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Vitamin-D deficiency is a global concern. Gene mutations in the vitamin D receptor’s (VDR) ligand binding domain (LBD) variously alter the ligand binding affinity, heterodimerization with retinoid X receptor (RXR) and inhibit coactivator interactions. These LBD mutations may result in partial or total hormone unresponsiveness. A plethora of evidence reports that selective long chain polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and arachidonic acid (AA) bind to the ligand-binding domain of VDR and lead to transcriptional activation. We, therefore, hypothesize that selective PUFAs would modulate the dynamics and kinetics of VDRs, irrespective of the deficiency of vitamin-D. The spatial arrangements of the selected PUFAs in VDR active site were examined by in-silico docking studies. The docking results revealed that PUFAs have fatty acid structure-specific binding affinity towards VDR. The calculated EPA, DHA & AA binding energies (Cdocker energy) were lesser compared to vitamin-D in wild type of VDR (PDB id: 2ZLC). Of note, the DHA has higher binding interactions to the mutated VDR (PDB id: 3VT7) when compared to the standard Vitamin-D. Molecular dynamic simulation was utilized to confirm the stability of potential compound binding of DHA with mutated VDR complex. These findings suggest the unique roles of PUFAs in VDR activation and may offer alternate strategy to circumvent vitamin-D deficiency.

Peptidoglycan, an essential component of the bacterial cell wall plays a critical role in protecting bacteria against osmotic lysis. The ATP-dependent MurC-F ligases are crucial for the early stages of peptidoglycan biosynthesis. MurE ligase is third in the series and catalyzes the addition of l-Lysine (l-Lys) in Gram-positive bacteria or meso-diaminopimelic acid (meso-A2pm) in most Gram-negative bacteria to form UDP-N-acetylmuramoyl-l-Ala-d-Glu-l-Lys/A2pm. The high substrate specific for l-Lys or meso-A2pm makes this enzyme an attractive target for the development of antibacterial agents. Several MurE inhibitors have been reported including phosphinates, peptidosulfonamides, napthylfuran-2-ones, benzene-1,3-dicarboxylic acids, phosphorylatedhydroxyethylamines, natural compounds, 5-benzylidenethiazolidin-4-ones, N-alkyl-2-alkynyl-4(1H)-quinolones, rhodanine substituted d-glutamic acids, 2,5-dimethyl pyrroles, 2,5-disubstitued furans, tetrahydroisoquinolines etc. In the present review we present an update status and structural information of MurE enzyme inhibitors which may be utilized for the design of potent inhibitors against this enzyme.

A methodology involving rice husk (RH), rice husk charcoal (RHC), and activated rice husk charcoal (ARHC) as an effective adsorbent to eliminate malachite green dye from aqueous solution using adsorption process by varying the pH, initial dye concentration (mg/L), contact time, temperature, and adsorbent doses (g/L). The surface characteristics were observed under scanning electron microscopy (SEM), and Fourier transform infrared (FTIR) spectroscopy was used to identify the chemical bonds present on the adsorbent surface. Data obtained from adsorption system at equilibrium condition were fitted to isotherm models such as Langmuir and Freundlich model where it was found that unlike raw RH and RHC equilibrium, data for ARHC fitted best to Langmuir model with 1000 mg/g as maximum adsorption capacity at 303 K, indicating homogeneous monolayer adsorption by the mesopores. The adsorption kinetics for all three adsorbents were observed to fit the pseudosecond-order model better. The negative value of ΔH and ΔS obtained from the thermodynamic study indicates that the process is exothermic and involves an associative mechanism respectively. Boyd plot was used to understand the mass transfer mechanism. Moreover, fixed-bed column studies were performed using ARHC as the adsorbent. At different experimental conditions such as inlet flow rate (Q), initial dye concentration (C0), bed height (Lb), and pH, it was observed that the adsorption capacity (kd*) of MG dye on ARHC in a fixed bed continuous flow in a column mode, ranged between 0.008 and 0.177 (g/g). Present investigation and comparison with other reported adsorbents concluded that RH, RHC, and ARHC can be used as efficient and environment-friendly adsorbents for the removal of dissolved malachite green from contaminated water. However, ARHC was proved to be the best-suited candidate among the three adsorbents.

