Advancements in Nanotechnology for Enhanced Antifungal Drug Delivery: A Comprehensive Review.

Infections caused by fungi can be mildly bothersome or fatal, causing life-threatening conditions or even death. Antifungal drugs have used synthetic chemicals, organic compounds, and phytoconstituents in their formulations to treat fungal infections. Research into novel antifungal drugs has progressed more rapidly than into antibacterial treatments. This can be attributed to the low resistance of fungal infections to antifungal bioactivities and the relatively low incidence of these diseases. Carrier systems based on nanotechnology have generated much interest recently because of the incredible potential of these systems. By using nanoarchitecture as a better carrier and drug delivery system (DDS), we can have greater antifungal effectiveness, bioavailability, targeted action, and less cytotoxicity, a development made possible using nanotechnology. This review discusses various nanocarrier-based technologies in addition to other nanotechnological methods. These include liposomes, transfersomes, ethosomes, niosomes, dendrimers, polymeric nanoparticles, polymer nanocomposites, metallic nanoparticles, carbon nanomaterials, etc. This review focused on general information regarding fungi infections, different antifungal agent types and mechanisms of action, and an overview of formulation strategies such as nanotechnology systems, which are frequently researched for antifungal therapies. We concluded that new drug delivery systems are crucial to delivering antifungal medicines to their target site with the optimum concentration. The researchers also concentrated on these innovative drug delivery systems, which primarily focus on regulating and maintaining the release of antifungal drugs.

Intraocular Pressure Changes While Reading Smartphone Digital Text Versus Printed Text in Healthy Individuals and those with Glaucoma.

PRCIS: Reading results in a rise in intraocular pressure (IOP) which is greater while using smartphones compared with printed text among healthy and individuals with medically controlled primary open angle glaucoma (POAG). PURPOSE: To compare the effect of reading for 30 minutes using smartphone and printed text on IOP. PATIENTS AND METHODS: Sixty healthy volunteers and 22 patients with medically controlled POAG were asked to perform reading tasks using printed text followed by digital (smartphone) text under standardized conditions. IOP assessment was done using a rebound tonometer at baseline and subsequently at 10, 20, and 30 minutes of reading and 10 and 20 minutes post completion of reading tasks. IOP variations from baseline were measured and compared. Paired and independent ' T ' test analysis was performed to study IOP variations, and a P -value <0.05 was considered statistically significant. RESULTS: The mean baseline IOP among volunteers and patients withPOAG was 14.58 (±2.91) and 15.02 (±2.18) mmHg, respectively. There was a rise in IOP in all participants with reading using either of the modalities, which normalized after 20 minutes of cessation. There was a statistically significant difference in rise in IOP from baseline between the 2 modalities (printed text reading and smartphone reading) at 20 minutes {+0.78 & +2.01 ( P =0.002)} and 30 minutes {+0.64 & +1.72 ( P =0.004)} among healthy volunteers and at 20 minutes {+0.78 & +2.01 ( P =0.002)} among POAG patients. CONCLUSION: Reading is associated with the rise in IOP in both healthy volunteers and POAG individuals. The IOP rise is more marked with smartphone compared with printed text reading.

Utility of bone marrow examination in retinoblastoma and their correlation with hematological features.

Retinoblastoma makes up about 3% of all childhood malignancies. The frequency of metastatic retinoblastoma ranges from 4.8 to 11%. Assessing the bone marrow status of newly diagnosed patients is crucial because of the advantages of autologous bone marrow transplants for high-risk patients. This study aimed to determine the utility of bone marrow examination in cases of retinoblastoma and its correlation with hematological findings. This retrospective study was conducted at the Department of Pathology, King George's Medical University, Lucknow, India. A total of 34 cases of retinoblastoma with bone marrow examination were included in the study. Bone marrow infiltration was present in 17.65% (6/34) cases of retinoblastoma. Bone marrow aspirate myelogram showed that marrow metastasis in retinoblastoma was significantly linked with a reduced percentage of total myeloid cells (p=0.001) and segmented cells (p=0.006). The present study demonstrated that 15% (3/20) of retinoblastoma patients previously classified as nonmetastatic before bone marrow examination (stages I to III based on histology, imaging, and bone scan) had bone marrow metastases following bone marrow examination and were upgraded to stage IV. To conclude, a diligent and exhaustive search for metastatic cells in bone marrow is advised if the myelogram shows a reduced percentage of total myeloid and segmented cells. All stage II and stage III cases of retinoblastoma must undergo bone marrow examination for early metastasis detection, as it may result in an upgrade to stage IV disease, impacting the prognosis and necessitating distinct treatment modalities.

