A One-Pot Cascade Strategy toward Organocatalytic Enantioselective Construction of Fused Benzimidazoles.

Herein, we describe an asymmetric assembly of ortho-aromatic diamines and formyl tethered Michael acceptors forming chiral fused benzimidazoles. A cinchona-alkaloid-derived bifunctional squaramide catalyst enables the methodology through on-site dihydrobenzimidazole formation followed by an aza-Michael addition/oxidation cascade. This protocol stands out for its excellent catalytic efficiency over the background reaction and its mild conditions, making it more practical. Various Michael acceptors, including enones, ester, and thioester, were successful substrates in this study. Additionally, this methodology has demonstrated scalability and successfully showcased postsynthetic transformations.

Studies on cationic ocular emulsions containing bipartitioned oil droplets to codeliver cyclosporin A and etodolac.

Background: To prepare ocular emulsions containing bipartitioned oil droplets to entrap cyclosporin A (0.05% w/w) and etodolac (0.2% w/w) by using castor, olive and silicon oils. Methods: The physicochemical characterizations of prepared emulsions were performed. The drug's biodistribution profiles and pharmacokinetic parameters from emulsions were checked using the ultraperformance liquid chromatography-tandem mass spectrometry method in the ocular tissues of the healthy rabbit eye model. Results: The emulsions displayed 365.13 ± 7.21 nm size and 26.45 ± 2.09 mV zeta potential. The ferrying of two drugs after releasing from emulsions occurred across corneal/conjunctival tissues to enter the vitreous and sclera following a single drop administration into the rabbit's eyes. Conclusion: The dual drug-loaded emulsions were more likely to produce synergistic anti-inflammatory activity for managing moderate-to-severe dry eye disease.

Post-chemotherapy changes in retinal pigment epithelium in retinoblastoma eyes.

OBJECTIVE: Histopathological analysis of the retinal pigment epithelial (RPE) changes in retinoblastoma (RB) cases who received pre-surgical chemotherapy. DESIGN: Laboratory-based observational study. METHODS: Five-year analysis was performed to identify Retinoblastoma cases who underwent enucleation after receiving systemic chemotherapy. Grossly, RPE cells were observed in flat preparation in small calottes by staining with fluorescein stain in the raw specimens. They were documented under the objective of compound microscope and compared with hematoxylin and eosin-stained slides in the permanent tissue sections. RESULTS: Out of 51 cases of RB, post-chemotherapy enucleation was performed in 17 cases. Mean age of enucleation was 3.2 years. Endophytic RB (11 cases, 64.71%) was more common than the exophytic variety. Choroidal involvement was noted in 8 cases (47.06%), and optic nerve involvement was seen in 5 cases (29.4%). Focal and diffuse RPE changes were seen in one case each (5.88%). Central RPE cell changes near the cell nucleus were seen in all 17 cases (100%), which were documented by both fluorescein and Hematoxylin and eosin stain (100%). Drusens were observed in 8 cases (47.06%), and RPE proliferations were seen in 3 cases (17.65%). CONCLUSION: The study highlights the characteristic histopathological RPE changes after systemic chemotherapy in RB cases. These changes may be attributable to cell nucleus damage after chemotherapy.

Blood within the bone: orbital intraosseous venous malformation.

PURPOSE: Description of clinical features, radiological characteristics, and management strategies in primary orbital intraosseous venous malformation (OIVM) with pertinent literature review. METHODS: A retrospective analysis including clinical, radiologic, operative, and histopathological data of six cases of histopathologically proven OIVM was done. A comprehensive literature review was conducted using online databases and augmented with manual search to identify reported cases of OIVM. RESULTS: Study data showed five females and one male in young to middle-age group, with an average age of 30 years (range: 20-48 years). Proptosis was noted in five cases (83.33%), and the duration of symptoms ranged from 6 months to 10 years. Frontal and zygomatic bones were most frequently affected and expansile bony lesion was the most common CT scan finding. Three patients underwent pre-operative embolization of feeders followed by en bloc excision of mass and surgical reconstruction (50%); one patient was managed with partial excision (16.66%) while two were regularly followed-up after incision biopsy (33.33%). Histopathology revealed vascular spaces with endothelial lining, separated by bony trabeculae in all patients. Follow-up periods ranged from 6 to 48 months and no recurrence or progression were noted. CONCLUSIONS: OIVM is an exceptionally rare disorder with a gradually progressive benign course. Ophthalmologists need to be mindful of this entity during patient evaluation as it has propensity for large volume blood loss intra-operatively, owing to its vascular nature. Complete excision with reconstruction of resultant defect is the preferred treatment strategy and without known recurrence.