Importance: Five-year survival rates in patients undergoing vitrectomy for diabetic retinopathy (DR) vary from 68% to 95%. No study has been conducted in an Australian population. Background: We aimed to determine the survival rates of patients undergoing diabetic vitrectomy in an Australian population. Design: Retrospective audit, tertiary centre hospitals and private practices. Participants: All individuals in South Australia and the Northern Territory who underwent their first vitrectomy for diabetic complications between January 1, 2007 and December 31, 2011. Methods: An audit of all eligible participants has been completed previously. Survival status as of July 6, 2018 and cause of death were obtained using SA/NT DataLink. Kaplan-Meier survival curves and multivariate cox-regressions were used to analyse survival rates and identify risk factors for mortality. Main Outcome Measures: Five-, seven- and nine-year survival rates. Results: The 5-, 7- and 9-year survival rates were 84.4%, 77.9% and 74.7%, respectively. The most common cause of death was cardiovascular disease. Associated with increased mortality independent of age were Indigenous ethnicity (HR = 2.04, 95% confidence interval [CI]: 1.17-3.57, P = 0.012), chronic renal failure (HR = 1.76, 95% CI: 1.07-2.89, P = 0.026) and renal failure requiring dialysis (HR = 2.32, 95% CI: 1.25-4.32, P = 0.008). Conclusions and Relevance: Long-term survival rates after diabetic vitrectomy in Australia are similar to rates reported in other populations. Indigenous ethnicity and chronic renal failure were the most significant factors associated with long-term mortality. This information can guide allocation of future resources to improve the prognosis of these high risk groups.

A method associated with nanocellulose material derived from sugarcane bagasse as bio-adsorbent in order to decolorize Malachite green dye was carried out through batch process. Objective of this study was to appraise the performance of SB nanocellulose, was synthesized using bleaching treatment of sugarcane bagasse as agro-waste followed by alkaline hydrolysis, acid hydrolysis (using 50% sulfuric acid at 50 °C for 3 h), and freeze drying. The synthesized cellulose was characterized by Fourier transform infrared (FTIR) spectroscopy. The absorbance of the supernatant solution was measured at 617 nm in UV visible spectrophotometer. Adsorption process was carried out by varying the pH value (2, 4, 6, 7, 8), initial dye concentration (1, 5, 10, 15, 20, 25, 50 mg/L) contact time (15, 30, 45, 60, 120, 180 min), temperature (25, 30, 35, 40 °C), and adsorbent doses (2, 4, 6, 8 g/L). In case of SB Nano cellulose, percentage of dye removal with initial 20 mg/L dye solution was 98.35% at normal condition. The adsorption efficiency of the SB cellulose is still over 80% after four times of recycling. Adsorbent has some beneficial features like, it is renewable, inexpensive, high surface area, unique chemical composition, and top of it all these adsorbents exhibit high removal capacity in dye solution.

The ATP-dependent bacterial MurD enzyme catalyses the formation of the peptide bond between cytoplasmic intermediate UDP-N-acetylmuramoyl-L-alanine and D-glutamic acid. This is essential for bacterial cell wall peptidoglycan synthesis in both Gram-positive and Gram-negative bacteria. MurD is recognized as an important target for the development of new antibacterial agents. In the present study we prepared the 3D-stucture of the catalytic pocket of the Staphylococcus aureus MurD enzyme by homology modelling. Extra-precision docking, binding free energy calculation by the MM-GBSA approach and a 40 ns molecular dynamics (MD) simulation of 2-thioxothiazolidin-4-one based inhibitor $1 was carried out to elucidate its inhibition potential for the S. aureus MurD enzyme. Molecular docking results showed that Lys19, Gly147, Tyr148, Lys328, Thr330 and Phe431 residues are responsible for the inhibitor-protein complex stabilization. Binding free energy calculation revealed electrostatic solvation and van der Waals energy components as major contributors for the inhibitor binding. The inhibitor-modelled S. aureus protein complex had a stable conformation in response to the atomic flexibility and interaction, when subjected to MD simulation at 40 ns in aqueous solution. We designed some molecules as potent inhibitors of S. aureus MurD, and to validate the stability of the designed molecule D1-modelled protein complex we performed a 20 ns MD simulation. Results obtained from this study can be utilized for the design of potent S. aureus MurD inhibitors.