Atomistic to Mesoscopic Modelling of Thermophysical Properties of Graphene-Reinforced Epoxy Nanocomposites.

This research addresses the need for a multiscale model for the determination of the thermophysical properties of nanofiller-enhanced thermoset polymer composites. Specifically, we analyzed the thermophysical properties of an epoxy resin containing bisphenol-A diglyceryl ether (DGEBA) as an epoxy monomer and dicyandiamide (DICY) and diethylene triamine (DETA) as cross-linking agents. The cross-linking process occurs at the atomistic scale through the formation of bonds among the reactive particles within the epoxy and hardener molecules. To derive the interatomic coarse-grained potential for the mesoscopic model and match the density of the material studied through atomic simulations, we employed the iterative Boltzmann inversion method. The newly developed coarse-grained molecular dynamics model effectively reproduces various thermophysical properties of the DGEBA-DICY-DETA resin system. Furthermore, we simulated nanocomposites made of the considered epoxy additivated with graphene nanofillers at the mesoscopic level and verified them against continuum approaches. Our results demonstrate that a moderate amount of nanofillers (up to 2 wt.%) increases the elastic modulus and thermal conductivity of the epoxy resin while decreasing the Poisson's ratio. For the first time, we present a coarse-grained model of DGEBA-DICY-DETA/graphene materials, which can facilitate the design and development of composites with tunable thermophysical properties for a potentially wide range of applications, e.g., automotive, aerospace, biomedical, or energy ones.

Metabolic footprints in phosphate-starved plants.

Plants' requirement of Phosphorus (P) as an essential macronutrient is obligatory for their normal growth and metabolism. Besides restricting plants' primary growth, P depletion affects both primary and secondary metabolism and leads to altered levels of sugars, metabolites, amino acids, and other secondary compounds. Such metabolic shifts help plants optimize their metabolism and growth under P limited conditions. Under P deprivation, both sugar levels and their mobilization change that influences the expression of Pi starvation-inducible genes. Increased sugar repartitioning from shoot to root help root growth and organic acids secretion that in turn promotes phosphate (Pi) uptake from the soil. Other metabolic changes such as lipid remodeling or P reallocation from older to younger leaves release the P from its bound forms in the cell. In this review, we summarize the metabolic footprinting of Pi-starved plants with respect to the benefits offered by such metabolic changes to intracellular Pi homeostasis.

Netarsudil monotherapy as the initial treatment for open-angle glaucoma and ocular hypertension in Indian patients: A real-world evaluation of efficacy and safety.

Purpose: Glaucoma is the second leading cause of blindness worldwide, affecting more than 64 million people aged 40-80. The best way to manage primary open-angle glaucoma (POAG) is by lowering the intraocular pressure (IOP). Netarsudil is a Rho kinase inhibitor, the only class of antiglaucoma medications that reorganizes the extracellular matrix to improve the aqueous outflow through the trabecular pathway. Methods: An open-label, real-world, multicentric, observation-based 3-month study was performed for assessing the safety and ocular hypotensive efficacy of netarsudil ophthalmic solution (0.02% w/v) in patients with elevated IOP. Patients were given netarsudil ophthalmic solution (0.02% w/v) as a first-line therapy. Diurnal IOP measurements, best-corrected visual acuity, and adverse event assessments were recorded at each of the five visits (Day-1: screening day and first dosing day; subsequent observations were taken at 2 weeks, 4 weeks, 6 weeks, and 3 months). Results: Four hundred and sixty-nine patients from 39 centers throughout India completed the study. The mean IOP at baseline of the affected eyes was 24.84 ± 6.39 mmHg (mean ± standard deviation). After the first dose, the IOP was measured after 2, 4, and 6 weeks, with the final measurement taken at 3 months. The percentage reduction in IOP in glaucoma patients after 3 months of once-daily netarsudil 0.02% w/v solution use was 33.34%. The adverse effects experienced by patients were not severe in the majority of cases. Some adverse effects observed were redness, irritation, itching, and others, but only a small number of patients experienced severe reactions, as reported in a decreasing order: redness > irritation > watering > itching > stinging > blurring. Conclusion: We found that netarsudil 0.02% w/v solution monotherapy when used as the first-line treatment in primary open-angle glaucoma and ocular hypertension was both safe and effective.

