a gestational age of 23-32 weeks, with a stage 1 ROP will receive propranolol 0.2% eye micro-drops treatment until retinal vascularization has been completed, but for no longer than 90 days. Hemodynamic and respiratory parameters will be continuously monitored. Blood samplings checking metabolic, renal and liver functions, as well as electrocardiogram and echocardiogram, will be periodically performed to investigate treatment safety. Additionally, propranolol plasma levels will be measured at the steady state, on the 10th day of treatment. To assess the efficacy of topical treatment, the ROP progression from stage 1 ROP to stage 2 or 3 with plus will be evaluated by serial ophthalmologic examinations. Propranolol eye micro-drops could represent an ideal strategy in counteracting ROP, because it is definitely safer than oral administration, inexpensive and an easily affordable treatment. Establishing the optimal dosage and treatment schedule is to date a crucial issue. ClinicalTrials.gov Identifier NCT02504944, registered on July 19, 2015, updated July 12, 2016. EudraCT Number 2014-005472-29.

Grating visual acuity results in the early treatment for retinopathy of prematurity study.

PubMed

Dobson, Velma; Quinn, Graham E; Summers, C Gail; Hardy, Robert J; Tung, Betty; Good, William V

2011-07-01

To compare grating (resolution) visual acuity at 6 years of age in eyes that received early treatment (ET) for high-risk prethreshold retinopathy of prematurity (ROP) with that in eyes that underwent conventional management (CM). In a randomized clinical trial, infants with bilateral, high-risk prethreshold ROP (n = 317) had one eye undergo ET and the other eye undergo CM, with treatment only if ROP progressed to threshold severity. For asymmetric cases (n = 84), the high-risk prethreshold eye was randomized to ET or CM. Grating visual acuity measured at 6 years of age by masked testers using Teller acuity cards. Monocular grating acuity results were obtained from 317 of 370 surviving children (85.6%). Analysis of grating acuity results for all study participants with high-risk prethreshold ROP showed no statistically significant overall benefit of ET (18.1% vs 22.8% unfavorable outcomes; P = .08). When the 6-year grating acuity results were analyzed according to a clinical algorithm (high-risk types 1 and 2 prethreshold ROP), a benefit was seen in type 1 eyes (16.4% vs 25.2%; P = .004) undergoing ET, but not in type 2 eyes (21.3% vs 15.9%; P = .29). Early treatment of eyes with type 1 ROP improves grating acuity outcomes, but ET for eyes with type 2 ROP does not. APPLICATION TO CLINICAL MEDICINE: Type 1 eyes should be treated early; however, based on acuity results at 6 years of age, type 2 eyes should be cautiously monitored for progression to type 1 ROP. Trial Registration clinicaltrials.gov Identifier: NCT00027222.

Identification of missense mutations in the Norrie disease gene associated with advanced retinopathy of prematurity.

PubMed

Shastry, B S; Pendergast, S D; Hartzer, M K; Liu, X; Trese, M T

1997-05-01

Retinopathy of prematurity (ROP) is a retinal vascular disease occurring in infants with short gestational age and low birth weight and can lead to retinal detachment (ROP stages 4 and 5). X-linked familial exudative vitreoretinopathy is phenotypically similar to ROP and has been associated with mutations in the Norrie disease (ND) gene in some cases. To determine if similar mutations in the ND gene may play a role in the development of advanced ROP. Clinical examination and molecular genetic analysis were performed on 16 children, including 2 dizygotic and 1 monozygotic twin pairs, and their parents from 13 families. Sequencing of the amplified products revealed missense mutations (R121W and L108P) in the third exon of the ND gene in 4 patients. These mutations were not present in an unaffected premature twin, 2 children with regressed stage 3 ROP, the parents, or in 50 unrelated healthy control subjects. These findings suggest that mutations in the ND gene may play a role in the development of severe ROP in premature infants.

Mutations of the Norrie gene in Korean ROP infants.

PubMed

Kim, Jeong Hun; Yu, Young Suk; Kim, Jiyeon; Park, Seong Sup

2002-12-01

The present study was conducted to evaluate if there is a Norrie disease gene (ND gene) mutation involved in the retinopathy of prematurity (ROP), and to identify the possibility of a genetic abnormality that may be linked to the presence of ROP. Nineteen premature Korean infants, with a low birth weight (1500 g or less) or low gestational age (32 weeks or less), were included in the study. Eighteen infants had ROP, and the other did not. Genomic DNA was isolated from the peripheral blood leukocytes of these patients, and all three exons and their flanking areas, all known ND gene mutations regions, were evaluated following amplification by a polymerase chain reaction, but no ND gene mutations were detected. Any disagreement between the relationship of ROP to the ND gene mutation will need to be clarified by further investigation.

Retinopathy of prematurity: a review of risk factors and their clinical significance.

PubMed

Kim, Sang Jin; Port, Alexander D; Swan, Ryan; Campbell, J Peter; Chan, R V Paul; Chiang, Michael F

2018-04-19

Retinopathy of prematurity (ROP) is a retinal vasoproliferative disease that affects premature infants. Despite improvements in neonatal care and management guidelines, ROP remains a leading cause of childhood blindness worldwide. Current screening guidelines are primarily based on two risk factors: birth weight and gestational age; however, many investigators have suggested other risk factors, including maternal factors, prenatal and perinatal factors, demographics, medical interventions, comorbidities of prematurity, nutrition, and genetic factors. We review the existing literature addressing various possible ROP risk factors. Although there have been contradictory reports, and the risk may vary between different populations, understanding ROP risk factors is essential to develop predictive models, to gain insights into pathophysiology of retinal vascular diseases and diseases of prematurity, and to determine future directions in management of and research in ROP. Copyright © 2018 Elsevier Inc. All rights reserved.

Gene silencing in Tribolium castaneum as a tool for the targeted identification of candidate RNAi targets in crop pests.

PubMed

Knorr, Eileen; Fishilevich, Elane; Tenbusch, Linda; Frey, Meghan L F; Rangasamy, Murugesan; Billion, Andre; Worden, Sarah E; Gandra, Premchand; Arora, Kanika; Lo, Wendy; Schulenberg, Greg; Valverde-Garcia, Pablo; Vilcinskas, Andreas; Narva, Kenneth E

2018-02-01

RNAi shows potential as an agricultural technology for insect control, yet, a relatively low number of robust lethal RNAi targets have been demonstrated to control insects of agricultural interest. In the current study, a selection of lethal RNAi target genes from the iBeetle (Tribolium castaneum) screen were used to demonstrate efficacy of orthologous targets in the economically important coleopteran pests Diabrotica virgifera virgifera and Meligethes aeneus. Transcript orthologs of 50 selected genes were analyzed in D. v. virgifera diet-based RNAi bioassays; 21 of these RNAi targets showed mortality and 36 showed growth inhibition. Low dose injection- and diet-based dsRNA assays in T. castaneum and D. v. virgifera, respectively, enabled the identification of the four highly potent RNAi target genes: Rop, dre4, ncm, and RpII140. Maize was genetically engineered to express dsRNA directed against these prioritized candidate target genes. T 0 plants expressing Rop, dre4, or RpII140 RNA hairpins showed protection from D. v. virgifera larval feeding damage. dsRNA targeting Rop, dre4, ncm, and RpII140 in M. aeneus also caused high levels of mortality both by injection and feeding. In summary, high throughput systems for model organisms can be successfully used to identify potent RNA targets for difficult-to-work with agricultural insect pests.

A tip-localized RhoGAP controls cell polarity by globally inhibiting Rho GTPase at the cell apex.

PubMed

Hwang, Jae-Ung; Vernoud, Vanessa; Szumlanski, Amy; Nielsen, Erik; Yang, Zhenbiao

2008-12-23

Highly elongated eukaryotic cells (e.g., neuronal axons, fungal hyphae, and pollen tubes) are generated through continuous apically restricted growth (tip growth), which universally requires tip-localized Rho GTPases. We used the oscillating pollen tube as a model system to determine the function and regulation of Rho GTPases in tip growth. Our previous work showed that the spatiotemporal dynamics of the apical cap of the activated Rho-like GTPase from Plant 1 (ROP1) are critical for tip growth in pollen tubes. However, the underlying mechanism for the generation and maintenance of this dynamic apical cap is poorly understood. A screen for mutations that enhance ROP1-overexpression-induced depolarization of pollen-tube growth identified REN1 (ROP1 enhancer 1) in Arabidopsis, whose null mutations turn elongated pollen tubes into bulbous cells. REN1 encodes a novel Rho GTPase-activating protein (RhoGAP) required for restricting the ROP1 activity to the pollen-tube tip. REN1 was localized to exocytic vesicles accumulated in the pollen-tube apex, as well as to the apical plasma membrane at the site of ROP1 activation. The apical localization of REN1 and its function in controlling growth polarity was compromised by disruption of ROP1-dependent F-actin and vesicular trafficking, which indicates that REN1 targeting and function is regulated by ROP1 downstream signaling. Our findings suggest that the REN1 RhoGAP controls a negative-feedback-based global inhibition of ROP1. This function provides a critical self-organizing mechanism, by which ROP signaling is spatially limited to the growth site and temporally oscillates during continuous tip growth. Similar spatiotemporal control of Rho GTPase signaling may also play an important role in cell-polarity control in other systems, including tip growth in fungi and cell movement in animals.

Evaluation of Modified Retinopathy of Prematurity Screening Guidelines Using Birth Weight as the Sole Inclusion Criterion

PubMed Central

Chalam, Kakarla V.; Lin, Selina; Murthy, Ravi K.; Brar, Vikram S.; Gupta, Shailesh K.; Radhakrishnan, Ravi

2011-01-01

Purpose: The purpose was to determine if birth weight (BW) alone can be the sole criterion for screening infants at risk for retinopathy of prematurity (ROP). Materials and Methods: In this retrospective, observational case series, 208 infants were screened for ROP using the American Association for Pediatric Ophthalmology and Strabismus (AAPOS) Guidelines (1997). Variables examined included gestational age (GA), birth weight (BW), and a composite variable BWGA Index [(grams × weeks)/1000], which takes into consideration both the birth weight and gestational age of the infant. Infants were divided into two groups: Group 1, BW ≤1250 g, and Group 2, BW >1250 g. Multivariate analysis was performed to detect factors predictive of ROP. Receiver operator characteristic (ROC) curves were generated to determine the efficacy of screening using the BW, GA, and BWGA Index. Statistical analyses were performed with logistic regression with a P-value of 0.05 or less indicating statistical significance. Results: Varying stages of ROP were present in 116 of 416 eyes. Of the 105 eyes in Group 2, only 1 eye developed stage 1 ROP. Only Group 1 eyes developed stage 3 or higher ROP. The ROC curve for BW alone gave an area under the curve (AUC) of 0.797 (standard error [SE] = 0.0329, P < 0.0001); for GA, AUC was 0.801 (SE = 0.0340, P < 0.0001) and for the BWGA Index, the AUC was 0.808 (SE = 0.0324, P < 0.0001). Using 1250-g BW as a criterion for ROP screening would have decreased the number of screenings by 24%, and did not exclude any ROP higher than stage 1. Conclusion: Data from our neonatal intensive care unit suggest that birth weight ≤ 1250 g alone is an adequate parameter to identify premature infants at risk for ROP. PMID:21887076

Detection of Human Toxoplasma-Specific Immunoglobulins A, M, and G with a Recombinant Toxoplasma gondii Rop2 Protein

PubMed Central

Martin, Valentina; Arcavi, Miriam; Santillan, Graciela; Amendoeira, Maria Regina R.; De Souza Neves, Elizabeth; Griemberg, Gloria; Guarnera, Eduardo; Garberi, Juan C.; Angel, Sergio O.

1998-01-01

The Toxoplasma gondii rhoptry protein Rop2 was expressed in Escherichia coli as a fusion protein containing 44 kDa of the 55-kDa mature Rop2, supplied with six histidyl residues at the N-terminal end (Rop2196–561). Humoral response during Toxoplasma infection of humans was analyzed by immunoglobulin G (IgG), IgA, and IgM enzyme-linked immunosorbent assay with Rop2196–561 as the antigen substrate. The analyzed sera were divided according to T. gondii-specific serological tests (IgG, IgA, or IgM indirect immunofluorescence and IgA or IgM immunosorbent agglutination assay) as group A (IgG+ IgA− IgM−; n = 35), group B (IgG+ IgA+ IgM+; n = 21), group C (IgG+ IgA+ IgM−; n = 5), and group D (IgG+ IgA− IgM+; n = 16). Twenty-six T. gondii-seronegative sera from individuals with other infections were also included (group E). Anti-Rop2 IgG antibodies were detected in 82.8% of group A sera and in 97.6% of the sera with acute-phase marker immunoglobulins (groups B, C, and D). The percentage of IgA antibody reactivity against Rop2196–561 was 17.1% in group A, 50% in group D, and 80.8% in groups B and C. The percentage of IgM antibody reactivity was 0% in groups A and C and 62% in groups B and D. Sera from group E failed to show IgA, IgM, or IgG antibody reactivity. Since T. gondii Rop2 elicits a strong humoral response from an early stage of infection, it is suggested that recombinant Rop2196–561 would be suitable for use in diagnostic systems, in combination with other T. gondii antigens, to detect specific IgG, IgA, and IgM antibodies. PMID:9729528

Influence of the blood glucose level on the development of retinopathy of prematurity in extremely premature children.

PubMed

Nicolaeva, Galina V; Sidorenko, Evgenyj I; Iosifovna, Amkhanitskaya Lyubov

2015-01-01

To investigate the influence of the blood glucose level on the development of retinopathy of prematurity (ROP) in extremely premature infants. Sixty-four premature infants with a gestational age of less than 30 weeks and a birth weight of less than 1500 g were included in the study. Children without ROP were allocated to Group 1 (n=14, gestational age 28.6 ± 1.4 weeks, birth weight 1162 ± 322 g), and children with spontaneous regression of ROP were allocated to Group 2 (n=32, gestational age 26.5 ± 1.2 weeks, birth weight 905 ± 224 g). Children with progressive ROP who underwent laser treatment were included in Group 3 (n=18, gestational age 25.4 ± 0.7 weeks, birth weight 763 ± 138 g). The glucose level in the capillary blood of the premature infants was monitored daily during the first 3 weeks of life. A complete ophthalmological screening was performed from the age of 1 month. The nonparametric signed-rank Wilcoxon-Mann-Whitney test was used for statistical analysis. The mean blood glucose level was 7.43 ± 2.6 mmol/L in Group 1, 7.8 ± 2.7 mmol/L in Group 2, and 6.7 ± 2.6 mmol/L in Group 3. There were no significant differences in the blood glucose levels between children with and without ROP, and also between children with spontaneously regressing ROP and progressive ROP (p>0.05). Additionally, there were no significant differences in the blood glucose levels measured at the first, second, and third weeks of life (p>0.05). The blood glucose level is not related to the development of ROP nor with its progression or regression. The glycemic level cannot be considered as a risk factor for ROP, but reflects the severity of newborns' somatic condition and morphofunctional immaturity.

Prevalence and risk factors of retinopathy of prematurity in Iran: a systematic review and meta-analysis.

PubMed

Azami, Milad; Jaafari, Zahra; Rahmati, Shoboo; Farahani, Afsar Dastjani; Badfar, Gholamreza

2018-04-02

Retinopathy of prematurity (ROP) refers to the developmental disorder of the retina in premature infants and is one of the most serious and most dangerous complications in premature infants. The prevalence of ROP in Iran is different in various parts of Iran and its prevalence is reported to be 1-70% in different regions. This study aims to determine the prevalence and risk factors of ROP in Iran. This review article was conducted based on the preferred reporting items for systematic review and meta-analysis (PRISMA) protocols. To find literature about ROP in Iran, a comprehensive search was done using MeSH keywords in several online databases such as PubMed, Ovid, Science Direct, EMBASE, Web of Science, CINAHL, EBSCO, Magiran, Iranmedex, SID, Medlib, IranDoc, as well as the Google Scholar search engine until May 2017. Comprehensive Meta-analysis Software (CMA) Version 2 was used for data analysis. According to 42 studies including 18,000 premature infants, the prevalence of ROP was reported to be 23.5% (95% CI: 20.4-26.8) in Iran. The prevalence of ROP stages 1, 2, 3, 4 and 5 was 7.9% (95% CI: 5.3-11.5), 9.7% (95% CI: 6.1-15.3), 2.8% (95% CI: 1.6-4.9), 2.9% (95% CI: 1.9-4.5) and 3.6% (95% CI: 2.4-5.2), respectively. The prevalence of ROP in Iranian girls and boys premature infants was 18.3% (95% CI: 12.8-25.4) and 18.9% (95% CI: 11.9-28.5), respectively. The lowest prevalence of ROP was in the West of Iran (12.3% [95% CI: 7.6-19.1]), while the highest prevalence was associated with the Center of Iran (24.9% [95% CI: 21.8-28.4]). The prevalence of ROP is increasing according to the year of study, and this relationship is not significant (p = 0.181). The significant risk factors for ROP were small gestational age (p < 0.001), low birth weight (p < 0.001), septicemia (p = 0.021), respiratory distress syndrome (p = 0.036), intraventricular hemorrhage (p = 0.005), continuous positive pressure ventilation (p = 0.023), saturation above 50% (p = 0.023), apnea (p = 0.002), frequency and duration of blood transfusion, oxygen therapy and phototherapy (p < 0.05), whereas pre-eclampsia decreased the prevalence of ROP (p = 0.014). Considering the high prevalence of ROP in Iran, screening and close supervision by experienced ophthalmologists to diagnose and treat the common complications of pre-maturity and prevent visual impairment or blindness is necessary.

Large spot transpupillary thermotherapy: a quicker laser for treatment of high risk prethreshold retinopathy of prematurity - a randomized study.

PubMed

Shah, Parag K; Narendran, V; Kalpana, N

2011-01-01

To compare structural and functional outcome and time efficiency between standard spot sized conventional pulsed mode diode laser and continuous mode large spot transpupillary thermotherapy (LS TTT) for treatment of high risk prethreshold retinopathy of prematurity (ROP). Ten eyes of five preterm babies having bilateral symmetrical high risk prethreshold ROP were included in this study. One eye of each baby was randomized to get either standard spot sized conventional pulsed mode diode laser or continuous mode LS TTT. There was no significant difference between structural or functional outcome in either group. The mean time taken for conventional diode laser was 20.07 minutes, while that for LS TTT was 12.3 minutes. LS TTT was 40% more time efficient than the conventional laser. It may be better suited for the very small fragile premature infants as it is quicker than the conventional laser.

Retinopathy of prematurity: the need for prevention

PubMed Central

Liegl, Raffael; Hellström, Ann; Smith, Lois EH

2016-01-01

More than 450,000 babies are born prematurely in the USA every year. The improved survival of even the most vulnerable low body weight preterm infants has, despite improving health outcomes, led to the resurgence in preterm complications including one of the major causes for blindness in children, retinopathy of prematurity (ROP). The current mainstay in ROP therapy is laser photocoagulation and the injection of vascular endothelial growth factor (VEGF) antibodies in the late stages of the disease after the onset of neovascularization. Both are proven options for ophthalmologists to treat the severe forms of late ROP. However, laser photocoagulation destroys major parts of the retina, and the injection of VEGF antibodies, although rather simple to administer, may cause a systemic suppression of normal vascularization, which has not been studied in sufficient depth. However, the use of neither VEGF antibody nor laser treatment prevents ROP, which should be the long-term goal. It should be possible to prevent ROP by more closely mimicking the intrauterine environment after preterm birth. Such preventive measures include preventing the toxic postbirth influences (eg, oxygen excess) as well as providing the missing intrauterine factors (eg, insulin growth factor 1) and are likely to also reduce other complications of premature birth as well as ROP. This review is meant to summarize the current knowledge on the prevention of ROP with a particular emphasize on the use of insulin growth factor 1 supplementation. PMID:28539804

Abnormal Complement Activation and Inflammation in the Pathogenesis of Retinopathy of Prematurity

PubMed Central

Rathi, Sonika; Jalali, Subhadra; Patnaik, Satish; Shahulhameed, Shahna; Musada, Ganeswara R.; Balakrishnan, Divya; Rani, Padmaja K.; Kekunnaya, Ramesh; Chhablani, Preeti Patil; Swain, Sarpras; Giri, Lopamudra; Chakrabarti, Subhabrata; Kaur, Inderjeet

2017-01-01

Retinopathy of prematurity (ROP) is a neurovascular complication in preterm babies, leading to severe visual impairment, but the underlying mechanisms are yet unclear. The present study aimed at unraveling the molecular mechanisms underlying the pathogenesis of ROP. A comprehensive screening of candidate genes in preterms with ROP (n = 189) and no-ROP (n = 167) was undertaken to identify variants conferring disease susceptibility. Allele and genotype frequencies, linkage disequilibrium and haplotypes were analyzed to identify the ROP-associated variants. Variants in CFH (p = 2.94 × 10−7), CFB (p = 1.71 × 10−5), FBLN5 (p = 9.2 × 10−4), CETP (p = 2.99 × 10−5), and CXCR4 (p = 1.32 × 10−8) genes exhibited significant associations with ROP. Further, a quantitative assessment of 27 candidate proteins and cytokines in the vitreous and tear samples of babies with severe ROP (n = 30) and congenital cataract (n = 30) was undertaken by multiplex bead arrays and further validated by western blotting and zymography. Significant elevation and activation of MMP9 (p = 0.038), CFH (p = 2.24 × 10−5), C3 (p = 0.05), C4 (p = 0.001), IL-1ra (p = 0.0019), vascular endothelial growth factor (VEGF) (p = 0.0027), and G-CSF (p = 0.0099) proteins were observed in the vitreous of ROP babies suggesting an increased inflammation under hypoxic condition. Along with inflammatory markers, activated macrophage/microglia were also detected in the vitreous of ROP babies that secreted complement component C3, VEGF, IL-1ra, and MMP-9 under hypoxic stress in a cell culture model. Increased expression of the inflammatory markers like the IL-1ra (p = 0.014), MMP2 (p = 0.0085), and MMP-9 (p = 0.03) in the tears of babies at different stages of ROP further demonstrated their potential role in disease progression. Based on these findings, we conclude that increased complement activation in the retina/vitreous in turn activated microglia leading to increased inflammation. A quantitative assessment of inflammatory markers in tears could help in early prediction of ROP progression and facilitate effective management of the disease, thereby preventing visual impairment. PMID:29312345

Avoiding endotracheal intubation of neonates undergoing laser surgery for retinopathy of prematurity.

PubMed

Woodhead, D D; Lambert, D K; Molloy, D A; Schmutz, N; Righter, E; Baer, V L; Christensen, R D

2007-04-01

Respiratory support of neonates during and following laser surgery for retinopathy of prematurity (ROP) is commonly accomplished using endotracheal intubation and mechanical ventilation. However, most patients undergoing ROP surgery have been weaned off mechanical ventilation days or weeks before the surgery. When they are electively re-intubated for ROP surgery, it can be difficult to extubate them postoperatively. One of the three level III neonatal intensive care units (NICUs) in the Intermountain Healthcare system initiated a program of using nasopharyngeal prongs, rather than endotracheal intubation, for respiratory support during ROP surgery. We performed an historic cohort analysis of all neonates undergoing ROP surgery during their NICU stay at the three level III NICU's between 1 January 2002 and 31 March 2006. Data collected included birth weight, gestational age at delivery and corrected gestational age at ROP surgery, whether or not they were intubated in the days immediately preceding the ROP surgery, whether or not they were electively intubated for the ROP surgery, the respiratory modality used during and the 3 days following ROP surgery, and all blood gas determinations and respiratory charges during this period. Fifty-four patients underwent ROP surgery during this period. All 23 from NICUs 'A' and 'B' had endotracheal intubation for surgery, while in NICU 'C' 24 were managed using nasopharyngeal prongs. The birth weights of those intubated for surgery (661+/-180 g, mean+/-s.d.) were similar to those not intubated (732+/-180 g). Similarly, the gestational age at birth did not differ between those intubated for surgery (25.2+/-1.3 week) and those not (25.6+/-2.1 week). The day following surgery, 77% (23/30) of those who had been intubated for surgery remained intubated and on mechanical ventilation, whereas only one (4%) of those not intubated for surgery was intubated in the postoperative period (P<0.001). On day 3 following surgery, 50% (15/30) of those intubated for surgery remained intubated and on mechanical ventilation, whereas none of those not intubated for surgery were intubated (P<0.001). Management with nasopharyngeal prongs did not result in higher PCO(2)s, or lower pH values, during or after surgery. Respiratory charges for the 3 days following surgery were 1762+/-678 dollars (mean+/-s.d.)/patient among those intubated versus 357+/-352 dollars/patient for those managed with nasopharyngeal prongs (P<0.001). Neonates undergoing laser surgery for ROP can often be supported intraoperatively and postoperatively using nasopharyngeal prongs, thus avoiding the need for endotracheal intubation.

Retinopathy of prematurity as a major cause of severe visual impairment and blindness in children in schools for the blind in Guadalajara city, Mexico.

PubMed

Zepeda-Romero, L C; Barrera-de-Leon, J C; Camacho-Choza, C; Gonzalez Bernal, C; Camarena-Garcia, E; Diaz-Alatorre, C; Gutierrez-Padilla, J A; Gilbert, C

2011-11-01

To determine the causes of blindness in students attending schools for the blind in Guadalajara city, Mexico and to assess the availability of screening for retinopathy of prematurity (ROP) in local neonatal intensive care units. Information on causes of blindness was obtained by interview with parents and teachers, review of records and examination. Causes of visual loss in children with a distance visual acuity of <6/60 (ie, severely visually impaired or blind) were determined and classified according to the WHO's classification system for children. Of 153 children in the two participating schools, 144 were severely visual impaired or blind. Their ages ranged from 4 months to 15 years and 58% were female. ROP was the most common cause of visual loss (34.7%), followed by optic nerve lesions (17.4%) and glaucoma (14.6%). 25/59 (42.3%) children aged 0-4 years were blind from ROP compared with 6/32 (18.8%) children aged 10-15 years. 78% of children blind from ROP had psychomotor delay and less than half (46%) had not received treatment for ROP. All five privately funded neonatal intensive care units in the city regularly screen for ROP compared with only four of the 12 units in the public sector. ROP is the leading cause of blindness in children in Mexico despite national guidelines being in place. Health policies promoting primary prevention through improved neonatal care need to be implemented. Advocacy is required so that the time ophthalmologists spend screening and treating ROP is included in their job description and hence salaried.

Clinical Models and Algorithms for the Prediction of Retinopathy of Prematurity: A Report by the American Academy of Ophthalmology.

PubMed

Hutchinson, Amy K; Melia, Michele; Yang, Michael B; VanderVeen, Deborah K; Wilson, Lorri B; Lambert, Scott R

2016-04-01

To assess the accuracy with which available retinopathy of prematurity (ROP) predictive models detect clinically significant ROP and to what extent and at what risk these models allow for the reduction of screening examinations for ROP. A literature search of the PubMed and Cochrane Library databases was conducted last on May 1, 2015, and yielded 305 citations. After screening the abstracts of all 305 citations and reviewing the full text of 30 potentially eligible articles, the panel members determined that 22 met the inclusion criteria. One article included 2 studies, for a total of 23 studies reviewed. The panel extracted information about study design, study population, the screening algorithm tested, interventions, outcomes, and study quality. The methodologist divided the studies into 2 categories-model development and model validation-and assigned a level of evidence rating to each study. One study was rated level I evidence, 3 studies were rated level II evidence, and 19 studies were rated level III evidence. In some cohorts, some models would have allowed reductions in the number of infants screened for ROP without failing to identify infants requiring treatment. However, the small sample size and limited generalizability of the ROP predictive models included in this review preclude their widespread use to make all-or-none decisions about whether to screen individual infants for ROP. As an alternative, some studies proposed approaches to apply the models to reduce the number of examinations performed in low-risk infants. Additional research is needed to optimize ROP predictive model development, validation, and application before such models can be used widely to reduce the burdensome number of ROP screening examinations. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Investigation of the effect of hemoglobin F and A levels on development of retinopathy of prematurity.

PubMed

Erdöl, Hidayet; Hacioglu, Dilek; Kola, Mehmet; Türk, Adem; Aslan, Yakup

2017-04-01

To investigate the effect of hemoglobin F (HbF) and hemoglobin A (HbA) levels on development of retinopathy of prematurity (ROP) in premature infants. In this prospective study, blood samples were collected from the side of the heel of 49 premature infants at postnatal months 0, 1, 2, and 3. HbF and HbA levels were measured in all samples and analyzed statistically. Furthermore, correlation analysis was performed regarding development of ROP, blood transfusion, and HbF and HbA levels. A total of 49 infants were included. The mean gestational age of the premature infants was 30.9 ± 2.7 weeks (range, 25-35 weeks); mean birth weight, 1542 ± 582 g (range, 520-3240 g). Of the 49 premature infants, stage 1 ROP or above developed in 26 (53%). Mean HbF levels were lower at postnatal months 1 and 2 in premature infants with ROP compared to those without ROP (P = 0.013 and 0.02, respectively); however, mean HbA levels were higher in the infants with ROP than the others (P = 0.034 and 0.029, respectively). Analysis of covariance that ignored transfusion revealed no difference between the means of Hb variants in the infants with and without ROP (P = 0.572 and 0.486). Blood transfusion significantly altered the levels of HbF and HbA in premature infants, and Hb variants have no direct effect on development of ROP. Copyright © 2017 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

A predictive score for retinopathy of prematurity in very low birth weight preterm infants

PubMed Central

Eckert, G U; Fortes Filho, J B; Maia, M; Procianoy, R S

2012-01-01

Aims This study describes the development of a score based on cumulative risk factors for the prediction of severe retinopathy of prematurity (ROP) comparing the performance of the score against the birth weight (BW) and gestational age (GA) in order to predict the onset of ROP. Methods A prospective cohort of preterm infants with BW⩽1500 g and/or GA⩽32 weeks was studied. The score was developed based on BW, GA, proportional weight gain from birth to the 6th week of life, use of oxygen in mechanical ventilation, and need for blood transfusions from birth to the 6th week of life. The score was established after linear regression, considering the impact of each variable on the occurrences of any stage and severe ROP. Receiver operating characteristic (ROC) curves were used to determine the best sensitivity and specificity values for the score. All variables were entered into an Excel spreadsheet (Microsoft) for practical use by ophthalmologists during screening sessions. Results The sample included 474 patients. The area under the ROC curve for the score was 0.77 and 0.88 to predict any stage and severe ROP, respectively. These values were significantly higher for the score than for BW (0.71) and GA (0.69) when measured separately. Conclusions ROPScore is an excellent index of neonatal risk factors for ROP, which is easy to record and more accurate than BW and GA to predict any stage ROP or severe ROP in preterm infants. The scoring system is simple enough to be routinely used by ophthalmologists during screening examination for detection of ROP. PMID:22193874

Retinal, visual, and refractive development in retinopathy of prematurity

PubMed Central

Moskowitz, Anne; Hansen, Ronald M; Fulton, Anne B

2016-01-01

The pivotal role of the neurosensory retina in retinopathy of prematurity (ROP) disease processes has been amply demonstrated in rat models. We have hypothesized that analogous cellular processes are operative in human ROP and have evaluated these presumptions in a series on non-invasive investigations of the photoreceptor and post-receptor peripheral and central retina in infants and children. Key results are slowed kinetics of phototransduction and deficits in photoreceptor sensitivity that persist years after ROP has completely resolved based on clinical criteria. On the other hand, deficits in post-receptor sensitivity are present in infancy regardless of the severity of the ROP but are not present in older children if the ROP was so mild that it never required treatment and resolved without a clinical trace. Accompanying the persistent deficits in photoreceptor sensitivity, there is increased receptive field size and thickening of the post-receptor retinal laminae in the peripheral retina of ROP subjects. In the late maturing central retina, which mediates visual acuity, attenuation of multifocal electroretinogram activity in the post-receptor retina led us to the discovery of a shallow foveal pit and significant thickening of the post-receptor retinal laminae in the macular region; this is most likely due to failure of the normal centrifugal movement of the post-receptor cells during foveal development. As for refractive development, myopia, at times high, is more common in ROP subjects than in control subjects, in accord with refractive findings in other populations of former preterms. This information about the neurosensory retina enhances understanding of vision in patients with a history of ROP, and taken as a whole, raises the possibility that the neurosensory retina is a target for therapeutic intervention. PMID:28539805

Visual impairment due to retinopathy of prematurity (ROP) in New Zealand: a 22-year review.

PubMed

Tan, Zachary; Chong, CheeFoong; Darlow, Brian; Dai, Shuan

2015-06-01

To evaluate retinopathy of prematurity (ROP)-related visual impairment in New Zealand children. 22-year retrospective review of medical records of children with moderate to severe visual impairment registered with the Blind and Low Vision Education Network New Zealand. The cohort was divided into two periods (1991-2004; 2005-2012) for analysis. 232 children with ROP were treated in the study period (109 in period 1, 123 in period 2). 36 children, 63.9% of whom were of male sex, were identified with subsequent significant visual impairment (27 in period 1, 9 in period 2). The incidence of new cases of visual impairment from ROP declined from 271.6 infants/100 000 live very preterm births per annum (period 1) to 146.1 per annum (period 2). Mean gestational age and mean birth weight were comparable between the two study periods. 75% of children with visual impairment from ROP received treatment for their condition (period 1, 74.1%; period 2, 77.8%) and modalities used changed significantly over time. The modal visual outcome overall was Snellen visual acuity <6/18-6/60 (55.6%) (period 1, 51.9%; period 2, 66.7%). The proportion of children with no light perception bilaterally decreased over time (period 1, 3.7%; period 2, 0%). There has been a reduction in the incidence of infants with significant visual impairment from ROP over time in New Zealand, likely due to progress in clinical management of ROP. Our study suggests the current ROP screening criteria of <31 weeks' gestation or <1250 g are of sufficient breadth. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

CPK3-phosphorylated RhoGDI1 is essential in the development of Arabidopsis seedlings and leaf epidermal cells

PubMed Central

Wu, Yan

2013-01-01

The regulation of Rho of plants (ROP) in morphogenesis of leaf epidermal cells has been well studied, but the roles concerning regulators of ROPs such as RhoGDIs are poorly understood. This study reports that AtRhoGDI1 (GDI1) acts as a versatile regulator to modulate development of seedlings and leaf pavement cells. In mutant gdi1, leaf pavement cells showed shorter lobes in comparison with those in wild type. In GDI1-14 seedlings (GDI1-overexpression line) the growth of lobes in pavement cells was severely suppressed and the development of seedlings was altered. These results indicate that GDI1 plays an essential role in morphogenesis of epidermal pavement cells through modulating the ROP signalling pathways. The interaction between GDI1 and ROP2 or ROP6 was detected in the leaf pavement cells using FRET analysis. Dominant negative, not constitutively active, DN-rop6 could weaken the effect caused by overexpression of GDI1; because the pleiotropic phenotype of GDI1-14 plants was eliminated in the hybrid line GDI1-14 DN-rop6. GDI1 could be phosphorylated by CPK3. Three conserved Ser/Thr residues in GDI1 were determined as targeted amino acids for CPK3. Overexpression of GDI1(3D), not GDI1(3A), could rescue the abnormal growth phenotypes of gdi1-1 seedlings, demonstrating the impact of GDI1 phosphorylation in the development of Arabidopsis. In summary, these results suggest that GDI1 regulation in morphogenesis of seedlings and leaf pavement cells could be undergone through modulating the ROP signalling pathways and the phosphorylation of GDI1 by CPK3 was required for the developmental modulation in Arabidopsis. PMID:23846874

Intravitreal foscarnet for recurring CMV retinitis in a congenitally infected premature infant.

PubMed

Tawse, Kirstin L; Baumal, Caroline R

2014-02-01

A girl born at 32 weeks' gestational age was diagnosed at birth with congenital cytomegalovirus (CMV) infection without ocular involvement. On day 19 of life, retinal examination requested for retinopathy of prematurity (ROP) identified bilateral CMV retinitis and stage 1 ROP. Treatment of macular threatening CMV infection with intravitreal foscarnet injections and intravenous ganciclovir for 6 weeks led to quiescence of retinitis. Bilateral recurrence of CMV retinitis occurred on day 89 of life, requiring a second course of intravitreal foscarnet injections and intravenous ganciclovir. Both the initial presentation and reactivation of CMV retinitis were identified on examination for ROP and would have gone unrecognized had the infant not met ROP screening criteria. This case demonstrates delayed presentation of CMV retinitis after initial negative retinal examination in a premature infant with congenital infection and concurrent ROP. Copyright © 2014 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.

Role of VEGF Inhibition in the Treatment of Retinopathy of Prematurity.

PubMed

Eldweik, Luai; Mantagos, Iason S

2016-01-01

Retinopathy of prematurity (ROP) is a potentially blinding disease characterized by retinal neovascularization, which eventually can lead to tractional retinal detachment. Improvements have been made regarding the management of retinopathy of prematurity (ROP) since it was described in the Cryotherapy for Retinopathy of Prematurity study. A more appropriate time for therapeutic intervention was defined by the Early Treatment for Retinopathy of Prematurity (ETROP) trial. Advances in screening strategies with the use of digital imaging systems are now available. All of this and the use of laser photocoagulation and vitreoretinal surgery have contributed to significant increases in favorable outcomes and decreases in child blindness secondary to ROP. Recently the use of vascular endothelial growth factor (VEGF) inhibitors has been introduced to the armamentarium for the treatment of ROP. The purpose of this review article is to evaluate the role of VEGF inhibition in the treatment of ROP.

Introduction of a proline residue into position 31 of the loop of the dimeric 4-alpha-helical protein ROP causes a drastic destabilization.

PubMed

Peters, K; Hinz, H J; Cesareni, G

1997-10-01

The exchange of an alanine with a proline residue in position 31 of the loop region of the dimeric 4-alpha-helical-bundle protein ROP causes a reduction in the alpha-helix content of 7% and a reduction in stability of about 40% compared to the wild type parameters. The Gibbs energy of unfolding by denaturants extrapolated linearly to zero denaturant concentration, delta G0D (buffer, 25 degrees C), has been determined to be 43 kJ (mol dimer)-1. The corresponding ROPwt value is 72 kJ (mol dimer)-1 (Steif et al., 1993). The extrapolated delta G0D values obtained from urea and GdmHCI un- and refolding studies are identical within error limits. Deconvolution of the stability values into enthalpy and entropy terms resulted in the following parameters. At T1/2 = 43 degrees C (Cprotein = 0.05 mg.ml-1) the ROP A31P mutant is characterized by delta Hv.H.0 = 272 kJ (mol dimer)-1, delta Cp = 7.2 kJ (mol dimer)-1 K-1, delta S0 = 762 J (mol dimer)-1 K-1. These parameters are only approximately 50% as large as the corresponding values of ROPwt. We assume that the significant reduction in stability reflects the absence of at least one hydrogen bond as well as deformation of the protein structure. This interpretation is supported by the reduction in the change in heat capacity observed for the A31P mutant relative to ROPwt, by the increased aggregation tendency of the mutant and by the reduced specific CD absorption at 222 nm. All results support the view that in the case of ROP protein the loop region plays a significant role in the maintenance of native structure and conformational stability.

PHARMACOLOGIC INTERVENTIONS FOR THE PREVENTION AND TREATMENT OF RETINOPATHY OF PREMATURITY

PubMed Central

Beharry, Kay D.; Valencia, G.B.; Lazzaro, D.R.; Aranda, J.V.

2016-01-01

Retinopathy of prematurity (ROP), a significant morbidity in prematurely born infants, is the most common cause of visual impairment and blindness in children and persists till adulthood. Strict control of oxygen therapy and prevention of intermittent hypoxia are key in the prevention of ROP, but pharmacologic interventions have decreased risk of ROP. Various drug classes such as methylxanthines (caffeine), VEGF inhibitors, anti-oxidants, and others have decreased ROP occurrence. The timing of pharmacologic intervention remains unsettled, but early prevention rather than controlling disease progression may be preferred. These drugs act through different mechanisms and synergistic approaches should be considered to maximize efficacy and safety. PMID:26831641

Genetic and Environmental Influences on Retinopathy of Prematurity

PubMed Central

Ortega-Molina, J. M.; Anaya-Alaminos, R.; Uberos-Fernández, J.; Solans-Pérez de Larraya, A.; Chaves-Samaniego, M. J.; Salgado-Miranda, A.; Piñar-Molina, R.; Jerez-Calero, A.; García-Serrano, J. L.

2015-01-01

Objective. The goals were to isolate and study the genetic susceptibility to retinopathy of prematurity (ROP), as well as the gene-environment interaction established in this disease. Methods. A retrospective study (2000–2014) was performed about the heritability of retinopathy of prematurity in 257 infants who were born at a gestational age of ≤32 weeks. The ROP was studied and treated by a single pediatric ophthalmologist. A binary logistic regression analysis was completed between the presence or absence of ROP and the predictor variables. Results. Data obtained from 38 monozygotic twins, 66 dizygotic twins, and 153 of simple birth were analyzed. The clinical features of the cohorts of monozygotic and dizygotic twins were not significantly different. Genetic factors represented 72.8% of the variability in the stage of ROP, environmental factors 23.08%, and random factors 4.12%. The environmental variables representing the highest risk of ROP were the number of days of tracheal intubation (p < 0.001), postnatal weight gain (p = 0.001), and development of sepsis (p = 0.0014). Conclusion. The heritability of ROP was found to be 0.73. The environmental factors regulate and modify the expression of the genetic code. PMID:26089603

Oral Propranolol: A New Treatment for Infants with Retinopathy of Prematurity?

PubMed

Bührer, Christoph; Bassler, Dirk

2015-01-01

Oral propranolol has improved the treatment of infantile hemangiomas, and a pediatric oral solution of propranolol has recently been licensed in the USA and Europe. In very preterm infants, infantile hemangiomas are associated with the occurrence of retinopathy of prematurity (ROP), and both diseases share a peculiar time course, featuring a lag phase after birth followed by rapid growth and then gradual regression. To identify clinical studies evaluating the use of oral propranolol in preterm infants with ROP. Two small bicentric, pilot, randomized controlled trials found a nonsignificant reduction of ROP requiring intervention by laser treatment or bevacizumab injection of similar magnitude. Together, 6 of 35 (17%) infants who had been receiving oral propranolol underwent ROP intervention, as opposed to 14 of 36 (39%) controls (relative risk 0.42, 95% CI: 0.15-1.16). Randomized controlled trials are ongoing that investigate early preventive oral propranolol starting at 1 week of age and propranolol eye drops in preterm infants with stage 2 ROP. Further, large interventional studies are required to determine the clinical benefit-risk ratio of oral propranolol to prevent vision-threatening ROP in very preterm infants. © 2015 S. Karger AG, Basel.

Association of Gestational Hypertensive Disorders with Retinopathy of prematurity: A Systematic Review and Meta-analysis.

PubMed

Chan, Priscilla Y L; Tang, Shu-Min; Au, Sunny C L; Rong, Shi-Song; Lau, Henry H W; Ko, Simon T C; Ng, Danny S C; Chen, Li Jia; Yam, Jason C S

2016-08-05

The role of gestational hypertensive disorders, which includes both pre-eclampsia and gestational hypertension, in the development of retinopathy of prematurity (ROP) has been controversial. Therefore, this systematic review and meta-analysis is to evaluate the association between gestational hypertensive disoders and ROP. Eligible studies published up to June 5, 2016 were identified from MEDLINE and EMBASE that evaluated the association between the two conditions. Totally 1142 published records were retrieved for screening, 925 of them eligible for detailed evaluation. Finally 19 studies involving 45281 infants with 5388 cases of ROP met our criteria for meta-analysis. Gestational hypertensive disorders were not associated with ROP (unadjusted OR: 0.89; P = 0.38; adjusted OR: 1.35; P = 0.18). Subgroup analyses also revealed no significant association between ROP with pre-eclampsia (unadjusted OR: 0.85; P = 0.29; adjusted OR:1.29; P = 0.28) or with gestational hypertension (unadjusted OR: 1.10; P = 0.39; adjusted OR: 1.25; P = 0.60) separately. Sensitivity analysis indicated our results were robust. We concluded no significant association between gestational hypertensive disorders and ROP. More large scale well-conducted prospective cohorts on the topic are needed.

Vascular endothelial growth factor (VEGF-634G/C) polymorphism and retinopathy of prematurity: a meta-analysis

PubMed Central

Malik, Manzoor Ahmad; Shukla, Swati; Azad, Shorya Vardhan; Kaur, Jasbir

2014-01-01

Purpose Vascular endothelial growth factor polymorphism (VEGF-634G/C, rs 2010963) has been considered a risk factor for the development of retinopathy of prematurity (ROP). However, the results remain controversial. Therefore, the aim of the present meta-analysis was to determine the association between VEGF-634G/C polymorphism and ROP risk. Methods Published literature from PubMed and other databases were retrieved. All studies evaluating the association between VEGF-634G/C polymorphism and ROP risk were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random or fixed effects model. A total of six case-control studies including 355 cases and 471 controls were included. Results By pooling all the studies, we found that VEGF-634G/C polymorphism was not associated with ROP risk at co-dominant and allele levels and no association was also found in dominant and recessive models. While stratifying on ethnicity level no association was observed in Caucasian and Asian population. Discussion This meta-analysis suggests that VEGF-634G/C polymorphism may not be associated with ROP risk, the association between single VEGF-634G/C polymorphism and ROP risk awaits further investigation. PMID:25473347

Genetic screening of Wnt signaling factors in advanced retinopathy of prematurity

PubMed Central

Takahashi, Hiroshi; Orimo, Hideo; Hiraoka, Miina; Ogata, Tsutomu; Azuma, Noriyuki

2010-01-01

Purpose To evaluate the possibility of genetic involvement in retinopathy of prematurity (ROP). Although ROP is most often associated with low birthweight and low gestational age, these factors do not necessarily predict the severity of ROP. The possible involvement of other factors, including genetic variants, has been considered. Familial exudative vitreoretinopathy (FEVR) is a hereditary vitreoretinal disorder with clinical manifestations similar to those of ROP. Three genes involving the wingless/int1 (Wnt) receptor signaling pathway—FZD4 for frizzled 4, LRP5 for low-density lipoprotein receptor-related protein 5, and ND for Norrie disease protein—are associated with the development of FEVR. Methods In the present study, 17 Japanese patients with advanced ROP were screened for these three candidate genes of FEVR. Genomic DNA from each patient was subjected to PCR and direct sequencing of the ND, FZD4, and LRP5 genes. Results One patient had a heterozygous mutation in the 5′ untranslated region of the ND gene. Another had a leucine insertion in the signal peptide of LRP5. None showed any mutation in FZD4. Conclusions These findings suggest that genetic changes in the Wnt receptor signaling pathway associate to the development of advanced ROP. PMID:21151595

Expert Diagnosis of Plus Disease in Retinopathy of Prematurity From Computer-Based Image Analysis.

PubMed

Campbell, J Peter; Ataer-Cansizoglu, Esra; Bolon-Canedo, Veronica; Bozkurt, Alican; Erdogmus, Deniz; Kalpathy-Cramer, Jayashree; Patel, Samir N; Reynolds, James D; Horowitz, Jason; Hutcheson, Kelly; Shapiro, Michael; Repka, Michael X; Ferrone, Phillip; Drenser, Kimberly; Martinez-Castellanos, Maria Ana; Ostmo, Susan; Jonas, Karyn; Chan, R V Paul; Chiang, Michael F

2016-06-01

Published definitions of plus disease in retinopathy of prematurity (ROP) reference arterial tortuosity and venous dilation within the posterior pole based on a standard published photograph. One possible explanation for limited interexpert reliability for a diagnosis of plus disease is that experts deviate from the published definitions. To identify vascular features used by experts for diagnosis of plus disease through quantitative image analysis. A computer-based image analysis system (Imaging and Informatics in ROP [i-ROP]) was developed using a set of 77 digital fundus images, and the system was designed to classify images compared with a reference standard diagnosis (RSD). System performance was analyzed as a function of the field of view (circular crops with a radius of 1-6 disc diameters) and vessel subtype (arteries only, veins only, or all vessels). Routine ROP screening was conducted from June 29, 2011, to October 14, 2014, in neonatal intensive care units at 8 academic institutions, with a subset of 73 images independently classified by 11 ROP experts for validation. The RSD was compared with the majority diagnosis of experts. The primary outcome measure was the percentage of accuracy of the i-ROP system classification of plus disease, with the RSD as a function of the field of view and vessel type. Secondary outcome measures included the accuracy of the 11 experts compared with the RSD. Accuracy of plus disease diagnosis by the i-ROP computer-based system was highest (95%; 95% CI, 94%-95%) when it incorporated vascular tortuosity from both arteries and veins and with the widest field of view (6-disc diameter radius). Accuracy was 90% or less when using only arterial tortuosity and 85% or less using a 2- to 3-disc diameter view similar to the standard published photograph. Diagnostic accuracy of the i-ROP system (95%) was comparable to that of 11 expert physicians (mean 87%, range 79%-99%). Experts in ROP appear to consider findings from beyond the posterior retina when diagnosing plus disease and consider tortuosity of both arteries and veins, in contrast with published definitions. It is feasible for a computer-based image analysis system to perform comparably with ROP experts, using manually segmented images.

