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Andrea Taloni,1,* Giulia Coco,2,* Davide Rastelli,3 Giacinta Buffon,2 Vincenzo Scorcia,1 Giuseppe Giannaccare4 1Department of Ophthalmology, University “Magna Graecia” of Catanzaro, Catanzaro, Italy; 2Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Rome, Italy; 3Department of Ophthalmology, Policlinico Casilino, Rome, Italy; 4Eye Clinic, Department of Surgical Sciences, University of Cagliari, Cagliari, Italy*These authors contributed equally to this workCorrespondence: Giuseppe Giannaccare, Full Professor of Ophthalmology, Eye Clinic, Department of Surgical Sciences, University of Cagliari, Via Università 40, Cagliari, 09124, Italy, Tel +0039 09613647041, Fax +0039 09613647094, Email giuseppe.giannaccare@gmail.comAbstract: Diabetic macular edema (DME) is a common sight-threatening complication of diabetic retinopathy (DR) and the leading cause of severe visual impairment among the working-age population. Several therapeutic options are available for the management of DME, including intravitreal corticosteroids. They have been traditionally used as second-line treatment, due to the risk of intraocular pressure increase and cataract-related adverse events. However, attention has recently been focused on the primary or early use of intravitreal corticosteroids, due to growing evidence of the crucial role of inflammation in the pathogenesis of DME. Furthermore, intravitreal steroid implants offer the additional advantage of a longer duration of action compared to anti-vascular endothelial growth factor agents (anti-VEGF). This review aims to summarize the available evidence on the efficacy and safety profile of dexamethasone (DEX) intravitreal implant, with a specific focus on clinical scenarios in which it might be considered or even preferred as first-line treatment option by adequate selection of patients, considering both advantages and possible adverse events. Patients with contraindications to anti-VEGF, DME with high inflammatory OCT biomarkers, pseudophakic patients and phakic patients’ candidates to cataract surgery as well as vitrectomized eyes may all benefit from first-line DEX implant. Additionally, DME not responders to anti-VEGF should be considered for a switch to DEX implant and a combination therapy of DEX implant and anti-VEGF could be a valid option in severe and persistent DME.Keywords: diabetic macular edema, DME, dexamethasone intravitreal implant, DEX implant, corticosteroids, Ozurdex

Dry eye disease (DED) incidence is continuously growing, positioning it to become an emergent health issue over the next few years. Several topical treatments are commonly used to treat DED; however, reports indicate that only a minor proportion of drug bioavailability is achieved by the majority of eye drops available on the market. In this context, enhancing drug ability to overcome ocular barriers and prolonging its residence time on the ocular surface represent a new challenge in the field of ocular carrier systems. Therefore, research has focused on the development of multi-functional nanosystems, such as nanoemulsions, liposomes, dendrimers, hydrogels, and other nanosized carriers. These systems are designed to improve topical drug bioavailability and efficacy and, at the same time, require fewer daily administrations, with potentially reduced side effects. This review summarizes the different nanotechnologies developed, their role in DED, and the nanotechnology-based eyedrops currently approved for DED treatment.

Cultivated rice ( Oryza sativa L.) is frequently exposed to multiple stresses, including Schizotetranychus oryzae mite infestation. Rice domestication has narrowed the genetic diversity of the species, leading to a wide susceptibility. This work aimed to analyze the response of two African rice species ( Oryza barthii and Oryza glaberrima ), weedy rice ( O. sativa f. spontanea ), and O. sativa cv. Nipponbare to S. oryzae infestation. Surprisingly, leaf damage, histochemistry, and chlorophyll concentration/fluorescence indicated that the African species present a higher level of leaf damage, increased accumulation of H 2 O 2 , and lower photosynthetic capacity when compared to O. sativa plants under infested conditions. Infestation decreased tiller number, except in Nipponbare, and caused the death of O. barthii and O. glaberrima plants during the reproductive stage. While infestation did not affect the weight of 1,000 grains in both O. sativa , the number of panicles per plant was affected only in O. sativa f. spontanea , and the percentage of full seeds per panicle and seed length were increased only in Nipponbare. Using proteomic analysis, we identified 195 differentially abundant proteins when comparing susceptible ( O. barthii ) and tolerant (Nipponbare) plants under control and infested conditions. O. barthii presents a less abundant antioxidant arsenal and is unable to modulate proteins involved in general metabolism and energy production under infested condition. Nipponbare presents high abundance of detoxification-related proteins, general metabolic processes, and energy production, suggesting that the primary metabolism is maintained more active compared to O. barthii under infested condition. Also, under infested conditions, Nipponbare presents higher levels of proline and a greater abundance of defense-related proteins, such as osmotin, ricin B-like lectin, and protease inhibitors (PIs). These differentially abundant proteins can be used as biotechnological tools in breeding programs aiming at increased tolerance to mite infestation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Buffon, Blasi, Lamb, Adamski, Schwambach, Ricachenevsky, Bertolazi, Silveira, Lopes and Sperotto.)

