The role of Tenonplasty in the management of limbal and scleral ischemia due to acute ocular chemical burns

Of the various manifestations of ocular chemical burns (OCBs), ischemia of the limbus and the peri-limbal sclera indicates poor prognosis and in severe cases threaten the integrity of the globe. Tenonplasty is a surgical procedure which involves advancing the Tenon’s capsule over the ischemic areas to provide a vascular supply and to enable migration of the conjunctival epithelium. This review aims to provide an overview of the diagnosis of limbal ischemia and its management with Tenonplasty. A literature review was conducted using the keywords “Tenonplasty,” “Tenon’s capsule,” “ocular chemical injury,” “ocular thermal injury,” “Tenon advancement,” “scleral ischemia,” and “limbal ischemia,” and outcomes were studied from seven selected articles. In addition to clinical evaluation, in vivo imaging techniques such as anterior segment optical coherence tomography angiography can provide an objective method of measuring and monitoring the ischemia and re-perfusion of the peri-limbal vasculature. Tenonplasty can be performed in eyes with acute OCBs with scleral or limbal ischemia by dissecting the Tenon’s layer from the orbit and securing it to the limbus. The indications, mechanism of action, peri-operative considerations, surgical technique, and post-operative care of Tenonplasty are discussed in detail. The average time for post-operative re-epithelization ranges from 1 to 6 months with the formation of a symblepharon being the most common complication. In conclusion, Tenonplasty is a globe-salvaging procedure in cases with severe limbal and scleral ischemia because of OCBs and has good anatomical outcomes priming the globe for subsequent re-constructive and vision-restoring surgeries.     

A novel N-hydroxy-N′-aminoguanidine derivative inhibits ribonucleotide reductase activity: Effects in human HL-60 promyelocytic leukemia cells and synergism with arabinofuranosylcytosine (Ara-C)

Ribonucleotide reductase (RR; EC 1.17.4.1) is responsible for the de novo conversion of ribonucleoside diphosphates into deoxyribonucleoside diphosphates, which are essential for DNA replication. RR is upregulated in tumor cells and therefore considered to be an excellent target for cancer chemotherapy.ABNM-13 (N-hydroxy-2-(anthracene-2-yl-methylene)-hydrazinecarboximidamide), a novel N-hydroxy-N′-aminoguanidine has been designed to inhibit RR activity using 3D molecular space modeling techniques. In this study, we evaluated its effect on human HL-60 promyelocytic leukemia cells. ABNM-13 proved to be a potent inhibitor of RR which was displayed by significant alterations of deoxyribonucleoside triphosphate (dNTP) pool balance and a highly significant decrease of incorporation of radiolabeled cytidine into DNA of HL-60 cells. Diminished RR activity caused replication stress which was consistent with activation of Chk1 and Chk2, resulting in downregulation/degradation of Cdc25A. In contrast, Cdc25B was upregulated, leading to dephosphorylation and activation of Cdk1. The combined disregulation of Cdc25A and Cdc25B was the most likely cause for ABNM-13 induced S-phase arrest. Finally, we combined ABNM-13 with the first-line antileukemic agent arabinofuranosylcytosine (Ara-C) and found that ABNM-13 synergistically potentiated the antineoplastic effects of Ara-C.Due to these promising results, ABNM-13 deserves further preclinical and in vivo testing.     

Senior triaging of ENT emergency clinic referrals alleviates pressures on the outpatient department

IntroductionThe ear, nose and throat (ENT) emergency clinic is managed by foundation year (FY) doctors from taking referrals to discharging patients, under the supervision of a registrar. FYs learn essential skills and knowledge on how to manage common ENT problems. The clinic is often overloaded because of a high patient demand, and this limits the opportunities for teaching. We hypothesised that the clinic bookings would be better managed if referrals from general practitioners (GPs) were triaged by registrars.MethodsTelephone referrals from GPs for the ENT emergency clinic were directed to the on-call ENT registrar, between 8am and 1pm from Monday to Friday, and to the FY outside of this period. Consecutive referrals to the emergency clinic were analysed in a baseline audit and a post-intervention cycle.ResultsA total of 646 and 611 patients were given clinic appointments in the first and second cycles, respectively. Clinic session overbookings decreased from 85% to 46.3%. Appointments for referrals that were deemed inappropriate had reduced from 22% to 12.1%.Discussion and ConclusionInvolvement of a registrar in taking referrals for the ENT emergency clinic was associated with a reduction in clinic overbookings. It is feasible and productive to involve a senior decision maker in the operational management of the emergency clinic, while preserving the delivery of this service by FYs for its training value.     

On the specific heat capacity of HITEC-salt nanocomposites for concentrated solar power applications

High specific heat capacity or C_P of molten salt is crucial for concentrated solar power plants as it will enhance the energy density of thermal energy storage. It can be achieved by doping nanoparticles into molten salts. However, reported results show inconsistency in C_P enhancement (positive and negative). Since the results are based on Differential Scanning Calorimeter (DSC) measurements of small batches (<10 mg), the average C_P obtained from these results may not represent the bulk-C_P of the nanocomposite, which is an important parameter from an application viewpoint. Moreover, the methods of salt-nanoparticle composite production lack industrial scalability. In this work, we examined a potentially scalable method based on mechanical shear mixing. The molten-salt of choice was HITEC due to its lower melting point, while inexpensive alumina and silica nanoparticles were used as dopants. To compare and contrast variability in C_P enhancement, the sample selection was made by random sampling; DSC measurement was performed on small-sized batches (<10 mg), and the T-history method was applied on large-sized batches (20 g). While DSC tests indicated a mean decrease in C_P for alumina (−43%) and an increase in C_P for silica nanocomposite (+15%), T-history tests indicated a mean decrement in the bulk-C_P for both alumina (−49%) and silica nanocomposites (−3%). This anomalous behavior in C_P values was further compared using a nonparametric statistical test, the Mann–Whitney U test, which revealed that the C_P of small-sized batches is statistically different from that of large-sized batches. Given their industrial scale of usage, the C_P of the nanocomposite must be measured using both DSC and T-history methods to ascertain the effect of nanoparticles.

The current study highlights the importance of testing the bulk-C_P and statistical inference for examining the specific heat capacity of nanoparticle-infused salt composites using DSC and T-history tests.     

Factors controlling the pharmacokinetics,biodistribution and intratumoral penetration of nanoparticles

Nanoparticle drug delivery to the tumor is impacted by multiple factors: nanoparticles must evade clearance by renal filtration and the reticuloendothelial system, extravasate through the enlarged endothelial gaps in tumors, penetrate through dense stroma in the tumor microenvironment to reach the tumor cells, remain in the tumor tissue for a prolonged period of time, and finally release the active agent to induce pharmacological effect. The physicochemical properties of nanoparticles such as size, shape, surface charge, surface chemistry (PEGylation, ligand conjugation) and composition affect the pharmacokinetics, biodistribution, intratumoral penetration and tumor bioavailability. On the other hand, tumor biology (blood flow, perfusion, permeability, interstitial fluid pressure and stroma content) and patient characteristics (age, gender, tumor type, tumor location, body composition and prior treatments) also have impact on drug delivery by nanoparticles. It is now believed that both nanoparticles and the tumor microenvironment have to be optimized or adjusted for optimal delivery. This review provides a comprehensive summary of how these nanoparticle and biological factors impact nanoparticle delivery to tumors, with discussion on how the tumor microenvironment can be adjusted and how patients can be stratified by imaging methods to receive the maximal benefit of nanomedicine. Perspectives and future directions are also provided.