Efficacy of Dexamethasone Intravitreal Implant For Refractory Macular Edema Caused by Retinal Vein Occlusion

Purpose: To investigate efficacy of dexamethasone intravitreal (DEX) implant in treating refractory macular edema caused by retinal vein occlusion. Methods: Retrospective chart review. Results: Twenty-two eyes with refractory macular edema caused by retinal vein occlusion were treated with a mean of 2.2 DEX over 12 months. Patient had previously received a mean of 7 treatments (laser, bevacizumab, and/or triamcinolone) for macular edema present for at least 4 months duration (mean 20.8 ± 17.6 months, range 4–72 months) before starting DEX. Mean baseline visual acuity was 20/91, and mean central subfield thickness was 506 μm. DEX improved mean best-corrected visual acuity to 20/75 and 20/66 at 7 weeks and 6 months follow-up, although it worsened to 20/132 at 12 months. Mean central subfield thickness improved to 292, 352, and 356 μm at 7 weeks, 6 months, and 12 months follow-up, respectively. There was a statistically significant association between number of DEX treatments and central subfield thickness (P = 3.28 × 10−9). There was a statistically significant association between number of days followed and best-corrected visual acuity (P = 0.006). Six of 12 (50%) phakic patients developed visually significant cataract requiring surgery. Five of 22 (23%) patients developed ocular hypertension (intraocular pressure > 30) and consequently did not undergo further treatment with DEX. Conclusion: DEX resulted in sustained anatomical reduction of retinal vein occlusion–associated refractory macular edema, although this did not translate into long-term best-corrected visual acuity improvement in either phakic or pseudophakic patients, possibly related to chronic structural alterations in the retina despite reduction of edema

Structure–activity relationships of antibacterial peptides

Antimicrobial peptides play a crucial role in innate immunity, whose components are mainly peptide-based molecules with antibacterial properties. Indeed, the exploration of the immune system over the past 40 years has revealed a number of natural peptides playing a pivotal role in the defence mechanisms of vertebrates and invertebrates, including amphibians, insects, and mammalians. This review provides a discussion regarding the antibacterial mechanisms of peptide-based agents and their structure–activity relationships (SARs) with the aim of describing a topic that is not yet fully explored. Some growing evidence suggests that innate immunity should be strongly considered for the development of novel antibiotic peptide-based libraries. Also, due to the constantly rising concern of antibiotic resistance, the development of new antibiotic drugs is becoming a priority of global importance. Hence, the study and the understanding of defence phenomena occurring in the immune system may inspire the development of novel antibiotic compound libraries and set the stage to overcome drug-resistant pathogens. Here, we provide an overview of the importance of peptide-based antibacterial sources, focusing on accurately selected molecular structures, their SARs including recently introduced modifications, their latest biotechnology applications, and their potential against multi-drug resistant pathogens. Last, we provide cues to describe how antibacterial peptides show a better scope of action selectivity than several anti-infective agents, which are characterized by non-selective activities and non-targeted actions toward pathogens

Ranibizumab For Diabetic Macular Edema Refractory To Multiple Prior Treatments

Purpose: Diabetic macular edema can be refractory to multiple treatment modalities. Although there have been anecdotal reports of ranibizumab showing efficacy when other modalities provided limited benefit, little has been published on treatment for refractory diabetic macular edema. This study sought to investigate this observation further. Methods: Retrospective chart review. Results: Thirty-three eyes of 22 patients with refractory diabetic macular edema were treated with 0.3 mg intravitreal ranibizumab. This group of eyes received an average of 5.1 prior treatments (macular laser, intravitreal bevacizumab, triamcinolone acetonide, or dexamethasone implant). The mean best corrected visual acuity before the initial ranibizumab injection was 20/110 and the mean central subfield thickness was 384 μm. After 7 visits over an average of 48 weeks, during which an average of 6 ranibizumab injections were administered, the mean visual acuity improved to 20/90 and the mean central subfield thickness improved to 335 μm. Both central subfield thickness and best corrected visual acuity improved with number of days of follow-up in a statistically significant fashion (P < 0.01). Similarly, both central subfield thickness and visual acuity improved with number of ranibizumab injections in a linear fashion, but this was not statistically significant. Conclusion: Ranibizumab can improve diabetic macular edema refractory to prior treatments of laser photocoagulation, intravitreal triamcinolone acetonide, and bevacizumab

Treatment Strategies for Refractory Diabetic Macular Edema: Switching Anti-VEGF Treatments, adopting corticosteroid-based treatments, and combination therapy