Advancements in genetically modified herbicide tolerance technology opened a new way to manage weed populations in crop fields. Since then, many important genetically modified crops that are tolerant to various herbicides have been developed and commercialized. Herbicides primarily act by disrupting key enzymes involved in essential metabolic or physiological processes associated with growth and development of plants. Most of the herbicide tolerant plants have been developed by introducing point mutations (non-GM approach) in the target site of herbicide action, due to the advantage of easier registration/release for commercial cultivation as well as wider public acceptance. Of the various herbicides, Imidazolinones are probably the most widely targeted ones for developing herbicide tolerant crops through non-GM approach. In rice, different mutant lines presenting amino acids changes in acetolactate synthase (ALS) have the ability to tolerate different Imidazolinones, including point mutations of Glycine to Glutamate in position 628, Serine to Asparagine in position 627, and a double mutation Tryptophan to Leucine in position 548/Serine to Isoleucine in position 627. The use of specific herbicides in combination of these mutant lines provides a reliable approach to eliminate weeds in the fields. However, the continuous overuse of a single herbicide multiple times in a growing season increases the potential risk of evolution of resistant weeds, which has become a major concern in agriculture worldwide. For this reason, the development of novel mutations in ALS (Os02g30630) to generate rice plants more tolerant to Imidazolinones than the available mutant rice lines is still a hot topic in plant-herbicide interaction field. Keeping that in mind, we carried out molecular docking experiments of Imidazolinone herbicides imazapic, imazapyr, imazaquin, and imazethapyr to evaluate the interaction of these molecules in the binding cavity of ALS from rice, being able to identify the most important amino acids responsible for the stability of these four herbicides. After introducing point mutations in these specific positions (one at a time) using Alanine scanning mutagenesis method and recalculating the effect in the affinity of herbicide-ALS interaction, we were able to propose novel amino acid residues (mainly Lysine in position 230 and Arginine in position 351) on the structure of ALS presenting a highest impact in the binding of Imidazolinones to ALS when compared to the already known amino acid mutations. This rational approach allows the researcher/farmer to choose the number of point mutations to be inserted in a rice cultivar, which will be dependent on the type of Imidazolinone used. To obtain a rice cultivar capable to tolerate the four Imidazolinone tested at the same time, we suggest six amino acid mutations at positions Val170, Phe180, Lys230, Arg351, Trp548, and Ser627 in the OsALS1., (Copyright © 2020 Buffon, Lamb, Lopes, Sperotto and Timmers.)

Purpose: This study aims to characterize the orofacial myofunctional profile of patients with sleep disorders and to relate them to the severity of the polysomnography result., Methods: A cross-sectional, field study of patients referred to polysomnography with a random sample of adult patients of both genders complaining of snoring who were not receiving any form of treatment for sleep disorder. An anthroposcopic speech-language evaluation was performed and the results of the polysomnography examination were collected in order to respond to the objectives of the study., Results: There was a significant association between the severity of the sleep disorder and environmental variables, such as smoking and alcoholism; also with individual characteristics, such as race, body mass index, waist circumference and systemic arterial hypertension. From the point of view of the myofunctional characteristics, there was a positive relationship between the severity of Obstructive Sleep Apnea and Hypopnea Syndrome with mental muscle contraction, Mallampati class, tongue dorsum elevation, tongue thickness, uvula characteristics, extension and mobility of the soft palate, and alteration in the respiratory pattern., Conclusion: This study made it possible to describe a trend of the existence of orofacial myofunctional alterations in individuals with Sleep Apnea and Obstructive Hypopnea Syndrome and also revealed that the greater the degree of impairment of orofacial structures, the greater the degree of disturbance is also revealed.

Rice is the staple food for over half of the world's population. Infestation of Schizotetranychus oryzae (Acari: Tetranychidae) causes great losses in rice productivity. To search for rice genotypes that could better tolerate S. oryzae infestation, we evaluated morphological and production parameters in Brazilian cultivars, and identified two cultivars with contrasting responses. Leaf damage during infestation was similar for all cultivars. However, infestation in Puitá INTA-CL resulted in reduction in the number of seeds per plant, percentage of full seeds, weight of 1,000 seeds, and seed length, whereas infestation in IRGA 423 increased weight of 1,000 seeds and seed length. Reduction in seed weight per plant caused by infestation was clearly higher in Puitá INTA-CL (62%) compared to IRGA 423 (no reduction detected), thus Puitá INTA-CL was established as susceptible, and IRGA 423 as tolerant to S. oryzae infestation. Photosynthetic parameters were less affected by infestation in IRGA 423 than in Puitá INTA-CL, evidencing higher efficiency of energy absorption and use. S. oryzae infestation also caused accumulation of H 2 O 2 , decreased cell membrane integrity (indicative of cell death), and accelerated senescence in leaves of Puitá INTA-CL, while leaves of IRGA 423 presented higher levels of total phenolics compounds. We performed proteomics analysis of Puitá INTA-CL and IRGA 423 leaves after 7 days of infestation, and identified 60 differentially abundant proteins (28 more abundant in leaves of Puitá INTA-CL and 32 in IRGA 423). Proteins related to plant defense, such as jasmonate synthesis, and related to other mechanisms of tolerance such as oxidative stress, photosynthesis, and DNA structure maintenance, together with energy production and general metabolic processes, were more abundant in IRGA 423. We also detected higher levels of silicon (as amorphous silica cells) in leaves of infested IRGA 423 plants compared to Puitá INTA-CL, an element previously linked to plant defense, indicating that it could be involved in tolerance mechanisms. Taken together, our data show that IRGA 423 presents tolerance to S. oryzae infestation, and that multiple mechanisms might be employed by this cultivar. These findings could be used in biotechnological approaches aiming to increase rice tolerance to mite infestation.