Retinopathy of prematurity: the high cost of screening regional and remote infants.

PubMed

Yu, Tzu-Ying; Donovan, Tim; Armfield, Nigel; Gole, Glen A

2018-01-25

Demand for retinopathy of prematurity (ROP) screening is increasing for infants born at rural and regional hospitals where the service is not generally available. The health system cost for screening regional/remote infants has not been reported. The objective of this study is to evaluate the cost of ROP screening at a large centralized tertiary neonatal service for infants from regional/rural hospitals. This is a retrospective study to establish the cost of transferring regional/rural infants to the Royal Brisbane and Women's Hospital for ROP screening over a 28-month period. A total of 131 infants were included in this study. Individual infant costs were calculated from analysis of clinical and administrative records. Economic cost of ROP screening for all transfers from regional/rural hospitals to Royal Brisbane and Women's Hospital. The average economic cost of ROP screening for this cohort was AUD$5110 per infant screened and the total cost was AUD$669 413. The average cost per infant screened was highest for infants from a regional centre with a population of 75 000 (AUD$14 856 per child), which was also geographically furthest from Brisbane. No infant in this cohort transferred from a regional nursery reached criteria for intervention for ROP by standard guidelines. Health system costs for ROP screening of remote infants at a centralized hospital are high. Alternative strategies using telemedicine can now be compared with centralized screening. © 2018 Royal Australian and New Zealand College of Ophthalmologists.

Analysis of risk factors in the development of retinopathy of prematurity.

PubMed

Knezević, Sanja; Stojanović, Nadezda; Oros, Ana; Savić, Dragana; Simović, Aleksandra; Knezević, Jasmina

2011-01-01

Retinopathy of prematurity (ROP) is a multifactorial disease that occurs most frequently in very small and very sick preterm infants, and it has been identified as the major cause of childhood blindness. The aim of this study was to evaluate ROP incidence and risk factors associated with varying degrees of illness. The study was conducted at the Centre for Neonatology, Paediatric Clinic of the Clinical Centre Kragujevac, Serbia, in the period from June 2006 to December 2008. Ophthalmologic screening was performed in all children with body weight lower than 2000 g or gestational age lower than 36 weeks. We analyzed eighteen postnatal and six perinatal risk factors and the group correlations for each of the risk factors. Out of 317 children that were screened, 56 (17.7%) developed a mild form of ROP, while 68 (21.5%) developed a severe form. Univariate analysis revealed a large number of statistically significant risk factors for the development of ROP, especially the severe form. Multivariate logistical analysis further separated two independent risk factors: small birth weight (p = 0.001) and damage of central nervous system (p = 0.01). Independent risk factors for transition from mild to severe forms of ROP were identified as: small birth weight (p = 0.05) and perinatal risk factors (p = 0.02). Small birth weight and central nervous system damage were risk factors for the development of ROP, perinatal risk factors were identified as significant for transition from mild to severe form of ROP.

Evaluation of maternal attachment, self-efficacy, levels of depression, and anxiety in mothers who have babies diagnosed with retinopathy of prematurity.

PubMed

Özyurt, Gonca; Özyurt, Ayhan; Ozturk, Taylan; Yaman, Aylin; Berk, A Tulin

2018-04-01

The aim of this study is to evaluate the emotional stress and its effects on parental self-efficacy and mother-infant attachment in mothers whose babies were diagnosed with retinopathy of prematurity (ROP). Study sample was consisted of voluntarily participating 82 mothers whose babies were first diagnosed with ROP, 83 mothers of preterm babies without ROP, and 85 mothers of term babies admitting for their routine visits. Sociodemographic data form maternal attachment scale, state-trait anxiety inventory, Edinburgh postnatal depression scale, and parental self-efficacy scale were applied to study participants, and the overall results of three groups were statistically compared. The sociodemographic features of three study groups were similar. Statistical significant differences were found in depression and state anxiety levels among study groups, while maternal attachment scale and trait anxiety level scores and parental self-efficacy scale total score were similar in study groups. Maternal depression and state-anxiety levels were tend to be higher in mother of children diagnosed with ROP and prematurity; however, there were no statistically significant differences between levels of mothers' of premature children with or without ROP. This is the first study in literature assessing the additional effect of ROP on the anxiety and depression levels of recent mothers, as well as mother-infant attachment and parental self-efficacy. Supporting of mothers having an infant with diagnosed ROP is crucial because of feeling themselves inefficient and responsible for all interventions applied to their babies.

Retinopathy of Prematurity Is Associated with Increased Systolic Blood Pressure in Adults Who Were Born Preterm.

PubMed

Kistner, Anna; Jacobson, Lena; Östergren, Jan; Hellström, Ann

2017-01-01

Adults born preterm are at risk of developing cardiovascular morbidities. The aim of this study was to evaluate the relationship between retinopathy of prematurity (ROP) and blood pressure (BP) and salivary cortisol levels during adulthood. Sixty-nine subjects (mean age 22.6 years) were included. Subjects were adults who were: (a) ex-preterm infants with severe ROP (n = 22), born at gestational age (GA) <30 weeks with a birth weight (BW) <1,000 g, (b) ex-preterm infants with no/mild ROP (n = 21), born at GA <28 weeks with a BW <1,000 g, or (c) full-term controls (n = 26). Anthropometric data, office BP, ambulatory BP, and morning and evening salivary cortisol were analyzed. As adults, ex-preterm infants with severe ROP had on average 7.4 mm Hg higher systolic office BP than those with no/mild ROP (p = 0.019) and controls (p = 0.007). A high cortisol level, tall height, and severe ROP were independent predictors of higher ambulatory systolic BP during adulthood in forward stepwise regression analysis, independent of GA. Our results indicate that preterm infants with severe abnormal retinal vascular development during the neonatal period may be at an increased risk for increased BP during adulthood. We found no differences between those with no/mild ROP as infants and controls with regard to BP data. © 2017 The Author(s) Published by S. Karger AG, Basel.

Influence of Computer-Generated Mosaic Photographs on Retinopathy of Prematurity Diagnosis and Management.

PubMed

Patel, Samir N; Klufas, Michael A; Douglas, Christina E; Jonas, Karyn E; Ostmo, Susan; Berrocal, Audina; Capone, Antonio; Martinez-Castellanos, Maria A; Chau, Felix; Drenser, Kimberly; Ferrone, Philip; Orlin, Anton; Tsui, Irena; Wu, Wei-Chi; Gupta, Mrinali P; Chiang, Michael F; Chan, R V Paul

2016-11-01

Telemedicine is becoming an increasingly important component of clinical care for retinopathy of prematurity (ROP), but little information exists regarding the role of mosaic photography for ROP telemedicine diagnosis. To examine the potential effect of computer-generated mosaic photographs on the diagnosis and management of ROP. In this prospective cohort study performed from July 12, 2011, through September 21, 2015, images were acquired from ROP screening at 8 academic institutions, and ROP experts interpreted 40 sets (20 sets with individual fundus photographs with ≥3 fields and 20 computer-generated mosaic photographs) of wide-angle retinal images from infants with ROP. All experts independently reviewed the 40 sets and provided a diagnosis and management plan for each set presented. The primary outcome measure was the sensitivity and specificity of the ROP diagnosis by experts that was calculated using a consensus reference standard diagnosis, determined from the diagnosis of fundus photographs by 3 experienced readers in combination with the clinical diagnosis based on ophthalmoscopic examination. Mean unweighted κ statistics were used to analyze the mean intergrader agreement among experts for diagnosis of zone, stage, plus disease, and category. Nine ROP experts (4 women and 5 men) who have been practicing ophthalmology for a mean of 10.8 years (range, 3-24 years) consented to participate. Diagnosis by the mosaic photographs compared with diagnosis by multiple individual photographs resulted in improvements in sensitivity for diagnosis of stage 2 disease or worse (95.9% vs 88.9%; difference, 7.0; 95% CI, 3.5 to 10.5; P = .02), plus disease (85.7% vs 63.5%; difference, 22.2; 95% CI, 7.6 to 36.9; P = .02), and treatment-requiring ROP (84.4% vs 68.5%; difference, 15.9; 95% CI, 0.8 to 31.7; P = .047). With use of the κ statistic, mosaic photographs, compared with multiple individual photographs, resulted in improvements in intergrader agreement for diagnosis of plus disease or not (0.54 vs 0.40; mean κ difference, 0.14; 95% CI, 0.07 to 0.21; P = .004), stage 3 disease or worse or not (0.60 vs 0.52; mean κ difference, 0.06; 95% CI, -0.06 to 0.18; P = .04), and type 2 ROP or not (0.58 vs 0.51; mean κ difference, 0.07; 95% CI, 0.03 to 0.11; P = .04). After viewing the mosaic photographs, experts altered their choice of management in 42 of 180 responses (23.3%; 95% CI, 17.1%-29.5%). Compared with multiple individual photographs, computer-generated mosaic photographs were associated with improved accuracy of image-based diagnosis for certain categories (eg, plus disease, stage 2 disease or worse, and treatment-requiring ROP) of ROP by experts. It is unclear, however, whether these findings are generalizable, and the results of this study may not be relevant to mosaic grading of other retinal vascular conditions.

Astigmatism Progression in the Early Treatment for Retinopathy of Prematurity Study to 6 years of age

PubMed Central

Davitt, Bradley V.; Quinn, Graham E.; Wallace, David K.; Dobson, Velma; Hardy, Robert J.; Tung, Betty; Lai, Dejian; Good, William V.

2011-01-01

Purpose To examine the prevalence of astigmatism (≥1.00 diopter (D)) and high astigmatism (≥2.00 D) from 6 months post term due date to 6 years postnatal, in preterm children with birth weight ≤ 1251g who developed high-risk prethreshold retinopathy of prematurity (ROP) and participated in the Early Treatment for ROP (ETROP) Study. Design Observational Cohort Study Participants 401 infants who developed high-risk prethreshold ROP in one or both eyes and were randomized to early treatment (ET) versus conventional management (CM). Refractive error was measured by cycloplegic retinoscopy. Eyes were excluded if they received additional retinal, glaucoma, or cataract surgery. Intervention Eyes were randomized to receive laser photocoagulation at high-risk prethreshold ROP or to receive treatment only if threshold ROP developed. Main Outcome Measures Astigmatism and high astigmatism at each study visit. Results For both ET and CM eyes, there was a consistent increase in prevalence of astigmatism over time, increasing from 42% at 4 years to 52% by 6 years for the group of ET eyes and from 47% to 54% in the CM eyes. There was no statistically significant difference between the slopes (rate of change per month) of the ET and CM eyes for both astigmatism and high astigmatism. (P=0.75) Conclusions By 6 years of age, over 50% of eyes with high-risk prethreshold ROP developed astigmatism ≥ 1.00 D, and nearly 25% of such eyes had high astigmatism (≥ 2.00 D). Presence of astigmatism was not influenced by timing of treatment, zone of acute-phase ROP, or presence of plus disease. However, there was a trend toward higher prevalence of astigmatism and high astigmatism in eyes with ROP residua. Most astigmatism was with-the-rule (75º –105º). More eyes with Type 2 than Type 1 had astigmatism by 6 years. These findings reinforce the need for follow-up eye examinations through early grade school years in infants with high risk prethreshold ROP. PMID:21872933

Mutation spectrum of NDP, FZD4 and TSPAN12 genes in Indian patients with retinopathy of prematurity.

PubMed

Rathi, Sonika; Jalali, Subhadra; Musada, Ganeswara Rao; Patnaik, Satish; Balakrishnan, Divya; Hussain, Anjli; Kaur, Inderjeet

2018-02-01

Retinopathy of prematurity (ROP) is a vasoproliferative eye disease in preterm infants. Based on its phenotypic similarities with familial exudative vitreo retinopathy (FEVR), the present study was conducted to screen the Norrin signalling pathway genes (already been implicated in FEVR) for understanding their involvement among Indian patients with ROP. The study cohort consisted of patients with ROP (n=246) and controls (n=300) that included full term (n=110) and preterm babies devoid of ROP (n=190). Screening of the NDP, FZD4, TSPAN12 genes were accomplished by resequencing the entire coding and untranslated regions (UTR). The genotype data of the patients with ROP were analysed in the background of their clinical manifestations and further analysed in conjunction with other available data on these genes worldwide. Two novel variants in intron 1 (IVS1 +16A>G) and 3'UTR (c.5 22T>C) along with a previously reported change in the 5'UTR (c.395_409del14bp) were observed in the NDP gene in three patients with ROP. Screening of the FZD4 revealed four heterozygous variants, p.(Pro33Ser), p.(Pro168Ser), p.(Ile192Ile) and p.(Ile360Val), a compound heterozygous (p.(Pro33Ser)/p.(Pro168Ser)) and a 3'UTR (c*G>T) variants in the study cohort. Variants p.(Pro33Ser) and p.(Pro168Ser) were found to be significantly associated with ROP. A heterozygous variant p.(Leu119Arg) in TSPAN12 gene was observed in a patient with threshold ROP. However, a formal genotype-phenotype correlation could not be established due to the low frequencies of the variant alleles in these genes. This is a first study that revealed association of few variants in Norrin signalling genes among Indian patients with ROP that warrants further detailed investigation worldwide. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Efficacy of Intravitreal injection of 2-Methoxyestradiol in regression of neovascularization of a retinopathy of prematurity rat model.

PubMed

Said, Azza Mohamed Ahmed; Zaki, Rania Gamal Eldin; Salah Eldin, Rania A; Nasr, Maha; Azab, Samar Saad; Elzankalony, Yaser Abdelmageuid

2017-04-04

Retinopathy of prematurity (ROP) is one of the targets for early detection and treatment to prevent childhood blindness in world health organization programs. The purpose of study was to evaluate the efficacy of intravitreal injection of 2-Methoxyestradiol (2-ME) nanoemulsion in regressing neovascularization of a ROP rat model. A prospective comparative case - control animal study conducted on 56 eyes of 28 healthy new born Sprague Dawley male albino rat. ROP was induced in 21 rats then two concentrations of 2-ME nanoparticles were injected in right eyes of 14 rats (low dose; study group I, high dose; study group II). A blank nanoemulsion was injected in the right eyes of seven rats (control positive group I). No injections performed in contralateral left eyes (control positive group II). Seven rats (14 eyes) were kept in room air (control negative group). On postnatal day 17, eyeballs were enucleated. Histological structure of the retina was examined using Hematoxylin and eosin staining. Vascular endothelial growth factor (VEGF) and glial fibrillary acidic protein (GFAP) expressions were detected by immunohistochemical studies. Intravitreal injection of 2-ME (in the two concentrations) caused marked regression of the new vascular tufts on the vitreal side with normal organization and thickness of the retina especially in study group II, which also show negative VEGF immunoreaction. Positive GFAP expression was detected in the control positive groups and study group (I). Intravitreal injection of 2-Methoxyestradiol nanoemulsion is a promising effective method in reduction of neovascularization of a ROP rat model.

Pharmacologic interventions for the prevention and treatment of retinopathy of prematurity.

PubMed

Beharry, Kay D; Valencia, Gloria B; Lazzaro, Douglas R; Aranda, Jacob V

2016-04-01

Retinopathy of prematurity (ROP), a significant morbidity in prematurely born infants, is the most common cause of visual impairment and blindness in children and persists till adulthood. Strict control of oxygen therapy and prevention of intermittent hypoxia are the keys in the prevention of ROP, but pharmacologic interventions have decreased risk of ROP. Various drug classes such as methylxanthines (caffeine), VEGF inhibitors, antioxidants, and others have decreased ROP occurrence. The timing of pharmacologic intervention remains unsettled, but early prevention rather than controlling disease progression may be preferred. These drugs act through different mechanisms, and synergistic approaches should be considered to maximize efficacy and safety. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Review of the mechanisms and therapeutic avenues for retinal and choroidal vascular dysfunctions in retinopathy of prematurity.

PubMed

Rivera, José Carlos; Madaan, Ankush; Zhou, Tianwei Ellen; Chemtob, Sylvain

2016-12-01

Retinopathy of prematurity (ROP) is a multifactorial disease and the main cause of visual impairment and blindness in premature neonates. The inner retina has been considered the primary region affected in ROP, but choroidal vascular degeneration and progressive outer retinal dysfunctions have also been observed. This review focuses on observations regarding neurovascular dysfunctions in both the inner and outer immature retina, the mechanisms and the neuronal-derived factors implicated in the development of ROP, as well potential therapeutic avenues for this disorder. Alterations in the neurovascular integrity of the inner and outer retina contribute to the development of ROP. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Postnatal corticosteroids and risk of retinopathy of prematurity.

PubMed

Movsas, Tammy Z; Spitzer, Alan R; Gewolb, Ira H

2016-08-01

To investigate the association between postnatal steroids and retinopathy of prematurity (ROP) in neonates born with birth weights at the limit of viability (<500 g). Data from the Pediatrix BabySteps Clinical Warehouse were retrospectively reviewed. The study population consisted of 1,472 neonates with birth weights of <500 g who were discharged alive from 167 NICUs between 1996 and 2013. Statistical significance for unadjusted comparisons between groups was determined using the χ(2) or t test. Logistic regression was used to calculate odds of ROP. In multivariate analysis, the odds of any ROP for steroid treated infants was 1.6 (95% CI, 1.2-2.2) compared to nontreated infants; the odds of advanced ROP was 1.7 (95% CI, 1.3-2.3). In our large study cohort of critically low birth weight infants ROP was more common in neonates exposed to postnatal steroids. Copyright © 2016 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

Retinopathy of prematurity: molecular pathology and therapeutic strategies.

PubMed

Mechoulam, Hadas; Pierce, Eric A

2003-01-01

Retinopathy of prematurity (ROP) is an ischemia-induced proliferative retinopathy, which affects premature infants with low birth weight. It is a leading cause of visual impairment and blindness in children, and shares pathophysiological characteristics with other common ocular diseases such as diabetic retinopathy, central vein occlusion, and age-related macular degeneration. Pathologically similar inherited diseases such as Norrie disease suggest a possible genetic component in the susceptibility to ROP. The process of retinal neovascularization in ROP and in animal models of oxygen-induced retinopathy is complex, and involves angiogenic factors, such as vascular endothelial growth factor, and basement membrane components. Potential medical therapies for ROP, including modulators of angiogenic factors, inhibitors of basement membrane changes, endogenous inhibitors such as pigment epithelium derived factor, and anti-inflammatory drugs, have shown efficacy against neovascularization in several animal models. Some of these therapies are in clinical trials now for diabetic retinopathy and age-related macular degeneration, and in the future may prove efficacious for the treatment of ROP.

HYPOTHESIS SETTING AND ORDER STATISTIC FOR ROBUST GENOMIC META-ANALYSIS.

PubMed

Song, Chi; Tseng, George C

2014-01-01

Meta-analysis techniques have been widely developed and applied in genomic applications, especially for combining multiple transcriptomic studies. In this paper, we propose an order statistic of p-values ( r th ordered p-value, rOP) across combined studies as the test statistic. We illustrate different hypothesis settings that detect gene markers differentially expressed (DE) "in all studies", "in the majority of studies", or "in one or more studies", and specify rOP as a suitable method for detecting DE genes "in the majority of studies". We develop methods to estimate the parameter r in rOP for real applications. Statistical properties such as its asymptotic behavior and a one-sided testing correction for detecting markers of concordant expression changes are explored. Power calculation and simulation show better performance of rOP compared to classical Fisher's method, Stouffer's method, minimum p-value method and maximum p-value method under the focused hypothesis setting. Theoretically, rOP is found connected to the naïve vote counting method and can be viewed as a generalized form of vote counting with better statistical properties. The method is applied to three microarray meta-analysis examples including major depressive disorder, brain cancer and diabetes. The results demonstrate rOP as a more generalizable, robust and sensitive statistical framework to detect disease-related markers.

Optical Coherence Tomography of Fovea Before and after Laser Treatment in Retinopathy of Prematurity

PubMed Central

Narang, Subina; Singh, Amrita; Jain, Suksham; Sood, Sunandan; Chawla, Deepak

2014-01-01

Purpose: To study the fovea in preterm babies with Type I retinopathy of prematurity (ROP) before and after laser treatment using optical coherence tomography (OCT). Materials and Methods: This was a prospective observational case-control study including preterm neonates undergoing screening for ROP from May 2009 to July 2011. Group 1 included 30 eyes of 15 neonates with Type I ROP. A 532-nm laser was used for treatment in all cases for Group 1. Group 2 included 14 eyes of 7 preterm neonates without ROP that served as controls. OCT was performed under sedation in the lateral position before and after laser treatment. P <0.05 was considered statistically significant. Results: The mean initial central macular thickness (CMT) was comparable in both groups (P = 0.832) and statistically significantly correlated with gestational age (P = 0.015). No adverse effects on the anterior segment or posterior segment were observed. There was no significant difference in CMT before and after laser treatment in Group 1 (P = 0.007). There was one case of cystoid macular edema after laser treatment. Conclusion: The macula in preterm babies with Type 1 ROP was comparable to those without ROP. Gestational age was the only predictor of CMT. PMID:25371634

Preclinical screening for retinopathy of prematurity risk using IGF1 levels at 3 weeks post-partum.

PubMed

Pérez-Muñuzuri, Alejandro; Couce-Pico, Maria Luz; Baña-Souto, Ana; López-Suárez, Olalla; Iglesias-Deus, Alicia; Blanco-Teijeiro, José; Fernández-Lorenzo, José Ramón; Fraga-Bermúdez, José María

2014-01-01

Following current recommendations for preventing retinopathy of prematurity (ROP) involves screening a large number of patients. We performed a prospective study to establish a useful screening system for ROP prediction and we have determined that measuring serum levels of IGF1 at week three and the presence of sepsis have a high predictive value for the subsequent development of ROP. A total of 145 premature newborn, with birthweight <1500 g and/or <32 weeks gestational age, were enrolled. 26.9% of them showed some form of retinopathy. A significant association was found between the development of retinopathy and each of the following variables: early gestational age, low birthweight, requiring mechanical ventilation, oxygen treatment, intracranial haemorrhage, sepsis during the first three weeks, bronchopulmonary dysplasia, the need for erythrocyte transfusion, erythropoietin treatment, and low levels of serum IGF1 in the third week. A multiple logistic regression analysis was used to obtain curves for the probability of developing ROP, based on the main factors linked with ROP, namely serum levels of IGF1 and presence of sepsis. Such preclinical screening has the ability to identify patients with high-risk of developing retinopathy and should lead to better prediction for ROP, while at the same time optimising the use of clinical resources, both human and material.

Retinopathy of prematurity and induced changes in arterial oxygen saturation with near infrared spectrophotometry: a retrospective cohort study

NASA Astrophysics Data System (ADS)

von Siebenthal, K.; Keel, M.; Dietz, V.; Fauchere, J. C.; Martin, X.; Wolf, Martin; Duc, G.; Bucher, H. U.

1996-10-01

Near-infrared spectrophotometry (NIRS) is a noninvasive method for measuring oxygenated and deoxygenated hemoglobin in the neonatal brain. Using oxygen as a tracer, it is possible to calculate cerebral blood flow (cbf) and hemoglobin concentration (cHbc), which corresponds to cerebral blood volume, by inducing small changes in arterial oxygen saturation. Variability of tcpO2 is considered to be associated with severe retinopathy of prematurity (ROP). A preliminary analysis without control found a 51 percent incidence of ROP in infants subjected to NIRS measurements whereas among infants who were not exposed to oxygen changes, only 29 percent developed ROP. A controlled study with matched pairs was performed. Thirty-nine premature newborns who had received NIRS recordings were matched with 39 out of 172 infants who had not received NIRS. Using this controlled study design there was no difference in the incidence and severity of ROP between the two groups. The conclusions are that: 1) small changes in oxygen saturation of 3 to 10 percent to measure cbf and cHbc did not increase the incidence or the degree of severity of ROP. 2) A controlled study design is important. Analyses of uncontrolled data would have led to the conclusion that oxygen changes as used with NIRS increase the risk of ROP.

Prophylactic propranolol for prevention of ROP and visual outcome at 1 year (PreROP trial).

PubMed

Sanghvi, Kishore Pratap; Kabra, Nandkishor S; Padhi, Phalguni; Singh, Umesh; Dash, Swarup Kumar; Avasthi, Bhupendra S

2017-09-01

To evaluate the role of prophylactic propranolol in the prevention of retinopathy of prematurity (ROP) in infants ≤32 weeks of gestational age and their visual outcome at 1 year of corrected gestational age. Randomised double blind placebo controlled trial, parallel group nrolment with allocation ratio of 1:1. Two level III neonatal intensive care units. 109 preterm neonates of ≤32 weeks of gestation with postnatal age ≤8 days old. Study group: Infants with gestational age between 26 and 32 weeks were started on propranolol prophylaxis (0.5 mg/kg/dose every 12 hours) on seventh completed day of life, till a corrected gestational age of 37 weeks or complete vascularisation of retina whichever was later. Control group infants received a placebo. Primary : ROP of all grades; Secondary : evaluation of complications due to propranolol, ROP needing treatment with laser and/or antivascular endothelial growth factor (anti-VEGF) and visual outcome at 12 months corrected age. Prophylactic propranolol in the prescribed dose of 1 mg/kg/day showed a decreasing trend in the incidence of ROP (56.8% vs 68.6%; p=0.39), need for laser therapy (21.56% vs 31.37%; p=0.37), treatment with anti-VEGF (3.92% vs 15.68%; p=0.09) or visual outcomes at 1 year in the study and control groups, respectively, though these reductions were not statistically significant. Decreasing trends favouring propranolol in all other ROP-related outcomes were also noted in the study group. Prophylactic propranolol in the prescribed dose of 1 mg/kg/day showed a decreasing trend in all outcomes of ROP though statistically not significant. CTRI/2013/11/004131. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The Efficacy of Propranolol in Retinopathy of Prematurity and its Correlation with the Platelet Mass Index.

PubMed

Korkmaz, Levent; Baştuğ, Osman; Ozdemir, Ahmet; Korkut, Sabriye; Karaca, Cagatay; Akin, Mustafa Ali; Gunes, Tamer; Kurtoglu, Selim; Ozturk, Mehmet Adnan

2017-01-01

Retinopathy of Prematurity (ROP) is a proliferative vitreoretinopathy which is one of the most frequent causes of blindness in children. In an attempt to find a solution to this important problem in preterm children, the search for new, effective treatment modalities with fewer side effects is underway. In our study, which was planned for this reason, we aimed to investigate the effects of propranolol treatment applied to cases of ROP in various stages during the second phase (known as the neovascularization-hypoxia phase) and to determine the correlation of these effects with the platelet mass index (PMI). A total of 171 preterm infants at risk of ROP were selected randomly for inclusion in the study. All of the patients were classified according to their stage of ROP and were divided into control and treatment groups. While the cases in the control group were administered physiological saline solution, those in the treatment group were administered propranolol in the period that corresponded to the second stage of the disease. The thrombocyte and PMI values in the first and second stages of each study group were recorded. A significant difference was found between the control and treatment groups of the stage 2 ROP study subjects. In the stage 2 ROP study group, no significant difference was detected between the control and treatment cases in terms of platelet counts in phase 1 or in the PMI values and the thrombolytic counts in phase 2. On the other hand, in phase 2 of the stage 2 ROP study subjects significant differences were detected between the control and treatment group in terms of PMI values. In the study, it was found in the stage 2 ROP study group that propranolol reduced the need for laser photocoagulation significantly. Also, in parallel to the efficacy of propranolol in this study group, a decrease was observed in PMI values.

Diagnostic discrepancies in retinopathy of prematurity classification

PubMed Central

Campbell, J. Peter; Ryan, Michael C.; Lore, Emily; Tian, Peng; Ostmo, Susan; Jonas, Karyn; Chan, R.V. Paul; Chiang, Michael F.

2016-01-01

Objective To identify the most common areas for discrepancy in retinopathy of prematurity (ROP) classification between experts. Design Prospective cohort study. Subjects, Participants, and/or Controls 281 infants were identified as part of a multi-center, prospective, ROP cohort study from 7 participating centers. Each site had participating ophthalmologists who provided the clinical classification after routine examination using binocular indirect ophthalmoscopy (BIO), and obtained wide-angle retinal images, which were independently classified by two study experts. Methods Wide-angle retinal images (RetCam; Clarity Medical Systems, Pleasanton, CA) were obtained from study subjects, and two experts evaluated each image using a secure web-based module. Image-based classifications for zone, stage, plus disease, overall disease category (no ROP, mild ROP, Type II or pre-plus, and Type I) were compared between the two experts, and to the clinical classification obtained by BIO. Main Outcome Measures Inter-expert image-based agreement and image-based vs. ophthalmoscopic diagnostic agreement using absolute agreement and weighted kappa statistic. Results 1553 study eye examinations from 281 infants were included in the study. Experts disagreed on the stage classification in 620/1553 (40%) of comparisons, plus disease classification (including pre-plus) in 287/1553 (18%), zone in 117/1553 (8%), and overall ROP category in 618/1553 (40%). However, agreement for presence vs. absence of type 1 disease was >95%. There were no differences between image-based and clinical classification except for zone III disease. Conclusions The most common area of discrepancy in ROP classification is stage, although inter-expert agreement for clinically-significant disease such as presence vs. absence of type 1 and type 2 disease is high. There were no differences between image-based grading and the clinical exam in the ability to detect clinically-significant disease. This study provides additional evidence that image-based classification of ROP reliably detects clinically significant levels of ROP with high accuracy compared to the clinical exam. PMID:27238376

Synthesis and characterization of poly-L-leucine initialized and immobilized by rehydrated hydrotalcite: understanding stability and the nature of interaction.

PubMed

Miranda, Ronald-Alexander; Finocchio, Elisabetta; Llorca, Jordi; Medina, Francisco; Ramis, Gianguido; Sueiras, Jesús E; Segarra, Anna M

2013-10-07

PLLs were synthesized by the ring-opening polycondensation (ROP) method using α-L-leucine N-carboxyanhydride (NCA) and initialized by triethylamine (Et3N), water or rehydrated hydrotalcite (HTrus). The role of temperature, different initiators and water in ROP was further investigated. In general, the initiators used in the polymerization reaction lead to PLL alpha-helical chains containing 5-40 monomers with NCA endgroups via a monomer-activated mechanism. However, the water has a twofold effect on ROP, as both a nucleophile and a base, which involves competition between two different types of initiating mechanisms (nucleophilic attack or deprotonation of the NCA monomer) in the polymerization reaction. This competition provides as a main product NCA endgroups with an alpha-helical structure and leads to the formation of the PLL cyclic-chains and beta-sheet structures which reduce the polymer Mw and the PD of the polypeptide. Furthermore, the water can hydrolyze the NCA endgroups resulting in PLL alpha-helical chains that contain living groups as the main product. On the other hand, the HTrus presents a double role: as both an initiator and a support. The polymers synthesized in the presence of HTrus presented a HT-carboxylate endgroup. The PLLs immobilized in HTrus through an anion-exchange method performed for just 30 minutes presented the PLL immobilized in the interlayer space of the HTrus. The PLL chains of the immobilized counterpart are stabilized by H-bonding with the M-OH of the HT structure. All the polypeptides and biohybrid materials synthesized have been characterized using different techniques (EA, ICP, XRD, Raman, MALDI-TOF, ESI-TOF, FT-IR at increasing temperatures, TG/DT analyses and TEM).

Prediction of severe retinopathy of prematurity using the WINROP algorithm in a cohort from Malopolska. A retrospective, single-center study.

PubMed

Jagła, Mateusz; Peterko, Anna; Olesińska, Katarzyna; Szymońska, Izabela; Kwinta, Przemko

2017-01-01

Retinopathy of prematurity (ROP) is one of the leading avoidable causes of blindness in childhood in developed countries. Accurate diagnosis and treatment are essential for preventing the loss of vision. WINROP (https://www.winrop.com) is an online monitoring system which predicts the risk for ROP requiring treatment based on gestational age, birth weight, and body weight gain. To validate diagnostic accuracy of the WINROP algorithm for the detection of severe ROP in a single centre cohort of Polish, high-risk preterm infant population. Medical records of neonates born before 32 weeks of gestation admitted to the third level neonatal centre in a 2-year retrospective investigation 79 patients were included in the study: their gestational age, birth weight and body weight gain were set in the WINROP system. The algorithm evaluated the risk for ROP divided into low or high-risk of disease and identified infants with high risk of developing severe ROP (type 1 ROP). Out of 79 patients 37 received a high-risk alarm, of whom 22 developed severe ROP. Low-risk alarm was triggered in 42 infants; five of them developed type 1 ROP. The sensitivity of the WINROP was found to be 81.5% (95% CI 61.9-93.7), specificity 71.2% (95% CI 56.9-82.9), negative predictive value (NPV) 88.1% (95% CI 76.7-94.3), and positive predictive value (PPV) 59.5 (95% CI 48.1-69.9), respectively. The accuracy of the test significantly increased after combined WINROP and surfactant therapy as an additional factor - sensitivity 96.3% (95% CI 81.0-99.9), specificity 63.5% (95% CI 49.0-76.4), NPV 97.1% (95% CI 82.3-99.6), and PPV 57.8 (95% CI 48.7-66.4). The WINROP algorithm sensitivity from the Polish cohort was not as high as that reported in developed countries. However, combined with additional factors (e.g. surfactant treatment) it can be useful for identifying the risk groups of sight-threatening ROP. The accuracy of the WINROP algorithm should be validated in a large multi-center prospective study in a Polish population of preterm infants.

Case series of infants presenting with end stage retinopathy of prematurity to two tertiary eye care facilities in Mexico: underlying reasons for late presentation.

PubMed

Zepeda-Romero, Luz C; Meza-Anguiano, Alonso; Barrera-de León, Juan C; Angulo-Castellanos, Eusebio; Ramirez-Ortiz, Marco A; Gutiérrez-Padilla, José A; Gilbert, Clare E

2015-06-01

To describe the characteristics of infants with bilateral Stage 4b or 5 ROP (i.e. with subtotal or total retinal detachment) who presented to eye departments in two major cities in Mexico, to identify reasons why they may have become blind in order to recommend how programs could be improved. A large case-series of infants with Stage 4b or 5 ROP in both eyes confirmed by ultrasound who attended the ROP Clinic, Hospital Civil de Guadalajara from September 2010 to November 2012, and the Department of Ophthalmology, Hospital Infantil de Mexico Federico Gomez from December 2011 to December 2012 were identified from the diagnostic databases of each hospital. Mothers of infants in Guadalajara had a telephone interview. 89/94 eligible infants were included in the study, 48 in Guadalajara and 41 in Mexico City. Cases came from 22 of the 32 states in Mexico. Half of the infants attending Guadalajara 24/48 (50 %) had been cared for in NICUs without ROP screening programs and were not examined. Among the 24 infants cared for in NICUs with ROP programs, 7/24 (29.1 %) mothers reported that their infant had not been examined while in the NICU, and a further 9/24 (37.5 %) were either not referred for screening after discharge or they did not attend. Two infants had failed laser treatment. Strategies and resources to prevent end stage ROP have not been firmly established in Mexico. There is an urgent need to expand the coverage and quality of ROP programs, to ensure that existing screening guidelines are better adhered to, and to improve communication with parents.

A systematic study on the prevention and treatment of retinopathy of prematurity in China.

PubMed

Xu, Shuman; Liang, Zhijiang; Du, Qiyun; Li, Zhankui; Tan, Guangming; Nie, Chuan; Yang, Yang; Lv, Xuzai; Zhang, Chunyi; Luo, Xianqiong

2018-02-14

To identify the prevention situation, the main factors influencing prevention effects and to develop control measures over retinopathy of prematurity in China. Using stratified random sampling method, we randomly selected 23 provincial and ministerial hospitals (8 in Guangdong province, 5 in Hunan province and 10 in Shaanxi province), 81 municipal hospitals (38 in Guangdong province, 19 in Hunan province and 24 in Shaanxi province), 180 district and county hospitals (76 in Guangdong province, 57 in Hunan province and 47 in Shaanxi province) in China. A total of 284 hospitals were enrolled in the study, with questionnaires distributed investigating the status and constrain factors of ROP presentation. Significant outcomes were analyzed thereafter by SPSS 19.0. The screening rate of ROP in medical institutions from eastern, central and western China were 84.6%, 35.0% and 56.7%, respectively. The screening rate of tertiary and secondary medical institutions were 84.6% and 25.7% in the eastern, 35.0% and 4.9% in the central, 56.7% and 5.9% in the western region. Screening was carried out better in the tertiary than that in the secondary and primary institutions. Treatment for ROP was available in 15.7% of all the tertiary hospitals surveyed. Lack of professionals, equipments and technologies were considered to be major restrain factors for screening. The ROP screening and treatment status have demonstrated significant regional diversity due to uneven distribution of medical resources in China. Developed areas had established intraregional cooperation models, whereas less-developed areas should consider set up a large-scale, three-level ROP prevention network. It is of paramount importance that education and training towards ophthalmologists should be vigorously strengthened. It is strongly recommended that implement ROP telemedicine and integrated ROP prevention and management platforms through the Internet should be established.

Neonatal Risk Factors for Treatment-Demanding Retinopathy of Prematurity: A Danish National Study.

PubMed

Slidsborg, Carina; Jensen, Aksel; Forman, Julie Lyng; Rasmussen, Steen; Bangsgaard, Regitze; Fledelius, Hans Callø; Greisen, Gorm; la Cour, Morten

2016-04-01

One goal of the study was to identify "new" statistically independent risk factors for treatment-demanding retinopathy of prematurity (ROP). Another goal was to evaluate whether any new risk factors could explain the increase in the incidence of treatment-demanding ROP over time in Denmark. A retrospective, register-based cohort study. The study included premature infants (n = 6490) born in Denmark from 1997 to 2008. The study sample and the 31 candidate risk factors were identified in 3 national registers. Data were linked through a unique civil registration number. Each of the 31 candidate risk factors were evaluated in univariate analyses, while adjusted for known risk factors (i.e., gestational age [GA] at delivery, small for gestational age [SGA], multiple births, and male sex). Significant outcomes were analyzed thereafter in a backward selection multiple logistic regression model. Treatment-demanding ROP and its associations to candidate risk factors. Mechanical ventilation (odds ratio [OR], 2.84; 95% confidence interval [CI], 1.99-4.08; P < 0.01) and blood transfusion (OR, 1.97; 95% CI, 1.20-3.14; P = 0.01) were the only new statistically independent risk factors, in addition to GA at delivery, SGA, multiple births, and male sex. Modification in these prognostic factors for ROP did not cause an increase in treatment-demanding ROP. In a large study population, blood transfusion and mechanical ventilation were the only new statistically independent risk factors to predict the development of treatment-demanding ROP. Modification in the neonatal treatment with mechanical ventilation or blood transfusion did not cause the observed increase in the incidence of preterm infants with treatment-demanding ROP during a recent birth period (2003-2008). Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Progression and timing of treatment of zone I retinopathy of prematurity.

PubMed

Soh, Yuka; Fujino, Takahiro; Hatsukawa, Yoshikazu

2008-09-01

To clarify the progression of zone I retinopathy of prematurity (ROP) and elucidate the most suitable time and method of treatment. Interventional case series. Forty-six eyes of 23 zone I ROP infants were studied at a single institution. Birth weight ranged from 448 to 954 g, and gestational age ranged from 22 to 26 weeks. Fundus examination was started at 29 or 30 weeks postmenstrual age and was performed once or more per week. The first treatment was performed using laser photocoagulation or cryotherapy when zone I ROP progressed to the following criteria. Treatment criteria A included 35 eyes of 18 cases of zone I any stage ROP with plus disease (Early Treatment for Retinopathy of Prematurity [ETROP] type 1), criteria B included five eyes of three cases of zone I stage 3 ROP with or without plus disease (ETROP type 1), criteria C included six eyes of four cases of stage 1 or stage 2 ROP without plus disease; the demarcation lines belonged, in large part, within the zone I area. Hazy media such as corneal opacity, miotic pupil, tunica vasculosa lentis, and hazy vitreous persisted until approximately 32 weeks postmenstrual age. The mean period between stage 1 and stage 3 mild was one week, that between stage 1 and stage 3 moderate was 1.7 weeks, and that between stage 1 and stage 3 severe was 1.3 weeks. The period between stage 1 and the first treatment was zero to 20 days, and 60.9% of all the cases were treated within 10 days after stage 1. Six of 46 eyes had unfavorable outcomes. Surgical results of our treatment were comparable or better than those of other reports. Immediate treatment was required when zone I ROP was diagnosed behind persistent hazy media.

Eye Growth in Term- And Preterm-Born Eyes Modeled From Magnetic Resonance Images

PubMed Central

Munro, Robert J.; Fulton, Anne B.; Chui, Toco Y. P.; Moskowitz, Anne; Ramamirtham, Ramkumar; Hansen, Ronald M.; Prabhu, Sanjay P.; Akula, James D.

2015-01-01

Purpose. We generated a model of eye growth and tested it against an eye known to develop abnormally, one with a history of retinopathy of prematurity (ROP). Methods. We reviewed extant magnetic resonance images (MRIs) from term and preterm-born patients for suitable images (n = 129). We binned subjects for analysis based upon postmenstrual age at birth (in weeks) and ROP history (“Term” ≥ 37, “Premature” ≤ 32 with no ROP, “ROP” ≤ 32 with ROP). We measured the axial positions and curvatures of the cornea, anterior and posterior lens, and inner retinal surface. We fit anterior chamber depth (ACD), posterior segment depth (PSD), axial length (AL), and corneal and lenticular curvatures with logistic growth curves that we then evaluated for significant differences. We also measured the length of rays from the centroid to the surface of the eye at 5° intervals, and described the length versus age relationship of each ray, Lray(x), using the same logistic growth curve. We determined the rate of ray elongation, Eray(x), from Lray dy/dx. Then, we estimated the scleral growth that accounted for Eray(x), G(x), at every age and position. Results. Relative to Term, development of ACD, PSD, AL, and corneal and lenticular curvatures was delayed in ROP eyes, but not Premature eyes. In Term infants, G(x) was fast and predominantly equatorial; in age-matched ROP eyes, maximal G(x) was offset by approximately 90°. Conclusions. We produced a model of normal eye growth in term-born subjects. Relative to normal, the ROP eye is characterized by delayed, abnormal growth. PMID:26024095

Screening for retinopathy of prematurity in China: a neonatal units-based prospective study.

PubMed

Xu, Yu; Zhou, Xiaohong; Zhang, Qi; Ji, Xunda; Zhang, Qin; Zhu, Jianxing; Chen, Chao; Zhao, Peiquan

2013-12-19

To analyze the incidence and severity of retinopathy of prematurity (ROP) in China, and to explore the workload implications of applying different criteria. A prospective, neonatal units-based study undertaken in two tertiary level hospitals in Shanghai, China, from January 1, 2010 to December 31, 2012. All infants with birth weight (BW) of 2000 g or less and/or gestational age (GA) of 34 weeks or less were screened for ROP. Retinopathy of prematurity was classified using the international classification, and was treated in accordance with the recommendations of the Early Treatment for Retinopathy of Prematurity Cooperative Group. A total of 2825 (93.7%) of 3014 eligible infants were screened, and ROP was diagnosed in 503 infants (17.8%). One hundred ninety-one infants (6.8%) had type 1 or worse ROP and were treated with laser or vitrectomy. The mean GA of ROP patients was 29.9 ± 2.1 weeks and their mean BW was 1425 ± 266 g. Infants who needed treatment for ROP had a mean GA of 29.3 ± 2.1 weeks and mean BW of 1331 ± 330 g. Among these treated infants, 18 infants (9.4%) exceeded the United Kingdom's (UK) screening criteria, and 28 (14.7%) exceeded the criteria used in the United States (US). If narrower criteria, as in GA less than or equal to 33 weeks and/or BW less than or equal to 1750 g were adopted, almost 16.9% fewer infants would not have been examined, with no infant missing treatment. Larger, older infants are at risk in China and screening criteria used in the US and UK may not be suitable for China. Further population-based studies are recommended to determine the necessity of modifying the current ROP screening protocol.

Outcome of solid-state 532 nm green laser in high-risk retinopathy of prematurity at a tertiary care centre in India.

PubMed

Chhabra, Kanika; Kaur, Prempal; Singh, Karamjit; Aggarwal, Anand; Chalia, Dharamvir

2018-02-01

The purpose of this study was to analyse the outcome of solid-state green laser in high-risk retinopathy of prematurity (ROP) at a tertiary centre in India. Fifty-nine eyes of 30 infants with high-risk ROP were recruited in this prospective, interventional study. High-risk ROP included prethreshold type 1 ROP and APROP. Laser photocoagulation was performed with 532 nm solid-state green laser (Novus Spectra, Lumenis, GmbH, Germany). Of the 30 infants, 18 were males (60%) and 12 were females (40%). The mean birth weight was 1102.83 ± 196.27 g. The mean gestational age was 29.5 ± 1.47 weeks. Zone 1 disease was present in 10 eyes (16.95%) and zone 2 disease in 49 (83.05%) eyes. Out of 57 eyes with prethreshold type 1 ROP, 39 eyes (68.42%) had stage 2 and 18 eyes (31.58%) had stage 3. The postconceptional age at the time of treatment was 36.03 ± 2.32 weeks. The infants received mean 2710.24 ± 747.97 laser spots. Fifty (84.8%) eyes underwent laser in a single sitting and 9 eyes (15.2%) required 2 laser sittings. Mean time for regression of ROP was 5.8 ± 3.8 weeks (range 3-11 weeks). Total ROP regression was seen in 55 eyes (93.22%). Despite laser treatment, 4 (6.78%) eyes of three infants had unfavourable outcome. One infant developed intra-procedural bradycardia. Vitreous haemorrhage was seen in five eyes (8.4%). Solid-state 532 nm green laser is a safe and effective treatment for high-risk retinopathy of prematurity.

Current screening and treatments in retinopathy of prematurity in the US

PubMed Central

Suelves, Ana M; Shulman, Julia P

2016-01-01

Retinopathy of prematurity (ROP) is a complex disease characterized by an aberrant developmental retinal angiogenesis in preterm infants and can carry significant visual morbidity, including retinal detachment and blindness. Though large scale, randomized clinical trials have improved our understanding of the pathophysiology and progression of the disease, the management of ROP remains a challenge for ophthalmologists. This review addresses the up-to-date screening approach, diagnosis, and treatment guidelines for ROP in the US. PMID:28539800

Current screening and treatments in retinopathy of prematurity in the US.

PubMed

Suelves, Ana M; Shulman, Julia P

2016-01-01

Retinopathy of prematurity (ROP) is a complex disease characterized by an aberrant developmental retinal angiogenesis in preterm infants and can carry significant visual morbidity, including retinal detachment and blindness. Though large scale, randomized clinical trials have improved our understanding of the pathophysiology and progression of the disease, the management of ROP remains a challenge for ophthalmologists. This review addresses the up-to-date screening approach, diagnosis, and treatment guidelines for ROP in the US.

POSTNATAL SERUM INSULIN-LIKE GROWTH FACTOR I AND RETINOPATHY OF PREMATURITY.

PubMed

Jensen, Anne K; Ying, Gui-Shuang; Huang, Jiayan; Quinn, Graham E; Binenbaum, Gil

2017-05-01

Low serum IGF-1 has been associated with development of severe ROP, but no U.S. studies have been reported. We sought to determine the relationship between postnatal serum IGF-1 levels and severe ROP in a racially diverse U.S. cohort. Prospective cohort study of 74 infants with birth weight <1,251 g and a known ROP outcome at 3 Philadelphia hospitals. Weekly postnatal filter paper blood spot IGF-1 assays were measured through 42 weeks postmenstrual age. The cohort included 20 white, 45 black, 2 Asian, and 9 other infants; median gestational age was 27.6 weeks (range 23-33 weeks), and median birth weight was 975 g (range 490-1,250 g). During postmenstrual age Weeks 28 to 33, mean IGF-1 was 20.0 ng/mL (standard error 0.52) for no ROP (n = 46), 18.0 (0.49) for Stage 1 or 2 (n = 23), and 17.0 (0.70) for Stage 3 (n = 5, 2 lasered) (P = 0.003). Adjustment for birth weight and gestational age showed similar results. The presence and timing of an association between low postnatal serum IGF and ROP in a racially diverse U.S. sample were found to be consistent with those of European cohorts. This association provides the pathophysiological basis for growth-based predictive models, which could improve efficiency of ROP screening.

Evaluation of a recombinant rhoptry protein 2 enzyme-linked immunoassay for the diagnosis of toxoplasmosis acquired during pregnancy.

