Real-World Analysis of the Efficacy of Bimatoprost Sustained-Release Glaucoma Implant Where American Indians Comprise the Largest Minority Population

Steven R Sarkisian Jr,1 Evann C Mitchell2 1Research & Clinical Trials, Oklahoma Eye Surgeons, Oklahoma City, OK, USA; 2College of Medicine, University of Oklahoma, Oklahoma City, OK, USACorrespondence: Steven R Sarkisian Jr, Research & Clinical Trials, Oklahoma Eye Surgeons, 5600 N Portland Ave, Oklahoma City, OK, 73112, USA, Tel +1405 943-4413, Fax +1405 942-0115, Email [email protected]: To assess the effectiveness and safety of bimatoprost sustained release (SR) glaucoma implant as a treatment for open-angle glaucoma and ocular hypertension in a real-world private practice setting with a significant American Indian population.Methods: This retrospective study included 156 eyes from adult patients who received a single injection of bimatoprost implant between June 2020 and May 2022 at the Oklahoma Eye Surgeons. Patients were stratified by baseline intraocular pressure (IOP) (≥ 21 mmHg versus IOP< 21 mmHg). The co-primary endpoints were changes in the mean IOP and the number of topical IOP-lowering medications from baseline to Month 6.Results: At 6 months, eyes with baseline IOP≥ 21 mmHg had a significantly lower mean IOP (19.85± 8.01 versus 26.25± 4.84 mmHg; p< 0.0001) and the mean number of IOP-lowering medications (1.04± 1.44 versus 1.38± 1.50; p=0.048) compared with baseline. One year after implantation, 73.58% of eyes had a ≥ 20% reduction in IOP, 41.51% were medication-free and 30.19% were receiving at least one fewer medication. Among eyes with baseline IOP< 21 mmHg, there was a significant reduction in the mean number of IOP-lowering medicines by Month 6 (0.61± 1.03 versus 1.93± 1.21 at baseline; p< 0.0001), with no change in IOP. At 12 months, 24.27% of eyes had a ≥ 20% decrease in IOP, 43.69% of eyes did not require any medications and 63.11% had at least one fewer medication compared with baseline. An analysis using Welch’s two-sample t–test showed no significant differences in the outcomes between the overall population and the American Indian population (number of eyes, 23).Conclusion: Bimatoprost SR glaucoma implant lowered IOP in eyes with high, uncontrolled baseline IOP, while it reduced the number of medications in eyes with a controlled baseline IOP. No clinically meaningful and statistically significant differences in the efficacy of bimatoprost were observed in patients of American Indian descent.Keywords: intraocular pressure, open-angle glaucoma, ocular hypertension, prostaglandin analog, intracameral implant, ethnicity/rac

Rupture Energetics in Crustal Rock From Laboratory‐Scale Seismic Tomography

The energy released during earthquake rupture is partly radiated as seismic waves and mostly dissipated by frictional heating on the fault interface and by off‐fault fracturing of surrounding host rock. Quantification of these individual components is crucial to understand the physics of rupture. We use a quasi‐static rock fracture experiment combined with a novel seismic tomography method to quantify the contribution of off‐fault fracturing to the energy budget of a rupture and find that this contribution is around 3% of the total energy budget and 10% of the fracture energy Gc. The off‐fault dissipated energy changes the physical properties of the rock at the early stages of rupture, illustrated by the 50% drop in elastic moduli of the rock near the fault, and thus is expected to greatly influence later stages of rupture and slip. These constraints are a unique benchmark for calibration of dynamic rupture models

An evaluation of strategies used by the Landscapes and Policy Hub to achieve interdisciplinary and transdisciplinary research

The report presents an evaluation of the Landscapes and Policy Hub's approach to interdisciplinary and transdisciplinary research. The hub was a national, four year, $15 million collaborative research program. The focus of the evaluation was for researchers to reflect on the effectiveness of strategies used by the hub to facilitate interdisciplinarity (where researchers from different disciplines work together to solve problems) and transdisciplinarity (where researchers from different disciplines work in partnership with research users to solve problems). The evaluation was commissioned in the final phase of the hub’s life in the interests of improving performance of future interdisciplinary and transdisciplinary research. It was based on a number of strategies that had been implemented by the hub to encourage and facilitate interdisciplinary research occurring in partnership with research users. The aim of the evaluation was to improve performance of future interdisciplinary and transdisciplinary research. Six recommendations are presented