Purpose To present the visual and safety outcomes of surgery for primary idiopathic macular holes including predictors of visual acuity and the impact of combined phacovitrectomy surgery. Design Registry-style, prospective, nonrandomized, observational cohort study. Participants Patients with idiopathic macular holes undergoing primary surgery. Methods Surgeons were invited to submit clinical details of all macular hole cases receiving surgery. Baseline demographic and clinical information, and details of surgical intervention were collected. Primary follow-up data were collected at 3 months postoperatively or before revision surgery, and surgeons were also asked to submit data at 12 and 24 months postoperatively. Main Outcome Measures Visual acuity improvement ≥15 letters and ≥0 letters, change in mean visual acuity, visual acuity ≥70 letters (20/40), retinal detachment, and endophthalmitis. Results A total of 2455 eyes of 2366 patients were included in the study, and hole closure was achieved in 95.6% of eyes with a single procedure. Mean baseline vision was 48.3 letters. The proportion of successful eyes improving ≥15 letters at 3, 12, and 24 months was 59.1%, 69.4%, and 68.2%, respectively. The mean improvement in acuity at 3, 12, and 24 months was 16.0, 19.2, and 23.6 letters, and 92.4%, 93.4%, and 95.8% improved ≥0 letters at 3, 12, and 24 months, respectively. Eyes receiving SF6 gas had better visual acuities at all time points postoperatively (adjusted effect 3.4, 3.1, and 4.6 letters better at 3, 12, and 24 months vs. longer-acting gas, respectively). Combined phacovitrectomy in phakic eyes was associated with better corrected visual acuity postoperatively (vs. vitrectomy surgery alone), a difference that vanished when eyes went on to have subsequent cataract surgery. The rate of retinal detachment postoperatively was 1.3%, and the odds of detachment were greater in eyes receiving longer-acting gases versus SF6 gas (adjusted odds ratio, 2.2; 95% confidence interval, 1.04–4.77; P = 0.039). There were no reported cases of endophthalmitis. Conclusions Macular hole surgery substantially improved acuity in approximately two thirds of patients and was seldom associated with loss of vision. SF6 gas was associated with better visual outcomes, an effect that warrants further study.

Present study aimed to the production of calcium alginate–bentonite/​ activated biochar beads for implementation in methylene blue (MB) dye removal process and biodegradation study of dye-loaded composites by isolated bacteria, Lysinibacillus Sp. FTIR, TGA, SEM analysis of synthesized polymeric composite and biodegraded dye-loaded composite were performed to evaluate the surface characteristics and to identify the changes in biodegraded sample after biodegradation process. Experimental data of batch study were seemed to be extensively adjacent with the Langmuir isotherm and the maximum capacity for monolayer biosorption was 47.393 mg g − 1 at 303 K and with increasing temperature, it was decreased. Additionally, the biosorption kinetics confirmed that the pseudo 2nd order model was comparatively more applicable than pseudo 1st order, Elovich diffusion and Weber–Morris intraparticle model for describing MB biosorption. Estimated magnitude of thermodynamic variables specified that the MB dye removal system was favorable at lower temperatures and endothermic process. Biodegradation study of dye-loaded composite was carried out under different operational conditions (pH, inoculum dosage, temperature, etc.) and high biodegradation efficiency was found (% weight loss >70%). Experimental data obtained from biodegradation kinetics was modeled by applying Han and Levenspiel’s model and estimated values of μ max and K S as 0.0897 h−1 and 0.102 gL−1, respectively. The calculated value of Y x/s was obtained as 67.6 g of biomass/g of dye-loaded composite.

