Outcomes of Hyperbaric Oxygen Treatment for Central Retinal Artery Occlusion: A Single Center Experience.

PURPOSE: To describe the outcomes of hyperbaric oxygen therapy (HBOT) for patients with central retinal artery occlusion (CRAO) at a single tertiary care center. DESIGN: Retrospective clinical cohort study. METHODS: Medical records of all patients diagnosed with CRAO who received HBOT at Mayo Clinic in Rochester, Minnesota from 1/1/2009 to 12/31/2020 were reviewed to confirm diagnosis, time from onset to presentation, exam findings, treatments, and follow-up data. Main outcome measures included final visual acuity (VA) and number of lines of improvement. RESULTS: There were 41 patients diagnosed with CRAO who received HBOT during the 12 year study period. Median time from symptom onset to HBOT treatment was 9.5 hours (interquartile range [IQR] 6.5, 14.0 hours), and patients received a median of 4 HBOT sessions (IQR 2.5, 6.0 sessions). There were 20 patients who received HBOT within 9 hours, 14 (70%) of which had clinically meaningful improvement in VA of ≥0.3 logMAR. In comparison, of the 21 patients treated after 9 hours, 6 (28.6%) had VA improvement of ≥0.3 logMAR (p=0.008). For all patients, the median logMAR VA at presentation was 2.00 (IQR 1.70, 2.30) and the median logMAR VA at follow-up was 1.94 (IQR 1.00, 2.00) (p<0.001), with median lines of improvement of 3.0 (IQR 0.0, 7.0). For patients treated within 9 hours, the median logMAR VA at presentation was 2.00 (IQR 1.93, 2.30) and the median logMAR VA at follow-up was 1.70 (IQR 0.54, 2.00). Patients treated within 9 hours had statistically significant greater median lines of VA improvement than cases that were treated after >9 hours from symptom onset at 5.9 (IQR 3.0, 10.0) and 0.0 (IQR 0.0, 3.0), respectively (p<0.001). There was no difference in VA recovery associated with specific retinal exam findings such as cherry-red spot (p=0.22) and cilioretinal artery perfusion (p=0.36) compared to patients without those findings. CONCLUSION: There was a statistically significant improvement in VA after HBOT treatment in CRAO patients among patients that received early HBOT, with patients receiving the most benefit when receiving treatment within 9 hours. Randomized control trials in patients with CRAO are required to confirm the efficacy of HBOT.

Structural insights into i-motif DNA structures in sequences from the insulin-linked polymorphic region.

The insulin-linked polymorphic region is a variable number of tandem repeats region of DNA in the promoter of the insulin gene that regulates transcription of insulin. This region is known to form the alternative DNA structures, i-motifs and G-quadruplexes. Individuals have different sequence variants of tandem repeats and although previous work investigated the effects of some variants on G-quadruplex formation, there is not a clear picture of the relationship between the sequence diversity, the DNA structures formed, and the functional effects on insulin gene expression. Here we show that different sequence variants of the insulin linked polymorphic region form different DNA structures in vitro. Additionally, reporter genes in cellulo indicate that insulin expression may change depending on which DNA structures form. We report the crystal structure and dynamics of an intramolecular i-motif, which reveal sequences within the loop regions forming additional stabilising interactions that are critical to formation of stable i-motif structures. The outcomes of this work reveal the detail in formation of stable i-motif DNA structures, with potential for rational based drug design for compounds to target i-motif DNA.

Conditional Inhibition of Eip75B Eliminates the Effects of Mating and Mifepristone on Lifespan in Female Drosophila.

Mating in female Drosophila melanogaster causes midgut hypertrophy and reduced lifespan, and these effects are blocked by the drug mifepristone. Eip75B is a transcription factor previously reported to have pleiotropic effects on Drosophila lifespan. Because Eip75B null mutations are lethal, conditional systems and/or partial knock-down are needed to study Eip75B effects in adults. Previous studies showed that Eip75B is required for adult midgut cell proliferation in response to mating. To test the possible role of Eip75B in mediating the lifespan effects of mating and mifepristone, a tripartite FLP-recombinase-based conditional system was employed that provides controls for genetic background. Expression of a Hsp70-FLP transgene was induced in third instar larvae by a brief heat pulse. The FLP recombinase catalyzed the recombination and activation of an Actin5C-GAL4 transgene. The GAL4 transcription factor in turn activated expression of a UAS-Eip75B-RNAi transgene. Inhibition of Eip75B activity was confirmed by loss of midgut hypertrophy upon mating, and the lifespan effects of both mating and mifepristone were eliminated. In addition, the negative effects of mifepristone on egg production were eliminated. The data indicate that Eip75B mediates the effects of mating and mifepristone on female midgut hypertrophy, egg production, and lifespan.