Stimulation of translation by human Unr requires cold shock domains 2 and 4, and correlates with poly(A) binding protein interaction

The RNA binding protein Unr, which contains five cold shock domains, has several specific roles in post-transcriptional control of gene expression. It can act as an activator or inhibitor of translation initiation, promote mRNA turnover, or stabilise mRNA. Its role depends on the mRNA and other proteins to which it binds, which includes cytoplasmic poly(A) binding protein 1 (PABP1). Since PABP1 binds to all polyadenylated mRNAs, and is involved in translation initiation by interaction with eukaryotic translation initiation factor 4G (eIF4G), we investigated whether Unr has a general role in translational control. We found that Unr strongly stimulates translation in vitro, and mutation of cold shock domains 2 or 4 inhibited its translation activity. The ability of Unr and its mutants to stimulate translation correlated with its ability to bind RNA, and to interact with PABP1. We found that Unr stimulated the binding of PABP1 to mRNA, and that Unr was required for the stable interaction of PABP1 and eIF4G in cells. siRNA-mediated knockdown of Unr reduced the overall level of cellular translation in cells, as well as that of cap-dependent and IRES-dependent reporters. These data describe a novel role for Unr in regulating cellular gene expression

Incorporating life cycle assessment and ecodesign tools for green chemical engineering: a case study of competences and learning outcomes assessment

Chemical engineers assume a broad range of roles in industry, spanning the development of new process designs, the maintenance and optimization of complex systems, and the production of intermediate materials, final products and new technologies. The technical aptitude that enables chemical engineers to fulfill these various roles along the value chain makes them compelling participants in the environmental assessment of the product in question. Therefore, the introduction of life cycle assessment (LCA) and ecodesign concepts into the chemical engineering curriculum is essential to help these future professionals to face design problems with a holistic view of the technical, economic, social and environmental impacts of their solutions. The teaching of these and other disciplines by means of student-centered methods, based on a holistic structure, have demonstrated better teamwork and communication skills. For that reason, this paper proposes a Micro (Assess-Analyze-Act) (M-3A) model of assessment mainly focused on closing the loop of the learning activities. This model has been applied to an ecodesign case study of the "University master's Degree in chemical engineering" of the University of Cantabria/University of the Basque Country, with positive feedback of the students. They felt that the approach has allowed them to utilize their analytical skills in quantifying a situation before applying other subjective measures, and that the public discussion of the results was a satisfactory element for improving their communication skills. Moreover, the students found that the workload was nicely adjusted, highlighting the acquisition of 4 competences preferentially: teamwork, creativity; relevance of environmental issues and initiative and entrepreneurship. Finally, the students suggest that the application of this methodology into their degree could motivate future students improving their performance

Surfactant protein D modulates HIV infection of both T-cells and dendritic cells

Surfactant Protein D (SP-D) is an oligomerized C-type lectin molecule with immunomodulatory properties and involvement in lung surfactant homeostasis in the respiratory tract. SP-D binds to the enveloped viruses, influenza A virus and respiratory syncytial virus and inhibits their replication in vitro and in vivo. SP-D has been shown to bind to HIV via the HIV envelope protein gp120 and inhibit infectivity in vitro. Here we show that SP-D binds to different strains of HIV (BaL and IIIB) and the binding occurs at both pH 7.4 and 5.0 resembling physiological relevant pH values found in the body and the female urogenital tract, respectively. The binding of SP-D to HIV particles and gp120 was inhibited by the presence of several hexoses with mannose found to be the strongest inhibitor. Competition studies showed that soluble CD4 and CVN did not interfere with the interaction between SP-D and gp120. However, soluble recombinant DC-SIGN was shown to inhibit the binding between SP-D and gp120. SP-D agglutinated HIV and gp120 in a calcium dependent manner. SP-D inhibited the infectivity of HIV strains at both pH values of 7.4 and 5.0 in a concentration dependent manner. The inhibition of the infectivity was abolished by the presence of mannose. SP-D enhanced the binding of HIV to immature monocyte derived dendritic cells (iMDDCs) and was also found to enhance HIV capture and transfer to the T-cell like line PM1. These results suggest that SP-D can bind to and inhibit direct infection of T-cells by HIV but also enhance the transfer of infectious HIV particles from DCs to T-cells in vivo

EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF); Scientific Opinion on Flavouring Group Evaluation 08, Revision 5 (FGE.08Rev5): Aliphatic and alicyclic mono-, di-, tri-, and polysulphides with or without additional oxygenated functional groups from chemical groups 20 and 30

