Relationship between macular perfusion and lesion distribution in diabetic retinopathy.

BACKGROUND/OBJECTIVES: To assess the relationship between macular vessel density metrics and foveal avascular zone (FAZ) characteristics on optical coherence tomography angiography (OCTA) and lesion distribution in eyes with diabetic retinopathy (DR). SUBJECTS/METHODS: Patients with DR who underwent both Optos ultrawidefield (UWF) pseudocolor imaging and macular OCTA (Cirrus Angioplex, 6 × 6 mm) were included in this cross-sectional observational study. The distribution of DR lesions was assessed by comparing each of the peripheral ETDRS extended fields (3-7) against their corresponding ETDRS field, hence eyes were defined as either having predominantly peripheral lesions (PPL) or predominantly central lesions (PCL). En face OCTA images from the superficial and deep capillary plexuses (SCP and DCP) were then analysed using Image J software. Perfusion density (PD), vessel length density (VLD), and fractal dimensions (FD) were calculated following binarization and skeletonization of the images. RESULTS: Out of 344 eyes, 116 (33.72%) eyes had PPL and 228 (66.28%) eyes had PCL. For all DRSS levels, VLD, PD, and FD were not significantly different between eyes with PPL and PCL. The FAZ in eyes with PPL, however, was found to be more circular in shape compared to eyes with PCL (p = 0.037). CONCLUSION: Although the presence of PPL has been associated with a higher risk for diabetic retinopathy progression, the macular perfusion is similar in eyes with PPL and PCL. The FAZ is more circular in eyes with PPL, but the clinical relevance of this difference remains to be defined.

Biotinylated Photocleavable Semiconductor Colloidal Quantum Dot Supraparticle Microlaser.

Luminescent supraparticles of colloidal semiconductor nanocrystals can act as microscopic lasers and are hugely attractive for biosensing, imaging, and drug delivery. However, biointerfacing these to increase functionality while retaining their main optical properties remains an unresolved challenge. Here, we propose and demonstrate red-emitting, silica-coated CdSxSe1-x/ZnS colloidal quantum dot supraparticles functionalized with a biotinylated photocleavable ligand. The success of each step of the synthesis is confirmed by scanning electron microscopy, energy dispersive X-ray and Fourier transform infrared spectroscopy, ζ-potential, and optical pumping measurements. The capture and release functionality of the supraparticle system is proven by binding to a neutravidin functionalized glass slide and subsequently cleaving off after UV-A irradiation. The biotinylated supraparticles still function as microlasers; e.g., a 9 µm diameter supraparticle has oscillating modes around 625 nm at a threshold of 58 mJ/cm2. This work is a first step toward using supraparticle lasers as enhanced labels for bionano applications.

Inappropriate Use of Steroids in Superficial Dermatophytosis: An Uncommon Case of Erythroderma.

Erythroderma is a dermatological emergency presenting with generalized erythema and scaling involving <90% of the body surface.1 There are various causes of erythroderma, such as psoriasis, atopic dermatitis, phytophotodermatitis, pityriasis rubra pilaris, pemphigus foliaceus, cutaneous T-cell lymphoma, and drug eruptions.2 However, erythroderma induced by dermatophytosis is encountered rarely. We, here, describe a case of erythroderma developed secondary to extensive dermatophytosis.

Climate change effects on aquaculture production and its sustainable management through climate-resilient adaptation strategies: a review.

Aquaculture witnessed a remarkable growth as one of the fastest-expanding sector in the food production industry; however, it faces serious threat from the unavoidable impacts of climate change. Understanding this threat, the present review explores the consequences of climate change on aquaculture production and provides need based strategies for its sustainable management, with a particular emphasis on climate-resilient approaches. The study examines the multi-dimensional impacts of climate change on aquaculture which includes the shifts in water temperature, sea-level rise, ocean acidification, harmful algal blooms, extreme weather events, and alterations in ecological dynamics. The review subsequently investigates innovative scientific interventions and climate-resilient aquaculture strategies aimed at strengthening the adaptive capacity of aquaculture practices. Some widely established solutions include selective breeding, species diversification, incorporation of ecosystem-based management practices, and the implementation of sustainable and advanced aquaculture systems (aquaponics and recirculating aquaculture systems (RAS). These strategies work towards fortifying aquaculture systems against climate-induced disturbances, thereby mitigating risks and ensuring sustained production. This review provides a detailed insight to the ongoing discourse on climate-resilient aquaculture, emphasizing an immediate need for prudent measures to secure the future sustainability of fish food production sector.