A Simple and Sequential Strategy for the Introduction of Complexity and Hierarchy in Hydrogen-Bonded Organic Framework (HOF) Crystals for Environmental Applications.

Hydrogen-bonded organic frameworks (HOFs) are a new class of crystalline porous organic molecular materials (POMMs) with great potential for a diverse range of applications. HOFs face common challenges to POMMs, and in general to purely organic crystals, that is, the difficulty of integrating complexity in crystals. Herein, we propose a simple and sequential strategy for the formation of HOFs with hierarchical superstructures. The strategy is based on controlling the assembly conditions, avoiding the use of any surface functionalization or template, which allows to obtain hierarchical crystalline porous superstructures in an easy manner. As proof of concept, we obtained the first example of core-shell (HOF-on-HOF) crystals and HOFs with hierarchical superstructures having superhydrophobicity and trapping abilities for the capture of persistent water contaminants such as oils and microplastics. We expect that this strategy could serve as inspiration for the construction of more intricate multiscale structures that could greatly expand the library of HOF materials.

Structural descriptions of ligand interactions to RNA quadruplexes folded from the non-coding region of pseudorabies virus.

To rationalise the binding of specific ligands to RNA-quadruplex we investigated several naphthalene diimide ligands that interact with the non-coding region of Pseudorabies virus (PRV). Herein we report on the x-ray structure of the naphthalene diimide ND11 with an RNA G-quadruplex putative forming sequence from rPRV. Consistent with previously observed rPRV sequence it assembles into a bimolecular RNA G-quadruplex consisting of a pair of two tetrads stacked 3' to 5'. We observe that ND11 interacts by binding on both the externally available 5' and 3' quartets. The CUC (loop 1) is structurally altered to enhance the 5' mode of interaction. These loop residues are shifted significantly to generate a new ligand binding pocket whereas the terminal A14 residue is lifted away from the RNA G-quadruplex tetrad plane to be restacked above the bound ND11 ligand NDI core. CD analysis of this family of NDI ligands shows consistency in the spectra between the different ligands in the presence of the rPRV RNA G-quadruplex motif, reflecting a common folded topology and mode of ligand interaction. FRET melt assay confirms the strong stabilising properties of the tetrasubstituted NDI compounds and the contributions length of the substituted groups have on melt temperatures.

Structural Motifs at the Telomeres and Their Role in Regulatory Pathways.

Telomeres are specialized structures, found at the ends of linear chromosomes in eukaryotic cells, that play a crucial role in maintaining the stability and integrity of genomes. They are composed of repetitive DNA sequences, ssDNA overhangs, and several associated proteins. The length of telomeres is linked to cellular aging in humans, and deficiencies in their maintenance are associated with various diseases. Key structural motifs at the telomeres serve to protect vulnerable chromosomal ends. Telomeric DNA also has the ability to form diverse complex DNA higher-order structures, including T-loops, D-loops, R-loops, G-loops, G-quadruplexes, and i-motifs, in the complementary C-rich strand. While many essential proteins at telomeres have been identified, the intricacies of their interactions and structural details are still not fully understood. This Perspective highlights recent advancements in comprehending the structures associated with human telomeres. It emphasizes the significance of telomeres, explores various telomeric structural motifs, and delves into the structural biology surrounding telomeres and telomerase. Furthermore, telomeric loops, their topologies, and the associated proteins that contribute to the safeguarding of telomeres are discussed.

To Approve or not to Approve? A Comparative Analysis of State-Company-Indigenous Community Interactions in Mining in Canada and Sweden.