PubMed

Capobiango, Jaqueline Dario; Pagliari, Sthefany; Pasquali, Aline Kuhn Sbruzzi; Nino, Beatriz; Ferreira, Fernanda Pinto; Monica, Thaís Cabral; Tschurtschenthaler, Nely Norder; Navarro, Italmar Teodorico; Garcia, João Luis; Mitsuka-Breganó, Regina; Reiche, Edna Maria Vissoci

2015-09-01

The aim of this study was to evaluate an enzyme-linked immunoassay with recombinant rhoptry protein 2 (ELISA-rROP2) for its ability to detect Toxoplasma gondii ROP2-specific IgG in samples from pregnant women. The study included 236 samples that were divided into groups according to serological screening profiles for toxoplasmosis: unexposed (n = 65), probable acute infection (n = 48), possible acute infection (n = 58) and exposed to the parasite (n = 65). When an indirect immunofluorescence assay forT. gondii-specific IgG was considered as a reference test, the ELISA-rROP2 had a sensitivity of 61.8%, specificity of 62.8%, predictive positive value of 76.6% and predictive negative value of 45.4% (p = 0.0002). The ELISA-rROP2 reacted with 62.5% of the samples from pregnant women with probable acute infection and 40% of the samples from pregnant women with previous exposure (p = 0.0180). Seropositivity was observed in 50/57 (87.7%) pregnant women with possible infection. The results underscored that T. gondii rROP2 is recognised by specific IgG antibodies in both the acute and chronic phases of toxoplasmosis acquired during pregnancy. However, the sensitivity of the ELISA-rROP2 was higher in the pregnant women with probable and possible acute infections and IgM reactivity.

Retinopathy of prematurity: screening and treatment in Costa Rica.

PubMed

Tabarez-Carvajal, Ana Catalina; Montes-Cantillo, Milagro; Unkrich, Kelly H; Trivedi, Rupal H; Peterseim, Mae Millicent Winfrey

2017-12-01

To determine the recent demographic data, risk factors and results of retinopathy of prematurity (ROP) screening and treatment in Costa Rica. The medical records of all preterm infants meeting ROP screening criteria (≤34 weeks' gestational age (GA) or birth weight (BW) ≤1750g, and those determined at risk by neonatologists) in the national healthcare system, Costa Rica, January 2010-December 2014, were retrospectively reviewed. The numbers and percentages of infants with ROP, risk factors, percentage of patients treated and treatment outcomes were determined. Comparison is made with screening criteria and literature reports of ROP incidence in other countries. The study population included 3018 preterm infants. Overall, 585 patients (585/3018, 19.4%) were found to have ROP. Of these, 15.4% (90 patients) required laser treatment, and 53% of those requiring treatment had BW <1000g. Five babies requiring treatment were ≥32 weeks' GA but with BW ≤1750g. Aggressive posterior disease was found in nine patients, and two infants of those screened (2/3018, 0.07%) suffered severe visual impairment during the 5-year study period. We provide comprehensive data of ROP care in Costa Rica allowing assessment and comparison of screening criteria and protocol. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Assessing farm tractor incidents and awareness levels of operators for tractor safety issues in the Hatay province of Turkey.

PubMed

Keskin, S Görücü; Keskin, M; Soysal, Y

2012-04-01

Studies and statistical data on safety issues related to farm tractors and machinery are very limited in developing countries, including Turkey. This study was carried out to investigate tractor-related incidents in the Hatay province, located in the mid-south of Turkey. A questionnaire was conducted with 107 tractor operators using face-to-face interviews. Data were evaluated according to the incident type, machinery involved, and mechanism of injury or fatality. A total of 101 incidents were reported by 77 of the 107 respondents. Most of the incidents were due to tractor rollovers (65.4%), 14.8% of the incidents were due to entanglement of body parts in moving machinery, and 12.9% involved crashing into other vehicles or obstacles. The leading cause of the incidents was personal mistakes (60.4%). Fatalities resulted from 25.7% of the incidents, while 45.5% of the incidents caused non-fatal injuries. Only 5.6% of the tractors had a ROPS-enclosed cab. The percentage of ROPS-equipped tractors was 19.6%, while 41.3% of the tractors had a shade cover and 33.6% had no protective structure. Only one of the respondents used a seatbelt, although 44.9% of them stated that seatbelts should be used. It was also found that only 13.5% of the operators had training in work safety, while 95.1% stated that incidents might be reduced if people were trained. Development of appropriate policies and training programs are needed for safer operation of agricultural machinery to reduce injuries and fatalities due to farm accidents.

Retinopathy of prematurity: late complications in the baby boomer generation (1946-1964).

PubMed

Smith, Bradley T; Tasman, William S

2005-01-01

To report the natural history and late complications of retinopathy of prematurity (ROP) in members of the baby boomer generation (1946-1964). Retrospective observational series of 86 eyes from 47 adult ROP patients (aged 45 to 56 years) who did not receive treatment as infants. Posterior segment pathology, refractive status, lens status, and visual acuity were evaluated. Seventy-six eyes (88.4%) had posterior segment pathology due to ROP, including 22 (25.6%) with retinal detachments. The rates of myopia and cataract formation were 90.7% and 83.7%, respectively. Visual acuity was 20/200 or worse in 43 eyes (51.2%) and 20/60 or better in 35 (41.7%). There are significant late complications of ROP underscoring the importance of lifelong follow-up.

Bilateral large subconjunctival haemorrhages unmasking immune thrombocytopenic purpura during retinopathy of prematurity screening.

PubMed

Chandra, Parijat; Kumawat, Devesh; Kumar, Vinod; Tewari, Ruchir

2017-10-04

Although thrombocytopenia is known to be associated with pathogenesis of retinopathy of prematurity (ROP), immune thrombocytopenic purpura (ITP) is rare in infancy and not reported to occur with ROP. A preterm infant with aggressive posterior ROP developed bilateral massive subconjunctival haemorrhage after scleral indentation during screening. On evaluation, the infant was found to have severe ITP. Following intravenous transfusion of platelets and immunoglobulin, platelet counts improved and subconjunctival haemorrhage resolved over time. This case highlights the unusual presentation of ITP and also discusses the association of thrombocytopenia with ROP. Ophthalmologists should get prompt haematological work-up of such occurrences. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Health Issues of Premature Babies

MedlinePlus

... they leave the hospital for home. Retinopathy of Prematurity (ROP) What It Is: ROP is an eye ... sometimes seen in preterm babies include anemia of prematurity (a low red blood cell count) and heart ...

A Theoretical Model of Jigsaw-Puzzle Pattern Formation by Plant Leaf Epidermal Cells.

PubMed

Higaki, Takumi; Kutsuna, Natsumaro; Akita, Kae; Takigawa-Imamura, Hisako; Yoshimura, Kenji; Miura, Takashi

2016-04-01

Plant leaf epidermal cells exhibit a jigsaw puzzle-like pattern that is generated by interdigitation of the cell wall during leaf development. The contribution of two ROP GTPases, ROP2 and ROP6, to the cytoskeletal dynamics that regulate epidermal cell wall interdigitation has already been examined; however, how interactions between these molecules result in pattern formation remains to be elucidated. Here, we propose a simple interface equation model that incorporates both the cell wall remodeling activity of ROP GTPases and the diffusible signaling molecules by which they are regulated. This model successfully reproduces pattern formation observed in vivo, and explains the counterintuitive experimental results of decreased cellulose production and increased thickness. Our model also reproduces the dynamics of three-way cell wall junctions. Therefore, this model provides a possible mechanism for cell wall interdigitation formation in vivo.

[Why is it difficult to implement biomedical policy? the case of the Cancéropôles, the French cancer organizations].

PubMed

Vézian, Audrey

2014-01-01

This article examines the new organizations in cancer research in France called cancéropôles and created in 2003, whose mission is to coordinate actors from industry, research and clinical fields. Our research is based on a study of cancéropôles which embraces an evolutionary perspective on cluster formation and development. Our analysis reveals that although clear differences exist between them, our sample of the three established Cancéropôles display similar patterns of unsuccessful cases. Eventually, the identification of mechanisms that reduce their action in the cancer research environment raises questions about the factors that may influence any public action to a reconfiguration of the French biomedical sector. © 2014 médecine/sciences – Inserm.

RETINOPATHY OF PREMATURITY: LATE COMPLICATIONS IN THE BABY BOOMER GENERATION (1946–1964)

PubMed Central

Smith, Bradley T; Tasman, William S

2005-01-01

Purpose To report the natural history and late complications of retinopathy of prematurity (ROP) in members of the baby boomer generation (1946–1964). Methods Retrospective observational series of 86 eyes from 47 adult ROP patients (aged 45 to 56 years) who did not receive treatment as infants. Posterior segment pathology, refractive status, lens status, and visual acuity were evaluated. Results Seventy-six eyes (88.4%) had posterior segment pathology due to ROP, including 22 (25.6%) with retinal detachments. The rates of myopia and cataract formation were 90.7% and 83.7%, respectively. Visual acuity was 20/200 or worse in 43 eyes (51.2%) and 20/60 or better in 35 (41.7%). Conclusions There are significant late complications of ROP underscoring the importance of lifelong follow-up. PMID:17057805

Barley ROP Binding Kinase1 Is Involved in Microtubule Organization and in Basal Penetration Resistance to the Barley Powdery Mildew Fungus1[W

PubMed Central

Huesmann, Christina; Reiner, Tina; Hoefle, Caroline; Preuss, Jutta; Jurca, Manuela E.; Domoki, Mónika; Fehér, Attila; Hückelhoven, Ralph

2012-01-01

Certain plant receptor-like cytoplasmic kinases were reported to interact with small monomeric G-proteins of the RHO of plant (ROP; also called RAC) family in planta and to be activated by this interaction in vitro. We identified a barley (Hordeum vulgare) partial cDNA of a ROP binding protein kinase (HvRBK1) in yeast (Saccharomyces cerevisiae) two-hybrid screenings with barley HvROP bait proteins. Protein interaction of the constitutively activated (CA) barley HvROPs CA HvRACB and CA HvRAC1 with full-length HvRBK1 was verified in yeast and in planta. Green fluorescent protein-tagged HvRBK1 appears in the cytoplasm and nucleoplasm, but CA HvRACB or CA HvRAC1 can recruit green fluorescent protein-HvRBK1 to the cell periphery. Barley HvRBK1 is an active kinase in vitro, and activity is enhanced by CA HvRACB or GTP-loaded HvRAC1. Hence, HvRBK1 might act downstream of active HvROPs. Transient-induced gene silencing of barley HvRBK1 supported penetration by the parasitic fungus Blumeria graminis f. sp. hordei, suggesting a function of the protein in basal disease resistance. Transient knockdown of HvRBK1 also influenced the stability of cortical microtubules in barley epidermal cells. Hence, HvRBK1 might function in basal resistance to powdery mildew by influencing microtubule organization. PMID:22415513

[Retinopathy of prematurity in multiple births: risk analysis for plus disease].

PubMed

García-Serrano, J L; Ramírez-García, M C; Piñar-Molina, R

2009-04-01

To analyze the risk factors associated with plus disease in retinopathy of prematurity (ROP). Over a period of 8.5 years we carried out a prospective study of ROP in twins and triplets. Fifty-four multiple-birth infants with low birth weight (< or =1500 g) and low gestational age (32< or = weeks) were admitted to the University Hospital of Granada. Logistic regression analyses showed the following variables to be associated with an increased risk of plus disease: severe ROP, large area of avascular retina, low gestational age, low birth weight, a patent ductus arteriosus, length of mechanical ventilation, adverse events increase, low 5 min Apgar scores and poor postnatal weight gain (in the first 4 to 6 weeks of life). Using multiple logistic regression, only the grade of ROP (OR: 5.5; p < 0.009) and poor postnatal weight gain (OR: 0.58; p < 0.04) were predictive factors of development of plus disease. Infants with disease gained an average 3.9 +/- 3.1 g/day in the first 6 weeks of life, compared to a mean of 11.84 +/- 8.3 g/day for those without plus disease (p < 0.0001). Advanced ROP stages and poor weight gain were the most significant factors associated with plus disease. Twins who gained weight at more than 7 g/day in the first 4-6 weeks of life had a significantly reduced risk of plus disease. A good weight gain is an effective strategy against avoidable blindness due to ROP.

Incidence and risk factors for retinopathy of prematurity in a Brazilian reference service.

PubMed

Gonçalves, Eduardo; Násser, Luciano Sólia; Martelli, Daniella Reis; Alkmim, Isadora Ramos; Mourão, Thalita Veloso; Caldeira, Antônio Prates; Martelli, Hercílio

2014-01-01

Retinopathy of prematurity (ROP) is a known cause of blindness in which diagnosis and timely treatment can prevent serious harm to the child. This study aimed to evaluate the incidence of ROP and its association with known risk factors. Longitudinal incidence study in the neonatal intensive care unit (NICU) of Universidade Estadual de Montes Claros. Newborns admitted to the NICU with gestational age less than 32 weeks and/or birth weight less than 1,500 grams, were followed up over a two-year period. The assessment and diagnosis of ROP were defined in accordance with a national protocol. The chi-square test or Fisher's exact test were used to determine associations between independent variables and ROP. Analysis on the independent effect of the variables on the results was performed using multiple logistic regression. The incidence of ROP was 44.5% (95% confidence interval, CI = 35.6-46.1) in the study population. The risk factors associated with the risk of developing the disease were: birth weight less than 1,000 grams (odds ratio, OR = 4.14; 95% CI = 1.34-12.77); gestational age less than 30 weeks (OR = 6.69; 95% CI = 2.10-21.31); use of blood derivatives (OR = 4.14; 95% CI = 2.99-8.99); and presence of sepsis (OR = 1.99; 95% CI = 1.45-2.40). The incidence of ROP was higher than that found in the literature. The main risk factors were related to extreme prematurity.

Retinal Angiogenesis Is Mediated by an Interaction between the Angiotensin Type 2 Receptor, VEGF, and Angiopoietin

PubMed Central

Sarlos, Stella; Rizkalla, Bishoy; Moravski, Christina J.; Cao, Zemin; Cooper, Mark E.; Wilkinson-Berka, Jennifer L.

2003-01-01

There is evidence that angiotensin II, vascular endothelial growth factor (VEGF), angiopoietins, and their cognate receptors participate in retinal angiogenesis. We investigated whether angiotensin type 2-receptor blockade (AT2-RB) reduces retinal angiogenesis and alters the expression of VEGF/VEGF-R2 and angiopoietin-Tie2. Retinopathy of prematurity (ROP) was induced in Sprague Dawley (SD) rats by exposure to 80% oxygen from postnatal (P) days 0 to 11, followed by 7 days in room air. ROP shams were in room air from P0–18. A group of ROP rats received the AT2-RB, PD123319, by mini-osmotic pump (5 mg/kg/day) from P11–18 (angiogenesis period). Evaluation of the retinal status of the AT2 receptor indicated that this receptor, as assessed by real-time PCR, immunohistochemistry, and in vitro autoradiography, was present in the retina, was more abundant than the AT1 receptor in the neonatal retina, and was increased in the ROP model. AT2-RB reduced retinal angiogenesis. VEGF and VEGF-R2 mRNA were increased in ROP and localized to blood vessels, ganglion cells, and the inner nuclear layer, and were decreased by PD123319. Angiopoietin2 and Tie2, but not angiopoietin1 mRNA were increased with ROP, and angiopoietin2 was reduced with PD123319. This study has identified a potential retinoprotective role for AT2-RB possibly mediated via interactions with VEGF- and angiopoietin-dependent pathways. PMID:12937129

Receptor-like kinases as surface regulators for RAC/ROP-mediated pollen tube growth and interaction with the pistil

PubMed Central

Zou, Yanjiao; Aggarwal, Mini; Zheng, Wen-Guang; Wu, Hen-Ming; Cheung, Alice Y.

2011-01-01

Background RAC/ROPs are RHO-type GTPases and are known to play diverse signalling roles in plants. Cytoplasmic RAC/ROPs are recruited to the cell membrane and activated in response to extracellular signals perceived and mediated by cell surface-located signalling assemblies, transducing the signals to regulate cellular processes. More than any other cell types in plants, pollen tubes depend on continuous interactions with an extracellular environment produced by their surrounding tissues as they grow within the female organ pistil to deliver sperm to the female gametophyte for fertilization. Scope We review studies on pollen tube growth that provide compelling evidence indicating that RAC/ROPs are crucial for regulating the cellular processes that underlie the polarized cell growth process. Efforts to identify cell surface regulators that mediate extracellular signals also point to RAC/ROPs being the molecular switches targeted by growth-regulating female factors for modulation to mediate pollination and fertilization. We discuss a large volume of work spanning more than two decades on a family of pollen-specific receptor kinases and some recent studies on members of the FERONIA family of receptor-like kinases (RLKs). Significance The research described shows the crucial roles that two RLK families play in transducing signals from growth regulatory factors to the RAC/ROP switch at the pollen tube apex to mediate and target pollen tube growth to the female gametophyte and signal its disintegration to achieve fertilization once inside the female chamber. PMID:22476487

The optimal mixture of Toxoplasma gondii recombinant antigens (GRA1, P22, ROP1) for diagnosis of ovine toxoplasmosis.

PubMed

Holec-Gąsior, Lucyna; Ferra, Bartłomiej; Hiszczyńska-Sawicka, Elżbieta; Kur, Józef

2014-12-15

Toxoplasmosis, caused by Toxoplasma gondii, is the major parasitic disease affecting sheep. Infection not only results in significant reproductive losses in these animals, but has public health implications since consumption of infected meat can facilitate zoonotic transmission. Although several serological tests are currently used for diagnosis of ovine toxoplasmosis, production of reliable reagents is a constraint and therefore there is a need to develop new diagnostic tools. In this paper, we assess for the first time, the preliminary diagnostic utility of 19 T. gondii recombinant antigens (GRA1, GRA2ex2, GRA4, GRA5, GRA6, GRA9, SAG1, SAG4, BSR4, P22, ROP1, P36, MIC1ex2, MIC1ex34, MIC3, MAG1, BAG1, LDH1, and LDH2) in immunoglobulin G (IgG) enzyme-linked immunosorbent assays (IgG ELISAs). Following an initial evaluation, eight recombinant antigens (GRA1, GRA9, SAG1, SAG4, P22, MIC1ex2, MIC3, ROP1) were chosen for subsequent testing and comparison against the native Toxoplasma lysate antigen (TLA) in IgG ELISAs using 88 sera from naturally infected sheep and 20 sera from healthy animals. The reactivity of these antigens was variable with the best results for GRA1, P22, ROP1 and TLA. High sensitivity and specificity (100%) was noted for GRA1, ROP1 and TLA; P22 showed a slightly lower sensitivity (98.9%) but the same high specificity (100%). Four different combinations of these antigens (M1: GRA1+ROP1; M2: GRA1+P22; M3: P22+ROP1; M4: GRA1+P22+ROP1) were tested against the same pool of ovine sera; all IgG-positive serum samples were detected by all of the mixtures. However, the most effective for diagnosis of toxoplasmosis in sheep, based on the highest absorbance values, was the mixture M4 containing three proteins. High sensitivity and specificity (100%) was observed from tests containing either M4 or TLA antigens with a new pool of sera (93 seropositive and 35 seronegative). Thus, the present study shows that a cocktail of GRA1+P22+ROP1 recombinant proteins can be used to diagnose T. gondii infection in sheep, and consequently will assist in epidemiological studies. Copyright © 2014 Elsevier B.V. All rights reserved.

Quantifying and qualifying the use of topical anesthetics in retinopathy of prematurity examinations.

PubMed

Ahmed, Masih; Forcina, Blake; Bonsall, Dean

2016-04-01

The American Academy of Pediatrics advocates efforts to minimize discomfort and systemic effect of retinopathy of prematurity (ROP) examinations. Although many ophthalmologists use topical anesthetics, many do not believe them necessary. We present the results of the first survey to quantify the use of topical anesthetics in ROP examinations by clinicians who screen for ROP. The results show that although use of topical anesthetic is common, it is not universal. Copyright © 2016 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

Vision in former very low birthweight young adults with and without retinopathy of prematurity compared with term born controls: the NZ 1986 VLBW follow-up study.

PubMed

Darlow, Brian A; Elder, Mark J; Kimber, Bridget; Martin, Julia; Horwood, L John

2017-12-06

There are few data on visual outcomes in adulthood of former very low birthweight (VLBW; <1500 g) infants. We aimed to assess vision at 27-29 years in a national cohort of VLBW infants born in 1986 and assessed for retinopathy of prematurity (ROP) when no treatment was available, compared with term born controls. The cohort and controls attended a 2-day assessment in Christchurch as part of a larger study. Visual assessment included glasses prescription measured by focimeter, logarithm of the minimum angle of resolution (logMAR) distance visual acuity (VA), contrast sensitivity, autorefraction, retinal photographs and a questionnaire on vision-related everyday activities. Rates of reduced VA and myopia in the VLBW cohort at 27-29 were compared with the results of vision testing at 7-8 years. 250 VLBW adults (77% those alive) gave study consent and 229 (45 with a history of ROP) were assessed in Christchurch, plus 100 term born controls. VLBW adults with ROP had reduced VA compared with no ROP and controls (mean logMAR score (SD); 0.003 (0.19), -0.021 (0.16), -0.078 (0.09), P=0.001). There were no differences in myopia (>2 D) between the groups but high myopia (>5 D) was confined to those with ROP. VLBW adults with ROP drove a car less often and had higher difficulties with everyday activities scores due to eyesight. Between 7-8 and 27-29 years rates of reduced VA were stable but myopia increased. Former VLBW young adults with ROP have ongoing problems with vision affecting daily living and should continue in regular ophthalmological review. ACTRN12612000995875, Pre-results . © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Runway Operations Planning: A Two-Stage Solution Methodology

NASA Technical Reports Server (NTRS)

Anagnostakis, Ioannis; Clarke, John-Paul

2003-01-01

The airport runway is a scarce resource that must be shared by different runway operations (arrivals, departures and runway crossings). Given the possible sequences of runway events, careful Runway Operations Planning (ROP) is required if runway utilization is to be maximized. Thus, Runway Operations Planning (ROP) is a critical component of airport operations planning in general and surface operations planning in particular. From the perspective of departures, ROP solutions are aircraft departure schedules developed by optimally allocating runway time for departures given the time required for arrivals and crossings. In addition to the obvious objective of maximizing throughput, other objectives, such as guaranteeing fairness and minimizing environmental impact, may be incorporated into the ROP solution subject to constraints introduced by Air Traffic Control (ATC) procedures. Generating optimal runway operations plans was approached in with a 'one-stage' optimization routine that considered all the desired objectives and constraints, and the characteristics of each aircraft (weight class, destination, Air Traffic Control (ATC) constraints) at the same time. Since, however, at any given point in time, there is less uncertainty in the predicted demand for departure resources in terms of weight class than in terms of specific aircraft, the ROP problem can be parsed into two stages. In the context of the Departure Planner (OP) research project, this paper introduces Runway Operations Planning (ROP) as part of the wider Surface Operations Optimization (SOO) and describes a proposed 'two stage' heuristic algorithm for solving the Runway Operations Planning (ROP) problem. Focus is specifically given on including runway crossings in the planning process of runway operations. In the first stage, sequences of departure class slots and runwy crossings slots are generated and ranked based on departure runway throughput under stochastic conditions. In the second stage, the departure class slots are populated with specific flights from the pool of available aircraft, by solving an integer program. Preliminary results from the algorithm implementation on real-world traffic data are included.

A Theoretical Model of Jigsaw-Puzzle Pattern Formation by Plant Leaf Epidermal Cells

PubMed Central

Higaki, Takumi; Kutsuna, Natsumaro; Akita, Kae; Takigawa-Imamura, Hisako; Yoshimura, Kenji; Miura, Takashi

2016-01-01

Plant leaf epidermal cells exhibit a jigsaw puzzle–like pattern that is generated by interdigitation of the cell wall during leaf development. The contribution of two ROP GTPases, ROP2 and ROP6, to the cytoskeletal dynamics that regulate epidermal cell wall interdigitation has already been examined; however, how interactions between these molecules result in pattern formation remains to be elucidated. Here, we propose a simple interface equation model that incorporates both the cell wall remodeling activity of ROP GTPases and the diffusible signaling molecules by which they are regulated. This model successfully reproduces pattern formation observed in vivo, and explains the counterintuitive experimental results of decreased cellulose production and increased thickness. Our model also reproduces the dynamics of three-way cell wall junctions. Therefore, this model provides a possible mechanism for cell wall interdigitation formation in vivo. PMID:27054467

Recommended operating procedure No. 51: Glass source assessment sampling system (glass SASS). Final report, Jul 90-Jan 91

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grote, R.A.

1991-05-01

The report is a recommended operating procedure (ROP), prepared for use in research activities conducted by EPA's Air and Energy Engineering Research Laboratory (AEERL). The method described is applicable to the stack sampling of flue gas from a rotary kiln and to associated equipment of AEERL's Combustion Research Branch. It has been the standard method of sampling kiln flue gas due to the transient nature of the puff development and its capability to sample the maximum volume over the shortest time period. ROPs describe non-routine or experimental research operations where some judgment in application may be warranted. ROPs may notmore » be applicable to activities conducted by other research groups, and should not be used in place of standard operating procedures. Use of ROPs must be accompanied by an understanding of the purpose and scope. Questions should be directed to the author.« less

Different mechanisms at different temperatures for the ring-opening polymerization of lactide catalyzed by binuclear magnesium and zinc alkoxides.

PubMed

Sun, Yangyang; Cui, Yaqin; Xiong, Jiao; Dai, Zhongran; Tang, Ning; Wu, Jincai

2015-10-07

Two binuclear magnesium and zinc alkoxides supported by a bis-salalen type dinucleating heptadentate Schiff base ligand were synthesized and fully characterized. The two complexes are efficient initiators for the ring-opening polymerization (ROP) of L-lactide, affording polymers with narrow polydispersities and desirable molecular weights. Interestingly, the mechanisms for the ROP of lactide are different at different temperatures. At a high temperature of 130 °C, a coordination-insertion mechanism is reasonable for the bulk melt polymerization of lactide. At a low temperature, the alkoxide cannot initiate the ROP reaction; however, upon the addition of external benzyl alcohol into the system, the ROP of lactide can smoothly proceed via an "activated monomer" mechanism. In addition, these complexes display slight stereo-selectivity for the ring-opening polymerization of rac-lactide, affording partially isotactic polylactide in toluene with a Pm value of 0.59.

High or low oxygen saturation and severe retinopathy of prematurity: a meta-analysis.

PubMed

Chen, Minghua L; Guo, Lei; Smith, Lois E H; Dammann, Christiane E L; Dammann, Olaf

2010-06-01

Low oxygen saturation appears to decrease the risk of severe retinopathy of prematurity (ROP) in preterm newborns when administered during the first few weeks after birth. High oxygen saturation seems to reduce the risk at later postmenstrual ages (PMAs). However, previous clinical studies are not conclusive individually. To perform a systematic review and meta-analysis to report the association between severe ROP incidence of premature infants with high or low target oxygen saturation measured by pulse oximetry. Studies were identified through PubMed and Embase literature searches through May 2009 by using the terms "retinopathy of prematurity and oxygen" or "retinopathy of prematurity and oxygen therapy." We selected 10 publications addressing the association between severe ROP and target oxygen saturation measured by pulse oximetry. Using a random-effects model we calculated the summary-effect estimate. We visually inspected funnel plots to examine possible publication bias. Low oxygen saturation (70%-96%) in the first several postnatal weeks was associated with a reduced risk of severe ROP (risk ratio [RR]: 0.48 [95% confidence interval (CI): 0.31-0.75]). High oxygen saturation (94%-99%) at > or = 32 weeks' PMA was associated with a decreased risk for progression to severe ROP (RR: 0.54 [95% CI: 0.35-0.82]). Among preterm infants with a gestational age of < or = 32 weeks, early low and late high oxygen saturation were associated with a reduced risk for severe ROP. We feel that a large randomized clinical trial with long-term developmental follow-up is warranted to confirm this meta-analytic result.

Treatment for stage 4A retinopathy of prematurity: laser and/or ranibizumab.

PubMed

Sukgen, Emine Alyamaç; Koçluk, Yusuf

2017-02-01

Stage 4A retinopathy of prematurity (ROP) is a critical phase where retinal detachment develops, but fovea is preserved. The present study aims to evaluate the effect of the first treatment choice (laser photocoagulation (LPC) or intravitreal ranibizumab (IVR)) applied in this critical phase on the prognosis of the disease. Records of patients diagnosed with stage 4A ROP and whose first treatment was applied in our clinic were evaluated retrospectively. All patients were referred to our clinic for the treatment of advanced ROP . While group 1 was composed of the patients who were administered LPC as first treatment, group 2 included patients where IVR was applied as first treatment. The patients in both groups were referred to surgical treatment in the presence of progression. The present study included a total of 31 eyes in 16 patients with stage 4A ROP. Eighteen eyes of nine patients in group 1 were first applied LPC, and 13 eyes of seven patients in group 2 were first applied intravitreal ranibizumab. While anatomic outcomes of ten eyes in both groups were favorable, eight eyes in group 1 and three eyes in group 2 displayed progression and were referred to vitreoretinal surgery. Laser and/or IVR treatment may be effective as a non-surgical treatment for stage 4A ROP. Especially stage 4A ROP until 6 clock hours can regress without surgical treatment. However, in stage 4A with involvement wider than 6 clock hours, non-surgical regression is difficult. Prospective controlled large series studies are necessary.

The characteristics of premature infants with transient corneal haze.

PubMed

Lai, Yu-Hung; Chen, Hsiu-Lin; Yang, San-Nan; Chang, Shun-Jen; Chuang, Lea-Yea; Wu, Wen-Chuan

2018-01-01

The etiology of transient corneal haze in premature infants is not known and how it relates to clinical outcomes in premature infants is not clear. To study associated factors of transient corneal haze in premature infants. We performed a retrospective study of 261 premature infants from retinopathy of prematurity (ROP) screening in the neonatal intensive care unit at a tertiary referral hospital. Characteristics of premature infants with and without corneal haze were analyzed by correlation tests, Chi-square tests, and logistic regressions were used for statistical analyses. Associations between corneal haze and birth weight (BW), gestational age at birth (GA), central corneal thickness, intraocular pressure, and other systemic and ophthalmic data were evaluated. The incidence of corneal haze was 13.4%. Lower BW, lower GA, packed red blood cells (RBC) transfusion, more days on oxygen, older maternal age, bronchopulmonary disease, and stage 3 ROP are associated with corneal haze. The severity of corneal haze decreased with infants' postmenstrual age. Multivariate logistic regression analyses revealed that BW and maternal age are the most important predictors of corneal haze. Low BW and older maternal age are the most important predictors of corneal haze in premature infants. Premature infants with corneal haze could carry more systemic and ocular morbidities. Hence they may require more clinical attention. Corneal haze is unlikely to hinder the treatment of ROP. However, it is possible that corneal haze could hinder the examination of ROP in some infants. If corneal haze does interfere with ROP screening, a closer, more conservative follow-up schedule with a senior ophthalmologist experienced in managing ROP is recommended.

Simultaneous Expression from Both the Sense and Antisense Strand of the Erythropoietin Receptor Gene Mitigates Acute Lung Injury

DTIC Science & Technology

2017-09-01

Toronto) which immunoprecipitates EpoR but works poorly in immunoblots and not at in immunohistochemistry (Hu et al., Kidney Int. 2013 Sep;84(3):468-81...DAPI EpoR/GFP/DAPIGFP/DAPI C.. Ba/F32EpoR2Flag2GFP.cells 9 Figure 4. Screening the new MAbs to human RopE. Human embryonic kidney -293 (HEK-293) cells...ontogeny of EpoR and RopE expression Figure 7. Concordant RopE and EpoR expression was observed in the lung (left) and the kidney (right) that increase

Retinopathy of prematurity: Past, present and future

PubMed Central

Shah, Parag K; Prabhu, Vishma; Karandikar, Smita S; Ranjan, Ratnesh; Narendran, Venkatapathy; Kalpana, Narendran

2016-01-01

Retinopathy of prematurity (ROP) is a vasoproliferative disorder of the retina occurring principally in new born preterm infants. It is an avoidable cause of childhood blindness. With the increase in the survival of preterm babies, ROP has become the leading cause of preventable childhood blindness throughout the world. A simple screening test done within a few weeks after birth by an ophthalmologist can avoid this preventable blindness. Although screening guidelines and protocols are strictly followed in the developed nations, it lacks in developing economies like India and China, which have the highest number of preterm deliveries in the world. The burden of this blindness in these countries is set to increase tremendously in the future, if corrective steps are not taken immediately. ROP first emerged in 1940s and 1950s, when it was called retrolental fibroplasia. Several epidemics of this disease were and are still occurring in different regions of the world and since then a lot of research has been done on this disease. However, till date very few comprehensive review articles covering all the aspects of ROP are published. This review highlights the past, present and future strategies in managing this disease. It would help the pediatricians to update their current knowledge on ROP. PMID:26862500

THE CUTTING EDGE OF RETINOPATHY OF PREMATURITY CARE: Expanding the Boundaries of Diagnosis and Treatment.

PubMed

Yonekawa, Yoshihiro; Thomas, Benjamin J; Thanos, Aristomenis; Todorich, Bozho; Drenser, Kimberly A; Trese, Michael T; Capone, Antonio

2017-12-01

To discuss the latest advances and controversies in the diagnosis and care of infants with retinopathy of prematurity (ROP). Literature review. Retinopathy of prematurity remains a major global issue. Industrialized nations now treat profoundly premature infants with posterior and aggressive disease, and middle-income nations are experiencing ROP epidemics. Remote digital imaging may address the decreasing ratio of ROP providers to premature infants, in addition to improving patient care. Widefield angiography, optical coherence tomography, and the Wnt signaling pathway have provided new insights into ROP pathogenesis. Anti-vascular endothelial growth factor treatment is increasing in popularity, but the dearth of information to guide dosing, unpredictable reactivation, persistent vascular abnormalities, the "crunch" phenomenon, and the presently unknown effects of systemic vascular endothelial growth factor suppression remain issues to continue investigating. Neurodevelopmental delay has been raised as a potential consequence, but the evidence currently is weak. Vitrectomy is the treatment of choice for Stages 4 and 5. Illumination techniques, ab interno incisions, plasmin-assisted vitrectomy, staged surgery in the interest of corneal clearing for advanced Stage 5, and immediate sequential bilateral vitreoretinal surgery, are useful techniques. We are making progress in ROP management. Our goal as clinicians is to continue expanding the boundaries of our abilities to keep this blinding disease in check globally.

Low-temperature formation of Ga-oxide/GaN interface with remote oxygen plasma and its interface properties

NASA Astrophysics Data System (ADS)

Yamamoto, Taishi; Taoka, Noriyuki; Ohta, Akio; Truyen, Nguyen Xuan; Yamada, Hisashi; Takahashi, Tokio; Ikeda, Mitsuhisa; Makihara, Katsunori; Shimizu, Mitsuaki; Miyazaki, Seiichi

2018-06-01

The Ga-oxide/GaN structures formed by remote oxygen plasma (ROP) exposure at various temperatures (T s) and times have been systematically investigated. X-ray photoelectron spectroscopy clarified the formation of Ga2O3 layers with close-to-stoichiometric composition and a slight N incorporation of ∼6 at. %. Also, we found that a high T s increases the intensity of a signal related to the N–O bond, which is located near the Ga-oxide/GaN interfaces. Total photoelectron yield spectroscopy (PYS) also revealed that the ROP exposure at T s of 300 °C produces fewer filled defect states in the bandgap of GaN than at 500 °C. This difference in the filled defect states could be attributable to the amount of N–O bonds at the interface.

A Barley ROP GTPase ACTIVATING PROTEIN Associates with Microtubules and Regulates Entry of the Barley Powdery Mildew Fungus into Leaf Epidermal Cells[C][W

PubMed Central

Hoefle, Caroline; Huesmann, Christina; Schultheiss, Holger; Börnke, Frederik; Hensel, Götz; Kumlehn, Jochen; Hückelhoven, Ralph

2011-01-01

Little is known about the function of host factors involved in disease susceptibility. The barley (Hordeum vulgare) ROP (RHO of plants) G-protein RACB is required for full susceptibility of the leaf epidermis to invasion by the biotrophic fungus Blumeria graminis f. sp hordei. Stable transgenic knockdown of RACB reduced the ability of barley to accommodate haustoria of B. graminis in intact epidermal leaf cells and to form hairs on the root epidermis, suggesting that RACB is a common element of root hair outgrowth and ingrowth of haustoria in leaf epidermal cells. We further identified a barley MICROTUBULE-ASSOCIATED ROP-GTPASE ACTIVATING PROTEIN (MAGAP1) interacting with RACB in yeast and in planta. Fluorescent MAGAP1 decorated cortical microtubules and was recruited by activated RACB to the cell periphery. Under fungal attack, MAGAP1-labeled microtubules built a polarized network at sites of successful defense. By contrast, microtubules loosened where the fungus succeeded in penetration. Genetic evidence suggests a function of MAGAP1 in limiting susceptibility to penetration by B. graminis. Additionally, MAGAP1 influenced the polar organization of cortical microtubules. These results add to our understanding of how intact plant cells accommodate fungal infection structures and suggest that RACB and MAGAP1 might be antagonistic players in cytoskeleton organization for fungal entry. PMID:21685259

Computer-Based Image Analysis for Plus Disease Diagnosis in Retinopathy of Prematurity: Performance of the "i-ROP" System and Image Features Associated With Expert Diagnosis.

PubMed

Ataer-Cansizoglu, Esra; Bolon-Canedo, Veronica; Campbell, J Peter; Bozkurt, Alican; Erdogmus, Deniz; Kalpathy-Cramer, Jayashree; Patel, Samir; Jonas, Karyn; Chan, R V Paul; Ostmo, Susan; Chiang, Michael F

2015-11-01

We developed and evaluated the performance of a novel computer-based image analysis system for grading plus disease in retinopathy of prematurity (ROP), and identified the image features, shapes, and sizes that best correlate with expert diagnosis. A dataset of 77 wide-angle retinal images from infants screened for ROP was collected. A reference standard diagnosis was determined for each image by combining image grading from 3 experts with the clinical diagnosis from ophthalmoscopic examination. Manually segmented images were cropped into a range of shapes and sizes, and a computer algorithm was developed to extract tortuosity and dilation features from arteries and veins. Each feature was fed into our system to identify the set of characteristics that yielded the highest-performing system compared to the reference standard, which we refer to as the "i-ROP" system. Among the tested crop shapes, sizes, and measured features, point-based measurements of arterial and venous tortuosity (combined), and a large circular cropped image (with radius 6 times the disc diameter), provided the highest diagnostic accuracy. The i-ROP system achieved 95% accuracy for classifying preplus and plus disease compared to the reference standard. This was comparable to the performance of the 3 individual experts (96%, 94%, 92%), and significantly higher than the mean performance of 31 nonexperts (81%). This comprehensive analysis of computer-based plus disease suggests that it may be feasible to develop a fully-automated system based on wide-angle retinal images that performs comparably to expert graders at three-level plus disease discrimination. Computer-based image analysis, using objective and quantitative retinal vascular features, has potential to complement clinical ROP diagnosis by ophthalmologists.

Importance of early postnatal weight gain for normal retinal angiogenesis in very preterm infants: a multicenter study analyzing weight velocity deviations for the prediction of retinopathy of prematurity.

PubMed

Wu, Carolyn; Löfqvist, Chatarina; Smith, Lois E H; VanderVeen, Deborah K; Hellström, Ann

2012-08-01

To assess WINROP (https://winrop.com), an algorithm using postnatal weight measurements, as a tool for the prediction of retinopathy of prematurity (ROP) in a large geographically and racially diverse study population. WINROP analysis was performed retrospectively on conventionally at-risk infants from 10 neonatal intensive careunits.Weight measurements were entered into WINROP, which signals an alarm for an abnormal weight gain rate. Infants were classified into categories of no alarm (unlikely to develop type 1ROP)and alarm (at risk for developing type 1ROP).Use of WINROP requires that an infant has (1) gestational age less than 32 weeks at birth, (2) weekly weight measurements,(3) physiologic weight gain,and(4)absence of other pathologic retinal vascular disease. A total of 1706 infants with a median gestational age of 28 weeks (range, 22-31 weeks) and median birth weight of 1016 g (range, 378-2240 g) were included in the study analysis. An alarm occurred in 1101 infants (64.5%), with a median time from birth to alarm of 3 weeks (range, 0-12 weeks) and from alarm to treatment of 8 weeks (range, 1 day to 22 weeks). The sensitivity of WINROP was 98.6% and the negative predictive value was 99.7%. Two infants with type 1 ROP requiring treatment after 40 weeks' postmenstrual age did not receive an alarm. The WINROP system is a useful adjunct for ROP screening that identifies high-risk infants early to optimize care and potentially reduce the overall number of diagnostic ROP examinations.

Insertion and deletion mutations in the dinucleotide repeat region of the Norrie disease gene in patients with advanced retinopathy of prematurity.

PubMed

Hiraoka, M; Berinstein, D M; Trese, M T; Shastry, B S

2001-01-01

Retinopathy of prematurity (ROP) is a leading cause of blindness in premature children. It is a multifactorial disorder which causes fibrovascular tissue changes that affect the retina in low birth-weight and short gestational age infants. To determine the prevalence of Norrie disease (ND) gene mutations, clinical examination and molecular genetic analyses were performed in 100 pre-term babies of different ethnic backgrounds who developed advanced ROP. The leukocyte DNA was extracted, amplified by the polymerase chain reaction (PCR), and analyzed by single-strand conformation polymorphism (SSCP), G/T and C/A scanning, and by DNA sequencing. All three exons, including splice sites and the 3'-untranslated region, were screened. Of the 100 patients analyzed, 2 patients with advanced ROP showed a mobility shift in the DNA. In 1 patient, this mobility shift was caused by the insertion of an additional 12-bp CT repeat in exon 1, and in the second patient, there was a 14-bp deletion in the same exon of the ND gene, as evidenced by direct sequencing of the amplified products. Similar analyses of exons 2 and 3 and the 3'-untranslated region failed to detect additional mutations in the gene. None of the 130 normal, unrelated controls revealed similar changes. Taking into account the above results, as well as those of other studies, it appears that the ND gene mutations can account for 3% of cases of advanced ROP. Although the ND gene is not frequently involved in advanced ROP, the present large-scale study further supports the hypothesis that genetic influences may play an important role in the development of severe ROP in some premature infants.

Responses to Tobacco Smoking-Related Health Messages in Young People With Recent-Onset Schizophrenia.

PubMed

Coletti, Daniel J; Brunette, Mary; John, Majnu; Kane, John M; Malhotra, Anil K; Robinson, Delbert G

2015-11-01

Virtually no research has examined the responses of youth with recent-onset psychosis (ROP) to smoking-related health warnings. We examined predictors of response and tested hypotheses that participants with ROP would (a) assess warnings as less effective than a healthy comparison (HC) group, and (b) assess video warnings as more effective than pictures. ROP participants (n = 69) had <2 years of prior antipsychotic treatment; the HC group (n = 79) had no major mental illness. Participants viewed 10 pictorial warnings, 8 videos depicting similar messages, and were interviewed regarding tobacco use, health literacy, and smoking knowledge. We assessed response at baseline and at 4-week follow-up. ROP participants were more likely than HC to smoke tobacco (49.3% vs 10.1%) and had lower levels of health literacy and smoking-related knowledge. Cannabis was used by 46.4% of ROP participants. Effectiveness ratings were high for both picture and video warnings with no differences between media. ROP participants compared to HC and nonsmokers compared to smokers were more likely to perceive warnings as effective. Effectiveness was associated with negative affect and greater emotional arousal. We assessed 33 smokers at follow-up; 5 (15%) identified as nonsmokers, 15 (45%) made a quit attempt, and 16 (49%) reported that the warnings influenced their smoking. Results indicate that young people with psychotic disorders respond favorably to health warnings. Effective messages depict health consequences clearly, elicit negative emotions, and may impact smoking behavior. Future research is needed to understand the effects of mode of presentation and message comprehension on smoking behavior. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Next-generation sequencing analysis of gene regulation in the rat model of retinopathy of prematurity.

PubMed

Griffith, Rachel M; Li, Hu; Zhang, Nan; Favazza, Tara L; Fulton, Anne B; Hansen, Ronald M; Akula, James D

2013-08-01

The purpose of this study was to identify the genes, biochemical signaling pathways, and biological themes involved in the pathogenesis of retinopathy of prematurity (ROP). Next-generation sequencing (NGS) was performed on the RNA transcriptome of rats with the Penn et al. (Pediatr Res 36:724-731, 1994) oxygen-induced retinopathy model of ROP at the height of vascular abnormality, postnatal day (P) 19, and normalized to age-matched, room-air-reared littermate controls. Eight custom-developed pathways with potential relevance to known ROP sequelae were evaluated for significant regulation in ROP: The three major Wnt signaling pathways, canonical, planar cell polarity (PCP), and Wnt/Ca(2+); two signaling pathways mediated by the Rho GTPases RhoA and Cdc42, which are, respectively, thought to intersect with canonical and non-canonical Wnt signaling; nitric oxide signaling pathways mediated by two nitric oxide synthase (NOS) enzymes, neuronal (nNOS) and endothelial (eNOS); and the retinoic acid (RA) signaling pathway. Regulation of other biological pathways and themes was detected by gene ontology using the Kyoto Encyclopedia of Genes and Genomes and the NIH's Database for Annotation, Visualization, and Integrated Discovery's GO terms databases. Canonical Wnt signaling was found to be regulated, but the non-canonical PCP and Wnt/Ca(2+) pathways were not. Nitric oxide signaling, as measured by the activation of nNOS and eNOS, was also regulated, as was RA signaling. Biological themes related to protein translation (ribosomes), neural signaling, inflammation and immunity, cell cycle, and cell death were (among others) highly regulated in ROP rats. These several genes and pathways identified by NGS might provide novel targets for intervention in ROP.

Next Generation Sequencing Analysis of Gene Regulation in the Rat Model of Retinopathy of Prematurity

PubMed Central

Griffith, Rachel M.; Li, Hu; Zhang, Nan; Favazza, Tara L.; Fulton, Anne B.; Hansen, Ronald M.; Akula, James D.

2013-01-01

Purpose To identify the genes, biochemical signaling pathways and biological themes involved in the pathogenesis of retinopathy of prematurity (ROP). Methods Next-generation sequencing (NGS) was performed on the RNA transcriptome of rats with the Penn et al. (1994) oxygen-induced retinopathy (OIR) model of ROP at the height of vascular abnormality, postnatal day (P) 19, and normalized to age-matched, room-air-reared littermate controls. Eight custom developed pathways with potential relevance to known ROP sequelae were evaluated for significant regulation in ROP: The three major Wnt signaling pathways, canonical, planar cell polarity (PCP), and Wnt/Ca2+, two signaling pathways mediated by the Rho GTPases RhoA and Cdc42, which are respectively thought to intersect with canonical and noncanonical Wnt signaling, nitric oxide signaling pathways mediated by two nitrox oxide synthase (NOS) enzymes, neuronal (nNOS) and endothelial (eNOS), and the retinoic acid (RA) signaling pathway. Regulation of other biological pathways and themes were detected by gene ontology using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the NIH's Database for Annotation, Visualization and Integrated Discovery (DAVID)'s GO terms databases. Results Canonical Wnt signaling was found to be regulated, but the non-canonical PCP and Wnt/Ca2+ pathways were not. Nitric oxide (NO) signaling, as measured by the activation of nNOS eNOS, was also regulated, as was RA signaling. Biological themes related to protein translation (ribosomes), neural signaling, inflammation and immunity, cell cycle and cell death, were (among others) highly regulated in ROP rats. Conclusions These several genes and pathways identified by NGS might provide novel targets for intervention in ROP. PMID:23775346

A Novel Plasma Membrane-Anchored Protein Regulates Xylem Cell-Wall Deposition through Microtubule-Dependent Lateral Inhibition of Rho GTPase Domains.

PubMed

Sugiyama, Yuki; Wakazaki, Mayumi; Toyooka, Kiminori; Fukuda, Hiroo; Oda, Yoshihisa

2017-08-21

Spatial control of cell-wall deposition is essential for determining plant cell shape [1]. Rho-type GTPases, together with the cortical cytoskeleton, play central roles in regulating cell-wall patterning [2]. In metaxylem vessel cells, which are the major components of xylem tissues, active ROP11 Rho GTPases form oval plasma membrane domains that locally disrupt cortical microtubules, thereby directing the formation of oval pits in secondary cell walls [3-5]. However, the regulatory mechanism that determines the planar shape of active Rho of Plants (ROP) domains is still unknown. Here we show that IQD13 associates with cortical microtubules and the plasma membrane to laterally restrict the localization of ROP GTPase domains, thereby directing the formation of oval secondary cell-wall pits. Loss and overexpression of IQD13 led to the formation of abnormally round and narrow secondary cell-wall pits, respectively. Ectopically expressed IQD13 increased the presence of parallel cortical microtubules by promoting microtubule rescue. A reconstructive approach revealed that IQD13 confines the area of active ROP domains within the lattice of the cortical microtubules, causing narrow ROP domains to form. This activity required the interaction of IQD13 with the plasma membrane. These findings suggest that IQD13 positively regulates microtubule dynamics as well as their linkage to the plasma membrane, which synergistically confines the area of active ROP domains, leading to the formation of oval secondary cell-wall pits. This finding sheds light on the role of microtubule-plasma membrane linkage as a lateral fence that determines the planar shape of Rho GTPase domains. Copyright © 2017 Elsevier Ltd. All rights reserved.