Unveiling the Allergy-Meniere Connection: Exploring the Impact of Allergen Positivity on Meniere's Disease Severity.

Meniere's Disease is a rare ear disorder that can cause severe morbidity to the patient and has no definitive treatment to date. Endolymphatic hydrops is the critical event. Though symptomatology is well understood, the exact etiology of Endolymphatic hydrops attack is still unclear. Twenty-five consecutive patients of Meniere's Disease diagnosed in the Vertigo clinic aged 12 to 70 years were included. Their allergic status was evaluated using a skin prick test. Allergic and non-allergic patients were then identified. Comparison between the two groups was made to identify the effect of allergy on the severity of symptoms using vertigo scales, Functional level scale, Dizziness handicap index, and Pure tone average staging. The prevalence of allergy among Meniere's Disease patients was 56%. The most common allergen found in our study was tyrophagus(n = 8). Polysensitization was more common(n = 12). Airborne allergens were more common than food allergens. There was no significant relationship between the severity scales and the allergen positivity status (p > 0.05). The prevalence of allergy is more among patients with Meniere's Disease. The Endolymphatic sac is allergy prone. The occurrence of endolymphatic hydrops may be due to a cross-reaction of allergen-induced IgE antibodies to self-antigen. Management of the specific allergen may help decrease symptomatology in these patients. Allergen-specific therapies have a promising role in the treatment of allergic conditions and provide a long-term symptom-free period in affected individuals. This can be applied in patients with Meniere's Disease having associated allergic features based on their skin prick test results.

The Role of Trans Oral Robotic Surgery in the Carcinoma of Unknown Primary: A New Evidence in the Horizon?

The detection of the primary site in Carcinoma of Unknown Primary (CUP) is a challenging task which can significantly alter the course of management and also prognosis. Various modalities have been assessed with varying sensitivity and specificity. Imaging and cytological diagnosis have formed a key part of the diagnostic algorithm of CUP. Trans Oral Robotic Surgery offers the advantage of being both diagnostic as well as therapeutic with promising sensitivity and specificity and can form an integral part in the management of CUP. A prospective study was carried out at a tertiary care centre over a period of one year. Patients with unilateral neck swelling which was histopathologically proven squamous cell carcinoma neck metastasis were included in the study. They were evaluated with endoscopy and radiology according to the standard algorithm. When these failed to detect the primary, the patients underwent ipsilateral radical tonsillectomy and tongue base mucosal wedge biopsy via TORS. Post-operative histopathological examination was done on the resected specimens to detect the primary site. Transoral Robotic Surgery was able to localise primary in 50% of the patients enrolled in the study. Out of the primary site identified by TORS; 55.56% were located in the tonsil and 44.4% in the tongue base. TORS can offer promising detection rates of the occult primary in CUP and should form an integral part of the diagnostic algorithm.

Construction of a novel ternary synergistic CuFe2O4-SnO2-rGO heterojunction for efficient removal of cyanide from contaminated water.

Many industrial effluents release cyanide, a well-known hazardous and bio-recalcitrant pollutant, and thus, the treatment of cyanide wastewater is a major challenge. In the current study, a CuFe2O4-SnO2-rGO nanocomposite was synthesized to remove cyanide from an aqueous system. The structural and morphological characterizations of the nanomaterials were investigated by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and energy dispersive spectra (EDX) analysis. The results revealed that almost 97.7% cyanide removal occurred using the nanocomposite at an initial concentration of 100 mg L-1 within 1 h. The experimental data were fitted to various adsorption models, among which the Langmuir model fitted the data very well, confirming the monolayer adsorption process. The kinetic investigation revealed that the cyanide adsorption process followed a pseudo-second-order kinetic model, indicating a chemisorption process with a high cyanide adsorption capacity of 114 mg g-1. The result of the intraparticulate diffusion model fitting revealed a decreasing slope value (K) from stage 1 to stage 2, indicating that external mass transfer is the predominating step. Moreover, the CuFe2O4-SnO2-rGO nanocomposite shows excellent reusability.