Comprehensive Analysis of Solar Panel Performance and Correlations with Meteorological Parameters.

To mitigate the adverse effects of fossil fuel-based energy, mankind is in constant search of clean and cost-effective sources of energy, such as solar energy. The economic viability of a power plant to harness solar energy mostly depends on the efficiency of solar panels. Investigations over the years show that the solar panel efficiency significantly depends on the different meteorological parameters. Therefore, there is an imminent need for a correlation explaining the relations between the efficiency and different meteorological parameters. In this study, an effort has been made to analyze the effects of various meteorological parameters on the efficiency and subsequently propose a correlation between them. Initial investigations reveal that the optimal tilt angle for the maximum power output is 26°. The study demonstrates that efficiency is directly proportional to solar intensity and wind speed while being inversely proportional to temperature, humidity, and dew point temperature. Regression analysis of a data set comprising 100 data sets establishes a strong correlation between efficiency and five meteorological parameters: temperature, humidity, wind speed, solar intensity, and dew factor. The calculated efficiencies using the developed correlation deviate from the experimental values, with absolute errors ranging from 0.08 to 1.20%. The findings provided valuable insights for optimizing solar power plant performance by understanding the relationship between efficiency and meteorological parameters.

Transmittance characteristics of transparent hydrophobic acrylic foldable intraocular lenses that were in vivo for a prolonged period of time: A UV visible spectrophotometric study.

PURPOSE: To record experimental data on the spectral transmittance characteristics of transparent hydrophobic acrylic foldable IOLs, which were in vivo for a prolonged period of time and explanted under clinical indications and also to compare the data with that of corresponding control and crystalline lens along with review of the relevant literature. METHOD: Material and make of each of the explanted intraocular lenses (IOLs) as well as pre-explantation clinical status of the eyes were confirmed from the medical record. The transmittance of wavelength from 185 to 900 nm of each of the selected IOLs was measured using Shimadzu UV 2600 UV visible (UV-Vis) spectrophotometer in double-beam configuration and probe version 2.16 software. The data obtained were statistically analyzed. RESULTS: The mean transmittance of 12 clinically explanted IOLs at spectral range 300-700 nm was 49.5% ± SD 6.9%. This value was 10% and 38% less than the corresponding clear (59% ± SD 0.4%) and yellow (87.5% ± SD 0.4%) control, respectively. The mean transmittance of the analytes in the UV range was 43.3 ± SD 6.9%, and it was almost similar to the control. The data showed wide variations without good correlation, and it matches with the human crystalline lens at the age range of 50-60 years. All eyes were otherwise healthy, and none had age-related macular degeneration. CONCLUSION: In comparison with fresh IOL with a yellow filter, light transmittance at the spectral range 300-700 nm was found decreased in all the IOLs, which were in vivo for an average period of 12.25 ± 4.4 years. All IOLs transmitted variable amounts of UV radiation. More data are required for further analysis on the subject.

Hydrazine Hydrate in Asymmetric Synthesis: A Bifunctional Squaramide Catalytic Approach toward Fused Pyrazolines.

A unified strategy has been developed to utilize hydrazine hydrate in asymmetric organic synthesis by overcoming the rapid background reaction with dienone. The H-bond donor ability of the cinchona-alkaloid-derived squaramide catalyst unlocks this previously deemed infeasibility. The dissymmetric hydrazine addition to symmetrical dienones tolerates various substitutions, resulting in the formation of optically pure fused pyrazoline derivatives under mild reaction conditions. Furthermore, the scalability of this methodology and a successful demonstration of postsynthetic transformations have been accomplished.