Importance Visual outcomes following diabetic vitrectomy have not previously been studied in an Australian population. Background This analysis aimed to (1) determine the rate of, and factors associated with visual success following diabetic vitrectomy performed for Indigenous and non-Indigenous Australians, and (2) investigate factors predisposing to early progression to diabetic retinopathy (DR) requiring vitrectomy. Design Retrospective, population-based audit. Participants All patients undergoing vitrectomy for the complications of DR in South Australia (SA) and the Northern Territory (NT) between 2007 and 2011. Methods Medical records were audited and data collected, including demographics, diabetic history, past treatment for DR, indication for vitrectomy, and visual acuity pre- and post-operatively. Outcome measures Visual success (gain of ≥ 15 ETDRS letters) at 6 and 12 months post-operatively. Results 495 diabetic vitrectomies, for 404 eyes of 335 patients were performed in SA and NT between 2007 and 2011. 77 (23%) patients requiring diabetic vitrectomy were Indigenous Australians. 87% of patients undergoing diabetic vitrectomy had stable or improved vision at 1 year post-operatively. There was no significant difference between Indigenous and non-Indigenous eyes achieving visual success (P=0.929). Timely pre-operative laser treatment (P=0.03) and pre-operative visual acuity (P=0.01) were the predominant factors associated with visual success. Conclusions Indigenous patients are just as likely to have improved vision following diabetic vitrectomy as non-indigenous Australians. However, the small subset of Indigenous patients with blind eyes prior to vitrectomy are significantly less likely to improve from surgery. The underlying factors associated with poor outcomes in this group requires further exploration.

Infections due to resistant bacteria are the life-threatening and leading cause of mortality worldwide. The current therapy for bacterial infections includes treatment with various drugs and antibiotics. The misuse and over usage of these antibiotics leads to bacterial resistance. There are several mechanisms by which bacteria exhibit resistance to some antibiotics. These include drug inactivation or modification, elimination of antibiotics through efflux pumps, drug target alteration, and modification of metabolic pathway. However, it is difficult to treat infections caused by resistant bacteria by conventional existing therapy. In the present study binding affinities of some glitazones against ParE and MurE bacterial enzymes are investigated by in silico methods. As evident by extra-precision docking and binding free energy calculation (MM-GBSA) results, rivoglitazone exhibited higher binding affinity against both ParE and MurE enzymes compared to all other selected compounds. Further molecular dynamic (MD) simulations were performed to validate the stability of rivoglitazone/4MOT and rivoglitazone/4C13 complexes and to get insight into the binding mode of inhibitor. Thus, we hypothesize that structural modifications of the rivoglitazone scaffold can be useful for the development of an effective antibacterial agent.

Repositioning the drugs through poly-pharmacological approaches, including cancer therapy is gaining scientific interest, as many non-cancer targeting drugs have well-established safety profile but unexplored for its potential to combat cancer. The complex heterotrimeric protein Na+/K+ ATPase (NKA) is complex. It is existing on the plasma membrane of eukaryotic cells and makes use of ATP for the maintenance of sodium and potassium transport. It has three subunits, α, β and γ. The α-subunit has four isoforms namely α1, α2, α3, and α4. One of the published studies reports that the α1 subunit is over expressed and activated in certain malignancies like renal cell carcinoma, glioma, and melanoma. Thus, it is hypothesized that NKA has unique roles in cancer cell growth and development. For instance, Ouabain is a well-known inhibitor of NKA which is used primarily as a cardiac stimulant has also been recently reported for its potential anticancer properties in neuroblastoma cells. Consequently, the search for the molecules which has the potential to inhibit specific NKA in cancer cells gaining tremendous scientific attention. Recently perillyl alcohol has been reported for anticancer potential through NKA inhibition.Sinceperillyl alcohol has a cyclic ring in its structural frame,we opted the similar chemical signatures of Phyto terpenes and phytotannins of for our study.Thus, the present study opted for scaffold repurposing strategy using in-silico methods to identify and screen some of the well-known phytocompounds for its possible anticancer effects by inhibiting NKA.