Quality by Design Tool Assessed Ultraperformance Liquid Chromatography Method for the Analysis of Remogliflozin and Teneligliptin in Oral Dosage Form.

The UPLC methodology was used to establish a method for determining the qualitative and quantitative content of teneligliptin and remogliflozin tablets in oral solid dose form, as no simultaneous method was available. The developed liquid chromatography method consists of an X-Bridge C18 100 mm × 3.5 mm, 2.1 mm column with an economical 0.2 mL/min flow rate. A wavelength of 248 nm was used for detection, and the temperature of the column compartment was 30 °C. The method was evaluated using a static tool quality by design after it was validated as per the regulations. The data from validation result in linearity for both analytes with a correlation coefficient of more than 0.999. The accuracy data were found from a minimum of 98.1 to a maximum of 100.9. All of the validation results met the acceptance criteria. The stability of the analytical solutions proved for 24 h at bench and refrigerator temperatures. Studies of force degradation proved the stability indicating the nature of the method. A factorial design was used to evaluate the method performance.

Internal limiting membrane separation and posterior vitreous hyperreflective dots: novel OCT findings in Purtscher-like retinopathy.

BACKGROUND: Purtscher or Purtscher-like retinopathy is diagnosed by retinal hemorrhages and areas of retinal whitening on fundus examination, as well as a reduction in visual acuity due to microvascular occlusion of the precapillary retinal arterioles. We describe novel optical coherence tomography (OCT) findings of internal limiting membrane (ILM) separation and posterior hyperreflective dots in a case of Purtscher-like retinopathy in this report. METHODS: A 33-year-old man with acute pancreatitis and alcohol-induced liver disease presented to the retina department complaining of four days of painless vision loss in both eyes. Both eyes' anterior segment examination and intraocular pressure were normal. Dilated fundus examination of both eyes revealed confluent areas of retinal whitening, hemorrhages, and cotton-wool spots over the posterior pole, indicating Purtscher-like retinopathy. OCT scans through the macula revealed dense inner retinal reflectivity, thickening, and loss of retinal layer stratification, as well as outer retinal layer shadowing and islands of ILM separation, posterior vitreous hyperreflective dots, and minimal subfoveal fluid, all of which corresponded to areas of retinal whitening on fundus photographs. The patient was given a brief course of systemic steroids. RESULTS: On the tenth day after the presentation, visual acuity in the right eye had improved to 6/18 and finger counting at 1 m in the left eye. The retinal findings had faded. The retina had reverted to its normal thickness on the OCT scans, with minimal hyperreflectivity remaining. The ILM separation and posterior vitreous hyperreflective dots were no longer present. CONCLUSION: Following Purtscher or Purtscher-like retinopathy, we believe inflammation could play a major role in the development of these two novel OCT findings. This case offers an additional perspective on the underlying mechanisms responsible for the retinal manifestations observed in Purtscher or Purtscher-like retinopathy.

Antidiabetic Evaluation of Kigelia pinnata Root Bark Extract in Streptozotocin-Induced Type-2 Diabetes Model of Rats.