Astigmatism and biometric optic components of diode laser-treated threshold retinopathy of prematurity at 9 years of age

PubMed Central

Yang, C-S; Wang, A-G; Shih, Y-F; Hsu, W-M

2013-01-01

Purpose To assess the prevalence of astigmatism and its relationship with biometric optic components in preterm school children with diode laser-treated threshold retinopathy of prematurity (ROP). Methods A prospective, cross-sectional study in which cycloplegic keratometry, refraction, and ultrasound biometric measurement of optic components were performed on 24 consecutive preterm children with diode laser-treated threshold ROP at the age of 9 years. The study results were compared with data on 1021 age-matched full-term control children from a national survey. Results The laser-treated eyes had a mean astigmatism of 3.47 D, with a mean spherical equivalent of −4.49 D. Of the 46 eyes studied, 98% of eyes showed astigmatism ≥0.5 D and 50% had high astigmatism (>3.0 D). Most astigmatic eyes (97.7%) showed with-the-rule astigmatism, with the mean plus cylinder axis at 89.30o. Further correlation analysis showed the astigmatism in refraction was highly correlated with the corneal astigmatism (r=0.921, P<0.001) and the vertical corneal curvature (r=0.405, P=0.005). There was significantly steeper vertical corneal curvature (P=0.003) and flatter horizontal corneal curvature (P=0.031) in eyes with laser-treated ROP when compared with age-matched full-term controls. The eyes with laser-treated ROP also show significantly thicker lens (3.93 mm) and shallower anterior chamber depth (ACD; 2.92 mm) than full-term controls (P<0.001). Conclusions There is significantly higher prevalence and greater magnitude of astigmatism in eyes with laser-treated threshold ROP compared with full-term controls. The steeper vertical corneal curvature component contributes to the increased astigmatism in eyes with laser-treated ROP. PMID:23222565

Retinopathy of Prematurity.

ERIC Educational Resources Information Center

Trief, E.; And Others

1989-01-01

Retinopathy of prematurity (ROP) has increased due to a high incidence of premature, low birthweight infants. Stages of severity range from no visual damage to total blindness, and educational problems of ROP children parallel those of other visually impaired children, early intervention being crucial. Treatments are either pharmacological or…

Effect of two different doses of intravitreal bevacizumab with temporal retina-sparing laser photocoagulation for retinopathy of prematurity.

PubMed

Choi, A Young; Cho, Hochan; Kim, Yu Cheol

2018-01-01

This study aims to compare the efficacy and safety between two different doses of intravitreal bevacizumab (IVB) injection with temporal retina-sparing laser (TRSL) photocoagulation for retinopathy of prematurity (ROP). We retrospectively evaluated 22 eyes of ROP infants who underwent IVB combined with partial TRSL for stage 3+ zone I or posterior zone II ROP. Laser photocoagulation was applied on the avascular retina, sparing two-disc-diameter width temporal avascular area anterior to ridge. A half dose (0.625 mg) or minimal dose (0.25 mg) of IVB was conducted. Four eyes in minimal dose group were retreated with IVB and laser photocoagulation on the spared retina. Of those 4 retreated eyes, three developed preretinal hemorrhage around the ridge after the first treatment, resulting in fibrotic macular dragging. A half dose of IVB may be more effective than a minimal dose with partial TRSL for ROP. Preretinal hemorrhage may be a harbinger of poor prognosis.

Preparation of Bottlebrush Polymers via a One-Pot Ring-Opening Polymerization (ROP) and Ring-Opening Metathesis Polymerization (ROMP) Grafting-Through Strategy.

PubMed

Radzinski, Scott C; Foster, Jeffrey C; Matson, John B

2016-04-01

Bottlebrush polymers are synthesized using a tandem ring-opening polymerization (ROP) and ring-opening metathesis polymerization (ROMP) strategy. For the first time, ROP and ROMP are conducted sequentially in the same pot to yield well-defined bottlebrush polymers with molecular weights in excess of 10(6) Da. The first step of this process involves the synthesis of a polylactide macromonomer (MM) via ROP of d,l-lactide initiated by an alcohol-functionalized norbornene. ROMP grafting-through is then carried out in the same pot to produce the bottlebrush polymer. The applicability of this methodology is evaluated for different MM molecular weights and bottlebrush backbone degrees of polymerization. Size-exclusion chromatographic and (1)H NMR spectroscopic analyses confirm excellent control over both polymerization steps. In addition, bottlebrush polymers are imaged using atomic force microscopy and stain-free transmission electron microscopy on graphene oxide. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Analysis of fatal accidents with tractors in the Centre of Portugal: Ten years analysis.

PubMed

Antunes, Soraia M; Cordeiro, Cristina; Teixeira, Helena M

2018-06-01

Tractors have been described as one of the deadliest farming implements concerning agricultural activity. In Portugal, the scientific investigations about this problem are practically non-existent, with only statistical studies performed by entities related to road traffic safety, not in accordance to the study now performed, pinpointing the possibility of an underreporting of these accidents. This work aims to characterize the fatal tractor accidents in Portugal, autopsied at the Forensic Pathology Department of the Centre Branch of the National Institute of Legal Medicine and Forensic Sciences of Portugal, analysing several variables: gender, age, occupation, survival time, the victim position in the tractor, cause of death, toxicological and histological exams, year/month/day of the week, type of agricultural machine, existence of rollover protective structures (ROPS), type of accident, ground conditions, circumstantial information and geographic distribution of the accidents. All the autopsies between 2005 and 2014 were analysed. The victim profile corresponded to a man (89.5%), between 61 and 70 years old (33.3%), retired (43.9%), being the tractor driver (45.6%). In most of the cases, death occurred in less than 24h after the accident. These fatalities arose mainly in May and October. Rollover in sloping land was the most common type of accident, and cranioencephalic, thoracic and abdominal traumatic injuries were the main cause of death. In 16.2% of the cases, blood alcohol concentration was above the lower limit established in our road traffic law (<0.5g/L). There was lack information about the use of ROPS (95.9%), and even when existent, the protections were not used or were incorrectly used. This is the first national study involving the description of the forensic achievements in each autopsy related to tractor accidents, and the corresponding circumstances that contributed to the death. Many barriers remain about this matter, but the Portuguese government begin to design several laws to prevent this type of accidents. Future investigations should be performed to understand the real dimension of tractor accidents in Portugal, and to comprehend the efficiency of laws implemented by the government. Copyright © 2018 Elsevier B.V. All rights reserved.

Norrie disease gene sequence variants in an ethnically diverse population with retinopathy of prematurity.

PubMed

Hutcheson, Kelly A; Paluru, Prasuna C; Bernstein, Steven L; Koh, Jamie; Rappaport, Eric F; Leach, Richard A; Young, Terri L

2005-07-14

Retinopathy of prematurity (ROP) is a leading cause of visual loss in the pediatric population. Mutations in the Norrie disease gene (NDP) are associated with heritable retinal vascular disorders, and have been found in a small subset of patients with severe retinopathy of prematurity. Varying rates of progression to threshold disease in different races may have a genetic basis, as recent studies suggest that the incidence of NDP mutations may vary in different groups. African Americans, for example, are less likely to develop severe degrees of ROP. We screened a large cohort of ethnically diverse patients for mutations in the entire NDP. A total of 143 subjects of different ethnic backgrounds were enrolled in the study. Fifty-four patients had severe ROP (Stage 3 or worse). Of these, 38 were threshold in at least one eye (with a mean gestational age of 26.1 weeks and mean birth weight of 788.4 g). There were 36 patients with mild or no ROP, 31 parents with no history of retinal disease or prematurity, and 22 wild type (normal) controls. There were 70 African American subjects, 55 Caucasians, and 18 of other races. Severe ROP was noted in 29 African American subjects, 17 Caucasians, and 8 of other races. Seven polymerase chain reaction primer pairs spanning the NDP were optimized for denaturing high performance liquid chromatography and direct sequencing. Three primer pairs covered the coding region, and the remaining four spanned the 3' and 5' untranslated regions (UTR). Six of 54 (11%) infants with severe ROP had polymorphisms in the NDP. Five of the infants were African American, and one was Caucasian. Two parents were heterozygous for the same polymorphism as their child. One parent-child pair had a single base pair (bp) insertion in the 3' UTR region. Another parent-child pair had two mutations: a 14 bp deletion in the 5' UTR region of exon 1 and a single nucleotide polymorphism in the 5' UTR region of exon 2. No coding region sequence changes were found. No polymorphisms were observed in infants with mild or no ROP, or in the wild type controls. Of the six sequence alterations found, five were novel nucleotide changes: One in the 5' UTR region of exon 2, and four in the 3' UTR region of exon 3. The extent of NDP polymorphisms in this large, racially diverse group of infants is moderate. NDP polymorphisms may play a role in the pathogenesis of ROP, but do not appear to be a major causative factor.

Early light reduction for preventing retinopathy of prematurity in very low birth weight infants.

PubMed

Jorge, Eliane C; Jorge, Edson N; El Dib, Regina P

2013-08-06

Retinopathy of prematurity (ROP) is a complex condition of the developing retinal blood vessels and is one of the leading causes of preventable childhood blindness. Several risk factors for ROP have been studied over the past 50 years. Among them, general immaturity (low birth weight and low gestational age) and prolonged oxygen therapy have been consistently related to disease onset. However, it is understood that the progression of the disease is multifactorial and may be associated with others risk factors, such as multiple gestation, apnoea, intracranial haemorrhage, anaemia, sepsis, prolonged mechanical ventilation, multiple transfusions and light exposure. Furthermore, the precise role of these individual factors in the development of the disease has not yet been well established. To determine whether the reduction of early environmental light exposure reduces the incidence of retinopathy of prematurity (ROP) or poor ROP outcomes among very low birth weight infants. We searched the following databases: the Cochrane Neonatal Group Specialised Register, CENTRAL (The Cochrane Library), MEDLINE, EMBASE, CINAHL, HealthSTAR, Science Citation Index Database, CANCERLIT, the Oxford Database of Perinatal Trials and www.clinicaltrials.gov. We also searched previous reviews including cross-references, abstracts, conference and symposia proceedings, and contacted expert informants. This search was updated in October 2012. Randomised or quasi-randomised controlled trials that reduced light exposure to premature infants within the first seven days following birth were considered for this review. We also considered cluster-randomised controlled trials. Data on clinical outcomes including any acute ROP and poor ROP outcome were extracted by both review authors independently and consensus reached. We conducted data analysis according to the standards of the Cochrane Neonatal Review Group. Data from four randomised trials with a total of 897 participants failed to show any reduction in acute ROP or poor ROP outcome with the reduction of ambient light to premature infants' retinas. The overall methodological quality of the included studies was about evenly split between those in which the classification was unclear and those in which the studies were categorised as low risk of bias. There was no report on the secondary outcomes considered in this review: quality of life measures; and time of exposure to oxygen. The evidence shows that bright light is not the cause of retinopathy of prematurity and that the reduction of exposure of the retinas of premature infants to light has no effect on the incidence of the disease.

Automated Diagnosis of Plus Disease in Retinopathy of Prematurity Using Deep Convolutional Neural Networks.

PubMed

Brown, James M; Campbell, J Peter; Beers, Andrew; Chang, Ken; Ostmo, Susan; Chan, R V Paul; Dy, Jennifer; Erdogmus, Deniz; Ioannidis, Stratis; Kalpathy-Cramer, Jayashree; Chiang, Michael F

2018-05-02

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness worldwide. The decision to treat is primarily based on the presence of plus disease, defined as dilation and tortuosity of retinal vessels. However, clinical diagnosis of plus disease is highly subjective and variable. To implement and validate an algorithm based on deep learning to automatically diagnose plus disease from retinal photographs. A deep convolutional neural network was trained using a data set of 5511 retinal photographs. Each image was previously assigned a reference standard diagnosis (RSD) based on consensus of image grading by 3 experts and clinical diagnosis by 1 expert (ie, normal, pre-plus disease, or plus disease). The algorithm was evaluated by 5-fold cross-validation and tested on an independent set of 100 images. Images were collected from 8 academic institutions participating in the Imaging and Informatics in ROP (i-ROP) cohort study. The deep learning algorithm was tested against 8 ROP experts, each of whom had more than 10 years of clinical experience and more than 5 peer-reviewed publications about ROP. Data were collected from July 2011 to December 2016. Data were analyzed from December 2016 to September 2017. A deep learning algorithm trained on retinal photographs. Receiver operating characteristic analysis was performed to evaluate performance of the algorithm against the RSD. Quadratic-weighted κ coefficients were calculated for ternary classification (ie, normal, pre-plus disease, and plus disease) to measure agreement with the RSD and 8 independent experts. Of the 5511 included retinal photographs, 4535 (82.3%) were graded as normal, 805 (14.6%) as pre-plus disease, and 172 (3.1%) as plus disease, based on the RSD. Mean (SD) area under the receiver operating characteristic curve statistics were 0.94 (0.01) for the diagnosis of normal (vs pre-plus disease or plus disease) and 0.98 (0.01) for the diagnosis of plus disease (vs normal or pre-plus disease). For diagnosis of plus disease in an independent test set of 100 retinal images, the algorithm achieved a sensitivity of 93% with 94% specificity. For detection of pre-plus disease or worse, the sensitivity and specificity were 100% and 94%, respectively. On the same test set, the algorithm achieved a quadratic-weighted κ coefficient of 0.92 compared with the RSD, outperforming 6 of 8 ROP experts. This fully automated algorithm diagnosed plus disease in ROP with comparable or better accuracy than human experts. This has potential applications in disease detection, monitoring, and prognosis in infants at risk of ROP.

Delayed Luminance and Chromatic Contrast Sensitivity in Infants with Spontaneously Regressed Retinopathy of Prematurity

PubMed Central

Bosworth, Rain; Robbins, Shira L.; Granet, David B.; Dobkins, Karen

2013-01-01

Background The current study assessed whether contrast sensitivity is affected in preterm infants with a history of spontaneously regressed retinopathy of prematurity (ROP, Stages 1–3). Specifically, we employed luminance (light/dark) and chromatic (red/green) stimuli, which are mediated by the magnocellular (M) and parvocellular (P) subcortical pathways, respectively. Methods Contrast sensitivity (CS) was measured using forced choice preferential looking testing in 21 infants with a history of ROP and 41 control preterm infants who were born prematurely but did not develop ROP, tested between 8 and 47 weeks (2–11 months) postterm age. Infants were presented with chromatic and luminance drifting sinusoidal gratings, which appeared randomly on the left or right side of the monitor on each trial. The contrast of the stimuli varied across trials and was defined in terms of root mean squared cone contrast for long- and medium-wavelength cones. Results Between 8 and 25 weeks postterm, ROP infants had significantly worse CS, and there was a trend for greater impairment for Luminance than Chromatic CS. This delay was not seen at older ages between 26 and 47 weeks postterm. Conclusions These findings are consistent with the concept that early maturation of the M pathway is vulnerable to biological insult, as in the case of ROP, to a greater extent than is the P pathway. PMID:23744448

A new human IgG avidity test, using mixtures of recombinant antigens (rROP1, rSAG2, rGRA6), for the diagnosis of difficult-to-identify phases of toxoplasmosis.

PubMed

Drapała, Dorota; Holec-Gąsior, Lucyna; Kur, Józef; Ferra, Bartłomiej; Hiszczyńska-Sawicka, Elżbieta; Lautenbach, Dariusz

2014-07-01

The preliminary diagnostic utility of two mixtures of Toxoplasma gondii recombinant antigens (rROP1+rSAG2 and rROP1+rGRA6) in IgG ELISA and IgG avidity test has been evaluated. A total of 173 serum samples from patients with toxoplasmosis and seronegative people were examined. The sensitivity of IgG ELISA for rROP1+rSAG2 and rROP1+rGRA6 was 91.1% and 76.7%, respectively, while the reactivity for sera from patients where acute toxoplasmosis was suspected was higher, at 100% and 95.4%, respectively, than for people with chronic infection, at 88.2% and 70.6%. In this study a different trend in avidity maturation of IgG antibodies for two mixtures of proteins in comparison with native antigen was observed. The results suggest that a new IgG avidity test using the mixtures of recombinant antigens may be useful for the diagnosis of difficult-to-identify phases of toxoplasmosis. For this reason, selected mixtures after the additional tests on groups of sera with well-defined dates of infection could be used as a better alternative to the native antigens of the parasite in the serodiagnosis of human T. gondii infection. Copyright © 2014 Elsevier Inc. All rights reserved.

The Quest for Converting Biorenewable Bifunctional α-Methylene-γ-butyrolactone into Degradable and Recyclable Polyester: Controlling Vinyl-Addition/Ring-Opening/Cross-Linking Pathways.

PubMed

Tang, Xiaoyan; Hong, Miao; Falivene, Laura; Caporaso, Lucia; Cavallo, Luigi; Chen, Eugene Y-X

2016-11-02

α-Methylene-γ-butyrolactone (MBL), a naturally occurring and biomass-sourced bifunctional monomer, contains both a highly reactive exocyclic C═C bond and a highly stable five-membered γ-butyrolactone ring. Thus, all previous work led to exclusive vinyl-addition polymerization (VAP) product P(MBL) VAP . Now, this work reverses this conventional chemoselectivity to enable the first ring-opening polymerization (ROP) of MBL, thereby producing exclusively unsaturated polyester P(MBL) ROP with M n up to 21.0 kg/mol. This elusive goal was achieved through uncovering the thermodynamic, catalytic, and processing conditions. A third reaction pathway has also been discovered, which is a crossover propagation between VAP and ROP processes, thus affording cross-linked polymer P(MBL) CLP . The formation of the three types of polymers, P(MBL) VAP , P(MBL) CLP , and P(MBL) ROP , can be readily controlled by adjusting the catalyst (La)/initiator (ROH) ratio, which is determined by the unique chemoselectivity of the La-X (X = OR, NR 2 , R) group. The resulting P(MBL) ROP is degradable and can be readily postfunctionalized into cross-linked or thiolated materials but, more remarkably, can also be fully recycled back to its monomer thermochemically. Computational studies provided the theoretical basis for, and a mechanistic understanding of, the three different polymerization processes and the origin of the chemoselectivity.

Observation of an angular change in the structure of an RNA complex using Fluorescence Resonance Energy Transfer

NASA Astrophysics Data System (ADS)

Rahmanseresht, Sheema; Milas, Peker; Parrot, Louis; Goldner, Lori S.

Single-molecular-pair FRET is often used to study distance fluctuations of single molecules. It is harder to capture angular changes using FRET, because rotational motion of the dyes tends to wash out the angular sensitivity. Using a dye labeling scheme that minimizes the rotational motion of the dyes with respect to the RNA, we use spFRET to measure an angular change in structure of an RNA kissing complex upon protein binding. The model system studied here, R1inv-R2inv, is derived from the RNAI-RNAII complex in E.coli. RNA II is a primer for replication of the ColE1 plasmid; its function is modulated by interaction with RNA I, Rop protein is known to stabilize the bent R1inv-R2inv kissing complex against dissociation. The effect, if any, of Rop protein on the conformation of the kissing complex is not known. The eight minimized-energy NMR structures reported for R1inv-R2inv show a small difference in end-to-end distances and much larger differences in twist and bend angles. We compare a first-principles model with spFRET data to determine if the observed change in FRET is consistent with an angular change in structure, as suggested by the model. Grant Number: NSF DBI-1152386.

Successful Surgical Management of Retinopathy of Prematurity Showing Rapid Progression despite Extensive Retinal Photocoagulation.

PubMed

Gadkari, Salil S; Kulkarni, Sucheta R; Kamdar, Rushita R; Deshpande, Madan

2015-01-01

The management of retinopathy of prematurity (ROP) can be challenging in preterm babies with a gestational age <30 weeks, those with very low birth weight and multiple risk factors (eg., oxygen therapy for respiratory distress, sepsis, neonatal jaundice). A premature infant presented with "hybrid" zone 1 disease in the right eye and aggressive posterior ROP in the left eye. Both eyes were adequately treated with laser photocoagulation; however, the eyes deteriorated and progressed to stage 4 ROP. Both eyes eventually underwent intravitreal bevacizumab followed by lens sparing vitrectomy with good anatomical and visual outcome. Anticipation of progression despite laser photocoagulation in certain clinical scenarios, frequent follow-up and timely surgical intervention is paramount.

Retinopathy of prematurity: New developments bring concern and hope.

PubMed

Darlow, Brian A

2015-08-01

Blindness from retinopathy of prematurity (ROP) in Australian and New Zealand is an uncommon event although 3% of <31 weeks gestation infants receive treatment for the disease. New world-wide estimates of the incidence of blindness from ROP are much higher than previously at 20 000 children annually. The impact of severe ROP can be reduced through good evidence-based care of very preterm infants and careful organisation of eye examinations and follow-up services. Recent oxygen saturation targeting trial results might mean the adoption of higher targets than formerly in very preterm infants and will require vigilance to ensure all eligible infants are examined appropriately. A true screening examination for acute ROP might involve non-opthalmologists obtaining photographic retinal images and remote reading of these. Although treatment with laser gives good outcomes, there is interest in intravitreal anti-vascular endothelial factor agents, but issues concerning the systemic safety and retinal results of such treatment are unresolved. © 2015 The Author. Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

No advanced retinopathy of prematurity stages 4 or 5 in a large high-risk German cohort.

PubMed

Muether, Philipp S; Kribs, Angela; Hahn, Moritz; Schumacher, Jasmin; Eifinger, Frank; Kirchhof, Bernd; Roth, Bernhard; Fauser, Sascha

2012-03-01

Retinopathy of prematurity (ROP) remains a major cause of juvenile blindness. As screening recommendations are refined, decreasing gestational age (GA) and birth weight (BW) constitute an increasing risk for ROP. This retrospective case series reviews the screening results of a very immature cohort in Germany. We conducted ROP screening according to the German guidelines of 1999: all preterm infants with a GA of < 32 weeks and/or a BW of < 1501 g, or with GA ≥ 32 weeks and postnatal oxygen treatment for > 3 days, were assigned for screening. Dense laser coagulation was performed according to the current treatment criteria. All 767 consecutive inborn (patients born at the Department of Neonatology, University Hospital of Cologne, Germany) preterm infants of a tertiary medical centre of maximum care underwent complete screening from 2001 to 2009. The treatment incidence was 7.0%. No preterm infant developed stage 4/5 ROP. Mean GA and BW of untreated/treated preterm infants were 28.4/24.6 weeks and 1109/635 g, respectively. Increasing treatment incidence was associated with lower GA, but not with lower BW in logistic regression analysis. In this very immature high-risk cohort, advanced stages 4 and 5 were avoided throughout 9 years of screening. We suggest three factors that contributed to this outcome: (1) strict adherence to current ROP screening and treatment guidelines; (2) prompt and very dense laser coagulation if necessary; and (3) a specialised neonatal intensive care unit with experience of very immature babies.

Computer-Based Image Analysis for Plus Disease Diagnosis in Retinopathy of Prematurity

PubMed Central

Wittenberg, Leah A.; Jonsson, Nina J.; Chan, RV Paul; Chiang, Michael F.

2014-01-01

Presence of plus disease in retinopathy of prematurity (ROP) is an important criterion for identifying treatment-requiring ROP. Plus disease is defined by a standard published photograph selected over 20 years ago by expert consensus. However, diagnosis of plus disease has been shown to be subjective and qualitative. Computer-based image analysis, using quantitative methods, has potential to improve the objectivity of plus disease diagnosis. The objective was to review the published literature involving computer-based image analysis for ROP diagnosis. The PubMed and Cochrane library databases were searched for the keywords “retinopathy of prematurity” AND “image analysis” AND/OR “plus disease.” Reference lists of retrieved articles were searched to identify additional relevant studies. All relevant English-language studies were reviewed. There are four main computer-based systems, ROPtool (AU ROC curve, plus tortuosity 0.95, plus dilation 0.87), RISA (AU ROC curve, arteriolar TI 0.71, venular diameter 0.82), Vessel Map (AU ROC curve, arteriolar dilation 0.75, venular dilation 0.96), and CAIAR (AU ROC curve, arteriole tortuosity 0.92, venular dilation 0.91), attempting to objectively analyze vessel tortuosity and dilation in plus disease in ROP. Some of them show promise for identification of plus disease using quantitative methods. This has potential to improve the diagnosis of plus disease, and may contribute to the management of ROP using both traditional binocular indirect ophthalmoscopy and image-based telemedicine approaches. PMID:21366159

Frizzled-4 Variations Associated with Retinopathy and Intrauterine Growth Retardation: A Potential Marker for Prematurity and Retinopathy.

PubMed

Dailey, Wendy A; Gryc, Wojciech; Garg, Pooja G; Drenser, Kimberly A

2015-09-01

To present the association between mutations affecting the Wnt-signaling receptor protein (FZD4), inherited vitreoretinopathies, and retinopathy of prematurity (ROP). Retrospective analysis of prospective samples at a tertiary referral center. Patients referred to our practice for management of a variety of pediatric vitreoretinopathies were offered participation in an ophthalmic biobank (421 participants with vitreoretinopathies were included in this study). Full-term healthy infants (n = 98) were recruited to the study as controls. Patients with various vitreoretinopathies were prospectively enrolled in an ophthalmic biobank, approved by the Human Investigation Committee at William Beaumont Hospital. Retrospective genetic analysis of the FZD4 gene was performed (Sanger sequencing). Participants with a diagnosis of familial exudative vitreoretinopathy (FEVR), Norrie disease, Coats' disease, bilateral persistent fetal vasculature, and ROP were reviewed for the presence of a FZD4 variant. Data retrieval included status of retinopathy (including staging when possible), gestational age (GA), birth weight (BW) (when available), and family and birth histories. The association of FZD4 variants with the presence of vitreoretinopathy. The sequence variation p.[P33S(;)P168S] is the most prevalent FZD4 variant and is statistically significant for ROP and FEVR (P = 4.6E-04 and P = 2.4E-03, respectively) compared with full-term newborns (P = 1.7E-01). In addition, infants expressing the sequence variation tended to have significantly lower BWs for respective GA (P = 0.04). This suggests that the FZD4 p.[P33S(;)P168S] variant may be a risk factor for retinopathy and restricted intrauterine growth. Testing for FZD4 gene mutations is useful in patients with suspected FEVR and ROP. The relatively high prevalence of the p.[P33S(;)P168S] variant in ROP and intrauterine growth restriction suggests that it also may be a marker for increased risk of developing ROP and preterm birth. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

The alternative Medicago truncatula defense proteome of ROS—defective transgenic roots during early microbial infection

PubMed Central

Kiirika, Leonard M.; Schmitz, Udo; Colditz, Frank

2014-01-01

ROP-type GTPases of plants function as molecular switches within elementary signal transduction pathways such as the regulation of ROS synthesis via activation of NADPH oxidases (RBOH-respiratory burst oxidase homolog in plants). Previously, we reported that silencing of the Medicago truncatula GTPase MtROP9 led to reduced ROS production and suppressed induction of ROS-related enzymes in transgenic roots (MtROP9i) infected with pathogenic (Aphanomyces euteiches) and symbiotic microorganisms (Glomus intraradices, Sinorhizobium meliloti). While fungal infections were enhanced, S. meliloti infection was drastically impaired. In this study, we investigate the temporal proteome response of M. truncatula MtROP9i transgenic roots during the same microbial interactions under conditions of deprived potential to synthesize ROS. In comparison with control roots (Mtvector), we present a comprehensive proteomic analysis using sensitive MS protein identification. For four early infection time-points (1, 3, 5, 24 hpi), 733 spots were found to be different in abundance: 213 spots comprising 984 proteins (607 unique) were identified after S. meliloti infection, 230 spots comprising 796 proteins (580 unique) after G. intraradices infection, and 290 spots comprising 1240 proteins (828 unique) after A. euteiches infection. Data evaluation by GelMap in combination with a heatmap tool allowed recognition of key proteome changes during microbial interactions under conditions of hampered ROS synthesis. Overall, the number of induced proteins in MtROP9i was low as compared with controls, indicating a dual function of ROS in defense signaling as well as alternative response patterns activated during microbial infection. Qualitative analysis of induced proteins showed that enzymes linked to ROS production and scavenging were highly induced in control roots, while in MtROP9i the majority of proteins were involved in alternative defense pathways such as cell wall and protein degradation. PMID:25101099

Handheld Optical Coherence Tomography Angiography and Ultra-Wide-Field Optical Coherence Tomography in Retinopathy of Prematurity.

PubMed

Campbell, J Peter; Nudleman, Eric; Yang, Jianlong; Tan, Ou; Chan, R V Paul; Chiang, Michael F; Huang, David; Liu, Gangjun

2017-09-01

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness worldwide. Optical coherence tomography (OCT) has improved the care of adults with vitreoretinal disease, and OCT angiography (OCTA) is demonstrating promise as a technique to visualize the retinal vasculature with lower risk and cost than fluorescein angiography. However, to date, there are no commercially available devices able to obtain ultra-wide-field OCT or OCTA images in neonates. To obtain ultra-wide-field OCT and OCTA images in neonates with ROP using a prototype handheld OCT and OCTA device. This observational case series was conducted from March 1 to April 1, 2017, in an academic medical center among 4 neonates with ROP in the neonatal intensive care unit and in the operating room. Acquisition of wide-field OCT and OCTA images using a handheld prototype OCTA and ultra-wide-field OCT device. Images were obtained from 4 neonates (1 girl and 3 boys; mean age, 38 weeks' postmenstrual age [range, 34-43 weeks]) with various stages of ROP: 3 in the neonatal intensive care unit and 1 in the operating room. The system can obtain noncontact en face OCT images and horizontal line scans with an approximately 40° field of view and up to 100° (ultra-wide-field) using a contact lens-based approach in a single 2-second scan. In addition, 20° × 20° (approximately 4 × 4-mm) OCTA scans were obtained in patients with ROP in a single 2-second scan. Optical coherence tomography and OCTA are gaining popularity in pediatric retinal imaging. This study reports on OCTA and ultra-wide-field OCT images in 4 neonates with various stages of ROP that were obtained using a prototype handheld device. Additional studies will be needed to prove the clinical value of this technology.

The effects of mild-to-severe retinopathy of prematurity on the development of refractive errors and strabismus.

PubMed

Gursoy, Huseyin; Basmak, Hikmet; Bilgin, Burak; Erol, Nazmiye; Colak, Ertugrul

2014-06-01

To investigate the effects of mild-to-severe retinopathy of prematurity (ROP) on refractive state and the incidence of strabismus. Infants born ≤32 weeks of gestation were prospectively evaluated. Inclusion criteria were a follow-up of at least 6 months and at least stage 1 ROP. Group 1 included stage 1 ROP cases. Cases with stage 2 or 3 ROP without indication for treatment formed the second group. Group 3 included cases who received treatment for ROP. Logistic regression, adjusted for birth weight and gestational age, and multiple comparison tests were used to compare outcomes among groups. The mean follow-up time was 20.9 ± 6.6 months. In the first (n = 21), second (n = 22), and third groups (n = 23), the right spherical equivalents (SE) were 1.17 ± 1.33, -0.18 ± 3.09, and -1.08 ± 4.05 diopters, and the left SEs were 1.23 ± 1.34, -0.09 ± 3.24, and -1.46 ± 4.02 diopters, respectively (p = 0.026 for right SE and 0.008 for left SE). The incidences of anisometropia were 3/21, 4/22, and 11/23 in the first, second, and third groups, respectively (adjusted odds ratios [aOR] for group 3 vs 1 = 5.39, aOR for group 3 vs 2 = 4.06). Strabismus developed in 7/21, 6/22, and 10/23 in groups one, two, and three, respectively (aOR for group 3 vs 1 = 2.06, aOR for group 3 vs 2 = 2.27). Eighteen of these were esotropias. Refractive errors and strabismus were associated with mild-to-severe ROP. Esotropia was the most frequent type of strabismus.

Length of day during early gestation as a predictor of risk for severe retinopathy of prematurity.

PubMed

Yang, Michael B; Rao, Sujata; Copenhagen, David R; Lang, Richard A

2013-12-01

Fetal mice require light exposure in utero during early gestation for normal vascular development in the eye. Because angiogenic abnormalities in retinopathy of prematurity (ROP) are manifested in preterm infants, we investigated whether day length during early gestation was associated with severe ROP (SROP). Single-center, retrospective cohort study. We included a total of 343 premature infants (401-1250 g birth weight [BW], from 1998-2002): 684 eyes (1 eye each of 2 patients excluded) with 76 eyes developing SROP, defined as (1) classic threshold ROP in zone I or II, (2) type 1 ROP in zone I, or (3) in a few eyes, type 1 ROP in posterior zone II that was treated. For each infant, average day length (ADL) was calculated during different cumulative time periods and time windows after the estimated date of conception (EDC). Multiple logistic regression analysis (with generalized estimating equations to account for inter-eye correlation) was performed. Association of ADL during early gestation with SROP. In a model evaluating all 684 eyes with 76 eyes developing SROP, BW, gestational age, multiple births, race, per capita income in the mother's residence ZIP code, and ADL during the first 90 days after the EDC were factors associated with the development of SROP. Each additional hour of ADL (90 days) decreased the likelihood of SROP by 28% (P = 0.015; odds ratio [OR], 0.72; 95% confidence interval [CI], 0.55-0.94). In a model evaluating the subset of 146 prethreshold ROP eyes with 76 eyes developing SROP, each additional hour of ADL during the first 105 days after the EDC decreased the likelihood of SROP by 46% (P = 0.001; OR, 0.54; 95% CI, 0.37-0.78). Time windows when ADL was most closely associated with SROP were 31 to 60 days and 61 to 90 days after the EDC for the all eyes and the prethreshold ROP eyes models, respectively. Higher ADL during early gestation was associated with a lower risk for SROP and may imply a role for prophylactic light treatment during early gestation to decrease the risk of SROP. Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

The ROP18 and ROP5 allele types are highly predictive of mouse-virulence across globally distributed strains of Toxoplasma gondii

USDA-ARS?s Scientific Manuscript database

The protozoan parasite Toxoplasma gondii is one of the known most successful eukaryotic pathogens on Earth. Virulence of T. gondii strains varies greatly in mice, and mounting evidence suggests that such variations may be relevant to the manifestation of human toxoplasmosis. Polymorphic rhoptry-secr...

ADVANCES IN UNDERSTANDING AND MANAGEMENT OF RETINOPATHY OF PREMATURITY

PubMed Central

Hartnett, Mary Elizabeth

2016-01-01

The understanding, diagnosis and treatment of retinopathy of prematurity (ROP) have changed in the last seventy years since the original description of retrolental fibroplasia associated with high oxygenation. It is now recognized that ROP differs in appearance world-wide and as ever smaller and younger premature infants survive. New methods are being evaluated to image the retina, diagnose severe ROP, and determine windows of time for treatment to save eyes and improve visual and neural outcomes. New treatments to promote physiologic retinal vascular development, vascular repair, and inhibit vasoproliferation by regulating proteins involved in vascular endothelial growth factor, insulin-like growth factor, or erythropoietin signaling. Reducing excessive oxidative/nitrosative stress and understanding progenitor cells and neurovascular and glial vascular interactions are being studied. PMID:28012875

Spatial organization of xylem cell walls by ROP GTPases and microtubule-associated proteins.

PubMed

Oda, Yoshihisa; Fukuda, Hiroo

2013-12-01

Proper patterning of cellulosic cell walls is critical for cell shaping and differentiation of plant cells. Cortical microtubule arrays regulate the deposition patterns of cellulose microfibrils by controlling the targeting and trajectory of cellulose synthase complexes. Although some microtubule-associated proteins (MAPs) regulate the arrangement of cortical microtubules, knowledge about the overall mechanism governing the spacing of cortical microtubules is still limited. Recent studies reveal that ROP GTPases and MAPs spatially regulate the assembly and disassembly of cortical microtubules in developing xylem cells, in which localized secondary cell walls are deposited. Here, we review recent insights into the regulation of xylem cell wall patterning by cortical microtubules, ROP GTPases, and MAPs. Copyright © 2013 Elsevier Ltd. All rights reserved.

Fatal necrotising enterocolitis due to mydriatic eye drops.

PubMed

Ozgun, Uygur; Demet, Terek; Ozge, Koroglu A; Zafer, Dokumcu; Murat, Sezak; Mehmet, Yalaz; Nilgun, Kultursay

2014-05-01

Retinopathy of prematurity (ROP) is a serious problem of preterm infants which may lead to impairment of vision and even to blindness if untreated. Routine eye examination is necessary for early diagnosis and treatment of ROP in preterm infants. Mydriatic eye drops (cyclopentolate, tropicamide and phenylephrine) are applied before the ophthalmic examination. These agents are rarely absorbed to systemic circulation and in some cases result with serious side effects like skin rash, tachycardia, feeding intolerance, discomfort, apnea, gastric dilatation and ileus, despite different treatment models and dosage reducing strategies. We report here a preterm patient who died because of severe diffuse necrotizing enterocolitis (NEC) after topical application of 0.5% cyclopentolate and 1.25% phenylephrine during ROP screening to emphasise the serious side effects of these agents.

Visual outcome and refractive status in first 3 years of age in preterm infants suffered from laser-treated Type 1 retinopathy of prematurity (ROP): a 6-year retrospective review in a tertiary centre in Hong Kong.

PubMed

Lok, Julie Y C; Yip, Wilson W K; Luk, Abbie S W; Chin, Joyce K Y; Lau, Henry H W; Young, Alvin L

2018-02-01

To report the visual outcome and refractive status in first 3 years of age in preterm infants suffered from laser-treated Type 1 retinopathy of prematurity (ROP): a 6-year review in Hong Kong DESIGN: Retrospective case series METHODOLOGY: Clinical records of all infants suffered from Type 1 ROP who had undergone laser therapy between 2007 and 2012 were retrospectively reviewed. Basic demographic data, serial changes of refractive error, visual acuity, severity of ROP and laser were analyzed. Correlation with myopia and astigmatism progression, body weight, height, growth and gestational age were also analyzed. Among 494 babies screened, 14 Chinese babies (26 eyes) recruited with 1:1 male-to-female ratio in this study. All eyes showed gradual progression of myopia in first 3 years of age but no significant change of astigmatism. Further correlation analysis showed no correlation with laser energy consumed, birth weight (p = 0.14), head circumference growth (p = 0.57) and body weight growth (p = 0.71). However, severity of myopia was related to the post-conceptual age when receiving laser therapy (p < 0.005), gestation age (p = 0.02) and possibly body height growth with age (p = 0.05). Myopia in early life is one of the most common ocular sequelae in Type 1 ROP survivors. Early detection of refractive error is important for prompt correction and visual rehabilitation to prevent amblyopia.

The societal burden of blindness secondary to retinopathy of prematurity in Lima, Peru.

PubMed

Dave, Hreem B; Gordillo, Luz; Yang, Zhou; Zhang, Monica S; Hubbard, G Baker; Olsen, Timothy W

2012-10-01

To determine the cost-effectiveness of laser treatment for retinopathy of prematurity (ROP) in Lima, Peru. A cost-of-illness study (in US dollars) to determine the direct cost of treatment, the indirect lifetime cost of blindness, and the quality-adjusted life years. The direct cost of ROP-related treatment was determined by reviewing data retrospectively from a social security sector hospital. The indirect cost was determined using national economic data of Peru published by the Central Information Agency (CIA), including the per capita gross domestic product, the sex-adjusted income distribution, and years spent in the work force. Indirect costs per child that were avoided by treatment were calculated using the known natural history of ROP vs evidence-based treatment. For ROP-related neonatal blindness in Peru, we estimate the total indirect cost saving at $197,753 per child and the direct cost of laser treatment at $2496 per child. The societal lifetime cost saving per child is estimated at $195,257. The mean annual income per educated adult in Peru is $8000 and treating 1 child is equivalent to employing 24 educated Peruvians per year. The generational cost savings for society is approximately $516 million, or the equivalent of 64,500 educated Peruvian work years. The societal burden of blindness far exceeds the costs of treatment per child. Proper screening and treatment of ROP prevents blindness and leads to substantial cost savings for society. Public health policy in Peru and other middle-income countries should consider financial impact when allocating healthcare resources. Copyright © 2012 Elsevier Inc. All rights reserved.

BMDO Technologies for Biomedical Applications.

DTIC Science & Technology

1997-12-01

like diabetic retinopathy and retinitis pigmentosa . It can also be used to more precisely measure refrac- tive error (the degree of nearsightedness or...tism, interpupil distance, and ocular accommodation and can do so over telemedical routes. 2. A deformable mirror that improves retinal imaging for...1 kilogram at birth will develop retinopathy of prematurity (ROP). Children with ROP are diagnosed with retinal scarring, nearsightedness, and

Development of rod function in term born and former preterm subjects.

PubMed

Fulton, Anne B; Hansen, Ronald M; Moskowitz, Anne

2009-06-01

To provide an overview of some of our electroretinographic (ERG) and psychophysical studies of normal development of rod function and their application to retinopathy of prematurity (ROP). ERG responses to full-field stimuli were recorded from dark adapted subjects. Rod photoreceptor sensitivity (SROD) was calculated by fit of a biochemical model of the activation of phototransduction to the ERG a-wave. Dark adapted psychophysical thresholds for detecting 2 degrees spots in parafoveal (10 degrees eccentric) and peripheral (30 degrees eccentric) retina were measured and the difference between the thresholds, Delta10-30, was examined as a function of age. SROD and Delta10-30 in term born and former preterm subjects were compared. In term born infants, (1) the normal developmental increase in SROD changes proportionately with the amount of rod visual pigment, rhodopsin, and (2) rod-mediated function in central retina is immature compared with that in peripheral retina. In subjects born prematurely, deficits in SROD persist long after active ROP has resolved. Maturation of rod-mediated thresholds in the central retina is prolonged by mild ROP. Characterization of the development of normal rod and rod-mediated function provides a foundation for understanding ROP.

Development of Rod Function in Term Born and Former Preterm Subjects

PubMed Central

Fulton, Anne B.; Hansen, Ronald M.; Moskowitz, Anne

2009-01-01

Purpose Provide an overview of some of our electroretinographic and psychophysical studies of normal development of rod function and their application to retinopathy of prematurity (ROP). Methods Electroretinographic (ERG) responses to full-field stimuli were recorded from dark adapted subjects. Rod photoreceptor sensitivity, SROD, was calculated by fit of a biochemical model of the activation of phototransduction to the ERG a-wave. Dark adapted psychophysical thresholds for detecting 2° spots in parafoveal (10° eccentric) and peripheral (30° eccentric) retina were measured and the difference between the thresholds, Δ10-30, was examined as a function of age. SROD and Δ10-30 in term born and former preterm subjects were compared. Results In term born infants, (1) the normal developmental increase in SROD changes proportionately with the amount of rod visual pigment, rhodopsin, and (2) rod mediated function in central retina is immature compared to that in peripheral retina. In subjects born prematurely, deficits in rod photoreceptor sensitivity persist long after active ROP has resolved. Maturation of rod mediated thresholds in the central retina is prolonged by mild ROP. Conclusions Characterization of the development of normal rod and rod mediated function provides a foundation for understanding ROP. PMID:19483509

Runway Operations Planning: A Two-Stage Heuristic Algorithm

NASA Technical Reports Server (NTRS)

Anagnostakis, Ioannis; Clarke, John-Paul

2003-01-01

The airport runway is a scarce resource that must be shared by different runway operations (arrivals, departures and runway crossings). Given the possible sequences of runway events, careful Runway Operations Planning (ROP) is required if runway utilization is to be maximized. From the perspective of departures, ROP solutions are aircraft departure schedules developed by optimally allocating runway time for departures given the time required for arrivals and crossings. In addition to the obvious objective of maximizing throughput, other objectives, such as guaranteeing fairness and minimizing environmental impact, can also be incorporated into the ROP solution subject to constraints introduced by Air Traffic Control (ATC) procedures. This paper introduces a two stage heuristic algorithm for solving the Runway Operations Planning (ROP) problem. In the first stage, sequences of departure class slots and runway crossings slots are generated and ranked based on departure runway throughput under stochastic conditions. In the second stage, the departure class slots are populated with specific flights from the pool of available aircraft, by solving an integer program with a Branch & Bound algorithm implementation. Preliminary results from this implementation of the two-stage algorithm on real-world traffic data are presented.

Effect of ring-opening polymerization condition on the characteristic and mechanical properties of hydroxyapatite/poly(ethylene glutarate) biomaterials.

PubMed

Monvisade, Pathavuth; Siriphannon, Punnama; Tapcharoen, Walailak

2009-09-01

Preparation of hydroxyapatite/poly(ethylene glutarate) (HAp/PEG) composites was carried out by ring-opening polymerization (ROP) of cyclic oligo(ethylene glutarate) in porous HAp scaffolds using various reaction temperatures and times. The content of ROP-PEG interpenetrated into the porous HAp scaffold was about 13-18 wt % with the values of number average molecular weight (overline_M{n}) and weight average molecular weight (overline_M{W}) of 2120-3630 and 2760-5250 g/mol, respectively. The increase in polymerization time and temperature brought about increase in molecular weight of ROP-PEG, but decrease in its content. Compressive strength and compressive modulus of the HAp/PEG composites were about 5.8-20.1 and 105-208 MPa, respectively. These mechanical properties depend upon the effects of distribution, content, and molecular weight of ROP-PEG in the composites. In vitro bioactivity of the HAp/PEG composites was studied by soaking them in simulated body fluid (SBF) for 28 days. The formation of HAp nanocrystal on the composite surfaces through the consumption of calcium and phosphorus from the SBF solution was observed after soaking, indicating the bioactivity of these HAp/PEG composites.

Vitreous Bands Identified by Handheld Spectral-Domain Optical Coherence Tomography Among Premature Infants.

PubMed

Zepeda, Emily M; Shariff, Ayesha; Gillette, Thomas B; Grant, Laura; Ding, Leona; Tarczy-Hornoch, Kristina; Cabrera, Michelle T

2018-05-17

Handheld spectral-domain optical coherence tomography (SD-OCT) can provide insights into the complex interactions occurring at the vitreoretinal interface in retinopathy of prematurity (ROP) to enhance our understanding of ROP pathology. To characterize vitreous bands in premature infants with use of handheld SD-OCT. Prospective cohort study conducted from July 7, 2015, to February 28, 2017, at 2 university-based neonatal intensive care units. Seventy-three premature infants who required routine ROP screening examination were recruited. Informed consent was obtained from all legal guardians. Trained graders who were masked to the clinical assessment analyzed each SD-OCT scan of the right eye for vitreoretinal findings. A third trained grader mediated disagreements. Associations between the presence of vitreous bands in premature infants with ROP diagnoses and the presence of other vitreoretinal SD-OCT findings were investigated. Of the 73 infants recruited, 6 infants' parents withdrew their children from the study, and 2 infants were too hemodynamically unstable for imaging, leaving a total of 65 participants. Of these, 32 (49%) were female, 36 (55%) were white, 10 (15%) were Hispanic, 3 (5%) were Native American, 4 (6%) were African American, 4 (7%) were Asian/Pacific Islander, and 8 (12%) were other. The mean (SD) gestational age was 28 (2.7) weeks, the mean (SD) birth weight was 997 g (286 g), and the mean (SD) postmenstrual age at imaging was 34 (3) weeks (mean [SD] total of 3 [2] imaging sessions). Comparing the 24 infants (37%) who had a right eye vitreous band at any time with the 41 (63%) who did not, no difference in mean birth weight, gestational age, postmenstrual age at imaging, sex, or race/ethnicity was identified. No associations with ROP stage (eg, in 6 [25%] infants with vitreous bands vs 4 [9.8%] in those without; P = .23), presence of plus disease (2 [8%] vs 2 [5%]; P = .84), or type 1 ROP (3 [12%] vs 3 [7%]; P = .66) were identified. Vitreous bands were associated with epiretinal membrane detected on SD-OCT (P = .001) with an odds ratio of 9.4 (95% CI, 2.8-31.3) in 15 [62%] infants with vitreous bands vs 6 [15%] in those without. Vitreous bands were also associated with cystoid macular edema (in 15 [62%] infants with vitreous bands vs 1 [27%] in those without; P = .005) with an odds ratio of 4.5 (95% CI, 1.5-13.3). In this study, the development of vitreous bands was associated with both cystoid macular edema and epiretinal membrane. These findings suggest a tractional pathogenesis to these entities among premature infants. This study did not find a direct association between vitreous bands and severe ROP. Additional study is needed to determine whether vitreous bands represent subclinical hyaloidal organization leading to retinal detachment in advanced ROP.

Use of the "gl1" Mutant and the "CA-rop2" Transgenic Plants of "Arabidopsis thaliana" in the Biology Laboratory Course

ERIC Educational Resources Information Center

Zheng, Zhi-Liang

2006-01-01

This article describes the use of the "glabrous1 (g11)" mutant and constitutively active "(CA)-rop2" transgenic plants of "Arabidopsis thaliana" in teaching genetics laboratory for both high school and undergraduate students. The experiments provide students with F[subscript 1] and F[subscript 2] generations within a semester for genetic and…

Changes in systemic vascular endothelial growth factor levels after intravitreal injection of aflibercept in infants with retinopathy of prematurity.

