Anatomical Changes and Predictors of Angle Widening After Laser Peripheral Iridotomy: The Zhongshan Angle Closure Prevention Trial

PURPOSE: To assess anatomical changes after laser peripheral iridotomy (LPI) and predictors of angle widening based on anterior segment OCT (AS-OCT) and angle opening based on gonioscopy in mainland Chinese primary angle closure suspects (PACS). DESIGN: Prospective observational study. PARTICIPANTS: 454 subjects aged 50 to 70 years with PACS. METHODS: Subjects received clinical examinations including gonioscopy and AS-OCT imaging at baseline and 2 weeks after LPI as part of the Zhongshan Angle Closure Prevention (ZAP) Trial. PACS was defined as inability to visualize pigmented trabecular meshwork in two or more quadrants on static gonioscopy. LPI was performed on one eye per subject in a superior (between 11 to 1 o'clock) or temporal or nasal (at or below 10:30 or 1:30 o'clock) location. Biometric parameters in horizontal and vertical AS-OCT scans were measured and averaged. Multivariable linear and logistic regression modeling were performed to determine predictors of angle widening, defined as change in continuous measurements of mean angle opening distance (AOD750), poor angle widening, defined as the lowest quintile of change in mean AOD750, and poor angle opening, defined as residual PACS after LPI based on gonioscopy. MAIN OUTCOME MEASURES: Anatomical changes and predictors of angle widening and opening after LPI. RESULTS: 454 subjects were included in the analysis. 219 received superior LPIs and 235 received temporal or nasal LPIs. There were significant changes among most biometric parameters (p<0.006) after LPI, including greater AOD750 (p<0.001). 120 eyes (26.4%) had residual PACS after LPI. In multivariable regression analysis, several baseline parameters, including superior LPI location (p=0.004), smaller AOD750 (p<0.001), and greater iris curvature (p<0.001), were predictive of greater angle widening. Temporal or nasal LPI locations (OR=2.60, p<0.0001) and greater baseline AOD750 (OR=2.58, 0.1 mm increment, p<0.001) were most predictive of poor angle widening based on AS-OCT. Smaller mean gonioscopy grade (OR=0.34, 1 grade increment) was most predictive of poor angle opening based on gonioscopy. CONCLUSIONS: Superior LPI location results in significantly greater angle widening based on AS-OCT compared to temporal or nasal locations in a Chinese population with PACS. This supports consideration of superior LPI locations to optimize anatomical changes after LPI

Ocular Biometric Risk Factors for Progression of Primary Angle Closure Disease: The Zhongshan Angle Closure Prevention Trial

PURPOSE: To assess baseline ocular biometric risk factors for progression from primary angle closure suspect (PACS) to primary angle closure (PAC) or acute angle closure (AAC). DESIGN: Prospective observational study. PARTICIPANTS: 643 mainland Chinese aged 50 to 70 years with untreated PACS. METHODS: Participants received baseline clinical examinations including gonioscopy, anterior segment OCT (AS-OCT) imaging (Visante OCT, Carl Zeiss Meditec, Dublin, CA), and A-scan ultrasound biometry as part of the Zhongshan Angle Closure Prevention (ZAP) Trial. PACS was defined as inability to visualize pigmented trabecular meshwork in two or more quadrants based on static gonioscopy. PAC was defined as development of elevated intraocular pressure (IOP) > 24 mmHg or peripheral anterior synechiae (PAS). Progression was defined as development of PAC or an acute angle closure (AAC) attack. Multivariable logistic regression models were developed to assess biometric risk factors for progression. MAIN OUTCOME MEASURES: Progression from PACS to PAC or AAC over 6 years. RESULTS: 643 untreated eyes (609 non-progressors, 34 progressors) of 643 ZAP participants were included in the primary analysis. In a multivariable model with continuous parameters, narrower horizontal angle opening distance 500 μm from the scleral spur (AOD500; OR=1.10 per 0.01 mm decrease, p=0.03), flatter horizontal iris curvature (IC; OR=1.96 per 0.1 mm decrease, p=0.01), and older age (OR=1.11 per year increase, p=0.01) at baseline were significantly associated with progression (AUC=0.73). Smaller cumulative gonioscopy score was not associated with progression (OR=1.03 per 1 modified Shaffer grade decrease; p=0.85) when replacing horizontal AOD500 in the multivariable model. In a separate multivariable model with categorical parameters, participants in the lowest quartile of horizontal AOD500 (OR=3.10, p=0.002) and IC (OR=2.48, p=0.014) measurements and aged 59 years and older (OR=2.68, p=0.01) at baseline had higher odds of progression (AUC=0.72). CONCLUSIONS: Ocular biometric measurements can help risk stratify patients with early angle closure for more severe disease. AS-OCT measurements of biometric parameters describing the angle and iris are predictive of progression from PACS to PAC or AAC, whereas gonioscopy grades are not