Diabetes mellitus (DM) is the most common endocrine disorder characterized by increased blood glucose levels resulting from defective insulin secretion, resistance to insulin action, or both. DM is often associated with severe complications, and there is an increasing appreciation that cognitive function declines in DM. The aim of this research work was to evaluate Kigelia pinnata root bark extract in Streptozotocin (STZ)-induced type-2 diabetes. Experimental diabetes was induced by a single administration of STZ (60 mg/kg, intraperitoneal [i.p.]), immediately after the STZ administration, and all animals were fed with normal food and water. Nicotinamide was administered (120 mg/kg, i.p.) 15 min before STZ. The development of hyperglycemia was confirmed by the elevated blood glucose levels determined at fixed intervals, which was confirmed by measuring fasting blood glucose levels in rats' blood taken from the tail vein. Supplementation with ethanolic extract of K. pinnata root bark (EEKP) significantly reduced the elevated blood glucose in STZ-induced hyperglycemia in rats. EEKP significantly restored the biochemical and antioxidant defense system. On the final day of the protocol, the extract also reduced inflammatory cytokines in the blood serum.

Dual active pyrimidine-based carbocyclic nucleoside derivatives: synthesis, and in silico and in vitro anti-diabetic and anti-microbial studies.

Diabetes mellitus (DM) is a chronic metabolic disorder marked by high blood glucose levels, impairing glucose production in the body. Its prevalence has steadily risen over the past decades, leading to compromised immunity and heightened susceptibility to microbial infections. Immune dysfunction associated with diabetes raises vulnerability, while neuropathy dulls sensation in the extremities, reducing injury awareness. Hence, the development of novel chemical compounds for anti-diabetic and anti-infective treatments is imperative to mitigate adverse effects. In this study, we designed and synthesized pyrimidine-based carbocyclic nucleoside derivatives with C-4 substitution to assess their potential in inhibiting α-glucosidase for managing diabetes mellitus (DM) and microbial infections. Compounds 8b and 10a displayed promising IC50 values against α-glucosidase (43.292 nmol and 48.638 nmol, respectively) and noteworthy docking energies (-9.4 kcal mol-1 and -10.3 kcal mol-1, respectively). Additionally, compounds 10a and 10b exhibited better antimicrobial activity against Bacillus cereus, with the zone of inhibition values of 2.2 ± 0.25 mm and 1.4 ± 0.1 mm at a 100 µl concentration, respectively. Compound 10a also exhibited a modest zone of inhibition of 1.2 ± 0.15 mm against Escherichia coli at 100 µl.

Synthesis and Trace-Level Quantification of Mutagenic and Cohort-of-Concern Ciprofloxacin Nitroso Drug Substance-Related Impurities (NDSRIs) and Other Nitroso Impurities Using UPLC-ESI-MS/MS-Method Optimization Using I-Optimal Mixture Design.

Globally, the pharmaceutical industry has been facing challenges from nitroso drug substance-related impurities (NDSRIs). In the current study, we synthesized and developed a rapid new UPLC-MS/MS method for the trace-level quantification of ciprofloxacin NDSRIs and a couple of N-nitroso impurities simultaneously. (Q)-SAR methodology was employed to assess and categorize the genotoxicity of all ciprofloxacin N-nitroso impurities. The projected results were positive, and the cohort of concern (CoC) for all three N-nitroso impurities indicates potential genotoxicity. AQbD-driven I-optimal mixture design was used to optimize the mixture of solvents in the method. The chromatographic resolution was accomplished using an Agilent Poroshell 120 Aq-C18 column (150 mm × 4.6 mm, 2.7 µm) in isocratic elution mode with 0.1% formic acid in a mixture of water, acetonitrile, and methanol in the ratio of 475:500:25 v/v/v at a flow rate of 0.5 mL/min. Quantification was carried out using triple quadrupole mass detection with electrospray ionization (ESI) in a multiple reaction monitoring technique. The finalized method was validated successfully, affording ICH guidelines. All N-nitroso impurities revealed excellent linearity over the concentration range of 0.00125-0.0250 ppm. The Pearson correlation coefficient of each N-nitroso impurity was >0.999. The method accuracy recoveries ranged from 93.98 to 108.08% for the aforementioned N-nitrosamine impurities. Furthermore, the method was effectively applied to quantify N-nitrosamine impurities simultaneously in commercially available formulated samples, with its efficiency recurring at trace levels. Thus, the current method is capable of determining the trace levels of three N-nitroso ciprofloxacin impurities simultaneously from the marketed tablet dosage forms for commercial release and stability testing.

