Micropulse Transscleral Cyclophotocoagulation: A Hypothesis for the Ideal Parameters

MicroPulse transscleral cyclophotocoagulation (IRIDEX Corp., Mountain View, CA) is a novel technique that uses repetitive micropulses of active diode laser (On cycles) interspersed with resting intervals (Off cycles). It has been proposed that the OFF cycles allow thermal dissipation and, therefore, reduce collateral damage. The literature suggests that Micropulse has a better safety profile compared to traditional continuous-wave cyclophotocoagulation. However, because it is a relatively new technique, there are no clear guidelines stating the ideal laser parameters that would allow the best balance between high and sustained effectiveness with minimal side effects. This research reviewed the literature to approximate ideal parameters for single-session treatment. To simplify the comparison between studies, this study used Joules (J) as a way to standardize the energy levels employed. The reviewed clinical publications allowed reduction of these parameters to a range between 112 and 150 J of total energy, which allows a moderate IOP lowering effect of around 30% with few/no complications. An additional narrowing of the parameters was achieved after analyzing recently published experimental data. These data suggest a different mechanism of action for the Micropulse, similar to that of the pilocarpine. This effect was maximum at 150 J. Since clinical studies show few or no complications, even at those energy levels, it could be hypothesized that the ideal parameters can be located at a point closer to 150 J. This data also leads to the concept of dosimetry; the capacity to dose mTSCPC treatment based on desired IOP lowering effect and risk exposure. Further prospective studies are needed to test the proposed evidence-based hypothesis

Micropulse Transscleral Cyclophotocoagulation: A Hypothesis for the Ideal Parameters

MicroPulse transscleral cyclophotocoagulation (IRIDEX Corp., Mountain View, CA) is a novel technique that uses repetitive micropulses of active diode laser (On cycles) interspersed with resting intervals (Off cycles). It has been proposed that the OFF cycles allow thermal dissipation and, therefore, reduce collateral damage. The literature suggests that Micropulse has a better safety profile compared to traditional continuous-wave cyclophotocoagulation. However, because it is a relatively new technique, there are no clear guidelines stating the ideal laser parameters that would allow the best balance between high and sustained effectiveness with minimal side effects. This research reviewed the literature to approximate ideal parameters for single-session treatment. To simplify the comparison between studies, this study used Joules (J) as a way to standardize the energy levels employed. The reviewed clinical publications allowed reduction of these parameters to a range between 112 and 150 J of total energy, which allows a moderate IOP lowering effect of around 30% with few/no complications. An additional narrowing of the parameters was achieved after analyzing recently published experimental data. These data suggest a different mechanism of action for the Micropulse, similar to that of the pilocarpine. This effect was maximum at 150 J. Since clinical studies show few or no complications, even at those energy levels, it could be hypothesized that the ideal parameters can be located at a point closer to 150 J. This data also leads to the concept of dosimetry; the capacity to dose mTSCPC treatment based on desired IOP lowering effect and risk exposure. Further prospective studies are needed to test the proposed evidence-based hypothesis

Zinc Deficiency Leads to Lipid Changes in Drosophila Brain Similar to Cognitive-Impairing Drugs: An Imaging Mass Spectrometry Study

Several diseases and disorders have been suggested to be associated with zinc deficiency, especially learning and memory impairment. To have better understanding about the connection between lipid changes and cognitive impairments, we investigated the effects of a zinc-chelated diet on certain brain lipids ofDrosophila melanogasterby using time-of-flight secondary ion mass spectrometry (ToF-SIMS). The data revealed that there are increases in the levels of phosphatidylcholine and phosphatidylinositol in the central brains of the zinc-deficient flies compared to the control flies. In contrast, the abundance of phosphatidylethanolamine in the brains of the zinc-deficient flies is lower. These data are consistent with that of cognitive-diminishing drugs, thus providing insight into the biological and molecular effects of zinc deficiency on the major brain lipids and opening a new treatment target for cognitive deficit in zinc deficiency

Orientation of Pterin-6-Carboxylic Acid on Gold Capped Silicon Nanopillars Platforms: Surface Enhanced Raman Spectroscopy and Density Functional Theory Studies

The orientation of pterin-6-carboxylic acid on gold nanopillars was investigated by surface enhanced Raman spectroscopy and density functional theory methods. The experimentally vibrations from pterin-6-COOH free and attached to the Au surface display vibration features indicating chemical interaction of the pterin with the metal surface. The spectral feature evidenced that the pterin would adsorb on gold surface with a "lying down" configuration through the high intensity vibration of NH scissoring and rocking OH modes. The orientation study of pterins on gold nanopillars presented herein is believed to lead to new applications in biosensing field for detecting pterins of physiological importance

Nuclear WRAP53 promotes neuronal survival and functional recovery after stroke

Failure of neurons to efficiently repair DNA double-strand breaks (DSBs) contributes to cerebral damage after stroke. However, the molecular machinery that regulates DNA repair in this neurological disorder is unknown. Here, we found that DSBs in oxygen/glucose-deprived (OGD) neurons spatiotemporally correlated with the up-regulation of WRAP53 (WD40-encoding p53-antisense RNA), which translocated to the nucleus to activate the DSB repair response. Mechanistically, OGD triggered a burst in reactive oxygen species that induced both DSBs and translocation of WRAP53 to the nucleus to promote DNA repair, a pathway that was confirmed in an in vivo mouse model of stroke. Noticeably, nuclear translocation of WRAP53 occurred faster in OGD neurons expressing the Wrap53 human nonsynonymous single-nucleotide polymorphism (SNP) rs2287499 (c.202C>G). Patients carrying this SNP showed less infarct volume and better functional outcome after stroke. These results indicate that WRAP53 fosters DNA repair and neuronal survival to promote functional recovery after stroke