&lt;p&gt;The CEF Panel of the European Food Safety Authority was requested to evaluate 80 flavouring substances in the Flavouring Group Evaluation 08, Revision 4, using the Procedure in Commission Regulation (EC) No 1565/2000. Since the publication of the last revision of this FGE, the EFSA has been requested to evaluate additional toxicological data submitted for two flavouring substances, one substance 2,5-dihydroxy-2,5-dimethyl-1,4-dithiane [FL-no: 15.006], which support the evaluation of the candidate substance 2,5-dihydroxy-1,4-dithiane [FL-no: 15.134] and one on the candidate substance spiro(2,4-dithia-1-methyl-8-oxabicyclo[3.3.0]octane-3,3’-(1’-oxa-2’-methyl)-cyclopentane) and spiro(2,4-dithia-6-methyl-7-oxabicyclo[3.3.0]octane-3,3’-(1’-oxa-2’-methyl)-cyclopentane) [FL-no: 15.007], which have been included in the present revision of FGE.08. For the substances methyl methanethiosulphonate [FL-no: 12.159], 2-methylbutane-2-thiol [FL-no: 12.172], 2-methylpropane-2-thiol [FL-no: 12.174], ethyl-2-mercapto-2-methyl propanoate [FL-no: 12.304] and 2,4,4-trimethyl-1,3-oxathiane [FL-no: 16.057] there is an indication of a genotoxic potential in vitro. Therefore, without further genotoxicity data, the Panel concluded that the Procedure could not be applied to these five substances. For four substances, 3-mercaptooctanal [FL-no: 12.268], 3-mercaptodecanal [FL-no: 12.269], methanedithiol diacetate [FL-no: 12.271] and 3,5-dimethyl-1,2-dithiolane-4-one [FL-no: 12.295] no data on use as flavouring substances in Europe are available and no intake figures could be calculated, which preclude the evaluation of the four substances using the Procedure. The remaining 71 substances were evaluated through a stepwise approach that integrates information on the structure-activity relationships, intake from current uses, toxicological threshold of concern, and available data on metabolism and toxicity. The Panel concluded that 59 substances do not rise safety concerns at their levels of dietary intake, estimated on the basis of the MSDI approach. For 12 substances [FL-no: 12.093, 12.094, 12.097, 12.100, 12.112, 12.116, 12.120, 12.164, 12.167, 12.199, 15.102 and 15.125], evaluated through the Procedure, no appropriate NOAEL was available and additional data are required. The specifications for the materials of commerce have also been considered and for three substances, information on the specifications is lacking.&lt;/p&gt

Two novel human cytomegalovirus NK cell evasion functions target MICA for lysosomal degradation

NKG2D plays a major role in controlling immune responses through the regulation of natural killer (NK) cells, αβ and γδ T-cell function. This activating receptor recognizes eight distinct ligands (the MHC Class I polypeptide-related sequences (MIC) A andB, and UL16-binding proteins (ULBP)1–6) induced by cellular stress to promote recognition cells perturbed by malignant transformation or microbial infection. Studies into human cytomegalovirus (HCMV) have aided both the identification and characterization of NKG2D ligands (NKG2DLs). HCMV immediate early (IE) gene up regulates NKGDLs, and we now describe the differential activation of ULBP2 and MICA/B by IE1 and IE2 respectively. Despite activation by IE functions, HCMV effectively suppressed cell surface expression of NKGDLs through both the early and late phases of infection. The immune evasion functions UL16, UL142, and microRNA(miR)-UL112 are known to target NKG2DLs. While infection with a UL16 deletion mutant caused the expected increase in MICB and ULBP2 cell surface expression, deletion of UL142 did not have a similar impact on its target, MICA. We therefore performed a systematic screen of the viral genome to search of addition functions that targeted MICA. US18 and US20 were identified as novel NK cell evasion functions capable of acting independently to promote MICA degradation by lysosomal degradation. The most dramatic effect on MICA expression was achieved when US18 and US20 acted in concert. US18 and US20 are the first members of the US12 gene family to have been assigned a function. The US12 family has 10 members encoded sequentially through US12–US21; a genetic arrangement, which is suggestive of an ‘accordion’ expansion of an ancestral gene in response to a selective pressure. This expansion must have be an ancient event as the whole family is conserved across simian cytomegaloviruses from old world monkeys. The evolutionary benefit bestowed by the combinatorial effect of US18 and US20 on MICA may have contributed to sustaining the US12 gene family