This Special Section explores the interplay between Indigenous peoples, industry, and the state in five proposed and active mining projects in Canada and Sweden. The overall aim is to identify factors shaping the quality of Indigenous community-industry-state interactions in mining and mine development. An ambition underlying the research is to develop knowledge to help manage mining related land-use conflicts in Sweden by drawing on Canadian comparisons and experience. This paper synthesizes the comparative research that has been conducted across jurisdictions in three Canadian provinces and Sweden. It focuses on the interplay between the properties of the governance system, the quality of interaction and governance outcomes. We combine institutional and interactive governance theory and use the concept of governability to assess how and why specific outcomes, such as mutually beneficial interaction, collaboration, or opposition, occurred. The analysis suggests there are measures that can be taken by the Swedish Government to improve the governability of mining related issues, by developing alternative, and more effective, avenues to recognize, and protect, Sámi rights and culture, to broaden the scope and increase the legitimacy and transparency of the EIAs, to raise the quality of interaction and consultation, and to develop tools to actively stimulate and support collaboration and partnerships on equal terms. Generally, we argue that Indigenous community responses to mining must be understood within a larger framework of Indigenous self-determination, in particular the communities' own assessments of their opportunities to achieve their long-term objectives using alternative governing modes and types of interactions.

Genetic and Pathogenic Variability among Isolates of Sporisorium reilianum Causing Sorghum Head Smut.

Sporisorium reilianum, the causal agent of sorghum (Sorghum bicolor (L.) Moench) head smut, is present in most sorghum-producing regions. This seed replacement fungal disease can reduce yield by up to 80% in severely infected fields. Management of this disease can be challenging due to the appearance of different pathotypes within the pathogenic population. In this research, the genetic variability and pathogenicity of isolates collected from five Texas Counties was conducted. Due to the lack of available space, 21 out of 32 sequenced isolates were selected and evaluated for virulence patterns on the six sorghum differentials, Tx7078, BTx635, SC170-6-17 (TAM2571), SA281 (Early Hegari), Tx414, and BTx643. The results reveal the occurrence of a new pathotype, 1A, and four previously documented US pathotypes when the 21 isolates were evaluated for virulence patterns on the differentials. The most prevalent was pathotype 5, which was recovered from Brazos, Hidalgo, Nueces, and Willacy Counties, Texas. This pathotype was followed by 1A and 6 in frequency of recovery. Pathotype 4 was identified only from isolates collected from Hidalgo County, while pathotype 1 was from Burleson County, Texas. It appeared that the previous US head smut pathotypes (2 and 3) are no longer common, and the new pathotypes, 1A, 5, and 6, are now predominant. The phylogenetic tree constructed from the single-nucleotide polymorphism (SNP) data through the neighbor-joining method showed high genetic diversity among the tested isolates. Some of the diverse clades among the tested isolates were independent of their sampled locations. Notably, HS37, HS49, and HS65 formed a clade and were classified as 1A in the virulence study, while HS 61 and HS 66, which were collected from Nueces County, were grouped and identified as pathotype 5.

Temporal patterns of fucoxanthin in four species of European marine brown macroalgae.

Brown seaweeds are a rich source of carotenoids, particularly fucoxanthin, which has a wide range of potential health applications. Fucoxanthin fluctuates within and among seaweeds over time, frustrating efforts to utilise this resource. Thus, we require comprehensive analyses of long- and short-term concentrations across species in field conditions. Here, we used High Performance Liquid Chromatography to compare fucoxanthin content in four brown macroalgae, Ascophyllum nodosum, Fucus serratus, Fucus vesiculosus and Saccharina latissima, monthly for 1 year. F. serratus and F. vesiculosus had significantly higher fucoxanthin content (mg/g), which was highest in Spring (0.39 ± 0.04) and Autumn (0.45 ± 0.04) [mean (± SE)]. Two species, A. nodosum and F. serratus, were collected monthly at the same location for a further two non-consecutive years. For both A. nodosum and F. serratus, a significant interaction effect of seasons and years was identified, highlighting that there is variation in fucoxanthin content among and within species over time. We also show that fucoxanthin content differs significantly among months even within seasons. Therefore, it is not sufficient to assess fucoxanthin in single months to represent seasonality. We discuss how weather, nutrients and reproduction may have driven the seasonal variation, and reveal patterns of fucoxanthin concentration that can provide information concerning its availability for many important medical functions.