Staphylococcus aureus MurE enzyme catalyzes the addition of l-lysine as third residue of the peptidoglycan peptide moiety. Due to the high substrate specificity and its ubiquitous nature among bacteria, MurE enzyme is considered as one of the potential target for the development of new therapeutic agents. In the present work, induced fit docking (IFD), binding free energy calculation, and molecular dynamics (MD) simulation were carried out to elucidate the inhibition potential of 2-thioxothiazolidin-4-one based inhibitor 1 against S. aureus MurE enzyme. The inhibitor 1 formed majority of hydrogen bonds with the central domain residues Asn151, Thr152, Ser180, Arg187, and Lys219. Binding free-energy calculation by MM-GBSA approach showed that van der Waals (ΔGvdW, −57.30 kcal/mol) and electrostatic solvation (ΔGsolv, −36.86 kcal/mol) energy terms are major contributors for the inhibitor binding. Further, 30-ns MD simulation was performed to validate the stability of ligand–protein complex and also to get structural insight into mode of binding. Based on the IFD and MD simulation results, we designed four new compounds D1–D4 with promising binding affinity for the S. aureus MurE enzyme. The designed compounds were subjected to the extra-precision docking and binding free energy was calculated for complexes. Further, a 30-ns MD simulation was performed for D1/4C13 complex.

Purpose To describe the anatomic and visual outcomes of eyes undergoing reoperation after failed primary surgery for idiopathic macular hole. Design Prospective registry study. Participants One hundred three patients who had undergone failed macular hole surgery. Methods Unclosed idiopathic macular holes were identified from a large national prospective registry run by the Australian and New Zealand Society of Retinal Specialists. Unclosed idiopathic macular holes were defined as idiopathic macular holes that underwent vitrectomy surgery for the first time, but were never observed to close in the postoperative period. Surgeons were contacted to submit retrospectively details of subsequent management and long-term outcome of these eyes. Main Outcome Measures Macular hole closure; visual acuity (VA) change relative to baseline at 3, 12, and 24 months; and hole size at all time points. Results One hundred three patients with failed macular hole surgery were identified, among whom 53 underwent reoperation, 49 did not, and 1 was lost to follow-up. Macular hole closure was achieved in 45 of 53 patients (85%) undergoing revision surgery. Mean change in VA from baseline in eyes undergoing revision surgery versus eyes that did not was +2.8 letters versus −1.9 letters at 3 months ( P = 0.278), +8.2 letters versus −1.9 letters at 12 months ( P = 0.167), and +18.3 letters versus −3.4 letters at 24 months ( P = 0.022). Thirty-six percent of eyes with reoperated holes showed improved VA of 15 letters or more at 3 months after operation, increasing to 48% at 12 months and 65% at 2 years. Before revision surgery, mean macular hole size was observed to increase from 483 μm to 562 μm after failed primary surgery ( P = 0.046). Conclusions In eyes undergoing revision surgery, reoperation for unclosed macular holes was significantly better than observation, although these visual gains took some time to occur. The surgical success rate was lower than that for primary idiopathic macular hole. The selection criteria for revision surgery need to be defined.

Visual outcomes following diabetic vitrectomy have not previously been studied in an Australian population.This analysis aimed to determine the rate of, and factors associated with visual success following diabetic vitrectomy performed for Indigenous and non-Indigenous Australians, and investigate factors predisposing to early progression to diabetic retinopathy (DR) requiring vitrectomy.Retrospective, population-based audit.All patients undergoing vitrectomy for the complications of DR in South Australia (SA) and the Northern Territory (NT) between 2007 and 2011.Medical records were audited and data collected, including demographics, diabetic history, past treatment for DR, indication for vitrectomy and visual acuity pre and postoperatively.Visual success (gain of ≥15 ETDRS letters) at 6 and 12 months, postoperatively.A total of 495 diabetic vitrectomies, for 404 eyes of 335 patients were performed in SA and NT between 2007 and 2011. 77 (23%) patients requiring diabetic vitrectomy were Indigenous Australians. 87% of patients undergoing diabetic vitrectomy had stable or improved vision at 1 year, postoperatively. There was no significant difference between indigenous and non-indigenous eyes achieving visual success (P = 0.929). Timely preoperative laser treatment (P = 0.03) and preoperative visual acuity (P = 0.01) were the predominant factors associated with visual success.Indigenous patients are just as likely to have improved vision following diabetic vitrectomy as non-Indigenous Australians. However, the small subset of indigenous patients with blind eyes prior to vitrectomy are significantly less likely to improve from surgery. The underlying factors associated with poor outcomes in this group requires further exploration.