Silencing of SlSPX1 and SlSPX2 promote growth and root mycorrhization in tomato (Solanum lycopersicum L.) seedlings.

Owing to the essential requirement of phosphorus (P) for growth and development, plants tightly control inorganic phosphate (Pi) homeostasis. SPX-PHR regulatory circuit not only control phosphate homeostasis responses but also root mycorrhization by arbuscular mycorrhiza (AM) fungi. Besides sensing Pi deficiency, SPX (SYG1/Pho81/XPR1) proteins also control the transcription of P starvation inducible (PSI) genes by blocking the activity of PHR1 (PHOSPHATE STARVATION RESPONSE1) homologs in plants under Pi-sufficient conditions. However, the roles of SPX members in Pi homeostasis and AM fungi colonization remain to be fully recognized in tomato. In this study, we identified 17 SPX-domain containing members in the tomato genome. Transcript profiling revealed the high Pi-specific nature of their activation. Four SlSPX members have also induced in AM colonized roots. Interestingly, we found that SlSPX1 and SlSPX2 are induced by P starvation and AM fungi colonization. Further, SlSPX1 and SlSPX2 exhibited varying degrees of interaction with the PHR homologs in this study. Virus-induced gene silencing-based (VIGS) transcript inhibition of these genes alone or together promoted the accumulation of higher total soluble Pi in tomato seedlings and improved their growth. It also enhanced AM fungi colonization in the roots of SlSPX1 and SlSPX2 silenced seedlings. Overall, the present study provides evidence in support of SlSPX members being good candidates for improving AM fungi colonization potential in tomato.

The impact of physicochemical features of carbon electrodes on the capacitive performance of supercapacitors: a machine learning approach.

Hybrid electric vehicles and portable electronic systems use supercapacitors for energy storage owing to their fast charging/discharging rates, long life cycle, and low maintenance. Specific capacitance is regarded as one of the most important performance-related characteristics of a supercapacitor's electrode. In the current study, Machine Learning (ML) algorithms were used to determine the impact of various physicochemical properties of carbon-based materials on the capacitive performance of electric double-layer capacitors. Published experimental datasets from 147 references (4899 data entries) were extracted and then used to train and test the ML models, to determine the relative importance of electrode material features on specific capacitance. These features include current density, pore volume, pore size, presence of defects, potential window, specific surface area, oxygen, and nitrogen content of the carbon-based electrode material. Additionally, categorical variables as the testing method, electrolyte, and carbon structure of the electrodes are considered as well. Among five applied regression models, an extreme gradient boosting model was found to best correlate those features with the capacitive performance, highlighting that the specific surface area, the presence of nitrogen doping, and the potential window are the most significant descriptors for the specific capacitance. These findings are summarized in a modular and open-source application for estimating the capacitance of supercapacitors given, as only inputs, the features of their carbon-based electrodes, the electrolyte and testing method. In perspective, this work introduces a new wide dataset of carbon electrodes for supercapacitors extracted from the experimental literature, also giving an instance of how electrochemical technology can benefit from ML models.

Mesoscopic Modeling and Experimental Validation of Thermal and Mechanical Properties of Polypropylene Nanocomposites Reinforced By Graphene-Based Fillers.