Recent changes and drivers of the atmospheric evaporative demand in the Canary Islands

We analysed recent evolution and meteorological drivers of the atmospheric evaporative demand (AED) in the Canary Islands for the period 1961-2013. We employed long and high-quality time series of meteorological variables to analyse current AED changes in this region and found that AED has increased during the investigated period. Overall, the annual ETo, which was estimated by means of the FAO-56 Penman-Monteith equation, increased significantly by 18.2 mm decade-1 on average, with a stronger trend in summer (6.7 mm decade-1). In this study we analysed the contribution of (i) the aerodynamic (related to the water vapour that a parcel of air can store) and (ii) radiative (related to the available energy to evaporate a quantity of water) components to the decadal variability and trends of ETo. More than 90 % of the observed ETo variability at the seasonal and annual scales can be associated with the variability in the aerodynamic component. The variable that recorded more significant changes in the Canary Islands was relative humidity, and among the different meteorological factors used to calculate ETo, relative humidity was the main driver of the observed ETo trends. The observed trend could have negative consequences in a number of water-depending sectors if it continues in the future

Human Galectins Induce Conversion of Dermal Fibroblasts into Myofibroblasts and Production of Extracellular Matrix: Potential Application in Tissue Engineering and Wound Repair

Members of the galectin family of endogenous lectins are potent adhesion/growth-regulatory effectors. Their multi-functionality opens possibilities for their use in bioapplications. We studied whether human galectins induce the conversion of human dermal fibroblasts into myofibroblasts (MFBs) and the production of a bioactive extracellular matrix scaffold is suitable for cell culture. Testing a panel of galectins of all three subgroups, including natural and engineered variants, we detected activity for the proto-type galectin-1 and galectin-7, the chimera-type galectin-3 and the tandem-repeat-type galectin-4. The activity of galectin-1 required the integrity of the carbohydrate recognition domain. It was independent of the presence of TGF-beta 1, but it yielded an additive effect. The resulting MFBs, relevant, for example, for tumor progression, generated a matrix scaffold rich in fibronectin and galectin-1 that supported keratinocyte culture without feeder cells. Of note, keratinocytes cultured on this substratum presented a stem-like cell phenotype with small size and keratin-19 expression. In vivo in rats, galectin-1 had a positive effect on skin wound closure 21 days after surgery. In conclusion, we describe the differential potential of certain human galectins to induce the conversion of dermal fibroblasts into MFBs and the generation of a bioactive cell culture substratum. Copyright (C) 2011 S. Karger AG, Base

Exploring a Tetrahydroquinoline Antimalarial Hit from the Medicines for Malaria Pathogen Box and Identification of its Mode of Resistance as PfeEF2

New antimalarial treatments with novel mechanism of action are needed to tackle Plasmodium falciparum infections that are resistant to first-line therapeutics. Here we report the exploration of MMV692140 ( 2 ) from the Pathogen Box, a collection of 400 compounds that was made available by Medicines for Malaria Venture (MMV) in 2015. Compound 2 was profiled in in vitro models of malaria and was found to be active against multiple life-cycle stages of Plasmodium parasites. The mode of resistance, and putatively its mode of action, was identified as Plasmodium falciparum translation elongation factor 2 ( Pf eEF2), which is responsible for the GTP-dependent translocation of the ribosome along mRNA. The compound maintains activity against a series of drug-resistant parasite strains. The structural motif of the tetrahydroquinoline ( 2 ) was explored in a chemistry program with its structure-activity relationships examined, resulting in the identification of an analog with 30-fold improvement of antimalarial asexual blood stage potency

Analysis of Clostridium beijerinckii NCIMB 8052's transcriptional response to ferulic acid and its application to enhance the strain tolerance

Background: Plant-based cellulose presents the best source of renewable sugars for biofuel production. However, the lignin associated with plant cellulose presents a hurdle as hydrolysis of this component leads to the production of inhibitory compounds, such as ferulic acid. Results: The impacts of ferulic acid, a phenolic compound commonly found in lignin hydrolysates, on the growth, solvent production, and transcriptional responses of Clostridium beijerinckii NCIMB 8052 were determined. Addition of ferulic acid to growing cultures resulted in a decrease in the growth and solvent production by 30% and 25%, respectively, when compared to the control cultures. To better understand the toxicity of this compound, microarray analyses were performed using samples taken from these cultures at three different growth states. Several gene ontology terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were identified showing significant change at each status, including ATP-binding cassette (ABC) transporters, two component system, and oxidoreductase activity. Moreover, genes related with efflux systems and heat shock proteins were also strongly up-regulated. Among these, expression of the groESL operon was induced by more than fourfold and was consequently selected to improve C. beijerinckii tolerance to ferulic acid. Real-time quantitative PCR (RT-qPCR) analysis confirmed that C. beijerinckii harboring the plasmid, pSAAT-ptb_Gro, had a two-to fivefold increased groESL operon expression during growth of these cultures. Moreover, this strain was more tolerant to ferulic acid as the growth of this recombinant strain and its bioconversion of glucose into solvents were both improved. Conclusions: Using transcriptomics, we identified numerous genes that are differentially expressed when C. beijerinckii cultures were exposed to ferulic acid for varying amounts of time. The operon expressing groESL was consistently up-regulated, suggesting that this gene cluster may contribute to strain tolerance. This was confirmed as recombinant cultures showed both an enhanced growth and solvent yield in the presence of 0.5 g/L ferulic acidopen00