PubMed

Huang, Chung-Ying; Lien, Reyin; Wang, Nan-Kai; Chao, An-Ning; Chen, Kuan-Jen; Chen, Tun-Lu; Hwang, Yih-Shiou; Lai, Chi-Chun; Wu, Wei-Chi

2018-03-01

To investigate the levels of VEGF in the systemic circulation of patients with type 1 ROP who received intravitreal injections of 1 mg (0.025 mL) aflibercept (IVA) or 0.625 mg (0.025 mL) bevacizumab (IVB). Patients who had type 1 ROP and received either IVA or IVB were enrolled in this prospective study. Serum and plasma samples were collected prior to and up to 12 weeks after IVB or IVA treatment. The serum and plasma VEGF levels were measured using enzyme-linked immunosorbent assays (ELISAs), and the platelet levels in the blood were also quantified. The serum and plasma levels of VEGF, as well as the ratio of VEGF to platelet count (VEGF/PLT) were measured prior to and up to 12 weeks after anti-VEGF treatment. In total, 14 patients with type 1 ROP were enrolled in this study; five patients received IVA, and nine patients received IVB. Following either IVA or IVB treatment, all the eyes (100%) showed complete resolution of ROP-induced abnormal neovascularization and presented continued vascularization toward the peripheral retina. Compared to baseline, the serum VEGF levels were significantly reduced in the ROP patients up to 12 weeks after either IVA or IVB treatments (all P < 0.05). At 2, 4, and 8 weeks after intravitreal injection, the serum VEGF levels were more suppressed in the IVB group than in the IVA group (P = 0.039, P = 0.004, and P = 0.003, respectively). The serum VEGF/PLT ratio after IVA or IVB showed similar reductions and trends as the serum VEGF data. Changes in the plasma VEGF levels could not be properly assessed because some of the samples had VEGF levels below the detection limit of the ELISA. Serum VEGF levels and the VEGF/PLT ratio in patients with type 1 ROP were suppressed for 3 months after treatment with either IVA or IVB, but the suppression of systemic VEGF was more pronounced in patients treated with IVB than those treated with IVA.

Comparison of efficacy between anti-vascular endothelial growth factor (VEGF) and laser treatment in Type-1 and threshold retinopathy of prematurity (ROP).

PubMed

Li, Zijing; Zhang, Yichi; Liao, Yunru; Zeng, Rui; Zeng, Peng; Lan, Yuqing

2018-01-30

Retinopathy of Prematurity (ROP) is one of the most common causes of childhood blindness worldwide. Comparisons of anti-VEGF and laser treatments in ROP are relatively lacking, and the data are scattered and limited. The objective of this meta-analysis is to compare the efficacy of both treatments in type-1 and threshold ROP. A comprehensive literature search on ROP treatment was conducted using PubMed and Embase up to March 2017 in all languages. Major evaluation indexes were extracted from the included studies by two authors. The fixed-effects and random-effects models were used to measure the pooled estimates. The test of heterogeneity was performed using the Q statistic. Ten studies were included in this meta-analysis. Retreatment incidence was significantly increased for anti-VEGF (OR 2.52; 95% CI 1.37 to 4.66; P = 0.003) compared to the laser treatment, while the incidences of eye complications (OR 0.29; 95% CI 0.10 to 0.82; P = 0.02) and myopia were significantly decreased with anti-VEGF compared to the laser treatment. However, there was no difference in the recurrence incidence (OR 1.86; 95% CI 0.37 to 9.40; P = 0.45) and time between treatment and retreatment (WMD 7.54 weeks; 95% CI 2.00 to 17.08; P = 0.12). This meta-analysis indicates that laser treatment may be more efficacious than anti-VEGF treatment. However, the results of this meta-analysis also suggest that laser treatment may cause more eye complications and increase myopia. Large-scale prospective RCTs should be performed to assess the efficacy and safety of anti-VEGF versus laser treatment in the future.

Serious adverse events and visual outcomes of rescue therapy using adjunct bevacizumab to laser and surgery for retinopathy of prematurity. The Indian Twin Cities Retinopathy of Prematurity Screening database Report number 5.

PubMed

Jalali, Subhadra; Balakrishnan, Divya; Zeynalova, Zarifa; Padhi, Tapas Ranjan; Rani, Padmaja Kumari

2013-07-01

To report serious adverse events and long-term outcomes of initial experience with intraocular bevacizumab in retinopathy of prematurity (ROP). Consecutive vascularly active ROP cases treated with bevacizumab, in addition to laser and surgery, were analysed retrospectively from a prospective computerised ROP database. Primary efficacy outcome was regression of new vessels. Secondary outcomes included the anatomic and visual status. Serious systemic and ocular adverse events were documented. 24 ROP eyes in 13 babies, received single intraocular bevacizumab for severe stage 3 plus after failed laser (seven eyes), stage 4A plus (eight eyes), and stage 4B/5 plus (nine eyes). Drug was injected intravitreally in 23 eyes and intracamerally in one eye. New vessels regressed in all eyes. Vision salvage in 14 of 24 eyes and no serious neurodevelopmental abnormalities were noted up to 60 months (mean 30.7 months) follow-up. Complications included macular hole and retinal breaks causing rhegmatogenous retinal detachment (one eye); bilateral, progressive vascular attenuation, perivascular exudation and optic atrophy in one baby, and progression of detachment bilaterally to stage 5 in one baby with missed follow-up. One baby who received intracameral injection developed hepatic dysfunction. One eye of this baby also showed a large choroidal rupture. Though intraocular bevacizumab, along with laser and surgery salvaged vision in many otherwise progressive cases of ROP, vigilance and reporting of serious adverse events is essential for future rationalised use of the drug. We report one systemic and four ocular adverse events that require consideration in future use of the drug.

Systemic changes and adverse effects induced by retinopathy of prematurity screening.

PubMed

Jiang, Jing-Bo; Zhang, Zhi-Wei; Zhang, Jia-Wen; Wang, Yan-Li; Nie, Chuan; Luo, Xian-Qiong

2016-01-01

To estimate the potential systemic events during and after retinopathy of prematurity (ROP) screening. A prospective and descriptive designed study was conducted to detect the physiologic and pathological changes 24h before, during, and 72h after ROP screening. Control blood pressure (BP), saturation, pulse rate, and body temperature were routinely taken at various time internals before and after screening. Adverse effects pertain to cardiovascular system, respiratory system, gastric system, urinary system and nervous system were retrospect 0-72h after ROP screening at a 24-hour interval. Totally 1254 prematurity babies receiving ROP screening during Jan. 1(st) 2013 to Dec. 31(th) 2013 were enrolled in our survey. Compared to control vital sign data taken before the examination, there was a fluctuation in the diastolic BP with the increased 3.03 mm Hg (P=0.04) after 3 doses of mydriatic drops. Immediately after the examination, there was a further 12.64 mm Hg (P<0.01) increase in systolic BP and a 7.24 mm Hg (P<0.01) in diastolic BP. The mean pulse rate during examination was 22.4 bpm (P<0.01) higher than the 133.3±9.0 bpm control level. The oxygen saturation shared an average drop of 5% (P<0.01) during screening. In prematurity with postconceptional age less than 31wk, the incidence of apnea (23.5%), necrotizing enterocolitis (NEC) (8.7%), gastric residual (25.4%) and upper digestive tract hemorrhage (6.4%) also demonstrated a significant rise (P<0.01). In our study sample, ROP screening was associated with NEC, gastric residual and upper digestive tract hemorrhage. These gastrointestinal side effects, along with breath activity pattern change and vital signs indicators fluctuation, may be results of additional stress responses.

Facilitated versus self-guided training of non-ophthalmologists for grading pre-plus and plus disease using fundus images for retinopathy of prematurity screening

PubMed Central

Raufi, Nikolas N.; Morris, Caleb K.; Freedman, Sharon F.; Wallace, David K.; Prakalapakorn, S. Grace

2016-01-01

Purpose Retinopathy of prematurity (ROP) is an important cause of preventable blindness; barriers to screening necessitate novel approaches. While trained non-ophthalmologists can accurately grade retinal images for ROP, effective training protocols are not established. This study compares the effectiveness of facilitated versus self-guided training of non-ophthalmologists for grading retinal images for pre-plus or plus disease in ROP. Methods Forty-eight undergraduate and graduate students were trained to grade retinal images for the presence of pre-plus or plus disease. Students were randomly assigned to one of two training protocols. Both utilized identical electronic slideshows; one guided by an in-person facilitator, and the other was self-guided. After completing their respective training, students proficient in grading pre-plus and plus disease graded images in a telemedicine screening scenario. Accuracy of grading was compared to the reference standard of clinical examination. Results 83% (40/48) of trained students (91% in the facilitated vs. 77% in the self-guided group, p=0.26) were proficient and qualified to grade the ROP telemedicine screening scenario. Median accuracy for grading normal, pre-plus or plus disease was 69% (70% in the facilitated vs. 68% in the self-guided group, p=0.91). When considering the designation of pre-plus or plus disease by graders as a screening test for detecting plus disease (confirmed on clinical exam), the median sensitivity and specificity of all students was 95% and 64%, respectively. Conclusions Both facilitated- and self-guided teaching protocols yielded similar performance in ROP image grading for pre-plus or plus disease. Self-guided training protocols may be adequate to train non-ophthalmologists to grade retinal images for pre-plus and plus disease with high sensitivity. PMID:27224953

Prematures with and without Regressed Retinopathy of Prematurity: Comparison of Long-Term (6-10 Years) Ophthalmological Morbidity.

ERIC Educational Resources Information Center

Cats, Bernard P.; Tan, Karel E. W. P.

Reporting long-term ophthalmologic sequelae among ex-prematures at 6 to 10 years of age, this study compares 42 ex-premature infants who had had regressed forms of retinopathy of prematurity (ROP) during the neonatal period with 42 matched non-ROP ex-premature controls at 6 to 10 years of age. Subjects were subdivided into four groups: (1) ROP…

Telemedicine Applications in Pediatric Retinal Disease

PubMed Central

Pathipati, Akhilesh S.; Moshfeghi, Darius M.

2017-01-01

Teleophthalmology is a developing field that presents diverse opportunities. One of its most successful applications to date has been in pediatric retinal disease, particularly in screening for retinopathy of prematurity (ROP). Many studies have shown that using telemedicine for ROP screening allows a remote ophthalmologist to identify abnormal findings and implement early interventions. Here, we review the literature on uses of telemedicine in pediatric retinal disease and consider future applications. PMID:28333078

Bit selection using field drilling data and mathematical investigation

NASA Astrophysics Data System (ADS)

Momeni, M. S.; Ridha, S.; Hosseini, S. J.; Meyghani, B.; Emamian, S. S.

2018-03-01

A drilling process will not be complete without the usage of a drill bit. Therefore, bit selection is considered to be an important task in drilling optimization process. To select a bit is considered as an important issue in planning and designing a well. This is simply because the cost of drilling bit in total cost is quite high. Thus, to perform this task, aback propagation ANN Model is developed. This is done by training the model using several wells and it is done by the usage of drilling bit records from offset wells. In this project, two models are developed by the usage of the ANN. One is to find predicted IADC bit code and one is to find Predicted ROP. Stage 1 was to find the IADC bit code by using all the given filed data. The output is the Targeted IADC bit code. Stage 2 was to find the Predicted ROP values using the gained IADC bit code in Stage 1. Next is Stage 3 where the Predicted ROP value is used back again in the data set to gain Predicted IADC bit code value. The output is the Predicted IADC bit code. Thus, at the end, there are two models that give the Predicted ROP values and Predicted IADC bit code values.

Retinopathy of Prematurity-assist: Novel Software for Detecting Plus Disease

PubMed Central

Pour, Elias Khalili; Pourreza, Hamidreza; Zamani, Kambiz Ameli; Mahmoudi, Alireza; Sadeghi, Arash Mir Mohammad; Shadravan, Mahla; Karkhaneh, Reza; Pour, Ramak Rouhi

2017-01-01

Purpose To design software with a novel algorithm, which analyzes the tortuosity and vascular dilatation in fundal images of retinopathy of prematurity (ROP) patients with an acceptable accuracy for detecting plus disease. Methods Eighty-seven well-focused fundal images taken with RetCam were classified to three groups of plus, non-plus, and pre-plus by agreement between three ROP experts. Automated algorithms in this study were designed based on two methods: the curvature measure and distance transform for assessment of tortuosity and vascular dilatation, respectively as two major parameters of plus disease detection. Results Thirty-eight plus, 12 pre-plus, and 37 non-plus images, which were classified by three experts, were tested by an automated algorithm and software evaluated the correct grouping of images in comparison to expert voting with three different classifiers, k-nearest neighbor, support vector machine and multilayer perceptron network. The plus, pre-plus, and non-plus images were analyzed with 72.3%, 83.7%, and 84.4% accuracy, respectively. Conclusions The new automated algorithm used in this pilot scheme for diagnosis and screening of patients with plus ROP has acceptable accuracy. With more improvements, it may become particularly useful, especially in centers without a skilled person in the ROP field. PMID:29022295

Competency checklists for strabismus surgery and retinopathy of prematurity examination.

PubMed

McClatchey, Scott K; Lane, R Gary; Kubis, Kenneth C; Boisvert, Chantal

2012-02-01

To evaluate two checklist tools that are designed to guide, document, and assess resident training in strabismus surgery and examination of infants at risk for retinopathy of prematurity (ROP). A panel of staff surgeons from several teaching institutions evaluated the checklists and provided constructive feedback. All former residents who had been trained via the use of these checklist tools were asked to take self-assessment surveys on competency in strabismus surgery and ROP examination. A Likert 5-point scale was used for all evaluations, with 1 being the lowest rating and 5 the highest rating. Six experts in strabismus and seven in ROP rated the checklists. Their comments were used to revise the checklists, which were sent to the same group for reevaluation. The mean Likert score for the final checklists was 4.9 of 5.0 for both checklists. Of 16 former residents, 9 responded to the self-assessments with a mean overall score of 4.1 (of 5.0) for strabismus surgery and 3.9 for ROP examination. These checklist tools can be used to assess the quality of a resident's training and experience in these specific ophthalmology skills. They are complementary to other curriculum and assessment tools and can serve to organize the educational experience while ensuring a uniformity of training. Published by Mosby, Inc.

Adenosine receptors and caffeine in retinopathy of prematurity

PubMed Central

Chen, Jiang-Fan; Zhang, Shuya; Zhou, Rong; Lin, Zhenlang; Cai, Xiaohong; Lin, Jing; Huo, Yuqing; Liu, Xiaoling

2017-01-01

Retinopathy of prematurity (ROP) is a major cause of childhood blindness in the world and is caused by oxygen-induced damage to the developing retinal vasculature, resulting in hyperoxia-induced vaso-obliteration and subsequent delayed retinal vascularization and hypoxia-induced pathological neovascularization driven by vascular endothelial growth factor (VEGF) signaling pathway in retina. Current anti-VEGF therapy has shown some effective in a clinical trial, but is associated with the unintended effects on delayed eye growth and retinal vasculature development of preterm infants. Notably, cellular responses to hypoxia are characterized by robust increases in extracellular adenosine production and the markedly induced adenosine receptors, which provide a novel target for preferential control of pathological angiogenesis without affecting normal vascular development. Here, we review the experimental evidence in support of adenosine receptor-based therapeutic strategy for ROP, including the aberrant adenosine signaling in oxygen-induced retinopathy and the role of three adenosine receptor subtypes (A1R, A2AR, A2BR) in development and treatment of ROP using oxygen-induced retinopathy models. The clinical and initial animal evidence that implicate the therapeutic effect of caffeine (a non-selective adenosine receptor antagonist) in treatment of ROP are highlighted. Lastly, we discussed the translational potential as well therapeutic advantage of adenosine receptor- and caffeine-based therapy for ROR and possibly other proliferative retinopathy. PMID:28088487

Factors associated with failure to screen newborns for retinopathy of prematurity.

PubMed

Bain, Lisa Charo; Dudley, R Adams; Gould, Jeffrey B; Lee, Henry C

2012-11-01

To evaluate ROP screening rates in a population-based cohort; and to identify characteristics of patients that were missed. We used the California Perinatal Quality Care Collaborative data from 2005-2007 for a cross-sectional study. Using eligibility criteria, screening rates were calculated for each hospital. Multivariable regression was used to assess associations between patient clinical and sociodemographic factors and the odds of missing screening. Overall rates of missed ROP screening decreased from 18.6% in 2005 to 12.8% in 2007. Higher gestational age (OR = 1.25 for increase of 1 week, 95% CI, 1.21-1.29), higher birth weight (OR = 1.13; 95% CI, 1.10-1.15), and singleton birth (OR = 1.2; 95% CI, 1.07-1.34) were associated with higher probability of missing screening. Level II neonatal intensive care units and neonatal intensive care units with lower volume were more likely to miss screenings. Although ROP screening rates improved over time, larger and older infants are at risk for not receiving screening. Furthermore, large variations in screening rates exist among hospitals in California. Identification of gaps in quality of care creates an opportunity to improve ROP screening rates and prevent impaired vision in this vulnerable population. Copyright © 2012 Mosby, Inc. All rights reserved.

"I sleep better at night:" How peer review of radiation treatment plans indirectly improves quality of care across radiation treatment programs.

PubMed

Brundage, Michael D; Hart, Margaret; O'Donnell, Jennifer; Reddeman, Lindsay; Gutierrez, Eric; Foxcroft, Sophie; Warde, Padraig

Peer review of radiation oncology treatment plans is increasingly recognized as an important component of quality assurance in radiation treatment planning and delivery. Peer review of treatment plans can directly improve the quality of those plans and can also have indirect effects on radiation treatment programs. We undertook a systematic, qualitative approach to describing the indirect benefits of peer review, factors that were seen to facilitate or act as barriers to the implementation of peer review, and strategies to address these barriers across a provincial jurisdiction of radiation oncology programs (ROPs). Semistructured qualitative interviews were held with radiation oncology department heads and radiation therapy managers (or delegates) in all 14 ROPs in Ontario, Canada. We used a theoretically guided phenomenological qualitative approach to design and analyze the interview content. Themes were recorded by 2 independent reviewers, and any discordance was resolved by consensus. A total of 28 interviews were completed with 32 interviewees. Twenty-two unique themes addressed perceived benefits of peer review, relating to either peer review structure (n = 3), process (n = 9), or outcome (n = 10). Of these 22 themes, 19 related to indirect benefits to ROPs. In addition, 18 themes related to factors that facilitated peer review activities and 30 themes related to key barriers to implementing peer review were identified. Findings were consistent with, and enhanced the understanding of, previous survey-based assessments of the benefits and challenges of implementing peer review programs. Although challenges and concerns regarding the implementation of peer review were evident, the indirect benefits to radiation programs are numerous, far outweigh the implementation challenges, and strongly complement the direct individual-patient benefits that result from peer review quality assurance of radiation treatment plans. Copyright © 2016. Published by Elsevier Inc.

Decursin inhibits retinal neovascularization via suppression of VEGFR-2 activation.

PubMed

Kim, Jeong Hun; Kim, Jin Hyoung; Lee, You Mie; Ahn, Eun-Mi; Kim, Kyu-Won; Yu, Young Suk

2009-09-12

Pathologic angiogenesis in the retina leads to the catastrophic loss of vision. Retinopathy of prematurity (ROP), a vasoproliferative retinopathy, is a leading cause of blindness in children. We evaluated the inhibitory effect of decursin on retinal neovascularization. Anti-angiogenic activity of decursin was evaluated by vascular endothelial growth factor (VEGF)-induced proliferation, migration, and in vitro tube formation assay of human retinal microvascular endothelial cells (HRMECs). We also used western blot analysis to assess inhibition of vascular endothelial growth factor receptor-2 (VEGFR-2) phosphorylation by decursin. After intravitreal injection of decursin in a mouse model of ROP, retinal neovascularization was examined by fluorescence angiography and vessel counting in cross-sections. The toxicity of decursin was evaluated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in HRMECs as well as histologic and immunohistochemistry examination for glial fibrillary acidic protein in the retina. Decursin significantly inhibited VEGF-induced proliferation, migration, and the formation of capillary-like networks of retinal endothelial cells in a dose-dependent manner. Decursin inhibited VEGF-induced phosphorylation of VEGFR-2, blocking the VEGFR-2 signaling pathway. When intravitreously injected, decursin dramatically suppressed retinal neovascularization in a mouse model of ROP. Even in a high concentration, decursin never induced any structural or inflammatory changes to cells in retinal or vitreous layers. Moreover, the upregulation of glial fibrillary acidic protein expression was not detected in Mueller cells. Our data suggest that decursin may be a potent anti-angiogenic agent targeting the VEGFR-2 signaling pathway, which significantly inhibits retinal neovascularization without retinal toxicity and may be applicable in various other vasoproliferative retinopathies as well.

Decursin inhibits retinal neovascularization via suppression of VEGFR-2 activation

PubMed Central

Kim, Jeong Hun; Kim, Jin Hyoung; Lee, You Mie; Ahn, Eun-Mi; Kim, Kyu-Won

2009-01-01

Purpose Pathologic angiogenesis in the retina leads to the catastrophic loss of vision. Retinopathy of prematurity (ROP), a vasoproliferative retinopathy, is a leading cause of blindness in children. We evaluated the inhibitory effect of decursin on retinal neovascularization. Methods Anti-angiogenic activity of decursin was evaluated by vascular endothelial growth factor (VEGF)-induced proliferation, migration, and in vitro tube formation assay of human retinal microvascular endothelial cells (HRMECs). We also used western blot analysis to assess inhibition of vascular endothelial growth factor receptor-2 (VEGFR-2) phosphorylation by decursin. After intravitreal injection of decursin in a mouse model of ROP, retinal neovascularization was examined by fluorescence angiography and vessel counting in cross-sections. The toxicity of decursin was evaluated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in HRMECs as well as histologic and immunohistochemistry examination for glial fibrillary acidic protein in the retina. Results Decursin significantly inhibited VEGF-induced proliferation, migration, and the formation of capillary-like networks of retinal endothelial cells in a dose-dependent manner. Decursin inhibited VEGF-induced phosphorylation of VEGFR-2, blocking the VEGFR-2 signaling pathway. When intravitreously injected, decursin dramatically suppressed retinal neovascularization in a mouse model of ROP. Even in a high concentration, decursin never induced any structural or inflammatory changes to cells in retinal or vitreous layers. Moreover, the upregulation of glial fibrillary acidic protein expression was not detected in Mueller cells. Conclusions Our data suggest that decursin may be a potent anti-angiogenic agent targeting the VEGFR-2 signaling pathway, which significantly inhibits retinal neovascularization without retinal toxicity and may be applicable in various other vasoproliferative retinopathies as well. PMID:19756180

Peripheral self-reactivity regulates antigen-specific CD8 T-cell responses and cell division under physiological conditions.

PubMed

Swee, Lee Kim; Tan, Zhen Wei; Sanecka, Anna; Yoshida, Nagisa; Patel, Harshil; Grotenbreg, Gijsbert; Frickel, Eva-Maria; Ploegh, Hidde L

2016-11-01

T-cell identity is established by the expression of a clonotypic T-cell receptor (TCR), generated by somatic rearrangement of TCRα and β genes. The properties of the TCR determine both the degree of self-reactivity and the repertoire of antigens that can be recognized. For CD8 T cells, the relationship between TCR identity-hence reactivity to self-and effector function(s) remains to be fully understood and has rarely been explored outside of the H-2 b haplotype. We measured the affinity of three structurally distinct CD8 T-cell-derived TCRs that recognize the identical H-2 L d -restricted epitope, derived from the Rop7 protein of Toxoplasma gondii We used CD8 T cells obtained from mice generated by somatic cell nuclear transfer as the closest approximation of primary T cells with physiological TCR rearrangements and TCR expression levels. First, we demonstrate the common occurrence of secondary rearrangements in endogenously rearranged loci. Furthermore, we characterized and compared the response of Rop7-specific CD8 T-cell clones upon Toxoplasma gondii infection as well as effector function and TCR signalling upon antigenic stimulation in vitro Antigen-independent TCR cross-linking in vitro uncovered profound intrinsic differences in the effector functions between T-cell clones. Finally, by assessing the degree of self-reactivity and comparing the transcriptomes of naive Rop7 CD8 T cells, we show that lower self-reactivity correlates with lower effector capacity, whereas higher self-reactivity is associated with enhanced effector function as well as cell cycle entry under physiological conditions. Altogether, our data show that potential effector functions and basal proliferation of CD8 T cells are set by self-reactivity thresholds. © 2016 The Authors.

ENVIRONMENTAL TECHNOLOGY VERIFICATION REPORT - REMOVAL OF PRECURSORS TO DISINFECTION BY-PRODUCTS IN DRINKING WATER, PCI MEMBRANE SYSTEMS FYNE PROCESS MODEL ROP 1434 WITH AFC-30 NANOFILTRATON AT BARROW, AK - NSF 00/19/EPADW395

EPA Science Inventory

Equipment testing and verification of PCI Membrane Systems Inc. Fyne Process nanofiltraton systems Model ROP 1434 equipped with a C10 module containing AFC-30 tubular membranes was conducted from 3/16-5/11/2000 in Barrow, AS. The source water was a moderate alkalinity, moderately...

Rule Based System for Medicine Inventory Control Using Radio Frequency Identification (RFID)

NASA Astrophysics Data System (ADS)

Nugraha, Joanna Ardhyanti Mita; Suryono; Suseno, dan Jatmiko Endro

2018-02-01

Rule based system is very efficient to ensure stock of drug to remain available by utilizing Radio Frequency Identification (RFID) as input means automatically. This method can ensure the stock of drugs to remain available by analyzing the needs of drug users. The research data was the amount of drug usage in hospital for 1 year. The data was processed by using ABC classification to determine the drug with fast, medium and slow movement. In each classification result, rule based algorithm was given for determination of safety stock and Reorder Point (ROP). This research yielded safety stock and ROP values that vary depending on the class of each drug. Validation is done by comparing the calculation of safety stock and reorder point both manually and by system, then, it was found that the mean deviation value at safety stock was 0,03 and and ROP was 0,08.

Use of erythropoietin is associated with threshold retinopathy of prematurity (ROP) in preterm ELBW neonates: a retrospective, cohort study from two large tertiary NICUs in Italy.

PubMed

Manzoni, Paolo; Memo, Luigi; Mostert, Michael; Gallo, Elena; Guardione, Roberta; Maestri, Andrea; Saia, Onofrio Sergio; Opramolla, Anna; Calabrese, Sara; Tavella, Elena; Luparia, Martina; Farina, Daniele

2014-09-01

Retinopathy of prematurity (ROP) is a multifactorial disease with evidence of many associated risk factors. Erythropoietin has been reported to be associated with this disorder in a murine model, as well as in humans in some single-center reports. We reviewed the data from two large tertiary NICUs in Italy to test the hypothesis that the use of erythropoietin may be associated with the development of the most severe stages of ROP in extremely low birth weight (ELBW) neonates. Retrospective study by review of patient charts and eye examination index cards on infants with birth weight <1000g admitted to two large tertiary NICUs in Northern Italy (Sant'Anna Hospital NICU in Torino, and Ca' Foncello Hospital Neonatology in Treviso) in the years 2005 to 2007. Standard protocol of administration of EPO in the two NICUs consisted of 250 UI/kg three times a week for 6-week courses (4-week in 1001-1500g infants). Univariate analysis was performed to assess whether the use of EPO was associated with severe (threshold) ROP. A control, multivariate statistical analysis was performed by entering into a logistic regression model a number of neonatal and perinatal variables that - in univariate analysis - had been associated with threshold ROP. During the study period, 211 ELBW infants were born at the two facilities and survived till discharge. Complete data were obtained for 197 of them. Threshold retinopathy of prematurity occurred in 26.9% (29 of 108) of ELBW infants who received erythropoietin therapy, as compared with 13.5% (12 of 89) of those who did not receive erythropoietin (OR 2.35; 95% CI 1.121-4.949; p=0.02 in univariate analysis, and p=0.04 at multivariate logistic regression after controlling for the following variables: birth weight, gestational age, days on supplemental oxygen, systemic fungal infection, vaginal delivery). Use of erythropoietin was not significantly associated with other major sequelae of prematurity (intraventricular hemorrhage, bronchopulmonary dysplasia, necrotizing enterocolitis). © 2014 Elsevier Ireland Ltd. All rights reserved. Use of erythropoietin is an additional, independent predictor of threshold ROP in ELBW neonates. Larger prospective, population-based studies should further clarify the extent of this association. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Infantile Hemangiomas and Retinopathy of Prematurity: Clues to the Regulation of Vasculogenesis

PubMed Central

Hyland, Rachael M.; Komlósi, Katalin; Alleman, Brandon W.; Tolnai, Marina; Wood, Laura M.; Bell, Edward F.; Ertl, Tibor

2013-01-01

Retinopathy of prematurity (ROP) and infantile hemangiomas are vascular disorders that may share common mechanisms. This study examined a potential clinical association between these disorders in populations of preterm infants at two hospitals in the U.S. and Hungary. Clinically collected data from infants with gestational ages less than 32 weeks born between May 1, 2007 and December 31, 2010 seen in the University of Iowa Children’s Hospital or the Department of Obstetrics and Gynecology, University of Pécs, were abstracted from electronic medical records and entered into a study database. Demographic and clinical variables were examined as potential covariates to the disorders of interest. Data were initially analyzed by center and then combined through meta-analysis. Six hundred eighty-four subjects were studied, 236 from Pécs and 448 from Iowa. There were no significant demographic differences between populations. Univariate analysis on each study population yielded covariates to ROP in each population, including infantile hemangioma, which were entered into a logistic regression model. These models were combined through random effects meta-analysis and demonstrated a significant relationship between infantile hemangioma and ROP (odds ratio=1.84, 95% confidence interval 1.08–3.12). Conclusion Infantile hemangioma and ROP co-occur in premature infant populations. Further studies are needed to investigate the pathogenesis of both disorders. PMID:23408311

"What is the work of Recovery Oriented Practice? A systematic literature review".

PubMed

Chester, Polly; Ehrlich, Carolyn; Warburton, Loretta; Baker, David; Kendall, Elizabeth; Crompton, David

2016-08-01

Concepts of personal and social recovery in mental illness are constantly evolving because the journey is fluid and subject to change over time. Dynamic interactions between the complexities of human nature and mental illness create ever-altering landscapes of perplexity. The acknowledged ebb and flow of recovery in the presence of chronic and serious mental illness requires health professionals to provide a flexible suite of care, delivered through skills and methods that are responsive and meaningful to the recipient. We conducted a systematic search for qualitative literature that articulated the work of personally-supportive recovery-oriented practice (ROP) to determine the specific components of recovery-supportive work. Twenty-one articles were identified as meeting the inclusion criteria and were synthesized using a coding framework derived from Normalization Process Theory. We identified three kinds of recovery-supportive work required from health professionals: alleviating stigma, delivering effective recovery-supportive responses in the presence of complex health and social situations and managing challenges associated with the work of ROP. We discuss the resources needed for ROP and the barriers that inhibit health professionals' engagement in this work. By elucidating the work of ROP, we highlighted a disparity between health professionals' aspirations and achievements. These revelations could inform service delivery in order to better support consumer recovery in serious mental illness. © 2016 Australian College of Mental Health Nurses Inc.

Prevention of retinopathy of prematurity in preterm infants through changes in clinical practice and SpO₂technology.

PubMed

Castillo, Armando; Deulofeut, Richard; Critz, Ann; Sola, Augusto

2011-02-01

To identify whether pulse oximetry technology is associated with decreased retinopathy of prematurity (ROP) and laser treatment. Inborn infants <1250 g who had eye exams were compared at two centres in three periods. In Period 1, SpO₂ target was ≥93% and pulse oximetry technology was the same in both Centres. In Period 2, guidelines for SpO₂ 88-93% were implemented at both centres and Centre B changed to oximeters with signal extraction technology (SET(®)) while Centre A did not, but did so in Period 3. One ophthalmology department performed eye exams using international criteria. In 571 newborns <1250 g, birth weight and gestational age were similar in the different periods and centres. At Centre A, severe ROP and need for laser remained the same in Periods 1 and 2, decreasing in Period 3-6% and 3%, respectively. At Centre B, severe ROP decreased from 12% (Period 1) to 5% (Period 2) and need for laser decreased from 5% to 3%, remaining low in Period 3. In a large group of inborn infants <1250 g, a change in clinical practice in combination with pulse oximetry with Masimo SET, but not without it, led to significant reduction in severe ROP and need for laser therapy. Pulse oximetry selection is important in managing critically ill infants. © 2010 The Author(s)/Acta Paediatrica © 2010 Foundation Acta Paediatrica.

Clinical features of infants treated for severe retinopathy of prematurity: 8-yearstudy from a large tertiary neonatal intensive care unit in Turkey.

PubMed

Özen Tunay, Zühal; Özdemir, Özdemir; Ergintürk Acar, Damla; Petriçli, İkbal Seza; Oğuz, Şerife Suna

2016-01-05

The aim of this study was to report the gestational age (GA) and birth weight (BW) distribution of premature babies who needed treatment for retinopathy of prematurity (ROP) and to assess the timing of the treatment. The records of 9008 infants who were screened for ROP were examined and 556 infants who underwent laser therapy for ROP were reviewed. Sex, GA, BW, postnatal age, and postmenstrual (PM) age at the time of laser therapy were recorded. The babies were classified as in-born (Group 1) and out-born infants (Group 2). The mean GA was 27.3 weeks (range: 22-33 weeks) and the mean BW was 991.1 g (range: 520-2160 g). Of the treated infants, 7.0% were born later than 32 weeks and 8.3% were born over 1500 g. The mean postnatal age was 9.48 weeks (range: 5-22 weeks) and the mean PM age was 36.72 weeks (range: 29-48 weeks) at the time of treatment. Mean BWs and GAs were significantly higher and the mean postnatal age at the time of laser therapy was significantly earlier in Group 2. Infants with severe ROP had a wider range of BWs and GAs compared to those from developed countries and earlier treatment was needed for out-born infants.

Evaluation of Refractive Errors and Ocular Biometric Outcomes after Intravitreal Bevacizumab for Retinopathy of Prematurity.

PubMed

Gunay, Murat; Sekeroglu, Mehmet Ali; Bardak, Handan; Celik, Gokhan; Esenulku, Cenap Mahmut; Hekimoglu, Emre; Bardak, Yavuz

2016-06-01

To assess ocular biometric outcomes following intravitreal bevacizumab (IVB) monotherapy for retinopathy of prematurity (ROP) and compare these results with those of laser photocoagulated infants and with the ones with spontaneously regressed ROP. Premature infants including those who underwent IVB monotherapy (Group 1) or laser photocoagulation (Group 2) for ROP and infants with spontaneously regressed ROP (Group 3) were recruited for the study. Refractive errors and ocular biometric parameters (Axial length [AL], anterior chamber depth [ACD], and lens thickness [LT]) were measured at adjusted 1 year of age in all subjects. There was no significant difference of spherical equivalent (SE) value between the groups (P = 0.781). The incidence of high myopia was 7.4% in Group 1 and 12.7% in Group 2 (P = 0.081). No infants exhibited high myopia in Group 3. LT was greater in Group 2 when compared to Group 1 and Group 3 (P = 0.011). Lower SE was significantly correlated to longer AL in Group 1 (r = -0.656, P = 0.015). There was a significant positive correlation between SE and ACD values in Group 2 (r = 0.391, P = 0.005). The study showed no significant difference of SE between the groups. High myopia was only present among the treated infants either with IVB or laser. Infants who received laser treatment significantly had thicker lenses.

Adenosine receptors and caffeine in retinopathy of prematurity.

PubMed

Chen, Jiang-Fan; Zhang, Shuya; Zhou, Rong; Lin, Zhenlang; Cai, Xiaohong; Lin, Jing; Huo, Yuqing; Liu, Xiaoling

2017-06-01

Retinopathy of prematurity (ROP) is a major cause of childhood blindness in the world and is caused by oxygen-induced damage to the developing retinal vasculature, resulting in hyperoxia-induced vaso-obliteration and subsequent delayed retinal vascularization and hypoxia-induced pathological neovascularization driven by vascular endothelial growth factor (VEGF) signaling pathway in retina. Current anti-VEGF therapy has shown some effective in a clinical trial, but is associated with the unintended effects on delayed eye growth and retinal vasculature development of preterm infants. Notably, cellular responses to hypoxia are characterized by robust increases in extracellular adenosine production and the markedly induced adenosine receptors, which provide a novel target for preferential control of pathological angiogenesis without affecting normal vascular development. Here, we review the experimental evidence in support of adenosine receptor-based therapeutic strategy for ROP, including the aberrant adenosine signaling in oxygen-induced retinopathy and the role of three adenosine receptor subtypes (A 1 R, A 2A R, A 2B R) in development and treatment of ROP using oxygen-induced retinopathy models. The clinical and initial animal evidence that implicate the therapeutic effect of caffeine (a non-selective adenosine receptor antagonist) in treatment of ROP are highlighted. Lastly, we discussed the translational potential as well therapeutic advantage of adenosine receptor- and caffeine-based therapy for ROR and possibly other proliferative retinopathy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Anti-Vascular Endothelial Growth Factor and the Evolving Management Paradigm for Retinopathy of Prematurity.

PubMed

Darwish, Dana; Chee, Ru-Ik; Patel, Samir N; Jonas, Karyn; Ostmo, Susan; Campbell, J Peter; Chiang, Michael F; Chan, R V Paul

2018-05-29

Diagnosis and management of pediatric retinal conditions such as retinopathy of prematurity (ROP) have been evolving significantly with the availability of new technology and treatments. New imaging systems, telemedicine, tele-education, and anti‒vascular endothelial growth factor (VEGF) intravitreal pharmacotherapy are all changing the way we diagnose and deliver care to children with pediatric retinal disease. Fluorescein angiography and optical coherence tomography have the potential to improve our diagnosis and management of disease, and with improvements in retinal imaging, telemedicine is becoming more feasible. Telemedicine, tele-education, and computer-based image analysis may overcome many of the challenges we face in providing adequate care and access for children with pediatric retinal disease. Treatment options have also expanded with the use of anti-VEGF therapy. Although the use of intravitreal anti-VEGF for ROP has been documented in the literature for more than a decade, many questions still remain about its safety in the pediatric patient population. Several ongoing prospective studies are exploring the utility of anti-VEGF agents for ROP, with attention to the optimal dose of drug, systemic safety, and our understanding of recurrence of disease. This review aims to provide an update on current diagnostic and therapeutic modalities, focusing predominantly on the role of anti-VEGF therapy, for the management of ROP and other pediatric retinal vascular diseases. Copyright 2018 Asia-Pacific Academy of Ophthalmology.

Structural Evidence for a Sequential Release Mechanism for Activation of Heterotrimeric G Proteins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kapoor, Neeraj; Menon, Santosh T.; Chauhan, Radha

2010-01-12

Heptahelical G-protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptors couple to heterotrimeric G proteins to relay extracellular signals to intracellular signaling networks, but the molecular mechanism underlying guanosine 5'-diphosphate (GDP) release by the G protein {alpha}-subunit is not well understood. Amino acid substitutions in the conserved {alpha}5 helix of Gi, which extends from the C-terminal region to the nucleotide-binding pocket, cause dramatic increases in basal (receptor-independent) GDP release rates. For example, mutant G{alpha}{sub i1}-T329A shows an 18-fold increase in basal GDP release rate and, when expressed in culture, it causes a significant decrease in forskolin-stimulated cAMP accumulation. The crystal structure of G{alpha}{submore » i1}-T329A {center_dot} GDP shows substantial conformational rearrangement of the switch I region and additional striking alterations of side chains lining the catalytic pocket that disrupt the Mg{sup +2} coordination sphere and dislodge bound Mg{sup +2}. We propose a 'sequential release' mechanism whereby a transient conformational change in the {alpha}5 helix alters switch I to induce GDP release. Interestingly, this mechanistic model for heterotrimeric G protein activation is similar to that suggested for the activation of the plant small G protein Rop4 by RopGEF8.« less

Preparation and Characterization of Biomimetic Hydroxyapatite-Resorbable Polymer Composites for Hard Tissue Repair

NASA Astrophysics Data System (ADS)

Hiebner, Kristopher Robert

Autografts are the orthopedic "gold standard" for repairing bone voids. Autografts are osteoconductive and do not elicit an immune response, but they are in short supply and require a second surgery to harvest the bone graft. Allografts are currently the most common materials used for the repair of segmental defects in hard tissue. Unlike autografts, allografts can cause an undesirable immune response and the possibility of disease transmission is a major concern. As an alternative to the above approaches, recent research efforts have focused on the use of composite materials made from hydroxyapatite (HA) and bioresorbable polymers, such as poly-L-lactide (PLLA). Recent results have shown that the surface hydroxides on HA can initiate the ring opening polymerization (ROP) of L-lactide and other lactones creating a composite with superior interfacial strength. This thesis demonstrates that the surface of porous biologically derived HA substrates, such as coralline HA and trabecular bone, can be used to initiate the ROP of L-lactide and other lactones from the vapor phase. This process increases the strength of the porous scaffold through the deposition of a thin, uniform polymer coating, while maintaining the porous structure. The kinetics of the chemical vapor deposition polymerization (CVDP) are described using a quartz crystal microbalance (QCM). The reaction temperature and monomer vapor pressure are found to affect the rate of the polymerization. Also described in this thesis is the preparation of a porous polymer scaffold that mimics the structure of demineralized bone matrix (DBM). This demineralized bone matrix simulant (DBMS) is created using anorganic bovine bone as a template to initiate the polymerization of various lactones, followed by the removal of the HA scaffold. This material retained its shape and exhibits mechanical properties superior to DBM. Finally it is shown that HA can be used to initiate the ROP of a-caprolactam and the biocompatibility of various HA/bioresorbable polymer composites are described through the use of cell cultures run in collaboration with a research group specializing in immunology.

Pharmacological versus microvascular decompression approaches for the treatment of trigeminal neuralgia: clinical outcomes and direct costs

PubMed Central

Lemos, Laurinda; Alegria, Carlos; Oliveira, Joana; Machado, Ana; Oliveira, Pedro; Almeida, Armando

2011-01-01

In idiopathic trigeminal neuralgia (TN) the neuroimaging evaluation is usually normal, but in some cases a vascular compression of trigeminal nerve root is present. Although the latter condition may be referred to surgery, drug therapy is usually the first approach to control pain. This study compared the clinical outcome and direct costs of (1) a traditional treatment (carbamazepine [CBZ] in monotherapy [CBZ protocol]), (2) the association of gabapentin (GBP) and analgesic block of trigger-points with ropivacaine (ROP) (GBP+ROP protocol), and (3) a common TN surgery, microvascular decompression of the trigeminal nerve (MVD protocol). Sixty-two TN patients were randomly treated during 4 weeks (CBZ [n = 23] and GBP+ROP [n = 17] protocols) from cases of idiopathic TN, or selected for MVD surgery (n = 22) due to intractable pain. Direct medical cost estimates were determined by the price of drugs in 2008 and the hospital costs. Pain was evaluated using the Numerical Rating Scale (NRS) and number of pain crises; the Hospital Anxiety and Depression Scale, Sickness Impact Profile, and satisfaction with treatment and hospital team were evaluated. Assessments were performed at day 0 and 6 months after the beginning of treatment. All protocols showed a clinical improvement of pain control at month 6. The GBP+ROP protocol was the least expensive treatment, whereas surgery was the most expensive. With time, however, GBP+ROP tended to be the most and MVD the least expensive. No sequelae resulted in any patient after drug therapies, while after MDV surgery several patients showed important side effects. Data reinforce that, (1) TN patients should be carefully evaluated before choosing therapy for pain control, (2) different pharmacological approaches are available to initiate pain control at low costs, and (3) criteria for surgical interventions should be clearly defined due to important side effects, with the initial higher costs being strongly reduced with time. PMID:21941455

Decreased ocular blood flow after photocoagulation therapy in neonatal retinopathy of prematurity.

PubMed

Matsumoto, Tadashi; Itokawa, Takashi; Shiba, Tomoaki; Tomita, Masahiko; Hine, Kotaro; Mizukaki, Norio; Yoda, Hitoshi; Hori, Yuichi

2017-11-01

To evaluate the relationships between optic nerve head blood flow, expressed as mean blur rate (MBR) measured by laser speckle flowgraphy (LSFG), and photocoagulation therapy in neonates with retinopathy of prematurity (ROP). Case series study. We studied 5 ROP neonates either during sleep or under sedation both before and after photocoagulation, and evaluated 8 eyes in which the circulation could be measured three times consecutively. Correlations between the MBR-A (mean of all values), MBR-V (vessel mean) and MBR-T (tissue mean) and postmenstrual age were evaluated using Spearman's rank correlation coefficient. In addition, correlations between the relative MBR (-A, -V, -T) value and number of photocoagulation burns and the NV score were evaluated. Differences between post-treatment MBR in ROP subjects and normal neonates' MBR were estimated using analysis of covariance (ANCoVA), with adjustment for postmenstrual age. The relative MBR (-A, -V, -T) values after photocoagulation were 69.6 ± 16.0%, 66.7 ± 17.0% and 74.3 ± 14.6%, respectively. Postmenstrual age was significantly correlated with post-treatment MBR-A (r = 0.83, p = 0.0101), MBR-V (r = 0.85, p = 0.007) and MBR-T (r = 0.76, p = 0.0282). The relative MBR-T value was significantly correlated with the number of photocoagulation burns (r = -0.75, p = 0.033) and NV score (r = -0.72, p = 0.0437). The ANCoVA results showed no significant difference between post-treatment MBR and normal neonates' MBR. Photocoagulation improved the dilation of veins and tortuosity of arteries and reduced ocular blood flow in ROP subjects. Since the post-treatment MBR was not different from a normal neonate's MBR, it is suggested that the pre-treatment MBR was higher in severe ROP cases.

Efficacy of sucrose to reduce pain in premature infants during eye examinations for retinopathy of prematurity.

PubMed

Gal, Peter; Kissling, Grace E; Young, William O; Dunaway, Kimberly K; Marsh, Virginia A; Jones, Susan M; Shockley, Dawn H; Weaver, Nicole L; Carlos, Rita Q; Ransom, J Laurence

2005-06-01

Eye examinations for retinopathy of prematurity (ROP) are painful to the neonate. The use of topical anesthetic for eye examinations to evaluate ROP is routine in our neonatal intensive care unit (NICU), but does not completely suppress painful responses. Sweet solutions have been shown to reduce procedural pain in newborns. To examine whether the addition of sucrose 24% to topical anesthetic improves procedural pain control during the ROP eye examination. Neonates born at < or = 30 weeks' gestation were included in this placebo-controlled, double-blind, crossover study. Patients were randomly assigned to receive treatment with either proparacaine HCl ophthalmic solution 0.5% plus 2 mL of sucrose 24% or proparacaine HCl ophthalmic solution 0.5% plus 2 mL of sterile water (placebo) prior to an eye examination. In a subsequent eye examination, each patient received the alternate treatment. Oral sucrose and sterile water were prepared in the pharmacy in identical syringes, and physicians, nurses, and pharmacists in the NICU were blinded to the treatment given. Pain was measured using the Premature Infant Pain Profile (PIPP) scoring system, which measures both physical and physiologic measures of pain, and the scores were simultaneously assessed by 2 study nurses. PIPP scores were recorded 1 and 5 minutes before and after the eye examination and during initial placement of the eye speculum. The same ophthalmologist performed all eye examinations. Several different definitions of a pain response were investigated. Twenty-three infants were studied, with 12 receiving sucrose and 11 receiving placebo as the first treatment. For 3 of the 5 definitions of pain response, patients experienced significantly less pain at speculum insertion with sucrose than with placebo. After the ROP examination, pain responses were similar with either sucrose or placebo. Oral sucrose may reduce the immediate pain response in premature infants undergoing eye examination for ROP.

Sequential Right and Left Ventricular Assessment in Posttetralogy of Fallot Patients with Significant Pulmonary Regurgitation.

PubMed

Wijesekera, Vishva A; Raju, Rekha; Precious, Bruce; Berger, Adam J; Kiess, Marla C; Leipsic, Jonathon A; Grewal, Jasmine

2016-12-01

The natural history of right ventricular (RV) and left ventricular (LV) size and function among adults with tetralogy of Fallot (TOF) repair and hemodynamically significant pulmonary regurgitation (PR) is not known. The main aim of this study was to determine changes in RV and LV size and function over time in an adult population with TOF repair and hemodynamically significant pulmonary regurgitation. Forty patients with repaired TOF and hemodynamically significant PR were included. These patients were identified on the basis of having more than one CMR between January 2008 and 2015. Patients with a prosthetic pulmonary valve or any cardiac intervention between CMR studies were excluded. Rate of progression (ROP) of RV dilation was determined for both indexed right ventricular end-systolic volume (RVESVi) and indexed right ventricular end-diastolic volume (RVEDVi), and calculated as the difference between the last and first volumes divided by the number of years between CMR#1 and CMR#2. Subjects were also divided into two groups based on the distribution of the ROP of RV dilation: Group I-rapid ROP (>50th percentile) and Group II-slower ROP (≤50th percentile). The interval between CMR#1 and CMR#2 was 3.9 ± 1.7 years (range 1-8 years). We did find a significant change in RVEDVi and RVESVi over this time period, although the magnitude of change was small. Nine patients (23%) had a reduction in right ventricular ejection fraction (RVEF) by greater than 5%, 13 patients (33%) had an increase in RVEDVi by greater than 10 mL/m 2 and seven patients (18%) had an increase in RVESVi by greater than 10 mL/m 2 . Median ROP for RVEDVi was 1.8 (range -10.4 to 21.8) mL/(m 2 year); RVESVi 1.1 (range -5.8 to 24.5) mL/(m 2 year) and RVEF -0.5 (range -8 to 4)%/year. Patients with a rapid ROP had significantly larger RV volumes at the time of CMR#1 and lower RVEF as compared to the slow ROP group. There was no overall significant change in LVEDVi, LVESVi, or LVEF over this time period. We have demonstrated, in a small population of patients with hemodynamically significant PR, that there is a small increase in RV volumes and decrease in RVEF over a mean 4-year period. We believe it to be reasonable practice to perform CMR at least every 4 years in asymptomatic patients with repaired TOF and hemodynamically significant PR. We found that LV volumes and function remained stable during the study period, suggesting that significant progressive LV changes are less likely to occur over a shorter time period. Our results inform a safe standardized approach to monitoring adults with hemodynamically significant PR post TOF repair and assist in planning allocation of this expensive and limited resource. © 2016 Wiley Periodicals, Inc.