The development of nanocomposites relies on structure-property relations, which necessitate multiscale modeling approaches. This study presents a modeling framework that exploits mesoscopic models to predict the thermal and mechanical properties of nanocomposites starting from their molecular structure. In detail, mesoscopic models of polypropylene (PP)- and graphene-based nanofillers (graphene (Gr), graphene oxide (GO), and reduced graphene oxide (rGO)) are considered. The newly developed mesoscopic model for the PP/Gr nanocomposite provides mechanistic information on the thermal and mechanical properties at the filler-matrix interface, which can then be exploited to enhance the prediction accuracy of traditional continuum simulations by calibrating the thermal and mechanical properties of the filler-matrix interface. Once validated through a dedicated experimental campaign, this multiscale model demonstrates that with the modest addition of nanofillers (up to 2 wt %), the Young's modulus and thermal conductivity show up to 35 and 25% enhancement, respectively, whereas the Poisson's ratio slightly decreases. Among the different combinations tested, the PP/Gr nanocomposite shows the best mechanical properties, whereas PP/rGO demonstrates the best thermal conductivity. This validated mesoscopic model can contribute to the development of smart materials with enhanced mechanical and thermal properties based on polypropylene, especially for mechanical, energy storage, and sensing applications.

Reliability of Smart Phone Photographs for School Eye Screening.

Smartphone photographs capturing Bruckner's reflex have demonstrated reliability in identifying amblyogenic conditions in children. Assessing visual acuity for screening has been the traditional method since the inception of school screening. The present study aims to assess the reliability of smartphone photographs in detecting ocular morbidities in school children and to compare it with traditional vision screening. Two thousand five hundred and twenty school children underwent vision screening and smartphone cameraphotography by a trained research assistant followed by a comprehensive eye examination of all children by an ophthalmologist. Children with unaided visual acuity less than 6/12 in either of the eyes were graded as abnormal. Based upon the characteristics of the Bruckner's reflex, the photographs were graded as normal or abnormal by two investigators blinded to the clinical findings. Statistical analysis was performed to compare the sensitivity and specificity of traditional vision screening and photograph based screening, considering comprehensive eye examination as the gold standard. The sensitivity and specificity of vision screening was 81.88% and 97.35% whereas for photographs it was 94.69% and 98.85% respectively. When the two methods were compared, the p value was <0.05. We conclude that smartphone photography is better than traditional vision screening for detecting ocular morbidities in school children.

Host SPX-PHR regulatory circuit: the molecular dynamo steering mycorrhization in plants.

KEY MESSAGE: We highlight the newly emerged roles of plant SPX-PHR proteins beyond phosphate starvation responses in controlling arbuscular mycorrhizal colonization success in roots.

Binocular summation in comitant exotropia: Change after surgery.

PURPOSE: To assess the change in binocular summation (BiS) in comitant exotropia (XT) after strabismus surgery. METHODS: This is a prospective study on 20 patients who underwent surgery for comitant XT over a one year period. Patients with sensory exotropia and nystagmus were excluded. Best-corrected visual acuity (VA) and contrast sensitivity (CS) of both eyes separately and together (binocularly) were recorded. BiS score was calculated as binocular score minus better eye score. BiS score at the end of 3 months was compared with the preoperative data. RESULTS: The mean ± SD of BiS score increased from 2.95 ± 0.88 to 4.55 ± 0.68 (P-value < 0.0001) for VA (on ETDRS letters) and from 2.75 ± 0.44 to 4.5 ± 0.76 (P-value < 0.001 for CS (on Pelli-Robson chart) after surgery. CONCLUSION: There is significant improvement in BiS in XT after strabismus surgery. Authors recommend its inclusion in evaluation of functional outcome of XT surgery.

The enhanced phosphorus use efficiency in phosphate-deficient and mycorrhiza-inoculated barley seedlings involves activation of different sets of PHT1 transporters in roots.