Dhr96[1] mutation and maternal tudor[1] mutation increase life span and reduce the beneficial effects of mifepristone in mated female Drosophila.

Mating and receipt of male Sex Peptide hormone cause increased egg laying, increased midgut size and decreased life span in female Drosophila. Feeding mated females with the synthetic steroid mifepristone decreases egg production, reduces midgut size, and increases life span. Here, several gene mutations were assayed to investigate possible mechanisms for mifepristone action. Drosophila Dhr96 is a hormone receptor, and a key positive regulator of midgut lipid uptake and metabolism. Dhr96[1] null mutation increased female life span, and reduced the effects of mifepristone on life span, suggesting that Dhr96[1] mutation and mifepristone may act in part through the same mechanism. Consistent with this idea, lipidomics analysis revealed that mating increases whole-body levels of triglycerides and fatty-acids in triglycerides, and these changes are reversed by mifepristone. Maternal tudor[1] mutation results in females that lack the germ-line and produce no eggs. Maternal tudor[1] mutation increased mated female life span, and reduced but did not eliminate the effects of mating and mifepristone on life span. This indicates that decreased egg production may be related to the life span benefits of mifepristone, but is not essential. Mifepristone increases life span in w[1118] mutant mated females, but did not increase life span in w[1118] mutant virgin females. Mifepristone decreased egg production in w[1118] mutant virgin females, indicating that decreased egg production is not sufficient for mifepristone to increase life span. Mifepristone increases life span in virgin females of some, but not all, white[+] and mini-white[+] strains. Backcrossing of mini-white[+] transgenes into the w[1118] background was not sufficient to confer a life span response to mifepristone in virgin females. Taken together, the data support the hypothesis that mechanisms for mifepristone life span increase involve reduced lipid uptake and/or metabolism, and suggest that mifepristone may increase life span in mated females and virgin females through partly different mechanisms.

Healthcare Professionals' Perspectives on Improving Dietary Supplement Documentation in the Electronic Medical Record: Current Challenges and Opportunities to Enhance Quality of Care and Patient Safety.

Background: Around half the US population uses dietary supplements (DS), and concomitant use with medications is common. Many DS include bioactive substances that can interact with medications; therefore, accurate tracking is critical for patient safety. Unfortunately, documentation of patients' DS use is often missing or incomplete in the electronic medical record (EMR), leaving patients susceptible to potential adverse events. Novel approaches to assist healthcare professionals (HCPs) in capturing patients' DS use are needed. Objective: To assess HCPs' perspectives on challenges and facilitators of DS documentation in the EMR and their opinions on a proposed mHealth application (app) to aid in DS capture. Methods: HCPs, recruited from professional networks, largely in North Carolina, using purposive sampling, took part in semi-structured interviews. We inquired about HCPs' experiences with DS documentation in the EMR and their opinions about our proposed mHealth app. Interviews were recorded, transcribed, and coded. Thematic analysis included deductive codes based on the interview guide, and inductive codes that emerged during transcript review. Results: HCPs (N = 30) included 60% females, mean age 46 ± 10; 70% White. Pharmacists (20%), nurses (17%), and physicians (17%) were the most represented professions. Years in practice ranged from 3-35 years. Most HCPs were concerned about DS safety and potential supplement-drug interactions, and cited several barriers to accurate EMR DS documentation including time constraints, database inconsistencies, and poor patient-HCP communication about DS. HCPs' views on our proposed mHealth app were generally positive. They expressed that our proposed mHealth app could streamline documentation processes and enhance patient-provider communication. HCPs expressed desire for a high-quality mHealth app that includes access to evidence-based DS information, integrates with the EMR, and does not increase time burdens. Conclusion: HCPs believe documentation of patients' DS use is important but not accurately captured in the EMR. Support was expressed for our proposed barcode-scanning DS mHealth app.

Ruthenium ion catalysed C-C bond activation in lignin model compounds - towards lignin depolymerisation.