Microbial strategies for copper pollution remediation: Mechanistic insights and recent advances.

Environmental contamination is aninsistent concern affecting human health and the ecosystem. Wastewater, containing heavy metals from industrial activities, significantly contributes to escalating water pollution. These metals can bioaccumulate in food chains, posing health risks even at low concentrations. Copper (Cu), an essential micronutrient, becomes toxic at high levels. Activities like mining and fungicide use have led to Copper contamination in soil, water, and sediment beyond safe levels. Copper widely used in industries, demands restraint of heavy metal ion release into wastewater for ecosystem ultrafiltration, membrane filtration, nanofiltration, and reverse osmosis, combat heavy metal pollution, with emphasis on copper.Physical and chemical approaches are efficient, large-scale feasibility may have drawbackssuch as they are costly, result in the production of sludge. In contrast, bioremediation, microbial intervention offers eco-friendly solutions for copper-contaminated soil. Bacteria and fungi facilitate these bioremediation avenues as cost-effective alternatives. This review article emphasizes on physical, chemical, and biological methods for removal of copper from the wastewater as well asdetailing microorganism's mechanisms to mobilize or immobilize copper in wastewater and soil.

A long-term storable gel-laden chip composite built in a multi-well plate enablingin situcell encapsulation for high-throughput liver model.

Hydrogels are widely used as scaffold materials for constructingin vitrothree-dimensional microphysiological systems. However, their high sensitivity to various external cues hinders the development of hydrogel-laden, microscale, and high-throughput chips. Here, we have developed a long-term storable gel-laden chip composite built in a multi-well plate, which enablesin situcell encapsulation and facilitates high-throughput analysis. Through optimized chemical crosslinking and freeze-drying method (C/FD), we have achieved a high-quality of gel-laden chip composite with excellent transparency, uniform porosity, and appropriate swelling and mechanical characteristics. Besides collagen, decellularized extracellular matrix with tissue-specific biochemical compound has been applied as chip composite. As a ready-to-use platform,in situcell encapsulation within the gel has been achieved through capillary force generated during gel reswelling. The liver-mimetic chip composite, comprising HepG2 cells or primary hepatocytes, has demonstrated favorable hepatic functionality and high sensitivity in drug testing. The developed fabrication process with improved stability of gels and storability allows chip composites to be stored at a wide range of temperatures for up to 28 d without any deformation, demonstrating off-the-shelf products. Consequently, this provides an exceptionally simple and long-term storable platform that can be utilized for an efficient tissue-specific modeling and various biomedical applications.

Fungal infection mimicking soft tissue lesion: Role of on-site evaluation, special stain, and cellblock.

BACKGROUND: Fine-needle aspiration (FNA) cytology is a basic diagnostic method used for the investigation of superficial and deep lesions. The implementation of rapid on-site evaluation (ROSE) in cytological analysis can help in reducing the inadequacy rate and obtaining proper samples for further tests/analysis. CASE PRESENTATION: We report a case of 44-year-old male, who presented to our outpatient department with complaints of swelling in his right arm for the last 34 years. FNA with ROSE using 1% aq. toluidine blue helped identify the pathology (fungal lesion) in the patient with further confirmation by cellblock, periodic acid Schiff & Gomori methenamine silver stains. CONCLUSION: The role of FNA was significant in the above case, special stains prove their efficacy when sufficient sample is available. The differential diagnosis of fungal etiology should be considered in subcutaneous soft tissue lesions. There has been a major leap in diagnostic cytopathology with the advent of molecular testing. However, FNA still holds its charm.

Recommendations for diabetic macular edema management by retina specialists and large language model-based artificial intelligence platforms.