MAIN CONCLUSION: Transcriptional activation of subfamily II PHT1 members in roots is associated with the enhanced phosphorus use efficiency and growth promotion of barley seedlings inoculated with Glomus species. The arbuscular mycorrhizal (AM) fungi symbiotic associations in cereal crops are known to regulate growth in cultivar-specific manner and induce phosphate (Pi) transporters (PHT1) in roots. In the present study, we observed that both AM colonization of roots by Glomus species and phosphate starvation enhanced phosphorus use efficiency (PUE) in barley seedlings. Our search for the full complement of PHT1 members in the recently sequenced barley genome identified six additional genes, totaling their number to 17. Both AM colonization and Pi starvation triggered activation of common as well as different PHT1s. Pi starvation led to the robust upregulation of HvPHT1;6.2/6.3 at 7d and weak activation of HvPHT1;1 in shoots at 3d time-point. In roots, only HvPHT1;1, HvPHT1;6.2/6.3, HvPHT1;7, HvPHT1;8, HvPHT1;11.2 and HvPHT12 were induced at least one of the time-points. AM colonization specifically upregulated HvPHT1;11, HvPHT1;11.2, HvPHT1;12 and HvPHT1;13.1/13.2, members belonging to subfamily II, in roots. Sucrose availability seems to be obligatory for the robust activation of HvPHT1;1 as unavailability of this metabolite generally weakened its upregulation under Pi starvation. Intriguingly, lack of sucrose supply also led to induction of HvPHT1;5, HvPHT1;8, and HvPHT1;11.2 in either roots or shoot or both. The mRNA levels of HvPHT1;5 and HvPHT1;11.2 were not severely affected under combined deficiency of Pi and sucrose. Taken together, this study not only identify additional PHT1 members in barley, but also ascertain their AM, Pi and sucrose-specific transcript accumulation. The beneficial role of AM fungi in the promotion of PUE and barley seedlings' growth is also demonstrated.

Comparison between two intravitreal injection techniques with respect to fluid reflux, intraocular pressure, and therapeutic effect.

CONTEXT: Effect of fluid reflux on intraocular pressure (IOP) and therapeutic benefits. AIMS: The aim of this study is to compare two intravitreal injection techniques in terms of fluid reflux, short-term IOP changes, and therapeutic effect. SETTINGS AND DESIGN: A prospective, double-blinded, randomized interventional study. SUBJECTS AND METHODS: Sixty eyes were randomly allocated to two groups (direct intravitreal injection technique and oblique intravitreal injection technique). IOP was measured before and immediately after the injection of 0.1 ml comprising of bevacizumab (1.25 mg/0.05 ml) and dexamethasone (0.2 mg/0.05 ml) and then at 30 min after the injection. Occurrence and amount of vitreous reflux were recorded. Best-corrected visual acuity (BCVA) and central macular thickness (CMT) were assessed preinjection and 6 weeks postinjection. RESULTS: IOP (mmHg ± standard deviation) increased significantly immediately after injection to 24.30 ± 3.02 (direct intravitreal injection) and 31.50 ± 3.49 (oblique intravitreal injection). These pressure rise differed significantly between both groups (mean difference: 7.2, P < 0.0001). Thirty minutes after injection, there was no significant difference in IOP increase between the groups. Occurrence and amount of fluid reflux were significantly higher with direct intravitreal injection. There was no significant difference in BCVA and CMT outcome between both groups. CONCLUSIONS: Direct intravitreal injection technique has lower rise in IOP and higher incidence of fluid reflux than the oblique intravitreal technique. Fluid reflux does not cause a therapeutic compromise in terms of BCVA or CMT changes, so the reflux fluid must be the vitreous not the drug. Thus, direct injection technique seems to be the preferred technique.

Identification, structure analysis, and transcript profiling of purple acid phosphatases under Pi deficiency in tomato (Solanum lycopersicum L.) and its wild relatives.

Purple acid phosphatases (PAPs), a family of metallo-phosphoesterase enzymes, are involved in phosphorus nutrition in plants. In this study, we report that the tomato genome encodes 25 PAP members. Physio-biochemical analyses revealed relatively lower total root-associated acid phosphatase activity in the seedlings of Solanum pimpinellifolium than their cultivated tomato seedlings under Pi deficiency. Scrutiny of their transcript abundance shows that most of PAPs are activated, although to varying levels, under Pi deficiency in tomato. Further investigation demonstrates that the magnitude of induction of phosphate starvation inducible root-associated PAP homologs remains lower in the Pi-starved S. pimpinellifolium seedlings, hence, accounting for the lower acid phosphatase activity in this wild relative. Examination of their amino acid sequences revealed significant variation in their substrate-specificity defining residues. Among all members, only SlPAP15 possesses the critical lysine residue (R337) and atypical REKA motif in its C-terminal region. Homology modeling and docking studies revealed that ADP and ATP are preferred substrates of SlPAP15. We also identified other amino acid residues present in the vicinity of the active site, possibly facilitating such physical interactions. Altogether, the results presented here will help in the functional characterization of these genes in the tomato in the future.