Introduction: The pathophysiology of diabetic macular edema (DME) is complex, involving vascular endothelial growth factor (VEGF) and other inflammatory mediators. DME is currently treated first-line with intravitreal anti-VEGF treatments, though some cases are refractory to multiple anti-VEGF treatments. Areas covered: This article examines the evolution of treatment practices for DME, with discussion of the recent studies that guide treatment for refractory cases of DME. A literature search was performed using the following terms: anti-VEGF, DME, aflibercept, bevacizumab, ranibizumab, refractory macular edema, and VEGF. Expert opinion: Focal extrafoveal DME may be treated first-line with laser. In patients with center-involving DME and only mild vision loss, consider starting treatment with bevacizumab, especially when cost is an issue, whereas aflibercept may be considered more strongly in patients with moderate visual loss or worse. There are no standard protocols that define ‘treatment failure,’ but several studies have reported that switching from bevacizumab to either ranibizumab or aflibercept will result in further reduction of CSFT and improvement in BCVA. Further study with prospective randomized trials is warranted to validate these findings. Switching to intravitreal corticosteroids may be of particular benefit to pseudophakic patients. Anti-VEGF combination with sustained-release corticosteroids also appears promising for refractory DME

Cascade reaction based synthetic strategies targeting biologically intriguing indole polycycles

Indole polycycles are common structural frameworks of biologically intriguing small molecules of natural and synthetic origin and therefore remain interesting and challenging synthetic targets. Cascade reactions wherein a number of reactions occur in a sequential manner in the same reaction apparatus are highly efficient chemical processes which quickly build up molecular complexity. Synthetic approaches based on cascade reactions are highly useful as they tend to avoid multiple reaction work-up steps as well as purifications of all intermediary products. Therefore, in the last decade, a number of cascade reaction based approaches to build various molecular scaffolds of biological interest have been reported. However, a relatively smaller number of cascade reaction based synthetic strategies have targeted the indole polycycles. In this article, we have summarized some interesting cascade reaction based synthesis designs leading to complex indole polycycles including some biologically intriguing and natural product inspired indole frameworks

In a case of female-to-male sex reassignment, testosterone therapy switches on an underlying Brugada

Abstract Background The Brugada syndrome, diagnosed by a typical electrocardiographic pattern, is a genetic condition characterised by an increased risk of potentially lethal ventricular arrhythmias and sudden cardiac death. Even if its pathophysiological mechanism is unknown, its prevalence in male suggested a possible hormonal involvement. Case presentation In this case involving a woman who underwent a female-to-male sex reassignment, we documented that testosterone administration was able to switch on and, when stopped, to switch off a latent pattern of Brugada. Conclusions Our observation strongly supports a possible involvement of testosterone in the ECG manifestation of Brugada syndrome even if the general low prevalence of the Brugada syndrome does not support to screen every female-to-male sex reassignment

Boosted Cross-Linking and Characterization of High-Performing Self-Assembling Peptides

Tissue engineering (TE) strategies require the design and characterization of novel biomaterials capable of mimicking the physiological microenvironments of the tissues to be regenerated. As such, implantable materials should be biomimetic, nanostructured and with mechanical properties approximating those of the target organ/tissue. Self-assembling peptides (SAPs) are biomimetic nanomaterials that can be readily synthesized and customized to match the requirements of some TE applications, but the weak interactions involved in the self-assembling phenomenon make them soft hydrogels unsuited for the regeneration of medium-to-hard tissues. In this work, we moved significant steps forward in the field of chemical cross-linked SAPs towards the goal of stiff peptidic materials suited for the regeneration of several tissues. Novel SAPs were designed and characterized to boost the 4-(N-Maleimidomethyl) cyclohexane-1-carboxylic acid 3-sulpho-N-hydroxysuccinimide ester (Sulfo-SMCC) mediated cross-linking reaction, where they reached G′ values of ~500 kPa. An additional orthogonal cross-linking was also effective and allowed to top remarkable G′ values of 840 kPa. We demonstrated that cross-linking fastened the pre-existing self-aggregated nanostructures, and at the same time, a strong presence of ß-structures is necessary for an effective cross-linking of (LKLK)3-based SAPs. Combining strong SAP design and orthogonal cross-linking reactions, we brought SAP stiffness closer to the MPa threshold, and as such, we opened the door of the regeneration of skin, muscle and lung to biomimetic SAP technology

UN MODELLO ALLE DIFFERENZE FINITE DI UN PANNELLO FOTOVOLTAICO ACCOPPIATO A MATERIALE A CAMBIAMENTO DI FASE

La diffusione commerciale dei dispositivi fotovoltaici presenta negli ultimi anni un trend di crescita significativa a livello internazionale. Numerose ricerche sono state svolte al fine di incrementare l\u2019efficienza di conversione elettrica dei pannelli fotovoltaici e tra le soluzioni indagate \ue8 stato sperimentato l\u2019impiego di materiali a cambiamento di fase (MCF) per ridurre i picchi di temperatura di funzionamento. Nel lavoro \ue8 stato sviluppato un algoritmo di calcolo in grado di fornire l\u2019andamento temporale della temperatura di un pannello fotovoltaico accoppiato a materiale a cambiamento di fase (Sistema PV-MCF). La determinazione della distribuzione di temperature che interessano un sistema PV-MCF \ue8 stata affrontata con il metodo delle differenze finite in geometria monodimensionale. Sono state definite le equazioni di conservazione dell\u2019energia per ogni punto nodale in cui \ue8 stato discretizzato il sistema fisico, differenziandole per i nodi \u201cinterni\u201d e per i nodi \u201csuperficiali\u201d. Le equazioni alle differenze finite sono state formulate esplicitamente rispetto alla variabile temporale e sono state codificate in un apposito software. Il confronto con alcune soluzioni analitiche largamente impiegate nella bibliografia di settore ha permesso di verificare la correttezza e la validit\ue0 dell\u2019approccio sviluppato