Solventless sol-gel chemistry through ring-opening polymerization of bridged disilaoxacyclopentanes

DOE Office of Scientific and Technical Information (OSTI.GOV)

RAHIMIAN,KAMYAR; LOY,DOUGLAS A.

2000-05-01

Ring-opening polymerization (ROP) of disilaoxacyclopentanes has proven to be an excellent approach to sol-gel type hybrid organic-inorganic materials. These materials have shown promise as precursors for encapsulation and microelectronics applications. The polymers are highly crosslinked and are structurally similar to traditional sol-gels, but unlike typical sol-gels they are prepared by an organic base or Bronsted acid (formic or triflic acid), without the use of solvents and water, they have low VOC's and show little shrinkage during processing.

Regulation of dendrite growth and maintenance by exocytosis

PubMed Central

Peng, Yun; Lee, Jiae; Rowland, Kimberly; Wen, Yuhui; Hua, Hope; Carlson, Nicole; Lavania, Shweta; Parrish, Jay Z.; Kim, Michael D.

2015-01-01

ABSTRACT Dendrites lengthen by several orders of magnitude during neuronal development, but how membrane is allocated in dendrites to facilitate this growth remains unclear. Here, we report that Ras opposite (Rop), the Drosophila ortholog of the key exocytosis regulator Munc18-1 (also known as STXBP1), is an essential factor mediating dendrite growth. Neurons with depleted Rop function exhibit reduced terminal dendrite outgrowth followed by primary dendrite degeneration, suggestive of differential requirements for exocytosis in the growth and maintenance of different dendritic compartments. Rop promotes dendrite growth together with the exocyst, an octameric protein complex involved in tethering vesicles to the plasma membrane, with Rop–exocyst complexes and exocytosis predominating in primary dendrites over terminal dendrites. By contrast, membrane-associated proteins readily diffuse from primary dendrites into terminals, but not in the reverse direction, suggesting that diffusion, rather than targeted exocytosis, supplies membranous material for terminal dendritic growth, revealing key differences in the distribution of materials to these expanding dendritic compartments. PMID:26483382

Recycling domains in plant cell morphogenesis: small GTPase effectors, plasma membrane signalling and the exocyst.

PubMed

Zárský, Viktor; Potocký, Martin

2010-04-01

The Rho/Rop small GTPase regulatory module is central for initiating exocytotically ACDs (active cortical domains) in plant cell cortex, and a growing array of Rop regulators and effectors are being discovered in plants. Structural membrane phospholipids are important constituents of cells as well as signals, and phospholipid-modifying enzymes are well known effectors of small GTPases. We have shown that PLDs (phospholipases D) and their product, PA (phosphatidic acid), belong to the regulators of the secretory pathway in plants. We have also shown that specific NOXs (NADPH oxidases) producing ROS (reactive oxygen species) are involved in cell growth as exemplified by pollen tubes and root hairs. Most plant cells exhibit several distinct plasma membrane domains (ACDs), established and maintained by endocytosis/exocytosis-driven membrane protein recycling. We proposed recently the concept of a 'recycling domain' (RD), uniting the ACD and the connected endosomal recycling compartment (endosome), as a dynamic spatiotemporal entity. We have described a putative GTPase-effector complex exocyst involved in exocytic vesicle tethering in plants. Owing to the multiplicity of its Exo70 subunits, this complex, along with many RabA GTPases (putative recycling endosome organizers), may belong to core regulators of RD organization in plants.

Zinc complexes supported by methyl salicylato ligands: synthesis, structure, and application in ring-opening polymerization of L-lactide.

PubMed

Petrus, Rafał; Sobota, Piotr

2013-10-14

Two novel zinc alkoxides supported by chelating methyl salicylato (MesalO; MesalOH = methyl salicylate) ligands were successfully synthesized and characterized. Reaction of MesalOH with ZnEt2 (2:1) gives a tetranuclear cluster [Zn(MesalO)2]4 (1), which by addition of pyridine is transformed to the mononuclear compound [Zn(MesalO)2(py)2] (2). Compounds 1 and 2 were characterized by elemental analysis, NMR, IR, and single crystal X-ray diffraction. The catalytic activity of both compounds was tested for the ring-opening polymerization (ROP) of L-lactide (L-LA). It was found that compounds 1 and 2 are efficient initiators of the ROP of L-LA, yielding cyclic PLLA with weight average molecular weights up to 100 kDa for 2. The treatment of 2 with 1 equiv. of BnOH in toluene afforded a dimeric compound [Zn(OBn)(MesalO)(py)]2 (3). The addition of L-LA to a combination of 1 and 4 equiv. of BnOH in THF or 2 and 1 equiv. of BnOH in toluene led to the rapid and efficient generation of PLLA with end-capped BnO groups.

Detection of Clinically Significant Retinopathy of Prematurity Using Wide-angle Digital Retinal Photography

PubMed Central

Chiang, Michael F.; Melia, Michele; Buffenn, Angela N.; Lambert, Scott R.; Recchia, Franco M.; Simpson, Jennifer L.; Yang, Michael B.

2013-01-01

Objective To evaluate the accuracy of detecting clinically significant retinopathy of prematurity (ROP) using wide-angle digital retinal photography. Methods Literature searches of PubMed and the Cochrane Library databases were conducted last on December 7, 2010, and yielded 414 unique citations. The authors assessed these 414 citations and marked 82 that potentially met the inclusion criteria. These 82 studies were reviewed in full text; 28 studies met inclusion criteria. The authors extracted from these studies information about study design, interventions, outcomes, and study quality. After data abstraction, 18 were excluded for study deficiencies or because they were superseded by a more recent publication. The methodologist reviewed the remaining 10 studies and assigned ratings of evidence quality; 7 studies were rated level I evidence and 3 studies were rated level III evidence. Results There is level I evidence from ≥5 studies demonstrating that digital retinal photography has high accuracy for detection of clinically significant ROP. Level III studies have reported high accuracy, without any detectable complications, from real-world operational programs intended to detect clinically significant ROP through remote site interpretation of wide-angle retinal photographs. Conclusions Wide-angle digital retinal photography has the potential to complement standard ROP care. It may provide advantages through objective documentation of clinical examination findings, improved recognition of disease progression by comparing previous photographs, and the creation of image libraries for education and research. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references. PMID:22541632

The effectiveness of policy changes designed to increase the attendance rate for outpatient retinopathy of prematurity (ROP) screening examinations.

PubMed

Barry, Gerard P; Tauber, Kate; Emmanuel, Gregory; Horgan, Michael J; Simon, John W

2013-06-01

To determine the effectiveness of a series of policy changes designed to increase the attendance rate for outpatient retinopathy of prematurity (ROP) screening examinations. We retrospectively reviewed the records of consecutive neonatal intensive care unit patients before and after the implementation of policy changes. Policy changes included parent education forms, streamlined scheduling, and creation of a log for all patients seen. The primary outcome measure was attendance rates for the first outpatient appointment after discharge. The Fisher exact test was used to compare rates between the two groups. Before the policy was implemented, 22 of 52 (42%) neonates and their caregivers attended their first outpatient ROP screening examination on the recommended date. This rate improved significantly after policy implementation, when 46 of 57 (81%) neonates and their caregivers were seen on the recommended date (P < 0.01). The number of patients who ultimately met the criteria for conclusion of acute retinal screening examinations also significantly improved, from 47 of 52 (90%) of neonates in the pre-implementation group to 57 of 57 (100%) in the post-implementation group (P = 0.02). The attendance rates for initial outpatient ROP examinations and the number of patients who ultimately met criteria for conclusion of acute retinal screening examinations significantly improved after the implementation of new policies. Copyright © 2013 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.

Mobile phones for retinopathy of prematurity screening in Lagos, Nigeria, sub-Saharan Africa.

PubMed

Oluleye, Tunji S; Rotimi-Samuel, Adekunle; Adenekan, Adetunji

2016-01-01

Retinopathy of prematurity (ROP), thought to be rare in Nigeria, sub-Saharan Africa, has been reported in recent studies. Developing cost-effective screening is crucial for detecting retinal changes amenable to treatment. This study describes the use of an iPhone combined with a 20-D lens in screening for ROP in Lagos, Nigeria. The ROP screening program was approved by the Lagos University Teaching Hospital Ethical Committee. Preterm infants with birthweight of less than 1.5 kg or gestational age of less than 32 weeks were screened. In conjunction with the neonatologist, topical tropicamide (0.5%) and phenylephrine (2.5%) was used to dilate the pupils. A pediatric lid speculum was used. Indirect ophthalmoscopy was used to examine the fundus to ensure there were no missed diagnoses. An iPhone 5 with 20-D lens was used to examine the fundus. The App Filmic Pro was launched in the video mode. The camera flash served as the source of illumination. Its intensity was controlled by the app. The 20-D lens was used to capture the image of the retina, which was picked up by the camera system of the mobile phone. Another app, Aviary, was used to edit the picture. The images captured by the system were satisfactory for staging and determining the need for treatment. An iPhone combined with a 20-D lens appear to be useful in screening for ROP in resource-poor settings. More studies are needed in this area.

Ethnopharmacological survey of medicinal plants used in Daraa-Tafilalet region (Province of Errachidia), Morocco.

PubMed

Eddouks, Mohamed; Ajebli, Mohammed; Hebi, Morad

2017-02-23

We carried out an ethnobotanical survey in Tafilalet region. This region is classified by the UNESCO as a reserve of biosphere and represents an important area with important knowledge of traditional medicine, especially the use of medicinal plants for human healthcare. Furthermore, the geographic location of this region makes this site a diverse and interesting resource of herbal biodiversity. The study aimed to collect information about medicinal plants used in Tafilalet region as well as the indigenous knowledge related to the use of this natural resource in healthcare by the local population in order to preserve and protect this invaluable inheritance from loss and overlook. We aimed also to compare taxa used by the indigenous people of Tafilalet for health-care purposes in comparison with other regions of Morocco as well as neighboring countries. The total of informants interviewed in this study was 1616 (1500 were local inhabitants and 116 were herbalists). This enquiry was carried out through semi-structured and unstructured interviews and the sampling technique used was the stratified sample (9 stratums). Data obtained were analyzed calculating 6 indices: Use Value (UV), Family Use Value (FUV), Fidelity Level (FL), Rank Order Priority (ROP), Informant Consensus Factor (Fic) and Jaccard similarity Index (JI). 194 species belonging to 69 families were inventoried in this survey and 17 species were cited for the first time in an ethnobotanical survey in Morocco. The highest value of UV was obtained for Rosmarinus officinalis L. (UV=0.24) and Liliaceae was the family frequently used by inhabitants of Tafilalet (FUV=0.106). In addition, the highest value of FL was recorded for Cistus salviifolius L. and Daphne gnidium L. with FL value of 100% for both species and Origanium vulgare L. had the highest ROP with a value of 53% while the highest value of FIC was mentioned for digestive system disorders (FIC=0.29). Concerning the level of similarity between our study and other regions of Morocco, the province of Tata seems to be the most similar to Tafilalet (JI=42.97), while M'sila (Algeria) was the most similar to Tafilalet among areas in neighboring countries (JI=13.00). Despite the richness which characterizes Tafilalet regarding diversity and effectiveness of medicinal plants as well as the largest culture and knowledge related to the popular phytotherapy among local people in this region, several procedures must be realized to protect and to valorize this interesting inheritance. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Ring-opening polymerization of 19-electron [2]cobaltocenophanes: a route to high-molecular-weight, water-soluble polycobaltocenium polyelectrolytes.

PubMed

Mayer, Ulrich F J; Gilroy, Joe B; O'Hare, Dermot; Manners, Ian

2009-08-05

Water-soluble, high-molecular-weight polycobaltocenium polyelectrolytes have been prepared by ring-opening polymerization (ROP) techniques. Anionic polymerization of a strained 19-electron dicarba[2]cobaltocenophane followed by oxidation in the presence of ammonium chloride resulted in the formation of oligomers with up to nine repeat units. Thermal ROP of dicarba[2]cobaltocenophane followed by oxidation in the presence of ammonium nitrate resulted in the formation of high-molecular-weight polycobaltocenium nitrate, a redox-active cobalt-containing polyelectrolyte.

Intravitreal bevacizumab versus laser treatment in type 1 retinopathy of prematurity: report on fluorescein angiographic findings.

PubMed

Lepore, Domenico; Quinn, Graham E; Molle, Fernando; Baldascino, Antonio; Orazi, Lorenzo; Sammartino, Maria; Purcaro, Velia; Giannantonio, Carmen; Papacci, Patrizia; Romagnoli, Costantino

2014-11-01

To compare the structural outcome at 9 months of eyes treated with intravitreal injection of bevacizumab with fellow eyes treated with conventional laser photoablation in zone I type 1 retinopathy of prematurity (ROP). Single randomized controlled trial. All inborn babies with type 1 zone I ROP at a single institution were included in the study. One eye was randomized to receive an intravitreal injection of 0.5 mg bevacizumab; the fellow eye received conventional laser photoablation. Digital fundus photographs and fluorescein angiography (FA) using the RetCam (Clarity Medical Systems Inc., Pleasanton, CA) were performed before treatment and 9 months after treatment. Presence of retinal and choroidal abnormalities on FA at 9 months. Thirteen infants were enrolled; 1 died 3 months after birth. One laser-treated eye progressed to stage 5 retinal detachment. The remaining 23 eyes had favorable structural results at the 9-month follow-up and provided FA results. At 9 months of age, all eyes treated with a bevacizumab injection were noted to have abnormalities at the periphery (large avascular area, abnormal branching, shunt) or the posterior pole (hyperfluorescent lesion, absence of foveal avascular zone). These posterior and peripheral lesions were not observed in the majority of the lasered eyes. This study documents significant vascular and macular abnormalities of eyes in the bevacizumab group. Long-lasting implications of these abnormalities for visual function of the child need to be studied. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

The neurovascular relation in oxygen-induced retinopathy.

PubMed

Akula, James D; Mocko, Julie A; Benador, Ilan Y; Hansen, Ronald M; Favazza, Tara L; Vyhovsky, Tanya C; Fulton, Anne B

2008-01-01

Longitudinal studies in rat models of retinopathy of prematurity (ROP) have demonstrated that abnormalities of retinal vasculature and function change hand-in-hand. In the developing retina, vascular and neural structures are under cooperative molecular control. In this study of rats with oxygen-induced retinopathy (OIR) models of ROP, mRNA expression of vascular endothelial growth factor (VEGF), semaphorin (Sema), and their neuropilin receptor (NRP) were examined during the course of retinopathy to evaluate their roles in the observed neurovascular congruency. Oxygen exposures designed to induce retinopathy were delivered to Sprague-Dawley rat pups (n=36) from postnatal day (P) 0 to P14 or from P7 to P14. Room-air-reared controls (n=18) were also studied. Sensitivities of the rod photoreceptors (S(rod)) and the postreceptor cells (Sm) were derived from electroretinographic (ERG) records. Arteriolar tortuosity, T(A), was derived from digital fundus images using Retinal Image multi-Scale Analysis (RISA) image analysis software. mRNA expression of VEGF(164), semaphorin IIIA (Sema3A), and neuropilin-1 (NRP-1) was evaluated by RT-PCR of retinal extracts. Tests were performed at P15-P16, P18-P19, and P25-P26. Relations among ERG, RISA, and PCR parameters were evaluated using linear regression on log transformed data. Sm was low and T(A) was high at young ages, then both resolved by P25-P26. VEGF(164) and Sema3A mRNA expression were also elevated early and decreased with age. Low Sm was significantly associated with high VEGF(164) and Sema3A expression. Low S(rod) was also significantly associated with high VEGF(164). S(rod) and Sm were both correlated with T(A). NRP-1 expression was little affected by OIR. The postreceptor retina appears to mediate the vascular abnormalities that characterize OIR. Because of the relationships revealed by these data, early treatment that targets the neural retina may mitigate the effects of ROP.

The neurovascular relation in oxygen-induced retinopathy

PubMed Central

Akula, James D.; Mocko, Julie A.; Benador, Ilan Y.; Hansen, Ronald M.; Favazza, Tara L.; Vyhovsky, Tanya C.

2008-01-01

Purpose Longitudinal studies in rat models of retinopathy of prematurity (ROP) have demonstrated that abnormalities of retinal vasculature and function change hand-in-hand. In the developing retina, vascular and neural structures are under cooperative molecular control. In this study of rats with oxygen-induced retinopathy (OIR) models of ROP, mRNA expression of vascular endothelial growth factor (VEGF), semaphorin (Sema), and their neuropilin receptor (NRP) were examined during the course of retinopathy to evaluate their roles in the observed neurovascular congruency. Methods Oxygen exposures designed to induce retinopathy were delivered to Sprague-Dawley rat pups (n=36) from postnatal day (P) 0 to P14 or from P7 to P14. Room-air-reared controls (n=18) were also studied. Sensitivities of the rod photoreceptors (Srod) and the postreceptor cells (Sm) were derived from electroretinographic (ERG) records. Arteriolar tortuosity, TA, was derived from digital fundus images using Retinal Image multi-Scale Analysis (RISA) image analysis software. mRNA expression of VEGF164, semaphorin IIIA (Sema3A), and neuropilin-1 (NRP-1) was evaluated by RT–PCR of retinal extracts. Tests were performed at P15–P16, P18–P19, and P25–P26. Relations among ERG, RISA, and PCR parameters were evaluated using linear regression on log transformed data. Results Sm was low and TA was high at young ages, then both resolved by P25–P26. VEGF164 and Sema3A mRNA expression were also elevated early and decreased with age. Low Sm was significantly associated with high VEGF164 and Sema3A expression. Low Srod was also significantly associated with high VEGF164. Srod and Sm were both correlated with TA. NRP-1 expression was little affected by OIR. Conclusions The postreceptor retina appears to mediate the vascular abnormalities that characterize OIR. Because of the relationships revealed by these data, early treatment that targets the neural retina may mitigate the effects of ROP. PMID:19112532

The optimum time to employ telephotoscreening to detect retinopathy of prematurity.

PubMed Central

Yen, K G; Hess, D; Burke, B; Johnson, R A; Feuer, W J; Flynn, J T

2000-01-01

PURPOSE: Labor-intensive screening of infants in the neonatal intensive care units is the only way to detect retinopathy of prematurity (ROP). Our purpose is to determine if RetCam 120 photos, acquired by a neonatal nurse, can be used to screen for ROP by performing 2 screening examinations, at 32 to 34 weeks (exam 1) and at 38 to 40 weeks (exam 2) post-conceptional age. METHODS: RetCam examinations are performed by a nurse on infants at exam 1 and exam 2 intervals. At the same time, an examination is performed by an experienced ophthalmologist. Masked readers evaluate the photos for ROP and determine if each eye will progress to prethreshold or threshold disease. The data are compared to the clinical course of the eyes. RESULTS: Forty-six eyes were photographed at exam 1 and 50 eyes at exam 2 from July 1, 1999, to December 15, 1999. Sensitivity and specificity of detecting ROP were 76% and 100% for exam 2 and 46% and 100% for exam 1. Sensitivity and specificity of predicting prethreshold disease were 64% and 97% for exam 2 and 33% and 100% for exam 1. Sensitivity and specificity of predicting threshold were both 100% at exam 2 and 0% (one photo in category) and 95% at exam 1. CONCLUSION: A potential reason for low sensitivity is technical limitations of the Retcam, such as the difficulty in capturing peripheral retina in small eyes and the need for a better lid speculum. Images FIGURE 1 FIGURE 2A FIGURE 2B FIGURE 3 PMID:11190018

Refraction and visual acuity in a national Danish cohort of 4-year-old children of extremely preterm delivery.

PubMed

Fledelius, Hans C; Bangsgaard, Regitze; Slidsborg, Carina; laCour, Morten

2015-06-01

A recent threefold increase in laser treatment for advanced retinopathy of prematurity (ROP) triggered a nationwide preschool ophthalmic and developmental status among extremely preterm survivors. Here, we discuss refraction and visual acuity. Survivors (n = 178) from a national birth cohort (February 2004 to March 2006) of gestational age <28 weeks (PT) and 56 full-term (FT) controls attended for evaluation at age 4 years. Cycloplegic refraction and keratometry were achieved by Retinomax autokeratorefractor and visual acuities by symbol recognition (HOTV, logMAR). The refractive distribution presented a myopic tail (4.5%) and a hyperopic tail (11.9% ≥+2.5 D) as special preterm features, and corneas were more curved. Astigmatism and anisometropia were only marginally increased, and visual acuities were generally good. Best-corrected binocular median logMAR visual acuity was 0.1 in FT and 0.2 in PT, in Snellen equivalents 0.8 and 0.63. Snellen acuity ≤0.5 occurred across the ROP subgroups, but mainly in those with at least ROP stage 3. Two children had low vision. The overall fair outcome for refraction and function is in accordance with other recent northern Europe experience. The results differ in particular from the poorer ophthalmic outcomes reported in the pioneer US treatment studies (cryotherapy for ROP and ETROP). The diode laser ablations (n = 32) appeared effective in our series; except one child, all treated subjects had good or fair social vision at the age of 4 years. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Duration of anaemia during the first week of life is an independent risk factor for retinopathy of prematurity.

PubMed

Lundgren, Pia; Athikarisamy, Sam E; Patole, Sanjay; Lam, Geoffrey C; Smith, Lois E; Simmer, Karen

2018-05-01

This study evaluated the correlation between retinopathy of prematurity (ROP), anaemia and blood transfusions in extremely preterm infants. We included 227 infants born below 28 weeks of gestation at King Edward Memorial Hospital, Perth, Australia, from 2014-2016. Birth characteristics and risk factors for ROP were retrieved, and anaemia and severe anaemia were defined as a haemoglobins of <110 g/L and <80 g/L, respectively. Logistic regression was used for the analysis. Retinopathy of prematurity treatment was needed in 11% of cases and the mean number of blood transfusions (p < 0.01), and mean number of weeks of anaemia (p < 0.001) and of severe anaemia (p < 0.05), had positive associations with ROP cases warranting treatment. In the multivariate logistic regression analysis, the best-fit model of risk factors included anaemic days during first week of life, with an odds ratio (OR) of 1.46% and 95% confidence interval (CI) of 1.16-1.83 (p < 0.05), sepsis during the first 4 weeks of life (OR 3.14, 95% CI 1.10-9.00, p < 0.05) and days of ventilation (OR 1.03, 95% CI 1.01-1.06, p < 0.05). The duration of anaemia during the first week of life was an independent risk factor for ROP warranting treatment and preventing early anaemia may decrease this risk. ©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

A tool for computer-aided diagnosis of retinopathy of prematurity

NASA Astrophysics Data System (ADS)

Zhao, Zheen; Wallace, David K.; Freedman, Sharon F.; Aylward, Stephen R.

2008-03-01

In this paper we present improvements to a software application, named ROPtool, that aids in the timely and accurate detection and diagnosis of retinopathy of prematurity (ROP). ROP occurs in 68% of infants less than 1251 grams at birth, and it is a leading cause of blindness for prematurely born infants. The standard of care for its diagnosis is the subjective assessment of retinal vessel dilation and tortuosity. There is significant inter-observer variation in those assessments. ROPtool analyzes retinal images, extracts user-selected blood vessels from those images, and quantifies the tortuosity of those vessels. The presence of ROP is then gauged by comparing the tortuosity of an infant's retinal vessels with measures made from a clinical-standard image of severely tortuous retinal vessels. The presence of such tortuous retinal vessels is referred to as 'plus disease'. In this paper, a novel metric of tortuosity is proposed. From the ophthalmologist's point of view, the new metric is an improvement from our previously published algorithm, since it uses smooth curves instead of straight lines to simulate 'normal vessels'. Another advantage of the new ROPtool is that minimal user interactions are required. ROPtool utilizes a ridge traversal algorithm to extract retinal vessels. The algorithm reconstructs connectivity along a vessel automatically. This paper supports its claims by reporting ROC curves from a pilot study involving 20 retinal images. The areas under two ROC curves, from two experts in ROP, using the new metric to diagnose 'tortuosity sufficient for plus disease', varied from 0.86 to 0.91.

Evaluation of retinopathy of prematurity screening in reverse Kangaroo Mother Care: a pilot study.

PubMed

Padhi, T R; Sareen, D; Pradhan, L; Jalali, S; Sutar, S; Das, T; Modi, R R; Behera, U C

2015-04-01

To evaluate retinopathy of prematurity (ROP) screening practice in reverse Kangaroo Mother Care (R-KMC) with respect to stress and pain to the infant. In a pilot study we evaluated ROP screening practice in R-KMC in 20 babies at risk of ROP. The R-KMC differed from the conventional KMC with respect to the baby position where the baby lay supine on mother's chest. With the mother lying supine and the baby in R-KMC position, screening examinations were done with indirect ophthalmoscope. The outcome measures included stress (quantified by pulse, respiration, and oxygen saturation) and pain to the baby by observing facial expression (eye squeezing, crying, and brow bulge). The heart rate, respiratory rate, and SpO2 (%) were compared before and immediately after the procedure using paired t-test. Mean (±SD) gestational age and birth weight were 30.8±2.3 weeks and 1362.5±253.9 g, respectively. During examination in R- KMC position 8 babies (40%) were completely relaxed (no eye squeezing and crying), 10 (50%) were partially relaxed (no brow bulge) and 2 babies (10%) were not relaxed. A change in heart and respiration rate both by 10 per minute was recorded in 12 (60%) and 10 (50%) babies, respectively. Five babies (25%) had reduction in blood oxygen concentration below 92%. The majority of the mothers (19 of 20) were relaxed. ROP screening in R-KMC can be a baby friendly screening practice with respect to stress and pain to the infant and needs further evaluation in a larger cohort.

Effects of Intravitreal Ranibizumab in the Treatment of Retinopathy of Prematurity in Chinese Infants.

PubMed

Yi, Zuohuizi; Su, Yu; Zhou, Yunyun; Zheng, Hongmei; Ye, Meihong; Xu, Yonghong; Chen, Changzheng

2016-08-01

To evaluate the efficacy associated with intravitreal ranibizumab in the treatment of retinopathy of prematurity (ROP). A retrospective case series study. Infants diagnosed with Type 1 ROP, or aggressive posterior ROP (AP-ROP) were enrolled in the study. All infants in the study received intravitreal ranibizumab (0.25 mg/0.025 ml) as the initial treatment. Follow-up examinations were performed the day after treatment, then weekly for 1 month, bi-monthly for two additional months, then monthly until vascularization of zone III occurred. Additional treatments were initiated in cases of disease recurrence. Thirty-three premature infants (a total of 66 eyes) receiving intravitreal ranibizumab were included. The mean birth weight was 1291 ± 211 g (range: 650-1650 g) and the mean gestational age was 29.8 ± 1.6 weeks (range: 27.0-33.6 weeks). The mean gestational age at the time of the first injection was 35.8 ± 1.6 weeks (range: 32.7-38.4 weeks). The mean follow-up time was 12.9 ± 4.9 months (range: 6-22 months). Single injections were administered to 58 eyes (87.9%), whereas eight eyes (12.1%) received additional treatments. Recurrence was observed in eight eyes (12.1%), with a mean time to recurrence of 6.9 ± 1.8 weeks (range: 4-8 weeks). Intravitreal ranibizumab is effective for the treatment of retinopathy of prematurity, although a small amount of patients recurred. Compared with intravitreal bevacizumab, a higher incidence and shorter time to recurrence were observed after intravitreal ranibizumab treatment, thus longer and more frequent follow-ups are needed.

Progression of myopia and high myopia in the Early Treatment for Retinopathy of Prematurity study: findings at 4 to 6 years of age.

PubMed

Quinn, Graham E; Dobson, Velma; Davitt, Bradley V; Wallace, David K; Hardy, Robert J; Tung, Betty; Lai, Dejian; Good, William V

2013-04-01

To report the prevalence of myopia and high myopia in children <6 years of age born preterm with birth weights <1251 g who developed high-risk prethreshold retinopathy of prematurity and who participated in the Early Treatment for Retinopathy of Prematurity trial. Surviving children from the cohort of 401 participants who had developed high-risk prethreshold ROP in one or both eyes underwent cycloplegic retinoscopy at 6 and 9 months corrected age and yearly between 2 and 6 years postnatal age. Eyes were randomized to receive treatment at high-risk prethreshold ROP or conventional management with treatment only if threshold ROP developed. Myopia (spherical equivalent ≥0.25 D) or high myopia (≥5.00 D) in eyes at 4-, 5-, and 6-year examinations was reported. At ages 4, 5, and 6 years, there was no difference in the percentage of eyes with myopia (range, 64.8%-69.9%) and eyes with high myopia (range, 35.3%-39.4%) between earlier treated and conventionally managed eyes. Approximately two-thirds of eyes with high-risk prethreshold ROP during the neonatal period are likely to be myopic into the preschool and early school years. In addition, the increase in the proportion of eyes with high myopia that had been observed in both earlier-treated and conventionally managed eyes between ages 6 months and 3 years does not continue between ages 3 and 6 years. Copyright © 2013 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.

Short-term outcome after intravitreal ranibizumab injections for the treatment of retinopathy of prematurity.

PubMed

Castellanos, María Ana Martínez; Schwartz, Shulamit; García-Aguirre, Gerardo; Quiroz-Mercado, Hugo

2013-07-01

To evaluate ocular outcome in premature infants treated with intravitreal ranibizumab injections for retinopathy of prematurity (ROP) over a period of 3 years. An interventional case series. Premature infants with high-risk prethreshold or threshold ROP with plus disease received an off label monotherapy with intravitreal injections of ranibizumab. The primary outcome was treatment success defined as regression of neovascularisation (NV) and absence of recurrence. The secondary outcomes were ocular and systemic adverse events and visual acuity. Six eyes were included in the study and treated with intravitreal injections of ranibizumab. All showed complete resolution of NV after a single injection. The anti-angiogenic intravitreal injections allowed for continued normal vessel growth into the peripheral retina, without any signs of disease recurrence or progression during the follow up period. No ocular or systemic adverse effects were observed. Three years of follow up in a small series suggest that intravitreal ranibizumab injections for ROP result in apparently preserved ocular outcome. Further large scale studies are needed to address the long-term safety and efficacy.

Secretogranin III as a disease-associated ligand for antiangiogenic therapy of diabetic retinopathy

PubMed Central

LeBlanc, Michelle E.; Wang, Weiwen; Chen, Xiuping; Caberoy, Nora B.; Guo, Feiye; Shen, Chen; Ji, Yanli; Tian, Hong; Wang, Hui; Chen, Rui

2017-01-01

Diabetic retinopathy (DR) is a leading cause of vision loss with retinal vascular leakage and/or neovascularization. Current antiangiogenic therapy against vascular endothelial growth factor (VEGF) has limited efficacy. In this study, we applied a new technology of comparative ligandomics to diabetic and control mice for the differential mapping of disease-related endothelial ligands. Secretogranin III (Scg3) was discovered as a novel disease-associated ligand with selective binding and angiogenic activity in diabetic but not healthy vessels. In contrast, VEGF bound to and induced angiogenesis in both diabetic and normal vasculature. Scg3 and VEGF signal through distinct receptor pathways. Importantly, Scg3-neutralizing antibodies alleviated retinal vascular leakage in diabetic mice with high efficacy. Furthermore, anti-Scg3 prevented retinal neovascularization in oxygen-induced retinopathy mice, a surrogate model for retinopathy of prematurity (ROP). ROP is the most common cause of vision impairment in children, with no approved drug therapy. These results suggest that Scg3 is a promising target for novel antiangiogenic therapy of DR and ROP. PMID:28330905

Highly Active N,O Zinc Guanidine Catalysts for the Ring-Opening Polymerization of Lactide.

PubMed

Schäfer, Pascal M; Fuchs, Martin; Ohligschläger, Andreas; Rittinghaus, Ruth; McKeown, Paul; Akin, Enver; Schmidt, Maximilian; Hoffmann, Alexander; Liauw, Marcel A; Jones, Matthew D; Herres-Pawlis, Sonja

2017-09-22

New zinc guanidine complexes with N,O donor functionalities were prepared, characterized by X-Ray crystallography, and examined for their catalytic activity in the solvent-free ring-opening polymerization (ROP) of technical-grade rac-lactide at 150 °C. All complexes showed a high activity. The fastest complex [ZnCl 2 (DMEGasme)] (C1) produced colorless poly(lactide) (PLA) after 90 min with a conversion of 52 % and high molar masses (M w =69 100, polydispersity=1.4). The complexes were tested with different monomer-to-initiator ratios to determine the rate constant k p . Furthermore, a polymerization with the most active complex C1 was monitored by in situ Raman spectroscopy. Overall, conversion of up to 90 % can be obtained. End-group analysis was performed to clarify the mechanism. All four complexes combine robustness against impurities in the lactide with high polymerization rates, and they represent the fastest robust lactide ROP catalysts to date, opening new avenues to a sustainable ROP catalyst family for industrial use. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis and biomedical applications of functional poly(α-hydroxy acids) via ring-opening polymerization of O-carboxyanhydrides.

PubMed

Yin, Qian; Yin, Lichen; Wang, Hua; Cheng, Jianjun

2015-07-21

Poly(α-hydroxy acids) (PAHAs) are a class of biodegradable and biocompatible polymers that are widely used in numerous applications. One drawback of these conventional polymers, however, is their lack of side-chain functionalities, which makes it difficult to conjugate active moieties to PAHA or to fine-tune the physical and chemical properties of PAHA-derived materials through side-chain modifications. Thus, extensive efforts have been devoted to the development of methodology that allows facile preparation of PAHAs with controlled molecular weights and a variety of functionalities for widespread utilities. However, it is highly challenging to introduce functional groups into conventional PAHAs derived from ring-opening polymerization (ROP) of lactides and glycolides to yield functional PAHAs with favorable properties, such as tunable hydrophilicity/hydrophobicity, facile postpolymerization modification, and well-defined physicochemical properties. Amino acids are excellent resources for functional polymers because of their low cost, availability, and structural as well as stereochemical diversity. Nevertheless, the synthesis of functional PAHAs using amino acids as building blocks has been rarely reported because of the difficulty of preparing large-scale monomers and poor yields during the synthesis. The synthesis of functionalized PAHAs from O-carboxyanhydrides (OCAs), a class of five-membered cyclic anhydrides derived from amino acids, has proven to be one of the most promising strategies and has thus attracted tremendous interest recently. In this Account, we highlight the recent progress in our group on the synthesis of functional PAHAs via ROP of OCAs and their self-assembly and biomedical applications. New synthetic methodologies that allow the facile preparation of PAHAs with controlled molecular weights and various functionalities through ROP of OCAs are reviewed and evaluated. The in vivo stability, side-chain functionalities, and/or trigger responsiveness of several functional PAHAs are evaluated. Their biomedical applications in drug and gene delivery are also discussed. The ready availability of starting materials from renewable resources and the facile postmodification strategies such as azide-alkyne cycloaddition and the thiol-yne "click" reaction have enabled the production of a multitude of PAHAs with controlled molecular weights, narrow polydispersity, high terminal group fidelities, and structural diversities that are amenable for self-assembly and bioapplications. We anticipate that this new generation of PAHAs and their self-assembled nanosystems as biomaterials will open up exciting new opportunities and have widespread utilities for biological applications.

Color Fundus Photography versus Fluorescein Angiography in Identification of the Macular Center and Zone in Retinopathy of Prematurity

PubMed Central

Patel, Samir N.; Klufas, Michael A.; Ryan, Michael C.; Jonas, Karyn E.; Ostmo, Susan; Martinez-Castellanos, Maria Ana; Berrocal, Audina M.; Chiang, Michael F.; Chan, R.V. Paul

2016-01-01

Purpose To examine the utility of fluorescein angiography (FA) in identification of the macular center and the diagnosis of zone in patients with retinopathy of prematurity (ROP). Design Validity and reliability analysis of diagnostic tools Methods 32 sets (16 color fundus photographs; 16 color fundus photographs paired with the corresponding FA) of wide-angle retinal images obtained from 16 eyes of eight infants with ROP were compiled on a secure web site. 9 ROP experts (3 pediatric ophthalmologists; 6 vitreoretinal surgeons) participated in the study. For each image set, experts identified the macular center and provided a diagnosis of zone. Main Outcome Measures (1) Sensitivity and specificity of zone diagnosis (2) “Computer facilitated diagnosis of zone,” based on precise measurement of the macular center, optic disc center, and peripheral ROP. Results Computer facilitated diagnosis of zone agreed with the expert’s diagnosis of zone in 28/45 (62%) cases using color fundus photographs and in 31/45 (69%) cases using FA. Mean (95% CI) sensitivity for detection of zone I by experts as compared to a consensus reference standard diagnosis when interpreting the color fundus images alone versus interpreting the color fundus photographs and FA was 47% (35.3% – 59.3%) and 61.1% (48.9% – 72.4%), respectively, (t(9) ≥ (2.063), p = 0.073). Conclusions There is a marginally significant difference in zone diagnosis when using color fundus photographs compared to using color fundus photographs and the corresponding fluorescein angiograms. There is inconsistency between traditional zone diagnosis (based on ophthalmoscopic exam and image review) compared to a computer-facilitated diagnosis of zone. PMID:25637180

Mutations in the NDP gene: contribution to Norrie disease, familial exudative vitreoretinopathy and retinopathy of prematurity.

PubMed

Dickinson, Joanne L; Sale, Michèle M; Passmore, Abraham; FitzGerald, Liesel M; Wheatley, Catherine M; Burdon, Kathryn P; Craig, Jamie E; Tengtrisorn, Supaporn; Carden, Susan M; Maclean, Hector; Mackey, David A

2006-01-01

To examine the contribution of mutations within the Norrie disease (NDP) gene to the clinically similar retinal diseases Norrie disease, X-linked familial exudative vitreoretinopathy (FEVR), Coat's disease and retinopathy of prematurity (ROP). A dataset comprising 13 Norrie-FEVR, one Coat's disease, 31 ROP patients and 90 ex-premature babies of <32 weeks' gestation underwent an ophthalmologic examination and were screened for mutations within the NDP gene by direct DNA sequencing, denaturing high-performance liquid chromatography or gel electrophoresis. Controls were only screened using denaturing high-performance liquid chromatography and gel electrophoresis. Confirmation of mutations identified was obtained by DNA sequencing. Evidence for two novel mutations in the NDP gene was presented: Leu103Val in one FEVR patient and His43Arg in monozygotic twin Norrie disease patients. Furthermore, a previously described 14-bp deletion located in the 5' unstranslated region of the NDP gene was detected in three cases of regressed ROP. A second heterozygotic 14-bp deletion was detected in an unaffected ex-premature girl. Only two of the 13 Norrie-FEVR index cases had the full features of Norrie disease with deafness and mental retardation. Two novel mutations within the coding region of the NDP gene were found, one associated with a severe disease phenotypes of Norrie disease and the other with FEVR. A deletion within the non-coding region was associated with only mild-regressed ROP, despite the presence of low birthweight, prematurity and exposure to oxygen. In full-term children with retinal detachment only 15% appear to have the full features of Norrie disease and this is important for counselling parents on the possible long-term outcome.

Neonatal systemic inflammation in rats alters retinal vessel development and simulates pathologic features of retinopathy of prematurity.

PubMed

Hong, Hye Kyoung; Lee, Hyun Ju; Ko, Jung Hwa; Park, Ji Hyun; Park, Ji Yeon; Choi, Chang Won; Yoon, Chang-Hwan; Ahn, Seong Joon; Park, Kyu Hyung; Woo, Se Joon; Oh, Joo Youn

2014-05-15

Alteration of retinal angiogenesis during development leads to retinopathy of prematurity (ROP) in preterm infants, which is a leading cause of visual impairment in children. A number of clinical studies have reported higher rates of ROP in infants who had perinatal infections or inflammation, suggesting that exposure of the developing retina to inflammation may disturb retinal vessel development. Thus, we investigated the effects of systemic inflammation on retinal vessel development and retinal inflammation in neonatal rats. To induce systemic inflammation, we intraperitoneally injected 100 μl lipopolysaccharide (LPS, 0.25 mg/ml) or the same volume of normal saline in rat pups on postnatal days 1, 3, and 5. The retinas were extracted on postnatal days 7 and 14, and subjected to assays for retinal vessels, inflammatory cells and molecules, and apoptosis. We found that intraperitoneal injection of LPS impaired retinal vessel development by decreasing vessel extension, reducing capillary density, and inducing localized overgrowth of abnormal retinal vessels and dilated peripheral vascular ridge, all of which are characteristic findings of ROP. Also, a large number of CD11c+ inflammatory cells and astrocytes were localized in the lesion of abnormal vessels. Further analysis revealed that the number of major histocompatibility complex (MHC) class IIloCD68loCD11bloCD11chi cells in the retina was higher in LPS-treated rats compared to controls. Similarly, the levels of TNF-α, IL-1β, and IL-12a were increased in LPS-treated retina. Also, apoptosis was increased in the inner retinal layer where retinal vessels are located. Our data demonstrate that systemic LPS-induced inflammation elicits retinal inflammation and impairs retinal angiogenesis in neonatal rats, implicating perinatal inflammation in the pathogenesis of ROP.

Color fundus photography versus fluorescein angiography in identification of the macular center and zone in retinopathy of prematurity.

PubMed

Patel, Samir N; Klufas, Michael A; Ryan, Michael C; Jonas, Karyn E; Ostmo, Susan; Martinez-Castellanos, Maria Ana; Berrocal, Audina M; Chiang, Michael F; Chan, R V Paul

2015-05-01

To examine the usefulness of fluorescein angiography (FA) in identifying the macular center and diagnosis of zone in patients with retinopathy of prematurity (ROP). Validity and reliability analysis of diagnostic tools. Thirty-two sets (16 color fundus photographs and 16 color fundus photographs paired with the corresponding FA images) of wide-angle retinal images obtained from 16 eyes of 8 infants with ROP were compiled on a secure web site. Nine ROP experts (3 pediatric ophthalmologists and 6 vitreoretinal surgeons) participated in the study. For each image set, experts identified the macular center and provided a diagnosis of zone. (1) Sensitivity and specificity of zone diagnosis and (2) computer-facilitated diagnosis of zone, based on precise measurement of the macular center, optic disc center, and peripheral ROP. Computer-facilitated diagnosis of zone agreed with the expert's diagnosis of zone in 28 (62%) of 45 cases using color fundus photographs and in 31 (69%) of 45 cases using FA images. Mean (95% confidence interval) sensitivity for detection of zone I by experts compared with a consensus reference standard diagnosis when interpreting the color fundus images alone versus interpreting the color fundus photographs and FA images was 47% (range, 35.3% to 59.3%) and 61.1% (range, 48.9% to 72.4%), respectively (t(9) ≥ (2.063); P = .073). There is a marginally significant difference in zone diagnosis when using color fundus photographs compared with using color fundus photographs and the corresponding FA images. There is inconsistency between traditional zone diagnosis (based on ophthalmoscopic examination and image review) compared with a computer-facilitated diagnosis of zone. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparison of Refractive Error Changes in Retinopathy of Prematurity Patients Treated with Diode and Red Lasers.

PubMed

Roohipoor, Ramak; Karkhaneh, Reza; Riazi Esfahani, Mohammad; Alipour, Fateme; Haghighat, Mahtab; Ebrahimiadib, Nazanin; Zarei, Mohammad; Mehrdad, Ramin

2016-01-01

To compare refractive error changes in retinopathy of prematurity (ROP) patients treated with diode and red lasers. A randomized double-masked clinical trial was performed, and infants with threshold or prethreshold type 1 ROP were assigned to red or diode laser groups. Gestational age, birth weight, pretreatment cycloplegic refraction, time of treatment, disease stage, zone and disease severity were recorded. Patients received either red or diode laser treatment and were regularly followed up for retina assessment and refraction. The information at month 12 of corrected age was considered for comparison. One hundred and fifty eyes of 75 infants were enrolled in the study. Seventy-four eyes received diode and 76 red laser therapy. The mean gestational age and birth weight of the infants were 28.6 ± 3.2 weeks and 1,441 ± 491 g, respectively. The mean baseline refractive error was +2.3 ± 1.7 dpt. Posttreatment refraction showed a significant myopic shift (mean 2.6 ± 2.0 dpt) with significant difference between the two groups (p < 0.001). There was a greater myopic shift among children with zone I and diode laser treatment (mean 6.00 dpt) and a lesser shift among children with zone II and red laser treatment (mean 1.12 dpt). The linear regression model, using the generalized estimating equation method, showed that the type of laser used has a significant effect on myopic shift even after adjustment for other variables. Myopic shift in laser-treated ROP patients is related to the type of laser used and the involved zone. Red laser seems to cause less myopic shift than diode laser, and those with zone I involvement have a greater myopic shift than those with ROP in zone II. © 2016 S. Karger AG, Basel.

Evaluation of Factor V Leiden, Prothrombin G20210A, MTHFR C677T and MTHFR A1298C gene polymorphisms in retinopathy of prematurity in a Turkish cohort.

PubMed

Aydin, Hatip; Gunay, Murat; Celik, Gokhan; Gunay, Betul Onal; Aydin, Umeyye Taka; Karaman, Ali

2016-12-01

To assess Factor V Leiden (FVL) (rs6025), Prothrombin G20210A (rs1799963), MTHFR C677T (rs1801133), and MTHFR A1298C (rs1801131) gene mutations as risk factors in the development of retinopathy of prematurity (ROP). A total of 105 children were included in this cross-sectional study. Patients were divided into two groups. The study group consisted of 55 infants with a history of ROP and the control group comprised 50 healthy infants with term birth. All subjects were screened for the presence of certain mutations (FVL, Prothrombin G20210A, MTHFR C677T and MTHFR A1298C) by Real-Time PCR at 1 year of age. The mean gestational age (GA) and birth weight (BW) of the study group were, 28.65 ± 2.85 weeks and 1171 ± 385.74 g, respectively. There were no significant differences of genotype and allele frequency of Prothrombin G20210A, MTHFR A1298C and MTHFR C677T between the study and control groups (p > 0.05). Eight children (14.5 %) had heterozygous and one child (1.8%) had homozygous FVL mutation in the study group. One child (2%) in the control group had heterozygous FVL mutation. There was statistically significant differences of FVL allele and genotype frequencies between the groups (p < 0.05). The prevalence of FVL polymorphism (16.3 %) was higher in ROP patients than control subjects in this Turkish cohort. We suggest a possible association of FVL mutation with ROP at the end of the study.

Short-term treatment with VEGF receptor inhibitors induces retinopathy of prematurity-like abnormal vascular growth in neonatal rats.

PubMed

Nakano, Ayuki; Nakahara, Tsutomu; Mori, Asami; Ushikubo, Hiroko; Sakamoto, Kenji; Ishii, Kunio

2016-02-01

Retinal arterial tortuosity and venous dilation are hallmarks of plus disease, which is a severe form of retinopathy of prematurity (ROP). In this study, we examined whether short-term interruption of vascular endothelial growth factor (VEGF) signals leads to the formation of severe ROP-like abnormal retinal blood vessels. Neonatal rats were treated subcutaneously with the VEGF receptor (VEGFR) tyrosine kinase inhibitors, KRN633 (1, 5, or 10 mg/kg) or axitinib (10 mg/kg), on postnatal day (P) 7 and P8. The retinal vasculatures were examined on P9, P14, or P21 in retinal whole-mounts stained with an endothelial cell marker. Prevention of vascular growth and regression of some preformed capillaries were observed on P9 in retinas of rats treated with KRN633. However, on P14 and P21, density of capillaries, tortuosity index of arterioles, and diameter of veins significantly increased in KRN633-treated rats, compared to vehicle (0.5% methylcellulose)-treated animals. Similar observations were made with axitinib-treated rats. Expressions of VEGF and VEGFR-2 were enhanced on P14 in KRN633-treated rat retinas. The second round of KRN633 treatment on P11 and P12 completely blocked abnormal retinal vascular growth on P14, but thereafter induced ROP-like abnormal retinal blood vessels by P21. These results suggest that an interruption of normal retinal vascular development in neonatal rats as a result of short-term VEGFR inhibition causes severe ROP-like abnormal retinal vascular growth in a VEGF-dependent manner. Rats treated postnatally with VEGFR inhibitors could serve as an animal model for studying the mechanisms underlying the development of plus disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

Reference ranges for blood concentrations of nucleated red blood cells in neonates.