Lignin is the most abundant renewable feedstock to produce aromatic chemicals, however its depolymerisation involves the breaking of several C-O and C-C inter-unit linkages that connect smaller aromatic units that are present in lignin. Several strategies have been reported for the cleavage of the C-O inter-unit linkages in lignin. However, till today, only a few methodologies have been reported for the effective breaking or the conversion of the recalcitrant C-C inter unit linkages in lignin. Here we report the ruthenium ion catalysed oxidative methodology as an effective system to activate or convert the most recalcitrant inter unit linkages such as ß-5 and 5-5' present in lignin. Initially, we used biphenyl as a model compound to study the effectiveness of the RICO methodology to activate the 5-5' C-C linkage. After 4 h reaction at 22 °C, we achieved a 30% conversion with 75% selectivity towards benzoic acid and phenyl glyoxal as the minor product. To the best of our knowledge this is the first ever oxidative activation of the C-C bond that connects the two phenyl rings in biphenyl. DFT calculation revealed that the RuO4 forms a [3 + 2] adduct with one of the aromatic C-C bonds resulting in the opening of the phenyl ring. Biphenyl conversion could be increased by increasing the amount of oxidant; however, this is accompanied by a reduction in the carbon balance because of the formation of CO2 and other unknown products. We extended this RICO methodology for the oxidative depolymerisation of lignin model hexamer containing ß-5, 5-5' and ß-O-4 linkages. Qualitative and quantitative analyses of the reaction mixture were done using 1H, 13C NMR spectroscopy methods along with GC-MS and Gel Permeation Chromatographic (GPC) methods. Advanced 2D NMR spectroscopic methods such as HSQC, HMBC and 31P NMR spectroscopy after phosphitylation of the mixture were employed to quantitatively analyse the conversion of the ß-5, 5-5' and ß-O-4 linkages and to identify the products. After 30 min, >90% of the 5-5' and linkages and >80% of the ß-5' are converted with this methodology. This is the first report on the conversion of the 5-5' linkage in lignin model hexamer.

Staining- and aging-dependent changes in color and translucency of 3D-printed resin-modified ceramics.

PURPOSE: To evaluate staining- and aging-dependent changes in the color and translucency of 3D-printed resin-modified ceramics (RMC). METHODS: Specimens (n= 5 per condition and material) were fabricated from test materials: Permanent Crown Resin (PCR), Crowntec (CT), Vita Enamic (VE) and Tetric CAD (TC). Specimens were stained in wine, coffee, tea, and water (control) and exposed to artificial accelerated aging (AAA). Color measurements were obtained using a spectrophotometer at baseline (T0) and at 3.5 (T1) and 7 (T2) days after immersion. For AAA, measurements were obtained at baseline (T0) and after exposure to controlled irradiance of 150 kJ/m² (T1) and 300 kJ/m² (T2). Mean and standard deviations were calculated on CIEDE2000 color differences (ΔE00), translucency parameter (TP00) and treatment-dependent changes in the translucency parameter (ΔTP0 0). Differences between materials and test conditions were tested by one-way ANOVA (α= 0.05). Results were additionally interpreted using visual color difference thresholds in dentistry ΔE00= 0.8 for the 50:50 perceptibility threshold (PT) and ΔE00= 1.8 for the 50:50 acceptability threshold (AT). ΔTP00 values were interpreted using 5058;50 TPT00= 0.6 and 50:0% TAT00= 2.6. RESULTS: Statistically significant differences were found among the materials when exposed to the different test conditions. At the T0-T1 time interval, the highest color difference was found with wine (0.1-2.2) on all materials except CT, which showed the highest ΔE00 with AAA (2.5). The second highest color differences were obtained upon exposure to AAA (0.2-2.5) and tea (0.5-1.1). The TP00 at baseline ranged from 5.1 to 9.8. Significant differences in ΔTP00 were found among the tested materials and staining/aging conditions, but no significant differences were found among the staining/aging intervals (T0-T1, T0-T2 and T1-T2). CLINICAL SIGNIFICANCE: Staining- and artificial aging-dependent changes of 3D-printed and milled resin modified ceramics used for definitive restorations could represent a challenge in terms of restoration acceptability or dissatisfaction. Staining and aging conditions produced significant color changes, while translucency changes were not significant.