The aim of this paper is to solve the problems related to integrity, security, authenticity and non-repudiation of prevalent ERP based e-business application solution in Indian perspective. Traditional approaches and methodologies for implementing e-business solution have rarely achieved the requisite solution to the above problems even with the role based access control system. We have explored a methodology which emphasizes authentication in e-business with design of intelligent system. It ambitiously replaces the present day written signature authentication process with digital signatures having full compliance to integrity, security, authenticity and non-repudiation. The design also models in-depth functionalities, audit trail and keeps track of evidences of document tampering from any sources after the digital signature is placed in the system. The model is implemented successfully and is found to be at par with the prevalent written signature authentication system. We outline the plausible future work to model it for e-Governance system in Indian perspective.

We describe the abuse of a topical ocular anaesthetic in a contact lens wearer who developed microbial keratitis.

Cat scratch disease causes the majority of cases of neuroretinitis. Neuroretinitis is characterised by clinical features of papillitis, macular oedema and macular star. We report a case study of infection with Bartonella henselae most likely transmitted by a bull ant sting. The patient presented with blurred vision and reduced visual acuity after being stung by an ant in her garden some 7 days earlier. Further testing revealed positive serology to B henselae and the patient improved with appropriate treatment.

FRANZCO FRCOphthDepartment of Ophthalmology, FlindersMedical Centre and Flinders University,Bedford Park, South Australia, AustraliaE-mail address: bobwang@gmail.comSubmitted: 9 August 2010Revised: 24 December 2010Accepted for publication: 6 February2011This article describes a case of bilateralmultifocal central serous chorioretinopa-thy (CSCR) associated with endogenousCushing’s syndrome.

BACKGROUND To describe the morphology of a macular hole in the early postoperative period following vitrectomy with primary silicone oil tamponade. METHODS A case report with optical coherence tomography (OCT) scans prior to surgery, at 20 minutes postoperatively and then at 17 hours postoperatively. RESULTS OCT images of a 73-year-old woman with a stage 3 macular hole were obtained. At 20 minutes postoperatively, there was a reduction in intraretinal cysts and a reduction in macular hole size with elevated-open configuration. At 17 hours postoperatively, complete macular hole closure was noted. CONCLUSION OCT Images of a macular hole in the early postoperative period have been successfully obtained. Macular holes can close within 24 hours postoperatively and show morphological changes that may be predictive of closure within 20 minutes postoperatively.

The management of exudative retinal detachment in Coats disease can be very difficult with variable results. A case is presented of a 12 year old boy who was diagnosed with X-linked retinitis pigmentosa with an associated “Coat's Response”. The patient had a marked reduction in his left visual acuity due to intragel and subhyaloid haemorrhage as well as exudative retinal detachment. This was managed successfully with vitrectomy and endolaser, resulting in clearance of the haemorrhage and flattening of the retina. In our experience endolaser should be considered as viable therapeutic option in the management of this condition.

IT experts are feeling the strain of fast-paced, demanding work, and working measures for improved well-being are increasingly being established. One essential element of well-being is motivation. Motivation is critical in order to maintain smoothly working processes and quality in completed tasks. To detect and intercept situations where motivation begins to decrease, we need means to identify changes in motivation. To automatically detect such changes requires ways to measure motivation levels from data at hand. In this study, we present preliminary results towards defining measurable motivational factors. Our approach relies on emotional indicators of motivational change that can be detected automatically from software repositories. Our results show that the emotional content of commit comments and issue texts, extracted using sentiment analysis and emotion detection, is correlated to varying degrees with collaboration and risk metrics. We point to possibilities for future work on more sophisticated measures with more complex data.