Total synthesis of natural disaccharide sambubiose

A practical and robust synthetic method to obtain the natural disaccharide sambubiose (2O-β-D-xylopyranosyl-D-glucopyranose) is reported, exploring the key step in the synthesis, i.e., stereoselective O-glycosylation. Specifically, the best combinations of glycoside donors and acceptors were identified, stereospecific control of the reaction was achieved by screening several catalysts and protection/deprotection steps were evaluated and improved. The best result was obtained by coupling allyl 3,5,6-tri-O-benzyl-β-D-glucofuranoside with 2,3,4-tri-O-acetyl-Dxylopiranosyl-α-trichloro acetimidate in the presence of trimethylsilyl triflate as a catalyst giving the corresponding protected target compound as a correct single isomer. The latter was transformed accordingly into the desired final product by deprotection steps (deallylation, deacetylation, and debenzylation). Sambubiose was synthesized into a satisfactory and higher overall yield than previously reported and was also characterized

Evaluation of equilibrium moisture content in ligno-cellulosic residues of olive culture

The use of ligno-cellulosic residuals from agriculture as means for renewable energy production is well known; nonetheless significant problems still exist on development of bioenergy value chains. Moisture content and hygroscopicity are among these problems. Higher moisture content of the biomass means lower calorific value and higher perishability, hence storage difficulties. For this reason it is important to evaluate how the moisture content of the material varies while it is stored and how the calorific value of the feedstock is affected by it. The purpose of this study is to determine the variation of moisture content and its influence on lower calorific value (LCV) of four types of solid residual biomass: oven dried chipped olive tree trimmings, milled olive pomace; oven dried olive tree trimmings and fresh olive tree trimmings. Moisture content of the samples is calculated by means of thermogravimetric analysis (TGA) according to standard CEN/TS 14774-2:2004, while the LCVs are calculated by means of a calorimeter, following standard UNI EN 14918:2010. All the biomass samples were left to reach equilibrium moisture content (EMC) in a temperature and humidity controlled environment. Two different phases were analyzed with respect to moisture uptake rates: 1) fast moisture uptake rate phase (first four hours of exposure) and 2) slow moisture uptake rate, (the days following the first four hours of exposure). Samples experiencing fast moisture uptake rate, during the first four hours of exposure, were kept in a monitored ambient at T=22 \ub1 1oC and RH=59 \ub1 2%, while samples exposed to slow moisture uptake rate were kept in a climatic chamber at three different set of temperature and humidity controlled environment simulating the climatic conditions in different periods of the year in Enna province: 10oC - 80% RH (winter), 15oC - 70% RH (spring/autumn) and 20oC - 55% RH, (summer). The results obtained show that the olive pruning chips (0.425 mm to 1.00 mm and 1.00 mm to 2.00 mm particle size ranges) stored in a heap in a controlled climatic chamber require approximately 20 days to reach EMC. Depending on the particle size range EMCs reach the values of 6.2 and 7.5% by weight in the "summer" condition, 14.3% and 16.9% in "spring/autumn" condition, 24.1% and 28.2% in "winter" condition. Moisture is absorbed gradually over time and results show that in the first four hours, the dry sample exposed to ambient condition (T=22 \ub1 1 oC and RH=59 \ub1 2%) reaches a moisture content between 0.75 and 0.96% of its weight; the LCV at equilibrium is evaluated between 18, 576 J\u2022odg-1 and 18, 793 J\u2022odg-1, the higher value related to the bigger particle size range examined. Pomace heap under the same experimental set up and time period, reaches an equilibrium moisture content of 8.5% and 9.7% (summer conditions), 19.2% and 22.0% (spring/autumn condition) and between 30.9% and 34.1% (winter condition). Olive pomace accumulates moisture relatively faster than olive trimmings as dry sample recovers about 1.61% to 1.97% of moisture in the first four hours of exposure. The LCV at equilibrium is determined between 20, 145 J\u2022odg-1 and 20, 436 J\u2022odg-1. Pruning dried samples reach an EMC equal to 6.1% in approximately 25 days, with a LCV equal to18, 921 J\u2022odg-1 \ub1 1.9%. Heaps of fresh prunings reach an EMC of 8.2% in approximately 20 days; LCV of the feedstock is 19, 356 J\u2022odg-1\ub1 1.6%.\ua92006-2014 Asian Research Publishing Network (ARPN). All rights reserved