PubMed

Christensen, Robert D; Henry, Erick; Andres, Robert L; Bennett, Sterling T

2011-01-01

Previous studies reported a relationship between high nucleated red blood cells (NRBC) in neonates and the development of intraventricular hemorrhage (IVH) and/or retinopathy of prematurity (ROP). We sought to (1) establish reference ranges for NRBC in neonates based on a large data set, (2) compare NRBC from automated versus manual counts, (3) determine the effect of an elevated NRBC, on the day of birth, on the odds of developing grade ≥3 IVH or ROP. We analyzed all NRBC obtained during 8.5 years in a multihospital system, displaying the 5th and 95th percentile limits according to gestational age and postnatal age. NRBC counts were retrieved from 61,932 neonates, 26,536 of which were excluded from the data set. Comparing 9,000 samples run simultaneously on manual versus automated methods, the manual counts yielded slightly higher counts, but the difference is likely insignificant clinically. Altitude of the birth hospital did not correlate with NRBC, and no correlations were observed with cord pH or 1- or 5-min Apgar. An NRBC count >95th percentile limit was associated with higher odds of developing a grade ≥3 IVH (OR 4.28; 95% CI 3.17-5.77) and grade ≥3 ROP (OR 4.18; 95% CI 2.74-6.38). The figures of this report display reference ranges for NRBC according to gestational age and postnatal age. An NRBC count above the 95% limit at birth is associated with a higher risk of subsequently developing severe IVH and severe ROP. We speculate that this association is because an elevated NRBC count is a marker for prenatal hypoxia. Copyright © 2010 S. Karger AG, Basel.

Educational and social competencies at 8 years in children with threshold retinopathy of prematurity in the CRYO-ROP multicenter study.

PubMed

Msall, Michael E; Phelps, Dale L; Hardy, Robert J; Dobson, Velma; Quinn, Graham E; Summers, C Gail; Tremont, Michelle R

2004-04-01

To describe the educational status and special education services at 8 years among children who had threshold retinopathy of prematurity (ROP). A prospective study was conducted of a cohort of children who had birth weight of <1251 g and threshold ROP in the Cryotherapy for Retinopathy of Prematurity multicenter study. At age 5.5 years, visual status, functional skills, and social information were obtained. At 8 years, special education classes, developmental disabilities, rehabilitation therapies, and academic and social competencies were determined by questionnaire. Visual status was considered favorable/unfavorable on the basis of the better eye. Of 255 survivors, 216 (85%) were evaluated at both 5.5 and 8 years. Major impairments were significantly more prevalent in children with unfavorable versus favorable visual status: cerebral palsy (39% vs 16%), developmental disability (57% vs 22%), autism (9% vs 1%), and epilepsy (23% vs 3%). Special education services (63% vs 27%), below-grade-level academic performance (84% vs 48%), and school-based rehabilitation services were significantly less common in children with favorable visual status. Favorable visual status, favorable functional ratings at 5.5 years, markers of higher socioeconomic status, and nonblack race were associated with significantly lower rates of both special education placement and below-grade-level academic performance at age 8. On multivariate logistic regression, only favorable visual status and functional status remained significant predictors for decreasing special education placement. Threshold ROP is associated with high rates of developmental, educational, and social challenges in middle childhood; preserved vision was associated with a clear advantage, with more than half of the children with favorable visual status performing at grade level.

Pain score assessment in babies undergoing laser treatment for retinopathy of prematurity under sub-tenon anaesthesia.

PubMed

Novitskaya, E S; Kostakis, V; Broster, S C; Allen, L E

2013-12-01

To assess the tolerability and outcomes of laser treatment for retinopathy of prematurity (ROP) under sub-tenon anaesthetic with oral or rectal sedation using a reliable, multidimensional, and internationally accepted tool for assessment of neonatal pain. Sixty-two babies have had ROP laser treatment in our neonatal unit in the 7-year interval between 1 March 2005 and 28 February 2012; 44% (27 of the 62) were performed using sub-tenon anaesthesia. Pain scores were routinely assessed using the Neonatal Pain Agitation and Sedation Scale (N-PASS) every 10 min during laser treatment. The outcome and requirement for re-treatment in this group was compared with that in the intravenous sedation group. Pain scores were available in 19 of the 27 babies treated under sub-tenon anaesthesia. The mean pain score during treatment was 2.7 (SD ± 1.7, range 0.5-6.2). There was no statistically significant correlation between the mean pain score and duration of treatment (Spearman correlation coefficient (ρ) = 0.31; P = 0.09), number of laser burns (ρ = 0.32; P = 0.09), or post-menstrual age of the baby at the time of treatment (ρ = 0.38; P = 0.052). Treatments performed under sub-tenon anaesthesia were as successful as those performed under intravenous sedation. The mean pain scores during laser treatment under sub-tenon anaesthesia in our study were lower than those previously reported during ROP screening or heel-stick procedure.Conclusion Our study demonstrated that sub-tenon anaesthesia with oral or rectal sedation provides sufficient pain control for laser treatment for ROP without the need or risks of intravenous sedation and intubation.

Refractive Outcomes of Three-Port Lens-Sparing Vitrectomy for Retinopathy of Prematurity (An AOS Thesis)

PubMed Central

Holz, Eric R.

2009-01-01

Purpose: To study the refractive outcomes of 3-port lens-sparing vitrectomy (LSV) for subtotal retinal detachments due to retinopathy of prematurity (ROP). Lens-sparing vitrectomy may provide superior refractive outcomes by limiting induced myopia of prematurity. Methods: This is a retrospective, consecutive, nonrandomized, comparative (paired eye) study. Entrance criteria were previous complete ablative laser for threshold ROP in both eyes, followed by LSV in one eye for stage 4A traction retinal detachment. Both eyes then maintained complete retinal attachment. Main outcome variables were cycloplegic refraction, keratometry, and biometric values for axial length, lens thickness, and anterior chamber depth. Results: Nine patients met inclusion criteria. Lens-sparing vitrectomy eyes were significantly less myopic than control eyes (−6.78 D vs −10.33 D, P < .005). The reduction in myopia in LSV eyes was predominantly due to increased anterior chamber depth (3.81 mm ± 0.217 vs 2.96 mm ± 0.232, P < .005). There was a minor contribution from reduced corneal power in LSV eyes (43.89 D ± 0.253 vs 44.20 D ± 0.265, P < .005). There was a minor negative impact from increased lens thickness in LSV eyes (3.85 ± 0.32 mm vs 3.74 ± 0.31, P < .005). There was no significant difference in axial length or lens power between the LSV and control groups. Conclusions: The data demonstrate that infant eyes undergoing 3-port LSV for stage 4A ROP develop less myopia than fellow eyes treated with laser alone. The difference is due to posterior displacement of the lens-iris diaphragm with a smaller contribution from reduced corneal power. The reduction in myopia may improve functional outcomes following 3-port LSV for stage 4A ROP. PMID:20126504

T Cell Receptor-Major Histocompatibility Complex Interaction Strength Defines Trafficking and CD103+ Memory Status of CD8 T Cells in the Brain.

PubMed

Sanecka, Anna; Yoshida, Nagisa; Kolawole, Elizabeth Motunrayo; Patel, Harshil; Evavold, Brian D; Frickel, Eva-Maria

2018-01-01

T cell receptor-major histocompatibility complex (TCR-MHC) affinities span a wide range in a polyclonal T cell response, yet it is undefined how affinity shapes long-term properties of CD8 T cells during chronic infection with persistent antigen. Here, we investigate how the affinity of the TCR-MHC interaction shapes the phenotype of memory CD8 T cells in the chronically Toxoplasma gondii- infected brain. We employed CD8 T cells from three lines of transnuclear (TN) mice that harbor in their endogenous loci different T cell receptors specific for the same Toxoplasma antigenic epitope ROP7. The three TN CD8 T cell clones span a wide range of affinities to MHCI-ROP7. These three CD8 T cell clones have a distinct and fixed hierarchy in terms of effector function in response to the antigen measured as proliferation capacity, trafficking, T cell maintenance, and memory formation. In particular, the T cell clone of lowest affinity does not home to the brain. The two higher affinity T cell clones show differences in establishing resident-like memory populations (CD103 + ) in the brain with the higher affinity clone persisting longer in the host during chronic infection. Transcriptional profiling of naïve and activated ROP7-specific CD8 T cells revealed that Klf2 encoding a transcription factor that is known to be a negative marker for T cell trafficking is upregulated in the activated lowest affinity ROP7 clone. Our data thus suggest that TCR-MHC affinity dictates memory CD8 T cell fate at the site of infection.

Synthesis and structural studies of heterobimetallic alkoxide complexes supported by bis(phenolate) ligands: efficient catalysts for ring-opening polymerization of L-lactide.

PubMed

Chen, Hsuan-Ying; Liu, Mei-Yu; Sutar, Alekha Kumar; Lin, Chu-Chieh

2010-01-18

A series of heterobimetallic titanium(IV) complexes [LTi(O(i)Pr)(mu-O(i)Pr)(2)Li(THF)(2)], [LTi(O(i)Pr)(mu-O(i)Pr)(2)Na(THF)(2)], [LTi(mu-O(i)Pr)(2)Zn(O(i)Pr)(2)], and [LTi(mu-O(i)Pr)(2)Mg(O(i)Pr)(2)] (where L = bidentate bisphenol ligands) have been synthesized and characterized including a structural determination of [L(1)Ti(mu(2)-O(i)Pr)(2)(O(i)Pr)Li(THF)(2)] (1a). These complexes were investigated for their utility in the ring-opening polymerization (ROP) of l-lactide (LA). Polymerization activities have been shown to correlate with the electronic properties of the substituent within the bisphenol ligand. In contrast to monometallic titanium initiator 1e, all the heterobimetallic titanium initiators (Ti-Li, Ti-Na, Ti-Zn, and Ti-Mg) show enhanced catalytic activity toward ring-opening polymerization (ROP) of l-LA. In addition, the use of electron-donating methoxy or methylphenylsulfonyl functional ligands reveals the highest activity. The bisphenol bimetallic complexes give rise to controlled ring-opening polymerization, as shown by the linear relationship between the percentage conversion and the number-average molecular weight. The polymerization kinetics using 2c as an initiator were also studied, and the experimental results indicate that the reaction rate is first-order with respect to both monomer and catalyst concentration with a polymerization rate constant, k = 81.64 M(-1) min(-1).

Assessment of the antigenic and neuroprotective activity of the subunit anti-Toxoplasma vaccine in T. gondii experimentally infected mice.

PubMed

Gatkowska, Justyna; Wieczorek, Marek; Dziadek, Bożena; Dzitko, Katarzyna; Dziadek, Jarosław; Długońska, Henryka

2018-04-30

The aim of this study was to evaluate the immunogenic and immunoprotective activities and to determine the neuroprotective capacity of the tetravalent vaccine containing selected recombinant T. gondii antigens (ROP2 + ROP4 + SAG1 + MAG1) administered with safe adjuvants (MPL and alum) using male and female inbred mice. The tested antigenic combination provided partial protection against brain cyst formation, especially in males (reduction in cyst burden by 72%). The decrease in cyst burden was observed for the whole brain as well as for specified brain regions associated with natural defensive behaviors, emotion processing and integration of motor and sensory stimuli. The vaccine triggered a strong, specific immune response, regardless of sex, which was characterized by the antigen-specific in vitro synthesis of cytokines (IL-2, IFN-γ and IL-10) and in vivo production of systemic IgG1 and IgG2a immunoglobulins. Immunization prior to the parasite challenge seemed to influence T. gondii - associated behavioral and neurochemical changes, although the impact of vaccination strongly depended on sex and time post-infection. Interestingly, in the vaccinated and T. gondii infected mice there was a significant delay in the parasite-induced loss of aversion toward cat smell (cats are the definitive hosts of the parasite). The regained attraction toward feline scent in vaccinated males, observed during chronic parasite invasion, correlated with the increase in the dopamine metabolism. Copyright © 2018 Elsevier B.V. All rights reserved.

The omega-3 and retinopathy of prematurity relationship.

PubMed

Malamas, Angelakis; Chranioti, Angeliki; Tsakalidis, Christos; Dimitrakos, Stavros A; Mataftsi, Asimina

2017-01-01

The aim of this article is to examine the effect of omega-3 (ω-3) long-chain polyunsaturated fatty acids (LCPUFAs) intake on retinopathy of prematurity (ROP) by reviewing the experimental and clinical trials conducted on animal models and infants. LCPUFAs demonstrate cytoprotective and cytotherapeutic actions contributing to a number of anti-angiogenic and neuroprotective mechanisms within the retina. Their intake appears to have a beneficial effect on ischemia, oxidative stress, inflammation and cellular signaling mechanisms, influencing retinal cell gene expression and cellular differentiation. ω-3 LCPUFAs may modulate metabolic processes that activate molecules implicated in the pathogenesis of vasoproliferative and neurodegenerative retinal diseases such as ROP.

The omega-3 and retinopathy of prematurity relationship

PubMed Central

Malamas, Angelakis; Chranioti, Angeliki; Tsakalidis, Christos; Dimitrakos, Stavros A; Mataftsi, Asimina

2017-01-01

The aim of this article is to examine the effect of omega-3 (ω-3) long-chain polyunsaturated fatty acids (LCPUFAs) intake on retinopathy of prematurity (ROP) by reviewing the experimental and clinical trials conducted on animal models and infants. LCPUFAs demonstrate cytoprotective and cytotherapeutic actions contributing to a number of anti-angiogenic and neuroprotective mechanisms within the retina. Their intake appears to have a beneficial effect on ischemia, oxidative stress, inflammation and cellular signaling mechanisms, influencing retinal cell gene expression and cellular differentiation. ω-3 LCPUFAs may modulate metabolic processes that activate molecules implicated in the pathogenesis of vasoproliferative and neurodegenerative retinal diseases such as ROP. PMID:28251092

G protein-coupled receptor 91 signaling in diabetic retinopathy and hypoxic retinal diseases.

PubMed

Hu, Jianyan; Li, Tingting; Du, Xinhua; Wu, Qiang; Le, Yun-Zheng

2017-10-01

G protein-coupled receptor 91 (GPR91) is a succinate-specific receptor and activation of GPR91 could initiate a complex signal transduction cascade and upregulate inflammatory and pro-angiogenic cytokines. In the retina, GPR91 is predominately expressed in ganglion cells, a major cellular entity involved in the pathogenesis of diabetic retinopathy (DR) and other hypoxic retinal diseases. During the development of DR and retinopathy of prematurity (ROP), chronic hypoxia causes an increase in the levels of local succinate. Succinate-mediated GPR91 activation upregulates vascular endothelial growth factor (VEGF) through ERK1/2-C/EBP β (c-Fos) and/or ERK1/2-COX-2/PGE2 signaling pathways, which in turn, leads to the breakdown of blood-retina barriers in these disorders. In this review, we will have a brief introduction of GPR91 and its biological functions and a more detailed discussion about the role and mechanisms of GPR91 in DR and ROP. A better understanding of GPR91 regulation may be of great significance in identifying new biomarkers and drug targets for the prediction and treatment of DR, ROP, and hypoxic retinal diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Surgical treatment of advanced retinopathy of prematurity--last chance for vision. Report 2. Analysis of functional results].

PubMed

Baranov, A V; Troianovskiĭ, R L

2012-01-01

Functional results of staged surgical treatment of advanced retinopathy of prematurity (ROP) are analyzed between 2005 and 2010 in ophthalmologic department of city children's hospital ( St. Petersburg). A total of 154 children (303 eyes) were operated. The assessment of visual functions was performed using proposed original method. Subject vision was achieved in 65% of 20 eyes (6,6%) with 4B stage ROP. Fair anatomic results were achieved in 131 eyes of children with 5 stage ROP (283 eyes), light perception was preserved in 52 eyes (39,7%), capability to distinguish large objects appeared in 40 eyes (30,5%) and subject vision developed in 39 eyes (29,8%). Correlation between visual functions and environmental conditions was found, in particular presence or absence of long-term period of training in color and individual objects distinguishing. In a group of children training resulted in achievement of fair functions (subject vision, capability to distinguish large objects) in 81,2% of patients, where as in a group without training the same capabilities developed in 31,8% of cases only. Functional outcomes were also found to depend on CNS condition and time of surgery.

Systemic effects of screening for retinopathy of prematurity.

PubMed Central

Laws, D E; Morton, C; Weindling, M; Clark, D

1996-01-01

AIMS: To detect systemic complications of screening for retinopathy of prematurity (ROP), paying particular attention to the physical examination. METHODS: Oxygen saturation, pulse rate, and blood pressure were monitored before, during, and after 110 ROP screening examinations. RESULTS: Following topical mydriatics diastolic blood pressure was elevated by a mean of 6 (SD 7.2) mm Hg. Immediately after the examination there was a further rise in both systolic and diastolic pressure of 4.3 (14.5) mm Hg and 3.3 (11.6) mm Hg, respectively. Oxygen saturation and pulse rate remained stable during the control period and administration of eyedrops. Saturation fell by a median of 3% (95% confidence interval plus or minus 1.2%) after the examination while there was rise in pulse rate of 7 (SD 23.1) beats per minute. This change in pulse rate was not observed in infants on concurrent methylxanthine therapy. No infant had clinically significant changes at the end of the study. CONCLUSION: The initial changes in blood pressure may represent side effects of topical mydriatics but the later changes following the physical examination may be an additional response to the stress of ROP screening. PMID:8695564

Bilateral Coats' Disease Combined with Retinopathy of Prematurity

PubMed Central

Gursoy, Huseyin; Erol, Nazmiye; Bilgec, Mustafa Deger; Basmak, Hikmet; Kutlay, Ozden; Aslan, Huseyin

2015-01-01

Purpose. To report a case of bilateral Coats' disease combined with retinopathy of prematurity (ROP). Case. Retinal vascularization was complete in the right eye, whereas zone III, stage 3 ROP and preplus disease were observed in the left eye at 43 weeks of postmenstrual age (PMA) in a 31-week premature, 1200-g neonate. Intraretinal exudates developed and retinal hemorrhages increased in the left eye at 51 weeks of PMA. Diode laser photocoagulation (LP) was applied to the left eye. Exudates involved the macula, and telangiectatic changes developed one month following LP. Additional LP was applied to the left eye combined with intravitreal bevacizumab (IVB) injection at 55 weeks of PMA. Disease regressed one month after the additional therapy. At the 14-month examination of the baby, telangiectatic changes and intraretinal exudates were observed in the right eye. Diode LP was applied to the right eye combined with IVB injection. Exudates did not resolve completely, and cryotherapy was applied one month following LP. Retinal findings regressed three months following the cryotherapy. Conclusion. This is the first report of presumed bilateral Coats' disease combined with ROP. If Coats' disease could be diagnosed at early stages, it would be a disease associated with better prognosis. PMID:26413362

Glycolysis regulates pollen tube polarity via Rho GTPase signaling

PubMed Central

Chen, Wei; Gong, Pingping; Guo, Jingzhe; Li, Hui; Li, Ruizi; Xing, Weiman; Yang, Zhenbiao

2018-01-01

As a universal energy generation pathway utilizing carbon metabolism, glycolysis plays an important housekeeping role in all organisms. Pollen tubes expand rapidly via a mechanism of polarized growth, known as tip growth, to deliver sperm for fertilization. Here, we report a novel and surprising role of glycolysis in the regulation of growth polarity in Arabidopsis pollen tubes via impingement of Rho GTPase-dependent signaling. We identified a cytosolic phosphoglycerate kinase (pgkc-1) mutant with accelerated pollen germination and compromised pollen tube growth polarity. pgkc-1 mutation greatly diminished apical exocytic vesicular distribution of REN1 RopGAP (Rop GTPase activating protein), leading to ROP1 hyper-activation at the apical plasma membrane. Consequently, pgkc-1 pollen tubes contained higher amounts of exocytic vesicles and actin microfilaments in the apical region, and showed reduced sensitivity to Brefeldin A and Latrunculin B, respectively. While inhibition of mitochondrial respiration could not explain the pgkc-1 phenotype, the glycolytic activity is indeed required for PGKc function in pollen tubes. Moreover, the pgkc-1 pollen tube phenotype was mimicked by the inhibition of another glycolytic enzyme. These findings highlight an unconventional regulatory function for a housekeeping metabolic pathway in the spatial control of a fundamental cellular process. PMID:29702701

Genotyping Toxoplasma gondii from wildlife in Pennsylvania and identification of natural recombinants virulent to mice.

PubMed

Dubey, J P; Van Why, K; Verma, S K; Choudhary, S; Kwok, O C H; Khan, A; Behinke, M S; Sibley, L D; Ferreira, L R; Oliveira, S; Weaver, M; Stewart, R; Su, C

2014-02-24

Recent studies indicated the predominance of Toxoplasma gondii haplogroup 12 in wildlife in the USA. However, still little is known of the genetic diversity of this parasite circulating in wildlife. In the present study, we tested coyotes (Canis latrans), red foxes (Vulpes vulpes), white-tailed deer (Odocoileus virginianus), and geese (Branta canadensis) from the state of Pennsylvania for T. gondii infection. Antibodies to T. gondii were found in 160 of 367 animals, including 92 (34.5%) of 266 coyotes, 49 (62.0%) of 79 white-tailed deer, 17 (85.0%) of 20 red fox, and two of two Canada geese tested by the modified agglutination test (cut off titer 1:25). Tissues from 105 seropositive animals were bioassayed in mice, and viable T. gondii was isolated from 29 animals, including 10 of 53 coyotes, 11 of 16 foxes, 7 of 49 deer, and one of one goose. DNA isolated from culture-derived tachyzoites of these isolates was characterized initially using multilocus PCR-RFLP markers. Nine genotypes were revealed, including ToxoDB PCR-RFLP #1 (4 isolates), #2 (2 isolates), #3 (4 isolates), #4 (6 isolates), #5 (4 isolates), #54 (1 isolate), #141 (1 isolate), #143 (1 isolate), and #216 (6 isolates), indicating high genetic diversity of T. gondii in wildlife in Pennsylvania. Pathogenicity of six T. gondii isolates (5 of #216 and #141) was determined in outbred Swiss Webster mice. Three of #216 and the #141 isolates were acute virulent to mice, and the other 2 #216 isolates were intermediate virulent. To determine the extent of genetic variation of these as well as a few recently reported virulent isolates from wildlife in North America, intron sequences were generated. Analysis of intron sequences and PCR-RFLP genotyping results indicated that the #216 isolates are likely derived from recombination of the clonal type I and III lineages. To determine if T. gondii virulence can be predicted by typing, we genotyped a collection of strains using PCR-RFLP markers for polymorphic genes ROP5, ROP16, ROP18 and GRA15, which are known to interact with host immune response. The results showed that there is an association of genotypes of ROP5 and ROP18 with mouse-virulence, however, additional gene(s) may also contribute to virulence in distinct T. gondii genotypes. Published by Elsevier B.V.

Analysis of underlying causes of inter-expert disagreement in retinopathy of prematurity diagnosis. Application of machine learning principles.

PubMed

Ataer-Cansizoglu, E; Kalpathy-Cramer, J; You, S; Keck, K; Erdogmus, D; Chiang, M F

2015-01-01

Inter-expert variability in image-based clinical diagnosis has been demonstrated in many diseases including retinopathy of prematurity (ROP), which is a disease affecting low birth weight infants and is a major cause of childhood blindness. In order to better understand the underlying causes of variability among experts, we propose a method to quantify the variability of expert decisions and analyze the relationship between expert diagnoses and features computed from the images. Identification of these features is relevant for development of computer-based decision support systems and educational systems in ROP, and these methods may be applicable to other diseases where inter-expert variability is observed. The experiments were carried out on a dataset of 34 retinal images, each with diagnoses provided independently by 22 experts. Analysis was performed using concepts of Mutual Information (MI) and Kernel Density Estimation. A large set of structural features (a total of 66) were extracted from retinal images. Feature selection was utilized to identify the most important features that correlated to actual clinical decisions by the 22 study experts. The best three features for each observer were selected by an exhaustive search on all possible feature subsets and considering joint MI as a relevance criterion. We also compared our results with the results of Cohen's Kappa [36] as an inter-rater reliability measure. The results demonstrate that a group of observers (17 among 22) decide consistently with each other. Mean and second central moment of arteriolar tortuosity is among the reasons of disagreement between this group and the rest of the observers, meaning that the group of experts consider amount of tortuosity as well as the variation of tortuosity in the image. Given a set of image-based features, the proposed analysis method can identify critical image-based features that lead to expert agreement and disagreement in diagnosis of ROP. Although tree-based features and various statistics such as central moment are not popular in the literature, our results suggest that they are important for diagnosis.

Current role of cryotherapy in retinopathy of prematurity: a report by the American Academy of Ophthalmology.

PubMed

Simpson, Jennifer L; Melia, Michele; Yang, Michael B; Buffenn, Angela N; Chiang, Michael F; Lambert, Scott R

2012-04-01

To evaluate the role of cryotherapy in the current treatment of retinopathy of prematurity (ROP). Literature searches of PubMed and the Cochrane Library were conducted on December 2, 2009, for articles published after 1984. The searches included all languages and retrieved 187 relevant citations. Thirteen articles were deemed relevant to the assessment question and were rated according to the strength of evidence. Four articles reported results from 2 large multicenter randomized clinical trials, and the remaining 9 articles reported results of 3 small randomized trials that directly compared cryotherapy and laser. Neither of the multicenter randomized clinical trials was a direct comparison of cryotherapy with laser. These studies were used to evaluate the comparative trials based on treatment criteria, study populations, and clinical results. Higher percentages of poor structural and functional outcomes generally were seen in eyes treated with cryotherapy compared with eyes undergoing laser treatment. Higher rates of systemic complications and myopia also were identified after treatment with cryotherapy. Despite a relative paucity of level I evidence directly comparing cryotherapy and laser treatment for threshold ROP, the literature suggests that neonatal facilities should gain access to laser technology and laser-trained ophthalmic staff to achieve better outcomes for treatment of the disease. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Gene therapy knockdown of VEGFR2 in retinal endothelial cells to treat retinopathy.

PubMed

Simmons, Aaron B; Bretz, Colin A; Wang, Haibo; Kunz, Eric; Hajj, Kassem; Kennedy, Carson; Yang, Zhihong; Suwanmanee, Thipparat; Kafri, Tal; Hartnett, M Elizabeth

2018-05-05

Inhibition of vascular endothelial growth factor (VEGF) in retinopathy of prematurity (ROP) raises concerns for premature infants because VEGF is essential for retinovascular development as well as neuronal and glial health. This study tested the hypothesis that endothelial cell-specific knockdown of VEGF receptor 2 (VEGFR2), or downstream STAT3, would inhibit VEGF-induced retinopathy without delaying physiologic retinal vascular development. We developed an endothelial cell-specific lentiviral vector that delivered shRNAs to VEGFR2 or STAT3 and a green fluorescent protein reporter under control of the VE-cadherin promoter. The specificity and efficacy of the lentiviral vector-driven shRNAs were validated in vitro and in vivo. In the rat oxygen-induced retinopathy model highly representative of human ROP, the effects of endothelial cell knockdown of VEGFR2 or STAT3 were determined on intravitreal neovascularization (IVNV), physiologic retinal vascular development [assessed as area of peripheral avascular/total retina (AVA)], retinal structure, and retinal function. Targeted knockdown of VEGFR2 or STAT3 specifically in retinal endothelial cells by subretinal injection of lentiviral vectors into postnatal day 8 rat pup eyes efficiently inhibited IVNV, and knockdown of VEGFR2 also reduced AVA and increased retinal thickness without altering retinal function. Taken together, our results support specific knockdown of VEGFR2 in retinal endothelial cells as a novel therapeutic method to treat retinopathy.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shen, Yong; Desseaux, Solenne; Aden, Bethany

We report that surface-grafting thermoresponsive polymers allows the preparation of thin polymer brush coatings with surface properties that can be manipulated by variation of temperature. In most instances, thermoresponsive polymer brushes are produced using polymers that dehydrate and collapse above a certain temperature. This report presents the preparation and properties of polymer brushes that show thermoresponsive surface properties, yet are shape-persistent in that they do not undergo main chain collapse. The polymer brushes presented here are obtained via vapor deposition surface-initiated ring-opening polymerization (SI-ROP) of γ-di- or tri(ethylene glycol)-modified glutamic acid N-carboxyanhydrides. Vapor deposition SI-ROP of γ-di- or tri(ethylene glycol)-modifiedmore » L- or D-glutamic acid N-carboxyanhydrides affords helical surface-tethered polymer chains that do not show any changes in secondary structure between 10 and 70 °C. QCM-D experiments, however, revealed significant dehydration of poly(γ-(2-(2-methoxyethoxy)ethyl)-l-glutamate) (poly(L-EG 2-Glu)) brushes upon heating from 10 to 40 °C. At the same time, AFM and ellipsometry studies did not reveal significant variations in film thickness over this temperature range, which is consistent with the shape-persistent nature of these polypeptide brushes and indicates that the thermoresponsiveness of the films is primarily due to hydration and dehydration of the oligo(ethylene glycol) side chains. The results we present here illustrate the potential of surface-initiated NCA ring-opening polymerization to generate densely grafted assemblies of polymer chains that possess well-defined secondary structures and tunable surface properties. These polypeptide brushes complement their conformationally unordered counterparts that can be generated via surface-initiated polymerization of vinyl-type monomers and represent another step forward to biomimetic surfaces and interfaces.« less

Accommodation and convergence in 10-year-old prematurely born and full-term children: a population-based study.

PubMed

Larsson, Eva; Rydberg, Agneta; Holmström, Gerd

2012-09-01

To examine the accommodative amplitude and convergence in 10-year-old prematurely born children previously screened for retinopathy of prematurity (ROP) and to compare with full-term controls of the same age. Two-hundred and thirteen prematurely born and 217 children born at term were included. Accommodative amplitude and near-point convergence were assessed, together with best-corrected visual acuity (VA). A questionnaire was answered regarding possible problems at school. Binocular accommodation (P = 0.03) and convergence (P = 0.003) were significantly poorer in prematurely born children. Accommodation was correlated to neurological findings in the preterm group, but not to the degree of prematurity or stage of ROP. Regarding convergence there were no correlations to neurology, stage of ROP, or degree of prematurity. For neither accommodation nor convergence were any correlations with distance and near VA found. Preterm children had a higher prevalence of school problems, and there was an association with poor accommodation. Prematurely born children had poorer accommodation and convergence than full-term children, but no association with near VA was found. The reduction of accommodative amplitude and convergence was small and was probably of little clinical significance. However, it may have additional effects on other ophthalmological problems and school problems in the preterm group.

Causes of severe visual impairment and blindness in children in the Republic of Suriname.

PubMed

Heijthuijsen, Astrid Anna Maria; Beunders, Victoria Apollonia Annemarie; Jiawan, Dinesh; de Mesquita-Voigt, Anne-Marie Bueno; Pawiroredjo, Jerrel; Mourits, Maarten; Tanck, Michael; Verhoeff, Joost; Saeed, Peerooz

2013-07-01

To determine the causes of severe visual impairment and blindness (SVI/BL) in children in Suriname (Dutch Guyana) and to identify preventable and treatable causes. 4643 children under 16 years of age were recruited from two locations: 33 children attending the only school for the blind were examined and 4610 medical records were analysed at an eye clinic. Data have been collected using the WHO Prevention of Blindness Programme eye examination record for children. 65 children were identified with SVI/BL, 58.5% were blind and 41.5% were severely visually impaired (SVI). The major anatomical site of SVI/BL was the retina in 33.8%, lens in 15.4% and normal appearing globe in 15.4%. The major underlying aetiology of SVI/BL was undetermined in 56.9% (mainly cataract and abnormality since birth) and perinatal factors 21.5% (mainly retinopathy of prematurity (ROP)). Avoidable causes of SVI/BL accounted for 40% of cases; 7.7% were preventable and 32.3% were treatable with cataracts and ROP the most common causes (15.4% and 12.3%, respectively). More than a third of the SVI/BL causes are potentially avoidable, with childhood cataract and ROP the leading causes. Corneal scarring from vitamin A deficiency does not seem to be a continuing issue in Suriname.

A Barley Powdery Mildew Fungus Non-Autonomous Retrotransposon Encodes a Peptide that Supports Penetration Success on Barley.

PubMed

Nottensteiner, Mathias; Zechmann, Bernd; McCollum, Christopher; Hückelhoven, Ralph

2018-05-11

Pathogens overcome plant immunity by the means of secreted effectors. Host effector targets often act in pathogen defense but might also support fungal accommodation or nutrition. The barley ROP GTPase HvRACB is involved in accommodation of fungal haustoria of the powdery mildew fungus Blumeria graminis f.sp. hordei (Bgh) in barley epidermal cells. We found that HvRACB interacts with the ROP-interactive peptide 1 (ROPIP1) that is encoded on the active non-long terminal repeat retroelement Eg-R1 of Bgh. Over-expression of ROPIP1 in barley epidermal cells and host-induced post-transcriptional gene silencing (HIGS) of ROPIP1 suggested that ROPIP1 is involved in virulence of Bgh. Bimolecular fluorescence complementation and co-localization supported that ROPIP1 can interact with activated HvRACB in planta. We show that ROPIP1 is expressed by Bgh on barley and translocated into the cytoplasm of infected barley cells. ROPIP1 is recruited to microtubules upon co-expression of microtubule associated ROP GTPase ACTIVATING PROTEIN (HvMAGAP1) and can destabilize cortical microtubules. Data suggest that Bgh ROPIP targets HvRACB and manipulates host cell microtubule organization for facilitated host cell entry. This points to a possible neo-functionalization of retroelement-derived transcripts for the evolution of a pathogen virulence effector.

Ring opening polymerisation of lactide with uranium(iv) and cerium(iv) phosphinoaryloxide complexes.

PubMed

Sinclair, Fern; Hlina, Johann A; Wells, Jordann A L; Shaver, Michael P; Arnold, Polly L

2017-08-22

The C 3 -symmetric uranium(iv) and cerium(iv) complexes Me 3 SiOM(OAr P ) 3 , M = U (1), Ce (2), OAr P = OC 6 H 2 -6- t Bu-4-Me-2-PPh 2 , have been prepared and the difference between these 4f and 5f congeners as initiators for the ring opening polymerisation (ROP) of l-lactide is compared. The poorly controlled reactivity of the homoleptic analogue U(OAr P ) 4 (3) demonstrates the importance of the M-OSiMe 3 initiating group. The incorporation of a nickel atom in 1 to form the U-Ni heterobimetallic complex Me 3 SiOU(OAr P ) 3 Ni (4) may be the first example of the use of the inverse trans influence to switch the reactivity of a complex. This would imply the formation of the U-Ni bond strengthens the U-OSiMe 3 bond to such an extent that the ROP catalysis is switched off. Changing the conditions to immortal polymerisation dramatically increases polymerisation rates, and switches the order, with the Ce complex now faster than the U analogue, suggesting ligand protonolysis to afford a more open coordination sphere. For the ROP of rac-lactide, uranium complex 1 promotes heterotacticity at the highest levels of stereocontrol yet reported for an actinide complex.

An ethnobotanical survey of indigenous medicinal plants in Hafizabad district, Punjab-Pakistan.

PubMed

Umair, Muhammad; Altaf, Muhammad; Abbasi, Arshad Mehmood

2017-01-01

Present paper offers considerable information on traditional uses of medicinal plants by the inhabitants of Hafizabad district, Punjab-Pakistan. This is the first quantitative ethnobotanical study from the area comprising popularity level of medicinal plant species intendedby using relative popularity level (RPL) and rank order priority (ROP) indices.Ethnobotanical data were collected by interviewing 166 local informants and 35 traditional health practioners (THPs) from different localities of Hafizabad district. Demographic features of informants; life form, part used, methods of preparation, modes of application and ethnomedicinal uses were documented. Ethnobotanical data were analyzed using quantitative tools, i.e. Relative frequency citation (RFC), use value (UV), informant consensus factor (ICF) fidelity level (FL), RPL and ROP indices. A total of 85 species belonging to 71 genera and 34 families were documented along with ethnomedicinal uses. Solanum surattense, Withania somnifera, Cyperus rotundus, Solanum nigrum and Melia azedarach were the most utilized medicinal plant species with highest used value. The reported ailments were classified into 11 disease categories based on ICF values and highest number of plant species was reported to treat dermatological and gastrointestinal disorders. Withania somnifera and Ranunculus sceleratus with maximum FL (100%), were used against gastrointestinal and urinary disorders, respectively. The RPL and ROP values were calculated to recognize the folk medicinal plant wealth; six out of 32 plant species (19%) were found popular, based on citation by more than half of the maximum number of informant viz. 26. Consequently, the ROP value for these species was more than 75. The comparative assessment with reported literature revealed 15% resemblance and 6% variation to previous data;however79% uses of the reported species were recorded for the first time. The diversity of medicinal plant species and associated traditional knowledge is significant in primary health care system. Medicinal plant species with high RPL values should be screened for comprehensive phytochemical and pharmacological studies. This could be useful in novel drug discovery and to validate the ethomendicinal knowledge.

An ethnobotanical survey of indigenous medicinal plants in Hafizabad district, Punjab-Pakistan

PubMed Central

Umair, Muhammad; Altaf, Muhammad

2017-01-01

Present paper offers considerable information on traditional uses of medicinal plants by the inhabitants of Hafizabad district, Punjab-Pakistan. This is the first quantitative ethnobotanical study from the area comprising popularity level of medicinal plant species intendedby using relative popularity level (RPL) and rank order priority (ROP) indices.Ethnobotanical data were collected by interviewing 166 local informants and 35 traditional health practioners (THPs) from different localities of Hafizabad district. Demographic features of informants; life form, part used, methods of preparation, modes of application and ethnomedicinal uses were documented. Ethnobotanical data were analyzed using quantitative tools, i.e. Relative frequency citation (RFC), use value (UV), informant consensus factor (ICF) fidelity level (FL), RPL and ROP indices. A total of 85 species belonging to 71 genera and 34 families were documented along with ethnomedicinal uses. Solanum surattense, Withania somnifera, Cyperus rotundus, Solanum nigrum and Melia azedarach were the most utilized medicinal plant species with highest used value. The reported ailments were classified into 11 disease categories based on ICF values and highest number of plant species was reported to treat dermatological and gastrointestinal disorders. Withania somnifera and Ranunculus sceleratus with maximum FL (100%), were used against gastrointestinal and urinary disorders, respectively. The RPL and ROP values were calculated to recognize the folk medicinal plant wealth; six out of 32 plant species (19%) were found popular, based on citation by more than half of the maximum number of informant viz. 26. Consequently, the ROP value for these species was more than 75. The comparative assessment with reported literature revealed 15% resemblance and 6% variation to previous data;however79% uses of the reported species were recorded for the first time. The diversity of medicinal plant species and associated traditional knowledge is significant in primary health care system. Medicinal plant species with high RPL values should be screened for comprehensive phytochemical and pharmacological studies. This could be useful in novel drug discovery and to validate the ethomendicinal knowledge. PMID:28574986

Heteroleptic tin(II) initiators for the ring-opening (co)polymerization of lactide and trimethylene carbonate: mechanistic insights from experiments and computations.

PubMed

Wang, Lingfang; Kefalidis, Christos E; Sinbandhit, Sourisak; Dorcet, Vincent; Carpentier, Jean-François; Maron, Laurent; Sarazin, Yann

2013-09-27

The tin(II) complexes {LO(x)}Sn(X) ({LO(x)}(-) =aminophenolate ancillary) containing amido (1-4), chloro (5), or lactyl (6) coligands (X) promote the ring-opening polymerization (ROP) of cyclic esters. Complex 6, which models the first insertion of L-lactide, initiates the living ROP of L-LA on its own, but the amido derivatives 1-4 require the addition of alcohol to do so. Upon addition of one to ten equivalents of iPrOH, precatalysts 1-4 promote the ROP of trimethylene carbonate (TMC); yet, hardly any activity is observed if tert-butyl (R)-lactate is used instead of iPrOH. Strong inhibition of the reactivity of TMC is also detected for the simultaneous copolymerization of L-LA and TMC, or for the block copolymerization of TMC after that of L-LA. Experimental and computational data for the {LO(x)}Sn(OR)complexes (OR=lactyl or lactidyl) replicating the active species during the tin(II)-mediated ROP of L-LA demonstrate that the formation of a five-membered chelate is largely favored over that of an eight-membered one, and that it constitutes the resting state of the catalyst during this (co)polymerization. Comprehensive DFT calculations show that, out of the four possible monomer insertion sequences during simultaneous copolymerization of L-LA and TMC: 1) TMC then TMC, 2) TMC then L-LA, 3) L-LA then L-LA, and 4) L-LA then TMC, the first three are possible. By contrast, insertion of L-LA followed by that of TMC (i.e., insertion sequence 4) is endothermic by +1.1 kcal mol(-1), which compares unfavorably with consecutive insertions of two L-LA units (i.e., insertion sequence 3) (-10.2 kcal mol(-1)). The copolymerization of L-LA and TMC thus proceeds under thermodynamic control. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Early energy and protein intakes and associations with growth, BPD, and ROP in extremely preterm infants.

PubMed

Klevebro, Susanna; Westin, Vera; Stoltz Sjöström, Elisabeth; Norman, Mikael; Domellöf, Magnus; Edstedt Bonamy, Anna-Karin; Hallberg, Boubou

2018-05-29

Extremely preterm infants face substantial neonatal morbidity. Nutrition is important to promote optimal growth and organ development in order to reduce late neonatal complications. The aim of this study was to examine the associations of early nutritional intakes on growth and risks of bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) in a high-risk population. This population-based cohort study includes infants born before 27 0/7 weeks of gestational age without severe malformations and surviving ≥10 days. Intake of energy and protein on postnatal days 4-6 and association with weight standard deviation score (WSDS) from birth to day 7, as well as intakes of energy and protein on postnatal days 4-6 and 7 to 27, respectively, and association with composite outcome of death and BPD and separate outcomes of BPD and ROP were examined, and adjusted for potential confounders. The cohort comprised 296 infants with a median gestational age of 25 3/7 weeks. Expressed as daily intakes, every additional 10 kcal/kg/d of energy during days 4-6 was associated with 0.08 higher WSDS on day 7 (95% CI 0.06-0.11; p < 0.001). Between days 7 and 27, every 10 kcal/kg/d increase in energy intake was associated with a reduced risk of BPD of 9% (95% CI 1-16; p = 0.029) and any grade of ROP with a reduced risk of 6% (95% CI 2-9; p = 0.005) in multivariable models. This association was statistically significant in infants with ≤10 days of mechanical ventilation. In infants with >10 days of mechanical ventilation, a combined higher intake of energy and protein was associated with a reduced risk of BPD. Early provision of energy and protein may reduce postnatal weight loss and risk of morbidity in extremely preterm infants. Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Fatty Acid Binding Protein 4 Deficiency Protects against Oxygen-Induced Retinopathy in Mice

PubMed Central

Saint-Geniez, Magali; Ghelfi, Elisa; Liang, Xiaoliang; Yu, Chenwei; Spencer, Carrie; Abend, Stephanie; Hotamisligil, Gokhan; Cataltepe, Sule

2014-01-01

Retinopathy of prematurity (ROP) is a leading cause of blindness in children worldwide due to increasing survival rates of premature infants. Initial suppression, followed by increased production of the retinal vascular endothelial growth factor-A (VEGF) expression are key events that trigger the pathological neovascularization in ROP. Fatty acid binding protein 4 (FABP4) is an intracellular lipid chaperone that is induced by VEGF in a subset of endothelial cells. FABP4 exhibits a pro-angiogenic function in cultured endothelial cells and in airway microvasculature, but whether it plays a role in modulation of retinal angiogenesis is not known. We hypothesized that FABP4 deficiency could ameliorate pathological retinal vascularization and investigated this hypothesis using a well-characterized mouse model of oxygen-induced retinopathy (OIR). We found that FABP4 was not expressed in retinal vessels, but was present in resident macrophages/microglial cells and endothelial cells of the hyaloid vasculature in the immature retina. While FABP4 expression was not required for normal development of retinal vessels, FABP4 expression was upregulated and localized to neovascular tufts in OIR. FABP4−/− mice demonstrated a significant decrease in neovessel formation as well as a significant improvement in physiological revascularization of the avascular retinal tissues. These alterations in retinal vasculature were accompanied by reduced endothelial cell proliferation, but no effect on apoptosis or macrophage/microglia recruitment. FABP4−/− OIR samples demonstrated decreased expression of genes involved in angiogenesis, such as Placental Growth Factor, and angiopoietin 2. Collectively, our findings suggest FABP4 as a potential target of pathologic retinal angiogenesis in proliferative retinopathies. PMID:24802082

Facile preparation of well-defined AB2 Y-shaped miktoarm star polypeptide copolymer via the combination of ring-opening polymerization and click chemistry.

PubMed

Rao, Jingyi; Zhang, Yanfeng; Zhang, Jingyan; Liu, Shiyong

2008-10-01

Well-defined AB2 Y-shaped miktoarm star polypeptide copolymer, PZLL-b-(PBLG)2, was synthesized via a combination of ring-opening polymerization (ROP) of alpha-amino acid N-carboxyanhydride (NCA) and click chemistry, where PZLL is poly(epsilon-benzyloxycarbonyl-L-lysine) and PBLG is poly(gamma-benzyl-L-glutamate). First, two types of primary-amine-containing initiators, N-aminoethyl 3,5-bis(propargyloxyl)-benzamide and 3-azidopropylamine, were synthesized and employed for the ROP of NCA, leading to the formation of dialkynyl-terminated PZLL and azide-terminated PBLG, dialkynyl-PZLL and PBLG-N3, respectively. The subsequent copper(I)-catalyzed cycloaddition reaction between dialkynyl-PZLL and slightly excess PBLG-N3 led to facile preparation of PZLL-b-(PBLG)2 Y-shaped miktoarm star polypeptide copolymer. The excess PBLG-N3 was scavenged off by reacting with alkynyl-functionalized Wang resin. The obtained Y-shaped miktoarm star polypeptide copolymer was characterized by gel permeation chromatograph (GPC), Fourier transform-infrared spectroscopy (FT-IR), and (1)H NMR. Moreover, after the hydrolysis of protecting benzyl and benzyloxycarbonyl groups of PZLL-b-(PBLG)2, water-soluble pH-responsive Y-shaped miktoarm star polypeptide copolymer, PLL-b-(PLGA)2, was obtained, where PLL is poly(L-lysine) and PLGA is poly(L-glutamic acid). It can self-assemble into PLGA-core micelles at acidic pH and PLL-core micelles at alkaline pH, accompanied with the coil-to-helix transition of PLGA and PLL sequences, respectively. The spontaneous pH-responsive supramolecular assembly of PLL-b-(PLGA)2 miktoarm star polypeptide copolymer has been investigated via a combination of (1)H NMR, laser light scattering (LLS), transmission electron microscopy (TEM), and circular dichroism (CD) spectroscopy.

Miniaturized fundus camera

NASA Astrophysics Data System (ADS)

Gliss, Christine; Parel, Jean-Marie A.; Flynn, John T.; Pratisto, Hans S.; Niederer, Peter F.

2003-07-01

We present a miniaturized version of a fundus camera. The camera is designed for the use in screening for retinopathy of prematurity (ROP). There, but also in other applications a small, light weight, digital camera system can be extremely useful. We present a small wide angle digital camera system. The handpiece is significantly smaller and lighter then in all other systems. The electronics is truly portable fitting in a standard boardcase. The camera is designed to be offered at a compatible price. Data from tests on young rabbits' eyes is presented. The development of the camera system is part of a telemedicine project screening for ROP. Telemedical applications are a perfect application for this camera system using both advantages: the portability as well as the digital image.

Best packing of identical helices

NASA Astrophysics Data System (ADS)

Huh, Youngsik; Hong, Kyungpyo; Kim, Hyoungjun; No, Sungjong; Oh, Seungsang

2016-10-01

In this paper we prove the unique existence of a ropelength-minimizing conformation of the θ-spun double helix in a mathematically rigorous way, and find the minimal ropelength {{{Rop}}}* (θ )=-\\tfrac{8π }{t} where t is the unique solution in [-θ ,0] of the equation 2-2\\cos (t+θ )={t}2. Using this result, the pitch angles of the standard, triple and quadruple helices are around 39.3771^\\circ , 42.8354^\\circ and 43.8351^\\circ , respectively, which are almost identical with the approximated pitch angles of the zero-twist structures previously known by Olsen and Bohr. We also find the ropelength of the standard N-helix.

Is Your Biobank Up to Standards? A Review of the National Canadian Tissue Repository Network Required Operational Practice Standards and the Controlled Documents of a Certified Biobank.