Evaluating Trade-Offs Between Sustainability, Performance, and Cost of Green Machining Technologies

The growing demand to reduce environmental impacts has encouraged manufacturers to pursue various green manufacturing technologies and strategies. These solutions, though, may have a direct impact on several productivity metrics including availability, quality, service life, and cost. This study presents an approach to evaluate the trade-offs between the environmental, performance, and financial impacts of green machining technologies by combining green manufacturing principles into life cycle performance evaluation. The approach is validated by investigating the implications of reducing the processing time by increasing the cutting speed and chip load to green a horizontal milling process

Comparison of Saccharomyces cerevisiae strains of clinical and nonclinical origin by molecular typing and determination of putative virulence traits

Saccharomyces cerevisiae strains of clinical and nonclinical origin were compared by pulse field gel electrophoresis. Complete separation between strains of clinical origin and food strains by their chromosome length polymorphism was not obtained even though there was a tendency for the clinical and food strains to cluster separately. All the investigated strains, except for one food strain, were able to grow at temperatures ≥37 °C but not at 42 °C. Great strain variations were observed in pseudohyphal growth and invasiveness, but the characters were not linked to strains of clinical origin. The adhesion capacities of the yeast strains to a human intestinal epithelial cell line (Caco-2) in response to different nutritional availabilities were determined, as were the effects of the strains on the transepithelial electrical resistance (TER) across polarized monolayers of Caco-2 cells. The yeast strains displayed very low adhesion capacities to Caco-2 cells (0.6–6.2%), and no significant difference was observed between the strains of clinical and nonclinical origin. Both S. cerevisiae strains of clinical and non-clinical origin increased the TER of polarized monolayers of Caco-2 cells. Based on the results obtained in this study, no specific virulence factor was found that clearly separated the strains of clinical origin from the strains of nonclinical origin. On the contrary, all investigated strains of S. cerevisiae were found to strengthen the epithelial barrier function

Glycogen Synthase Kinase (GSK) 3β phosphorylates and protects nuclear myosin 1c from proteasome-mediated degradation to activate rDNA transcription in early G1 cells

Nuclear myosin 1c (NM1) mediates RNA polymerase I (pol I) transcription activation and cell cycle progression by facilitating PCAF-mediated H3K9 acetylation, but the molecular mechanism by which NM1 is regulated remains unclear. Here, we report that at early G1 the glycogen synthase kinase (GSK) 3β phosphorylates and stabilizes NM1, allowing for NM1 association with the chromatin. Genomic analysis by ChIP-Seq showed that this mechanism occurs on the rDNA as active GSK3β selectively occupies the gene. ChIP assays and transmission electron microscopy in GSK3β-/- mouse embryonic fibroblasts indicated that at G1 rRNA synthesis is suppressed due to decreased H3K9 acetylation leading to a chromatin state incompatible with transcription. We found that GSK3β directly phosphorylates the endogenous NM1 on a single serine residue (Ser-1020) located within the NM1 C-terminus. In G1 this phosphorylation event stabilizes NM1 and prevents NM1 polyubiquitination by the E3 ligase UBR5 and proteasome-mediated degradation. We conclude that GSK3β-mediated phosphorylation of NM1 is required for pol I transcription activation

Thermal Properties of Graphene, Carbon Nanotubes and Nanostructured Carbon Materials

Recent years witnessed a rapid growth of interest of scientific and engineering communities to thermal properties of materials. Carbon allotropes and derivatives occupy a unique place in terms of their ability to conduct heat. The room-temperature thermal conductivity of carbon materials span an extraordinary large range - of over five orders of magnitude - from the lowest in amorphous carbons to the highest in graphene and carbon nanotubes. I review thermal and thermoelectric properties of carbon materials focusing on recent results for graphene, carbon nanotubes and nanostructured carbon materials with different degrees of disorder. A special attention is given to the unusual size dependence of heat conduction in two-dimensional crystals and, specifically, in graphene. I also describe prospects of applications of graphene and carbon materials for thermal management of electronics.Comment: Review Paper; 37 manuscript pages; 4 figures and 2 boxe

Interleukin-6 gene (IL-6): a possible role in brain morphology in the healthy adult brain