PURPOSE: To study the role of artificial intelligence (AI) in developing diabetic macular edema (DME) management recommendations by creating and comparing responses to clinicians in hypothetical AI-generated case scenarios. The study also examined whether its joint recommendations followed national DME management guidelines. METHODS: The AI hypothetically generated 50 ocular case scenarios from 25 patients using keywords like age, gender, type, duration and control of diabetes, visual acuity, lens status, retinopathy stage, coexisting ocular and systemic co-morbidities, and DME-related retinal imaging findings. For DME and ocular co-morbidity management, we calculated inter-rater agreements (kappa analysis) separately for clinician responses, AI-platforms, and the "majority clinician response" (the maximum number of identical clinician responses) and "majority AI-platform" (the maximum number of identical AI responses). Treatment recommendations for various situations were compared to the Indian national guidelines. RESULTS: For DME management, clinicians (ĸ=0.6), AI platforms (ĸ=0.58), and the 'majority clinician response' and 'majority AI response' (ĸ=0.69) had moderate to substantial inter-rate agreement. The study showed fair to substantial agreement for ocular co-morbidity management between clinicians (ĸ=0.8), AI platforms (ĸ=0.36), and the 'majority clinician response' and 'majority AI response' (ĸ=0.49). Many of the current study's recommendations and national clinical guidelines agreed and disagreed. When treating center-involving DME with very good visual acuity, lattice degeneration, renal disease, anaemia, and a recent history of cardiovascular disease, there were clear disagreements. CONCLUSION: For the first time, this study recommends DME management using large language model-based generative AI. The study's findings could guide in revising the global DME management guidelines.

Novel 5-Substituted Oxindole Derivatives as Bruton's Tyrosine Kinase Inhibitors: Design, Synthesis, Docking, Molecular Dynamics Simulation, and Biological Evaluation.

Bruton's tyrosine kinase (BTK) is a non-RTK cytoplasmic kinase predominantly expressed by hemopoietic lineages, particularly B-cells. A new oxindole-based focused library was designed to identify potent compounds targeting the BTK protein as anticancer agents. This study used rational approaches like structure-based pharmacophore modeling, docking, and ADME properties to select compounds. Molecular dynamics simulations carried out at 20 ns supported the stability of compound 9g within the binding pocket. All the compounds were synthesized and subjected to biological screening on two BTK-expressing cancer cell lines, RAMOS and K562; six non-BTK cancer cell lines, A549, HCT116 (parental and p53-/-), U2OS, JURKAT, and CCRF-CEM; and two non-malignant fibroblast lines, BJ and MRC-5. This study resulted in the identification of four new compounds, 9b, 9f, 9g, and 9h, possessing free binding energies of -10.8, -11.1, -11.3, and -10.8 kcal/mol, respectively, and displaying selective cytotoxicity against BTK-high RAMOS cells. Further analysis demonstrated the antiproliferative activity of 9h in RAMOS cells through selective inhibition of pBTK (Tyr223) without affecting Lyn and Syk, upstream proteins in the BCR signaling pathway. In conclusion, we identified a promising oxindole derivative (9h) that shows specificity in modulating BTK signaling pathways.

Thread-powered cell lysis and isotachophoresis: unlocking microbial DNA for diverse molecular applications.

Central to the domain of molecular biology resides the foundational process of DNA extraction and purification, a cornerstone underpinning a myriad of pivotal applications. In this research, we introduce a DNA extraction and purification technique leveraging polypropylene (PP) threads. The process commences with robust cell lysis achieved through the vigorous agitation of interwoven PP threads. The friction between the threads facilitates cell lysis especially those microbes having tough cell wall. For purification of DNA, thread-based isotachophoresis was employed which makes the whole process swift and cost-effective. Lysed cell-laden threads were submerged in a trailing electrolyte which separated DNA from other cellular contents. The process was performed with a tailored ITP device. An electric field directs DNA, cell debris, trailing electrolyte, and leading electrolyte toward the anode. Distinct ion migration resulted in DNA concentrating on the PP thread's anode-proximal region. The SYBR green dye is used to visualize DNA as a prominent green zone under blue light. The purified DNA exhibits high purity levels of 1.82 ± 0.1 (A260/A280), making it suitable for various applications aiming at nucleic acid detection.