PubMed

Hartman, Victoria; Castillo-Pelayo, Tania; Babinszky, Sindy; Dee, Simon; Leblanc, Jodi; Matzke, Lise; O'Donoghue, Sheila; Carpenter, Jane; Carter, Candace; Rush, Amanda; Byrne, Jennifer; Barnes, Rebecca; Mes-Messons, Anne-Marie; Watson, Peter

2018-02-01

Ongoing quality management is an essential part of biobank operations and the creation of high quality biospecimen resources. Adhering to the standards of a national biobanking network is a way to reduce variability between individual biobank processes, resulting in cross biobank compatibility and more consistent support for health researchers. The Canadian Tissue Repository Network (CTRNet) implemented a set of required operational practices (ROPs) in 2011 and these serve as the standards and basis for the CTRNet biobank certification program. A review of these 13 ROPs covering 314 directives was conducted after 5 years to identify areas for revision and update, leading to changes to 7/314 directives (2.3%). A review of all internal controlled documents (including policies, standard operating procedures and guides, and forms for actions and processes) used by the BC Cancer Agency's Tumor Tissue Repository (BCCA-TTR) to conform to these ROPs was then conducted. Changes were made to 20/106 (19%) of BCCA-TTR documents. We conclude that a substantial fraction of internal controlled documents require updates at regular intervals to accommodate changes in best practices. Reviewing documentation is an essential aspect of keeping up to date with best practices and ensuring the quality of biospecimens and data managed by biobanks.

Causes of severe visual impairment and blindness in children in the Republic of Suriname

PubMed Central

Heijthuijsen, Astrid Anna Maria; Beunders, Victoria Apollonia Annemarie; Jiawan, Dinesh; de Mesquita-Voigt, Anne-Marie Bueno; Pawiroredjo, Jerrel; Mourits, Maarten; Tanck, Michael; Verhoeff, Joost; Saeed, Peerooz

2013-01-01

Aims To determine the causes of severe visual impairment and blindness (SVI/BL) in children in Suriname (Dutch Guyana) and to identify preventable and treatable causes. Methods 4643 children under 16 years of age were recruited from two locations: 33 children attending the only school for the blind were examined and 4610 medical records were analysed at an eye clinic. Data have been collected using the WHO Prevention of Blindness Programme eye examination record for children. Results 65 children were identified with SVI/BL, 58.5% were blind and 41.5% were severely visually impaired (SVI). The major anatomical site of SVI/BL was the retina in 33.8%, lens in 15.4% and normal appearing globe in 15.4%. The major underlying aetiology of SVI/BL was undetermined in 56.9% (mainly cataract and abnormality since birth) and perinatal factors 21.5% (mainly retinopathy of prematurity (ROP)). Avoidable causes of SVI/BL accounted for 40% of cases; 7.7% were preventable and 32.3% were treatable with cataracts and ROP the most common causes (15.4% and 12.3%, respectively). Conclusions More than a third of the SVI/BL causes are potentially avoidable, with childhood cataract and ROP the leading causes. Corneal scarring from vitamin A deficiency does not seem to be a continuing issue in Suriname. PMID:23603759

A Systematic Review and Meta-Analysis on the Safety of Vascular Endothelial Growth Factor (VEGF) Inhibitors for the Treatment of Retinopathy of Prematurity

PubMed Central

Pertl, Laura; Steinwender, Gernot; Mayer, Christoph; Hausberger, Silke; Pöschl, Eva-Maria; Wackernagel, Werner; Wedrich, Andreas; El-Shabrawi, Yosuf; Haas, Anton

2015-01-01

Introduction Laser photocoagulation is the current gold standard treatment for proliferative retinopathy of prematurity (ROP). However, it permanently reduces the visual field and might induce myopia. Vascular endothelial growth factor (VEGF) inhibitors for the treatment of ROP may enable continuing vascularization of the retina, potentially allowing the preservation of the visual field. However, for their use in infants concern remains. This meta-analysis explores the safety of VEGF inhibitors. Methods The Ovid Interface was used to perform a systematic review of the literature in the databases PubMed, EMBASE and the Cochrane Library. Results This meta-analysis included 24 original reports (including 1.457 eyes) on VEGF inhibitor treatment for ROP. The trials were solely observational except for one randomized and two case-control studies. We estimated a 6-month risk of retreatment per eye of 2.8%, and a 6-month risk of ocular complication without the need of retreatment of 1.6% per eye. Systemic complications were only reported as isolated incidents. Discussion VEGF inhibitors seem to be associated with low recurrence rates and ocular complication rates. They may have the benefit of potentially allowing the preservation of visual field and lower rates of myopia. Due to the lack of data, the risk of systemic side effects cannot be assessed. PMID:26083024

[Neurodevelopment in patients with retinopathy of prematurity treated with intravitreal bevacizumab. Case series].

PubMed

Martínez-García, Sarah Melania; Hernández-Da Mota, Sergio Eustolio; Rubio-Rangel, Araceli; Rojas-Flores, Ignacio; Vieyra-López, Mayra Edith; Martínez-Castellanos, María Ana; Zavala-Martínez, María Teresa; Gómez García, Anel

Retinopathy of prematurity (ROP) is an eye disease caused by an alteration in retinal vasculogenesis that may lead to partial or complete vision loss with a harmful impact in terms of neurodevelopment. The purpose of the present study was to determine the neurodevelopment in patients with type i retinopathy of prematurity treated with intravitreal bevacizumab. Case series. The inclusion criteria were: patients with type I ROP treated with a dose of 0.625mg/0.025ml of intravitreal bevacizumab. Demographic data and comorbidities were documented. Neurodevelopment was evaluated with the screening test of the Bayley Scale of Infant Development (BSID) in all patients between 11 and 28 weeks of age. Seven patients were included in the study. Four patients showed normal neurodevelopment according to the overall scores of the BSID scale. The distribution of high risk for neurodevelopmental delay in the different areas evaluated were as follows: 3 patients presented it in the cognitive area, one in the receptive communication area, one in the expressive area, one in the fine motor skills and 3 patients in the gross motor skills area. In these case series, the majority of patients treated with intravitreal bevacizumab for ROP showed normal neurodevelopment scores. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

Synthesis of well-defined bisbenzoin end-functionalized poly(ε-caprolactone) macrophotoinitiator by combination of ROP and click chemistry and its use in the synthesis of star copolymers by photoinduced free radical promoted cationic polymerization

PubMed Central

Uyar, Zafer; Degirmenci, Mustafa; Genli, Nasrettin; Yilmaz, Ayse

2017-01-01

Abstract A new well-defined bisbenzoin group end-functionalized poly(ε-caprolactone) macrophotoinitiator (PCL-(PI)2) was synthesized by combination of ring opening polymerization (ROP) and click chemistry. The ROP of ε-CL monomer in bulk at 110 °C, by means of a hydroxyl functional initiator namely, 3-cyclohexene-1-methanol in conjunction with stannous-2-ethylhexanoate, (Sn(Oct)2), yielded a well-defined PCL with a cyclohexene end-chain group (PCL-CH). The bromination and subsequent azidation of the cyclohexene end-chain group gave bisazido functionalized poly(ε-caprolactone) (PCL-(N3)2). Separately, an acetylene functionalized benzoin photoinitiator (PI-alkyne) was synthesized by using benzoin and propargyl bromide. Then the click reaction between PCL-(N3)2 and PI-alkyne was performed by Cu(I) catalysis. The spectroscopic studies revealed that poly(ε-caprolactone) with bisbenzoin photoactive functional group at the chain end (PCL-(PI)2) with controlled chain length and low-polydispersity was obtained. This PCL-(PI)2 macrophotoinitiator was used as a precursor in photoinduced free radical promoted cationic polymerization to synthesize an AB2-type miktoarm star copolymer consisting of poly(ε-caprolactone) (PCL, as A block) and poly(cyclohexene oxide) (PCHO, as B block), namely PCL(PCHO)2. PMID:29491778

Pathogenic role and therapeutic potential of pleiotrophin in mouse models of ocular vascular disease.

PubMed

Wang, Weiwen; LeBlanc, Michelle E; Chen, Xiuping; Chen, Ping; Ji, Yanli; Brewer, Megan; Tian, Hong; Spring, Samantha R; Webster, Keith A; Li, Wei

2017-11-01

Angiogenic factors play an important role in the pathogenesis of diabetic retinopathy (DR), neovascular age-related macular degeneration (nAMD) and retinopathy of prematurity (ROP). Pleiotrophin, a well-known angiogenic factor, was recently reported to be upregulated in the vitreous fluid of patients with proliferative DR (PDR). However, its pathogenic role and therapeutic potential in ocular vascular diseases have not been defined in vivo. Here using corneal pocket assays, we demonstrated that pleiotrophin induced angiogenesis in vivo. To investigate the pathological role of pleiotrophin we used neutralizing antibody to block its function in multiple in vivo models of ocular vascular diseases. In a mouse model of DR, intravitreal injection of pleiotrophin-neutralizing antibody alleviated diabetic retinal vascular leakage. In a mouse model of oxygen-induced retinopathy (OIR), which is a surrogate model of ROP and PDR, we demonstrated that intravitreal injection of anti-pleiotrophin antibody prevented OIR-induced pathological retinal neovascularization and aberrant vessel tufts. Finally, pleiotrophin-neutralizing antibody ameliorated laser-induced choroidal neovascularization, a mouse model of nAMD, suggesting that pleiotrophin is involved in choroidal vascular disease. These findings suggest that pleiotrophin plays an important role in the pathogenesis of DR with retinal vascular leakage, ROP with retinal neovascularization and nAMD with choroidal neovascularization. The results also support pleiotrophin as a promising target for anti-angiogenic therapy.

Refractive and Biometric Outcomes in Patients with Retinopathy of Prematurity Treated with Intravitreal Injection of Ranibizumab as Compared with Bevacizumab: A Clinical Study of Correction at Three Years of Age.

PubMed

Chen, Yen-Chih; Chen, San-Ni; Yang, Benjamin Chi-Lan; Lee, Kun-Hsien; Chuang, Chih-Chun; Cheng, Chieh-Yin

2018-01-01

To compare refractive and biometric outcomes in patients with type 1 retinopathy of prematurity (ROP) treated with intravitreal injection of ranibizumab (IVR) versus bevacizumab (IVB), at a corrected age of 3 years. A retrospective case series compared cycloplegic refractive statuses and biometric statuses in patients who received either IVR or IVB for type 1 ROP, from April 2011 to April 2014. A total of 62 eyes (33 patients) with type 1 ROP were evaluated (26 eyes in 13 IVR patients and 36 eyes in 20 IVB patients). There were no differences in birth statuses including gestational age and birth body weight between the two groups. The prevalence of refractive error greater than 1 D was higher in the IVB group ( p = 0.03), and there was a higher prevalence of high myopia (<-5.0 D, p = 0.03) in the IVB group. Comparisons in biometric finding showed that IVB patients had shallower anterior chamber depth ( p = 0.01). Both IVR and IVB showed low refractive errors, even followed at the corrected age of 3 years. No difference was noted between the two groups in refractive statuses. However, IVB was associated with shallower anterior chamber and higher prevalence of refractive error at the corrected age of 3 years. This trial is registered with NCT03334513.

Use of conserved key amino acid positions to morph protein folds.

PubMed

Reddy, Boojala V B; Li, Wilfred W; Bourne, Philip E

2002-07-15

By using three-dimensional (3D) structure alignments and a previously published method to determine Conserved Key Amino Acid Positions (CKAAPs) we propose a theoretical method to design mutations that can be used to morph the protein folds. The original Paracelsus challenge, met by several groups, called for the engineering of a stable but different structure by modifying less than 50% of the amino acid residues. We have used the sequences from the Protein Data Bank (PDB) identifiers 1ROP, and 2CRO, which were previously used in the Paracelsus challenge by those groups, and suggest mutation to CKAAPs to morph the protein fold. The total number of mutations suggested is less than 40% of the starting sequence theoretically improving the challenge results. From secondary structure prediction experiments of the proposed mutant sequence structures, we observe that each of the suggested mutant protein sequences likely folds to a different, non-native potentially stable target structure. These results are an early indicator that analyses using structure alignments leading to CKAAPs of a given structure are of value in protein engineering experiments. Copyright 2002 Wiley Periodicals, Inc.

Determinants of GBP Recruitment to Toxoplasma gondii Vacuoles and the Parasitic Factors That Control It

PubMed Central

Virreira Winter, Sebastian; Niedelman, Wendy; Jensen, Kirk D.; Rosowski, Emily E.; Julien, Lindsay; Spooner, Eric; Caradonna, Kacey; Burleigh, Barbara A.; Saeij, Jeroen P. J.; Ploegh, Hidde L.; Frickel, Eva-Maria

2011-01-01

IFN-γ is a major cytokine that mediates resistance against the intracellular parasite Toxoplasma gondii. The p65 guanylate-binding proteins (GBPs) are strongly induced by IFN-γ. We studied the behavior of murine GBP1 (mGBP1) upon infection with T. gondii in vitro and confirmed that IFN-γ-dependent re-localization of mGBP1 to the parasitophorous vacuole (PV) correlates with the virulence type of the parasite. We identified three parasitic factors, ROP16, ROP18, and GRA15 that determine strain-specific accumulation of mGBP1 on the PV. These highly polymorphic proteins are held responsible for a large part of the strain-specific differences in virulence. Therefore, our data suggest that virulence of T. gondii in animals may rely in part on recognition by GBPs. However, phagosomes or vacuoles containing Trypanosoma cruzi did not recruit mGBP1. Co-immunoprecipitation revealed mGBP2, mGBP4, and mGBP5 as binding partners of mGBP1. Indeed, mGBP2 and mGBP5 co-localize with mGBP1 in T. gondii-infected cells. T. gondii thus elicits a cell-autonomous immune response in mice with GBPs involved. Three parasitic virulence factors and unknown IFN-γ-dependent host factors regulate this complex process. Depending on the virulence of the strains involved, numerous GBPs are brought to the PV as part of a large, multimeric structure to combat T. gondii. PMID:21931713

Persistence of Retinopathy of Prematurity in an Infant with Tetralogy of Fallot

PubMed Central

Celik, Gokhan; Uludag, Gunay

2016-01-01

We report an infant with tetralogy of fallot (TOF) who was born at 35 weeks of gestation and of 1700 g birth weight and presented with persistent retinopathy of prematurity (ROP) at 6 months of age. Follow-up ophthalmic examinations were done at 2, 3, and 4 weeks of age. A demarcation line in Zone II was noticed on the first ocular examination done at 4 weeks of postnatal age. At 6 months of postnatal age, the infant still had an avascular peripheral retina with the demarcation line in Zone II. Even though this index subject did not have any typical risk factors for ROP, TOF seems to be the probable reason for developing as well as persistence of avascular retina. PMID:27525147

Molecular mechanisms controlling pavement cell shape in Arabidopsis leaves.

PubMed

Qian, Pingping; Hou, Suiwen; Guo, Guangqin

2009-08-01

Pavement cells have an interlocking jigsaw puzzle-shaped leaf surface pattern. Twenty-three genes involved in the pavement cell morphogenesis were discovered until now. The mutations of these genes through various means lead to pavement cell shape defects, such as loss or lack of interdigitation, the reduction of lobing, gaps between lobe and neck regions in pavement cells, and distorted trichomes. These phenotypes are affected by the organization of microtubules and microfilaments. Microtubule bands are considered corresponding with the neck regions of the cell, while lobe formation depends on patches of microfilaments. The pathway of Rho of plant (ROP) GTPase signaling cascades regulates overall activity of the cytoskeleton in pavement cells. Some other proteins, in addition to the ROPs, SCAR/WAVE, and ARP2/3 complexes, are also involved in the pavement cell morphogenesis.

Ring Opening Polymerization and Copolymerization of Cyclic Esters Catalyzed by Group 2 Metal Complexes Supported by Functionalized P-N Ligands.

PubMed

Harinath, Adimulam; Bhattacharjee, Jayeeta; Sarkar, Alok; Nayek, Hari Pada; Panda, Tarun K

2018-03-05

We report the preparation of alkali and alkaline earth (Ae) metal complexes supported by 2-picolylamino-diphenylphosphane chalcogenide [(Ph 2 P(=E)NHCH 2 (C 5 H 4 N)] [E = S (1-H); Se (2-H)] ligands. The treatment of the protic ligand, 1-H or 2-H, with alkali metal hexamethyldisilazides at room temperature afforded the corresponding alkali metal salts [M(THF) 2 (Ph 2 P(=E)NCH 2 (C 5 H 4 N)] [M = Li, E = S (3a), Se (3b)] and [{M(THF) n (Ph 2 P(=E)NCH 2 (C 5 H 4 N)} 2 ] [M = Na, E = S (4a), Se (4b); M = K, E = Se (5b)] in good yield. The homoleptic Ae metal complexes [κ 2 -(Ph 2 P(=Se)NCH 2 (C 5 H 4 N)Mg(THF)] (6b) and [κ 3 -{(Ph 2 P(=Se)NCH 2 (C 5 H 4 N)} 2 M(THF) n ] (M = Ca (7b), Sr (8b), Ba (9b)] were synthesized by the one-pot reaction of 2-H with [KN(SiMe 3 ) 2 ] and MI 2 in a 2:2:1 molar ratio at room temperature. The molecular structures of the protic-ligands 1-H and 2-H, as well as complexes 3a,b-5a,b and 6b-9b were established using single-crystal X-ray analysis. The Ae metal complexes 6b-9b were tested for ring-opening polymerization (ROP) of racemic lactide ( rac-LA) and copolymerization of rac-LA and ε-caprolactone (ε-CL) at room temperature. In the ROP of rac-LA, the calcium complex 7b exhibited high isoselectivity, with P i = 0.89, whereas both the barium and strontium complexes showed lower isoselectivity with P i = 0.78-0.62. In the copolymerization of rac-LA and ε-CL, both barium and strontium complexes proved to be efficient precatalysts for the formation of the block copolymer rac-LA-CL, but the reactivity of 9b was found to be better than that of 8b. All the polymers were fully characterized using differential scanning calorimetry, thermogravimetric analysis, and gel permeation chromatography analyses. Kinetic studies on the ROP reaction of LA confirmed that the rate of polymerization followed the order Ba ≫ Sr ≈ Ca.

Treatment of retinopathy of prematurity with topical ketorolac tromethamine: a preliminary study.

PubMed

Avila-Vazquez, Medardo; Maffrand, Roque; Sosa, Mirta; Franco, Maria; De Alvarez, Beatriz Vaca; Cafferata, Maria Luisa; Bergel, Eduardo

2004-08-07

Retinopathy of Prematurity (ROP) is a common retinal neovascular disorder of premature infants. It is of variable severity, usually heals with mild or no sequelae, but may progress to blindness from retinal detachments or severe retinal scar formation. This is a preliminary report of the effectiveness and safety of a new and original use of topical ketorolac in preterm newborn to prevent the progression of ROP to the more severe forms of this disease. From January 2001 to December 2002, all fifty nine preterm newborns with birthweight less than 1250 grams or gestational age less than 30 weeks of gestational age admitted to neonatal intensive care were eligible for treatment with topical ketorolac (0.25 milligrams every 8 hours in each eye). The historical comparison group included all 53 preterm newborns, with the same inclusion criteria, admitted between January 1999 and December 2000. Groups were comparable in terms of weight distribution, Apgar score at 5 minutes, incidence of sepsis, intraventricular hemorrhage and necrotizing enterocolitis. The duration of oxygen therapy was significantly longer in the control group. In the ketorolac group, among 43 children that were alive at discharge, one (2.3%) developed threshold ROP and cryotherapy was necessary. In the comparison group 35 children survived, and six child (17%) needed cryotherapy (Relative Risk 0.14, 95%CI 0.00 to 0.80, p = 0.041). Adjusting by duration of oxygen therapy did not significantly change these results. Adverse effects attributable to ketorolac were not detected. This preliminary report suggests that ketorolac in the form of an ophthalmic solution can reduce the risk of developing severe ROP in very preterm newborns, without producing significant adverse side effects. These results, although promising, should be interpreted with caution because of the weakness of the study design. This is an inexpensive and simple intervention that might ameliorate the progression of a disease with devastating consequences for children and their families. We believe that next logical step would be to assess the effectiveness of this intervention in a randomized controlled trial of adequate sample size.

Treatment of Retinopathy of Prematurity with topical ketorolac tromethamine: a preliminary study

PubMed Central

Avila-Vazquez, Medardo; Maffrand, Roque; Sosa, Mirta; Franco, Maria; de Alvarez, Beatriz Vaca; Cafferata, Maria Luisa; Bergel, Eduardo

2004-01-01

Background Retinopathy of Prematurity (ROP) is a common retinal neovascular disorder of premature infants. It is of variable severity, usually heals with mild or no sequelae, but may progress to blindness from retinal detachments or severe retinal scar formation. This is a preliminary report of the effectiveness and safety of a new and original use of topical ketorolac in preterm newborn to prevent the progression of ROP to the more severe forms of this disease. Methods From January 2001 to December 2002, all fifty nine preterm newborns with birthweight less than 1250 grams or gestational age less than 30 weeks of gestational age admitted to neonatal intensive care were eligible for treatment with topical ketorolac (0.25 milligrams every 8 hours in each eye). The historical comparison group included all 53 preterm newborns, with the same inclusion criteria, admitted between January 1999 and December 2000. Results Groups were comparable in terms of weight distribution, Apgar score at 5 minutes, incidence of sepsis, intraventricular hemorrhage and necrotizing enterocolitis. The duration of oxygen therapy was significantly longer in the control group. In the ketorolac group, among 43 children that were alive at discharge, one (2.3%) developed threshold ROP and cryotherapy was necessary. In the comparison group 35 children survived, and six child (17%) needed cryotherapy (Relative Risk 0.14, 95%CI 0.00 to 0.80, p = 0.041). Adjusting by duration of oxygen therapy did not significantly change these results. Adverse effects attributable to ketorolac were not detected. Conclusions This preliminary report suggests that ketorolac in the form of an ophthalmic solution can reduce the risk of developing severe ROP in very preterm newborns, without producing significant adverse side effects. These results, although promising, should be interpreted with caution because of the weakness of the study design. This is an inexpensive and simple intervention that might ameliorate the progression of a disease with devastating consequences for children and their families. We believe that next logical step would be to assess the effectiveness of this intervention in a randomized controlled trial of adequate sample size. PMID:15298714

Comparison of Intravitreal Bevacizumab, Intravitreal Ranibizumab and Laser Photocoagulation for Treatment of Type 1 Retinopathy of Prematurity in Turkish Preterm Children.

PubMed

Kabataş, Emrah Utku; Kurtul, Bengi Ece; Altıaylık Özer, Pınar; Kabataş, Naciye

2017-07-01

To evaluate effectiveness of treatment modalities, major complications and refractive errors in children who were treated with intravitreal bevacizumab (IVB), intravitreal ranibizumab (IVR) or laser photocoagulation (LP) for type 1 retinopathy of prematurity (ROP). Premature infants who underwent IVB monotherapy (Group 1), IVR monotherapy (Group 2) or LP (Group 3) for type 1 ROP and infants with spontaneously regressed ROP (Group 4) were included for the study. Major complications, recurrence rate, recurrence time, total retinal vascularization time and refractive errors at 18 months of corrected age (CA) were determined. Groups 1, 2, 3 and 4 included 24 eyes of 12 patients, 12 eyes of six patients, 72 eyes of 36 patients and 148 eyes of 74 patients, respectively. Recurrence of the disease occurred in two eyes of one patient in Group 1 at 52 weeks of postmenstrual age (PMA) and two eyes of one patient at 48 weeks of PMA in Group 2. In Group 3, disease did not regress after the first treatment in 10 eyes of five patients. The mean vascularization time in Group 1 was 73 ± 10.1 weeks of PMA and 61.8 ± 6.6 weeks of PMA in Group 2 (p = 0.027). Macular ectopia was seen in two eyes of one patient and exudative retinal detachment (ERD) occurred in two eyes of one patient in Group 3. Mean spherical equivalent was 1.49 ± 3.04 diopters (D) in Group 1, -1.79 ± 2.87D in Group 2, -1.27 ± 2.8 D in Group 3 and 1.52 ± 1.07 D in Group 4 at 18 months of CA. There was no significant difference in astigmatism values in all groups. IVB, IVR and LP are options that can successfully treat ROP. Myopia was observed to be the main refractive error in all treatment groups. Vascularization of the retina was completed later in the IVB group than in the IVR group.

Retinopathy of prematurity

MedlinePlus

... CO2) in the blood Infection Low blood acidity (pH) Low blood oxygen Respiratory distress Slow heart rate (bradycardia) Transfusions The rate of ROP in most premature infants has gone down greatly in developed countries over the ...

[Treatment with human recombinant erythropoietin and frequency of retinopathy of prematurity].

PubMed

Rudzińska, Iwona M; Kornacka, Maria K; Pawluch, Robert

2002-01-01

The aim of our study was to assess frequency of ROP in VLBW and ELBW treated with rhEPO in preventing anemia. In 36 newborns with birth weight 480 to 1490 g (median 1032 g) and 24 to 32 weeks of gestational age (median 28.0 weeks) we have estimated concentration of cord erythropoietin. According this concentration we have divided our material into two groups. In first group of 22 newborns with cord concentration of EPO < 10 mU/ml we started early erythropoietin (rhEPO) therapy which was continued by 6 weeks. Second group of 14 no early usage newborns had cord EPO concentration > 10 mU/ml. In second group the control level of serum EPO was measured in 15th day of life. In newborns from second group in which the EPO concentration during two weeks decreased below 10 mU/ml we started to use rhEPO as a late usage. First oculistic consultation took place in the 5th week of life according to the screening performed in our country. In the first group (n = 22) with early EPO treatment retinopathy was recognized in 15 preterm newborns (68.2%). Eight of them (53.3%) had advanced form of retinopathy ROP (III lub III+) and were undergone a laserotherapy. In the group of late usage of rhEPO (n = 14) 8 newborns (57.1%) had signs of retinopathy, but only 3 of them (37.5%) required laserotherapy because of advanced form of ROP (III lub III+).

Temperament and behavior in toddlers born preterm with related clinical problems.

PubMed

Cassiano, Rafaela Guilherme Monte; Gaspardo, Claudia Maria; Faciroli, Ricardo Augusto de Deus; Martinez, Francisco Eulógio; Linhares, Maria Beatriz Martins

2017-09-01

The aim of this study was to compare temperament and behavior profiles among groups of preterm toddlers differentiated by level of prematurity and the presence of bronchopulmonary dysplasia (BPD) or retinopathy of prematurity (ROP), controlling for neonatal clinical conditions and chronological age. The sample comprised 100 preterm toddlers segregated according to level of prematurity (75 very preterm and 25 moderate/late preterm) and presence of BPD (n=36) and ROP (n=63). Temperament was assessed by the Early Childhood Behavior Questionnaire and behavior by the Child Behavior Checklist. The MANOVA was performed with a post-hoc univariate test. The level of prematurity and the presence of BPD and ROP did not affect temperament and behavioral problems in toddlers born preterm. However, the covariates age and length of stay in NICU (Neonatal Intensive Care Unit) affected temperament and behavioral problems, respectively. The older toddlers showed higher inhibitory control and lower activity levels than younger toddlers (range of 18-36months-old). Additionally, toddlers who stayed in the NICU longer showed more pervasive development and emotionally reactive problems than toddlers who stayed in NICU for less time. The level of prematurity and the presence of bronchopulmonary dysplasia and retinopathy of prematurity did not affect temperament and behavioral problems in toddlers born preterm. However, a longer stay in the NICU increased the risk for behavioral problems, and age enhanced the regulation of temperament at toddlerhood. Copyright © 2017 Elsevier B.V. All rights reserved.

Corneal Aberrations in Former Preterm Infants: Results From The Wiesbaden Prematurity Study.

PubMed

Fieß, Achim; Schuster, Alexander K; Kölb-Keerl, Ruth; Knuf, Markus; Kirchhof, Bernd; Muether, Philipp S; Bauer, Jacqueline

2017-12-01

To compare corneal aberrations in former preterm infants to that of full-term infants. A prospective cross-sectional study was carried out measuring the corneal shape with Scheimpflug imaging in former preterm infants of gestational age (GA) ≤32 weeks and full-term infants with GA ≥37 weeks now being aged between 4 to 10 years. The main outcome measures were corneal aberrations including astigmatism (Zernike: Z2-2; Z22), coma (Z3-1; Z31), trefoil (Z3-3; Z33), spherical aberration (Z40) and root-mean square of higher-order aberrations (RMS HOA). Multivariable analysis was performed to assess independent associations of gestational age groups and of retinopathy of prematurity (ROP) occurrence with corneal aberrations adjusting for sex and age at examination. A total of 259 former full-term and 226 preterm infants with a mean age of 7.2 ± 2.0 years were included in this study. Statistical analysis revealed an association of extreme prematurity (GA ≤28 weeks) with higher-order and lower-order aberrations of the total cornea. Vertical coma was higher in extreme prematurity (P < 0.001), due to the shape of the anterior corneal surface, while there was no association with trefoil and spherical aberration. ROP was not associated with higher-order aberrations when adjusted for gestational age group. This study demonstrated that specific corneal aberrations were associated with extreme prematurity rather than with ROP occurrence.

Visual cycle modulation in neurovascular retinopathy.

PubMed

Akula, James D; Hansen, Ronald M; Tzekov, Radouil; Favazza, Tara L; Vyhovsky, Tanya C; Benador, Ilan Y; Mocko, Julie A; McGee, David; Kubota, Ryo; Fulton, Anne B

2010-08-01

Rats with oxygen-induced retinopathy (OIR) model the pediatric retinal disease retinopathy of prematurity (ROP). Recent findings in OIR rats imply a causal role for the rods in the ROP disease process, although only experimental manipulation of rod function can establish this role conclusively. Accordingly, a visual cycle modulator (VCM) - with no known direct effect on retinal vasculature - was administered to "50/10 model" OIR Sprague-Dawley rats to test the hypotheses that it would 1) alter rod function and 2) consequently alter vascular outcome. Four litters of pups (N=46) were studied. For two weeks, beginning on postnatal day (P) 7, the first and fourth litters were administered 6 mg kg(-1) N-retinylacetamide (the VCM) intraperitoneally; the second and third litters received vehicle (DMSO) alone. Following a longitudinal design, retinal function was assessed by electroretinography (ERG) and the status of the retinal vessels was monitored using computerized fundus photograph analysis. Rod photoreceptor and post-receptor response amplitudes were significantly higher in VCM-treated than in vehicle-treated rats; deactivation of phototransduction was also significantly more rapid. Notably, the arterioles of VCM-treated rats showed significantly greater recovery from OIR. Presuming that the VCM did not directly affect the retinal vessels, a causal role for the neural retina - particularly the rod photoreceptors - in OIR was confirmed. There was no evidence of negative alteration of photoreceptor function consequent to VCM treatment. This finding implicates the rods as a possible therapeutic target in neurovascular diseases such as ROP. Copyright 2010 Elsevier Ltd. All rights reserved.

Shape-Persistent, Thermoresponsive Polypeptide Brushes Prepared by Vapor Deposition Surface-Initiated Ring-Opening Polymerization of α-Amino Acid N -Carboxyanhydrides

DOE PAGES

Shen, Yong; Desseaux, Solenne; Aden, Bethany; ...

2015-04-20

We report that surface-grafting thermoresponsive polymers allows the preparation of thin polymer brush coatings with surface properties that can be manipulated by variation of temperature. In most instances, thermoresponsive polymer brushes are produced using polymers that dehydrate and collapse above a certain temperature. This report presents the preparation and properties of polymer brushes that show thermoresponsive surface properties, yet are shape-persistent in that they do not undergo main chain collapse. The polymer brushes presented here are obtained via vapor deposition surface-initiated ring-opening polymerization (SI-ROP) of γ-di- or tri(ethylene glycol)-modified glutamic acid N-carboxyanhydrides. Vapor deposition SI-ROP of γ-di- or tri(ethylene glycol)-modifiedmore » L- or D-glutamic acid N-carboxyanhydrides affords helical surface-tethered polymer chains that do not show any changes in secondary structure between 10 and 70 °C. QCM-D experiments, however, revealed significant dehydration of poly(γ-(2-(2-methoxyethoxy)ethyl)-l-glutamate) (poly(L-EG 2-Glu)) brushes upon heating from 10 to 40 °C. At the same time, AFM and ellipsometry studies did not reveal significant variations in film thickness over this temperature range, which is consistent with the shape-persistent nature of these polypeptide brushes and indicates that the thermoresponsiveness of the films is primarily due to hydration and dehydration of the oligo(ethylene glycol) side chains. The results we present here illustrate the potential of surface-initiated NCA ring-opening polymerization to generate densely grafted assemblies of polymer chains that possess well-defined secondary structures and tunable surface properties. These polypeptide brushes complement their conformationally unordered counterparts that can be generated via surface-initiated polymerization of vinyl-type monomers and represent another step forward to biomimetic surfaces and interfaces.« less

Molecular Dynamics Simulations of Hydrophobic Residues

NASA Astrophysics Data System (ADS)

Caballero, Diego; Zhou, Alice; Regan, Lynne; O'Hern, Corey

2013-03-01

Molecular recognition and protein-protein interactions are involved in important biological processes. However, despite recent improvements in computational methods for protein design, we still lack a predictive understanding of protein structure and interactions. To begin to address these shortcomings, we performed molecular dynamics simulations of hydrophobic residues modeled as hard spheres with stereo-chemical constraints initially at high temperature, and then quenched to low temperature to obtain local energy minima. We find that there is a range of quench rates over which the probabilities of side-chain dihedral angles for hydrophobic residues match the probabilities obtained for known protein structures. In addition, we predict the side-chain dihedral angle propensities in the core region of the proteins T4, ROP, and several mutants. These studies serve as a first step in developing the ability to quantitatively rank the energies of designed protein constructs. The success of these studies suggests that only hard-sphere dynamics with geometrical constraints are needed for accurate protein structure prediction in hydrophobic cavities and binding interfaces. NSF Grant PHY-1019147

Volume, size, professionals' specialization and nutrition management of NICUs and their association with treatment quality in VLBW infants.

PubMed

Miedaner, Felix; Langhammer, Kristina; Enke, Christian; Göpel, Wolfgang; Kribs, Angela; Nitzsche, Anika; Riedel, Rainer; Woopen, Christiane; Kuntz, Ludwig; Roth, Bernhard

2018-04-01

To assess the association of volume, size, the availability of highly-specialized professionals and nutrition management of NICUs with treatment quality among VLBW infants. A prospective multicenter study of 923 VLBW infants in 66 German NICUs, born between May and October 2013. Using multilevel modeling, we examined the association between the aforementioned organizational characteristics and treatment quality, measured via major morbidities (severe IVH, PVL, BPD, NEC, FIP, ROP, and discharge without severe complications) and medical process measures of VLBW infants. After risk-adjustment and accounting for other NICU characteristics, infants in low-volume NICUs were at higher risk of IVH, ROP and PVL. However, the initial effect of volume on process measures (growth velocity, administration of antenatal steroids) disappeared. Volume can only partially explain differences in the treatment quality of VLBWs. The underlying organizational mechanisms should be considered to improve the quality of care.

Biodegradable polyester-based eco-composites containing hemp fibers modified with macrocyclic oligomers

NASA Astrophysics Data System (ADS)

Conzatti, Lucia; Utzeri, Roberto; Hodge, Philip; Stagnaro, Paola

2016-05-01

An original compatibilizing pathway for hemp fibers/poly(1,4-butylene adipate-co-terephtalate) (PBAT) eco-composites was explored exploiting the capability of macrocyclic oligomers (MCOs), obtained by cyclodepolymerization (CDP) of PBAT at high dilution, of being re-converted into linear chains by entropically-driven ring-opening polymerization (ED-ROP) that occurs simply heating the MCOS in the bulk. CDP reaction of PBAT was carried out varying solvent, catalyst and reaction time. Selected MCOs were used to adjust the conditions of the ED-ROP reaction. The best experimental conditions were then adopted to modify hemp fibers. Eco-composites based on PBAT and hemp fibers as obtained or modified with PBAT macrocyclics or oligomers were prepared by different process strategies. The best fiber-PBAT compatibility was observed when the fibers were modified with PBAT oligomers before incorporation in the polyester matrix.

Improvement in Titanium Complexes Bearing Schiff Base Ligands in the Ring-Opening Polymerization of L-Lactide: A Dinuclear System with Hydrazine-Bridging Schiff Base Ligands.

PubMed

Tseng, Hsi-Ching; Chen, Hsing-Yin; Huang, Yen-Tzu; Lu, Wei-Yi; Chang, Yu-Lun; Chiang, Michael Y; Lai, Yi-Chun; Chen, Hsuan-Ying

2016-02-15

A series of titanium (Ti) complexes bearing hydrazine-bridging Schiff base ligands were synthesized and investigated as catalysts for the ring-opening polymerization (ROP) of L-lactide (LA). Complexes with electron withdrawing or steric bulky groups reduced the catalytic activity. In addition, the steric bulky substituent on the imine groups reduced the space around the Ti atom and then reduced LA coordination with Ti atom, thereby reducing catalytic activity. All the dinuclear Ti complexes exhibited higher catalytic activity (approximately 10-60-fold) than mononuclear L(Cl-H)-TiOPr2 did. The strategy of bridging dinuclear Ti complexes with isopropoxide groups in the ROP of LA was successful, and adjusting the crowded heptacoordinated transition state by the bridging isopropoxide groups may be the key to our successful strategy.

Automatic Tortuosity-Based Retinopathy of Prematurity Screening System

NASA Astrophysics Data System (ADS)

Sukkaew, Lassada; Uyyanonvara, Bunyarit; Makhanov, Stanislav S.; Barman, Sarah; Pangputhipong, Pannet

Retinopathy of Prematurity (ROP) is an infant disease characterized by increased dilation and tortuosity of the retinal blood vessels. Automatic tortuosity evaluation from retinal digital images is very useful to facilitate an ophthalmologist in the ROP screening and to prevent childhood blindness. This paper proposes a method to automatically classify the image into tortuous and non-tortuous. The process imitates expert ophthalmologists' screening by searching for clearly tortuous vessel segments. First, a skeleton of the retinal blood vessels is extracted from the original infant retinal image using a series of morphological operators. Next, we propose to partition the blood vessels recursively using an adaptive linear interpolation scheme. Finally, the tortuosity is calculated based on the curvature of the resulting vessel segments. The retinal images are then classified into two classes using segments characterized by the highest tortuosity. For an optimal set of training parameters the prediction is as high as 100%.

Inhibition of cell expansion by rapid ABP1-mediated auxin effect on microtubules

PubMed Central

Chen, Xu; Grandont, Laurie; Li, Hongjiang; Hauschild, Robert; Paque, Sébastien; Abuzeineh, Anas; Rakusová, Hana; Benkova, Eva; Perrot-Rechenmann, Catherine; Friml, Jiří

2014-01-01

The prominent and evolutionary ancient effect of the plant hormone auxin is the regulation of cell expansion1. Cell expansion requires ordered cytoskeleton arrangement2 but molecular mechanisms underlying its regulation by signaling molecules including auxin are unknown. Here we show in the model plant Arabidopsis thaliana that in elongating cells exogenous application of auxin or redistribution of endogenous auxin induces very rapid microtubule reorientation from transversal to longitudinal, coherent with the inhibition of cell expansion. This fast auxin effect requires Auxin Binding Protein1 (ABP1) and involves a contribution of downstream signaling components such as ROP6 GTPase, ROP-interactive protein RIC1 and microtubule severing protein Katanin. These components are required for rapid auxin and ABP1-mediated reorientation of microtubules to regulate cell elongation in roots and dark grown hypocotyls as well as asymmetric growth during gravitropic responses. PMID:25409144

[Human milk for neonatal pain relief during ophthalmoscopy].

PubMed

Ribeiro, Laiane Medeiros; Castral, Thaíla Corrêa; Montanholi, Liciane Langona; Daré, Mariana Firmino; Silva, Aline Carolina de Araújo; Antonini, Sonir Roberto Rauber; Scochi, Carmen Gracinda Silvan

2013-10-01

Ophthalmoscopy performed for the early diagnosis of retinopathy of prematurity (ROP) is painful for preterm infants, thus necessitating interventions for minimizing pain. The present study aimed to establish the effectiveness of human milk, compared with sucrose, for pain relief in premature infants subjected to ophthalmoscopy for the early diagnosis of ROP. This investigation was a pilot, quasi-experimental study conducted with 14 premature infants admitted to the neonatal intensive care unit (NICU) of a university hospital. Comparison between the groups did not yield a statistically significant difference relative to the crying time, salivary cortisol, or heart rate (HR). Human milk appears to be as effective as sucrose in relieving acute pain associated with ophthalmoscopy. The study's limitations included its small sample size and lack of randomization. Experimental investigations with greater sample power should be performed to reinforce the evidence found in the present study.

Nitroxide-mediated radical ring-opening copolymerization: chain-end investigation and block copolymer synthesis.

PubMed

Delplace, Vianney; Harrisson, Simon; Tardy, Antoine; Gigmes, Didier; Guillaneuf, Yohann; Nicolas, Julien

2014-02-01

Well-defined, degradable copolymers are successfully prepared by nitroxide-mediated radical ring opening polymerization (NMrROP) of oligo(ethylene glycol) methyl ether methacrylate (OEGMA) or methyl methacrylate (MMA), a small amount of acrylonitrile (AN) and cyclic ketene acetals (CKAs) of different structures. Phosphorous nuclear magnetic resonance allows in-depth chain-end characterization and gives crucial insights into the nature of the copoly-mer terminal sequences and the living chain fractions. By using a small library of P(OEGMA-co-AN-co-CKA) and P(MMA-co-AN-co-CKA) as macroinitiators, chain extensions with styrene are performed to furnish (amphiphilic) block copolymers comprising a degradable segment. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fully automated disease severity assessment and treatment monitoring in retinopathy of prematurity using deep learning

NASA Astrophysics Data System (ADS)

Brown, James M.; Campbell, J. Peter; Beers, Andrew; Chang, Ken; Donohue, Kyra; Ostmo, Susan; Chan, R. V. Paul; Dy, Jennifer; Erdogmus, Deniz; Ioannidis, Stratis; Chiang, Michael F.; Kalpathy-Cramer, Jayashree

2018-03-01

Retinopathy of prematurity (ROP) is a disease that affects premature infants, where abnormal growth of the retinal blood vessels can lead to blindness unless treated accordingly. Infants considered at risk of severe ROP are monitored for symptoms of plus disease, characterized by arterial tortuosity and venous dilation at the posterior pole, with a standard photographic definition. Disagreement among ROP experts in diagnosing plus disease has driven the development of computer-based methods that classify images based on hand-crafted features extracted from the vasculature. However, most of these approaches are semi-automated, which are time-consuming and subject to variability. In contrast, deep learning is a fully automated approach that has shown great promise in a wide variety of domains, including medical genetics, informatics and imaging. Convolutional neural networks (CNNs) are deep networks which learn rich representations of disease features that are highly robust to variations in acquisition and image quality. In this study, we utilized a U-Net architecture to perform vessel segmentation and then a GoogLeNet to perform disease classification. The classifier was trained on 3,000 retinal images and validated on an independent test set of patients with different observed progressions and treatments. We show that our fully automated algorithm can be used to monitor the progression of plus disease over multiple patient visits with results that are consistent with the experts' consensus diagnosis. Future work will aim to further validate the method on larger cohorts of patients to assess its applicability within the clinic as a treatment monitoring tool.

Causes of severe visual impairment and blindness in children attending schools for the visually handicapped in the Czech Republic.

PubMed

Kocur, I; Kuchynka, P; Rodný, S; Baráková, D; Schwartz, E C

2001-10-01

To describe the causes of severe visual impairment and blindness in children in schools for the visually handicapped in the Czech Republic in 1998. Pupils attending all 10 primary schools for the visually handicapped were examined. A modified WHO/PBL eye examination record for children with blindness and low vision was used. 229 children (146 males and 83 females) aged 6-15 years were included in the study: 47 children had severe visual impairment (20.5%) (visual acuity in their better eye less than 6/60), and 159 were blind (69.5%) (visual acuity in their better eye less than 3/60). Anatomically, the most affected parts of the eye were the retina (124, 54.2%), optic nerve (35, 15.3%), whole globe (25, 10.9%), lens (20, 8.7%), and uvea (12, 5.2%). Aetiologically (timing of insult leading to visual loss), the major cause of visual impairment was retinopathy of prematurity (ROP) (96, 41.9 %), followed by abnormalities of unknown timing of insult (97, 42.4%), and hereditary disease (21, 9.2%). In 90 children (40%), additional disabilities were present: mental disability (36, 16%), physical handicap (16, 7%), and/or a combination of both (19, 8%). It was estimated that 127 children (56%) suffer from visual impairment caused by potentially preventable and/or treatable conditions (for example, ROP, cataract, glaucoma). Establishing a study group for comprehensive evaluation of causes of visual handicap in children in the Czech Republic, as well as for detailed analysis of present practice of screening for ROP was recommended.

Ultra-low dose of intravitreal bevacizumab in retinopathy of prematurity.

PubMed

Şahin, A; Gürsel-Özkurt, Z; Şahin, M; Türkcü, F M; Yıldırım, A; Yüksel, H

2018-05-01

We aimed to investigate the effectivity of the 0.0625 mg dose of bevacizumab in patients with retinopathy of prematurity (ROP) and compare the results with 0.625 mg dose of intravitreal bevacizumab (IVB) injection. The medical records of the patients with type 1 ROP who received IVB monotherapy were retrospectively reviewed. Demographic and clinical characteristics of the patients were recorded. The patients were classified into two groups with respect to received dose of bevacizumab as follows: group F (n = 46) (full dose of bevacizumab-0.625 mg/0.025 ml) and group L (n = 45) (low dose (one tenth) of bevacizumab-0.0625 mg/0.025 ml). Both treatment dose regimens have similar outcomes. Moreover, the mean retinal vascularization time seemed to be significantly higher in group F compared to group L, 168 ± 65 and 97 ± 29 days, respectively (p < 0.001). Disappearance of plus sign is observed earlier in group F (2.45 ± 1.7 vs 3.66 ± 2.46 days, respectively, p = 0.03). The low dose (0.0625 mg) of IVB treatment was effective as full (0.625 mg) dose in ROP treatment. Moreover, our results showed that low-dose treatment might provide faster retinal vascularization than the regular used dose. On the other hand, disappearance of the plus sign takes longer time in patients treated with low dose compared to eyes treated with full dose of IVB that should be taken into account.

The anatomy of the rat eye with oxygen-induced retinopathy.

PubMed

Akula, James D; Favazza, Tara L; Mocko, Julie A; Benador, Ilan Y; Asturias, Ana L; Kleinman, Michael S; Hansen, Ronald M; Fulton, Anne B

2010-02-01

Prior studies have documented the intertwined developmental courses of retinal blood vessel tortuosity (in fundus photographs) and retinal dysfunction (in electroretinographs) in Sprague-Dawley rat models of retinopathy of prematurity (ROP). Two such models, the "50/10 model" and the "75 model," are named after the oxygen regimens used to induce retinopathy and are characterized by distinct neurovascular courses that span a range of disease severity. In this study of 50/10 and 75 model rats, retinal flatmounts were used to study the full vasculature at postnatal day (P) 15, P19 and P30. In addition, the layers of the neural retina were measured in toluidine blue-stained cross sections. Finally, gross anatomic features of the eye, including axial length, retinal surface area, and the ratio of anterior to posterior axial-lengths were evaluated. Both clock hours of neovascularization (NV) and percent avascular retina (AR) peaked at P19 and resolved by P30. Through P19, NV was found in every 50/10 model rat, but in only 60% of 75 model rats. AR was positively related to NV. All inner layers of the retina (outer plexiform layer through ganglion cell layer) were attenuated in 50/10 model rats but, in the 75 model, no layer differed significantly from that in controls. The eyes in both ROP models were smaller than those of age-matched controls. The ratio of anterior to posterior axial-lengths ranged from 0.45 in controls through 0.37 in the 75 model to 0.32 in the 50/10 model. Thus, eye growth is altered in these rat models of ROP.

Forecast skill score assessment of a relocatable ocean prediction system, using a simplified objective analysis method

NASA Astrophysics Data System (ADS)

Onken, Reiner

2017-11-01

A relocatable ocean prediction system (ROPS) was employed to an observational data set which was collected in June 2014 in the waters to the west of Sardinia (western Mediterranean) in the framework of the REP14-MED experiment. The observational data, comprising more than 6000 temperature and salinity profiles from a fleet of underwater gliders and shipborne probes, were assimilated in the Regional Ocean Modeling System (ROMS), which is the heart of ROPS, and verified against independent observations from ScanFish tows by means of the forecast skill score as defined by Murphy(1993). A simplified objective analysis (OA) method was utilised for assimilation, taking account of only those profiles which were located within a predetermined time window W. As a result of a sensitivity study, the highest skill score was obtained for a correlation length scale C = 12.5 km, W = 24 h, and r = 1, where r is the ratio between the error of the observations and the background error, both for temperature and salinity. Additional ROPS runs showed that (i) the skill score of assimilation runs was mostly higher than the score of a control run without assimilation, (i) the skill score increased with increasing forecast range, and (iii) the skill score for temperature was higher than the score for salinity in the majority of cases. Further on, it is demonstrated that the vast number of observations can be managed by the applied OA method without data reduction, enabling timely operational forecasts even on a commercially available personal computer or a laptop.

Retinopathy of Prematurity (ROP)

MedlinePlus

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