Background: Cytokines such as interleukin 6 (IL-6) have been implicated in dual functions in neuropsychiatric disorders. Little is known about the genetic predisposition to neurodegenerative and neuroproliferative properties of cytokine genes. In this study the potential dual role of several IL-6 polymorphisms in brain morphology is investigated. Methodology: In a large sample of healthy individuals (N = 303), associations between genetic variants of IL-6 (rs1800795; rs1800796, rs2069833, rs2069840) and brain volume (gray matter volume) were analyzed using voxel-based morphometry (VBM). Selection of single nucleotide polymorphisms (SNPs) followed a tagging SNP approach (e.g., Stampa algorigthm), yielding a capture 97.08% of the variation in the IL-6 gene using four tagging SNPs. Principal findings/results: In a whole-brain analysis, the polymorphism rs1800795 (−174 C/G) showed a strong main effect of genotype (43 CC vs. 150 CG vs. 100 GG; x = 24, y = −10, z = −15; F(2,286) = 8.54, puncorrected = 0.0002; pAlphaSim-corrected = 0.002; cluster size k = 577) within the right hippocampus head. Homozygous carriers of the G-allele had significantly larger hippocampus gray matter volumes compared to heterozygous subjects. None of the other investigated SNPs showed a significant association with grey matter volume in whole-brain analyses. Conclusions/significance: These findings suggest a possible neuroprotective role of the G-allele of the SNP rs1800795 on hippocampal volumes. Studies on the role of this SNP in psychiatric populations and especially in those with an affected hippocampus (e.g., by maltreatment, stress) are warranted.Bernhard T Baune, Carsten Konrad, Dominik Grotegerd, Thomas Suslow, Eva Birosova, Patricia Ohrmann, Jochen Bauer, Volker Arolt, Walter Heindel, Katharina Domschke, Sonja Schöning, Astrid V Rauch, Christina Uhlmann, Harald Kugel and Udo Dannlowsk

Engineered Picornavirus VPg-RNA Substrates: Analysis of a Tyrosyl-RNA Phosphodiesterase Activity

Using poliovirus, the prototypic member of Picornaviridae, we have further characterized a host cell enzymatic activity found in uninfected cells, termed “unlinkase,” that recognizes and cleaves the unique 5′ tyrosyl-RNA phosphodiester bond found at the 5′ end of picornavirus virion RNAs. This bond connects VPg, a viral-encoded protein primer essential for RNA replication, to the viral RNA; it is cleaved from virion RNA prior to its engaging in protein synthesis as mRNA. Due to VPg retention on nascent RNA strands and replication templates, but not on viral mRNA, we hypothesize that picornaviruses utilize unlinkase activity as a means of controlling the ratio of viral RNAs that are translated versus those that either serve as RNA replication templates or are encapsidated. To test our hypothesis and further characterize this enzyme, we have developed a novel assay to detect unlinkase activity. We demonstrate that unlinkase activity can be detected using this assay, that this unique activity remains unchanged over the course of a poliovirus infection in HeLa cells, and that unlinkase activity is unaffected by the presence of exogenous VPg or anti-VPg antibodies. Furthermore, we have determined that unlinkase recognizes and cleaves a human rhinovirus-poliovirus chimeric substrate with the same efficiency as the poliovirus substrate

‘Mind the gap’ - mapping services for young people with ADHD transitioning from child to adult mental health services

Background: Once considered to be a disorder restricted to childhood, Attention Deficit/Hyperactivity Disorder (ADHD) is now recognised to persist into adult life. However, service provision for adults with ADHD is limited. Additionally, there is little guidance or research on how best to transition young people with ADHD from child to adult services. Method: We report the findings of a survey of 96 healthcare professionals working in children’s (Child and Adolescent Mental Health Services and Community Paediatrics) and adult services across five NHS Trusts within the East Midlands region of England to gain a better understanding of the current provision of services for young people with ADHD transitioning into adult mental health services. Results: Our findings indicate a lack of structured guidelines on transitioning and little communication between child and adult services. Child and adult services had differing opinions on what they felt adult services should provide for ADHD cases. Adult services reported feeling ill-prepared to deal with ADHD patients, with clinicians in these services citing a lack of specific knowledge of ADHD and a paucity of resources to deal with such cases. Conclusions: We discuss suggestions for further research, including the need to map the national provision of services for adults with ADHD, and provide recommendations for commissioned adult ADHD services. We specifically advocate an increase in ADHD-specific training for clinicians in adult services, the development of specialist adult ADHD clinics and greater involvement of Primary Care to support the work of generic adult mental health services in adult ADHD management