Introduction  In Brazil, estimates show that 14.7% of the adult population smokes, and changes in smell and taste arising from tobacco consumption are largely present in this population, which is an aggravating factor to these dysfunctions. Objectives  The objective of this study is to systematically review the findings in the literature about the influence of smoking on smell and taste. Data Synthesis  Our research covered articles published from January 1980 to August 2014 in the following databases: MEDLINE (accessed through PubMed), LILACS, Cochrane Library, and SciELO. We conducted separate lines of research: one concerning smell and the other, taste. We analyzed all the articles that presented randomized controlled studies involving the relation between smoking and smell and taste. Articles that presented unclear methodologies and those whose main results did not target the smell or taste of the subjects were excluded. Titles and abstracts of the articles identified by the research strategy were evaluated by researchers. We included four studies, two of which were exclusively about smell: the first noted the relation between the perception of puff strength and nicotine content; the second did not find any differences in the thresholds and discriminative capacity between smokers and nonsmokers. One article considered only taste and supports the relation between smoking and flavor, another considered both sensory modalities and observes positive results toward the relation immediately after smoking cessation. Conclusion  Three of the four studies presented positive results for the researched variables.

High levels of Schizotetranychus oryzae phytophagous mite infestation on rice leaves can severely affect productivity. Physiological characterization showed that S. oryzae promotes a decrease in chlorophyll concentration and the establishment of a senescence process in rice leaves. Late-infested leaves also present high levels of superoxide radical and hydrogen peroxide accumulation, along with high levels of membrane integrity loss, which is indicative of cell death. To better understand the rice molecular responses to high levels of mite infestation, we employed the Multidimensional Protein Identification Technology (MudPIT) approach to identify differentially expressed proteins. We identified 83 and 88 proteins uniquely present in control and late-infested leaves, respectively, along with 11 and one proteins more abundant in control and late-infested leaves, respectively. S. oryzae infestation induces a decreased abundance of proteins related to translation, protease inhibition, and photosynthesis. On the other hand, infestation caused increased abundance of proteins involved in protein modification and degradation. Our results also suggest that S. oryzae infestation interferes with intracellular transport, DNA structure maintenance, and amino acid and lipid metabolism in rice leaves. Proteomic data were positively correlated with enzymatic assays and RT-qPCR analysis. Our findings describe the protein expression patterns of late-infested rice leaves and suggest several targets which could be tested in future biotechnological approaches aiming to avoid the population increase of phytophagous mite in rice plants., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Infestation of phytophagous mite Schizotetranychus oryzae in rice causes critical yield losses. To better understand this interaction, we employed Multidimensional Protein Identification Technology (MudPIT) approach to identify differentially expressed proteins. We detected 18 and 872 unique proteins in control and infested leaves, respectively, along with 32 proteins more abundant in control leaves. S. oryzae infestation caused decreased abundance of proteins related to photosynthesis (mostly photosystem II-related), carbon assimilation and energy production, chloroplast detoxification, defense, and fatty acid and gibberellin synthesis. On the contrary, infestation caused increased abundance of proteins involved in protein modification and degradation, gene expression at the translation level, protein partitioning to different organelles, lipid metabolism, actin cytoskeleton remodeling, and synthesis of jasmonate, amino acid, and molecular chaperones. Our results also suggest that S. oryzae infestation promotes cell-wall remodeling and interferes with ethylene biosynthesis in rice leaves. Proteomic data were positively correlated with enzymatic assays and RT-qPCR analysis. Our findings describe the protein expression patterns of infested rice leaves and suggest that the acceptor side of PSII is probably the major damaged target in the photosynthetic apparatus. These data will be useful in future biotechnological approaches aiming to induce phytophagous mite resistance in rice.

Abiotic stresses may result in significant losses in rice grain productivity. Protein regulation by the ubiquitin/proteasome system has been studied as a target mechanism to optimize adaptation and survival strategies of plants to different environmental stresses. This article aimed at highlighting recent discoveries about the roles ubiquitination may play in the exposure of rice plants to different abiotic stresses, enabling the development of modified plants tolerant to stress. Responses provided by the ubiquitination process include the regulation of the stomatal opening, phytohormones levels, protein stabilization, cell membrane integrity, meristematic cell maintenance, as well as the regulation of reactive oxygen species and heavy metals levels. It is noticeable that ubiquitination is a potential means for developing abiotic stress tolerant plants, being an excellent alternative to rice (and other cultures) improvement programs.