Malignant choroidal melanoma with vitreous seeds: supported by histopathology and field emission scanning electron microscopy study.

Aim: To report an exceptionally rare case of malignant choroidal melanoma with vitreous seeding, supported by histopathological and field emission scanning electron microscopic (FESEM) studies. Case report: A 58-year-old male with painless diminution of vision in his left eye for past 1 month was found to have a brown retrolental mass lesion on slit lamp examination in the left eye. Detailed fundus examination revealed choroidal melanoma in the left eye with pigmented seeds extending into the vitreous cavity and associated exudative retinal detachment. Ocular imaging was consistent with the diagnosis. Results: The eyeball was enucleated and the tumor was considered as stage IIB (AJCC 8th edition classification). Metastatic workup of the patient was negative. One half of the eyeball was subjected to field emission scanning electron microscopy to further study the nature and appearance of vitreous seeds. Discussion: Vitreous seeding in choroidal melanoma has been reported only in a handful of cases in literature. Histopathological confirmation of vitreous seeds was done in our case and morphological detailing was performed using FESEM study. Conclusions: Treatment naïve choroidal melanoma can very rarely have vitreous seeds. Early enucleation in such cases carries a favorable prognosis.

Validation of urinary reproductive hormone measurements using a novel smartphone connected reader.

Home use tests to monitor hormone trends during the menstrual cycle have been available over-the-counter for a long time. However, these tests often depend upon manual readouts and hence may lead to false analysis. Furthermore, a lot of these tests are also not quantitative. The aim of this study was to evaluate the accuracy of the quantitative home-based fertility monitor, Inito Fertility Monitor (IFM) and to use it to identify novel hormone trends in natural menstrual cycles. There were two aspects to our analysis: (i) Evaluating the efficacy of Inito Fertility Monitor in the measurement of urinary Estrone-3-glucuronide (E3G), Pregnanediol glucuronide (PdG) and Luteinizing hormone (LH), and (ii) A retrospective study of patients' hormone profiles using IFM. To evaluate the efficacy, the recovery percentage of the three hormones from IFM was evaluated using standard spiked solutions, the accuracy of measurement was calculated and the correlation between reproducible values from IFM and ELISA was established. During the validation of IFM, novel hormone trends were also observed. In order to reinforce the observations, a second group of 52 women was recruited. Assessment of the accuracy of IFM and evaluation of the volunteer urine samples was performed in a laboratory. Home assessment of hormone analysis was carried out using IFM. For the validation study, 100 women aged 21-45 years with cycle lengths ranging from 21 to 42 days were recruited. The participants had no previously diagnosed infertility conditions and their cycle lengths did not vary for more than 3 days from the expected cycle length. Daily first morning urine samples were collected from these 100 women. For the second group, 52 women were selected meeting the same criteria set for the validation study and IFM was provided to these women for testing at home. Coefficient of variation and recovery percentage of IFM with respect to laboratory based ELISA. Percentage occurrence of novel hormone trends and AUC analysis of a novel criteria identified for confirming ovulation. We observed that with all three hormones, IFM had an accurate recovery percentage. We found that the assay has an average CV of 5.05% in PdG measurement, 4.95% in E3G measurement and 5.57% in LH measurement. Furthermore, in predicting the concentration of E3G, PdG and LH in urine samples, we show that IFM has a high correlation with ELISA. In this study, we could also reproduce hormones trends across the menstrual cycle that have been observed by previous studies. We also identified a novel criterion for earlier confirmation of ovulation which could accurately distinguish ovulatory from anovulatory cycles with 100% specificity and had an area under the ROC curve of 0.98. In addition, we identified a new hormone trend which could be observed in 94.5% of the ovulatory cycles. The Inito Fertility Monitor is an effective tool for calculating the urinary concentrations of E3G, PdG and LH and can also be used to provide accurate fertility scores and confirm ovulation. We show that certain hormone trends associated with urinary E3G, PdG and LH could be accurately captured using IFM. In addition, we report a novel criterion for earlier confirmation of ovulation compared to existing criteria. Finally, we present a novel hormone pattern associated with most of the menstrual cycles by examining hormone profiles from the volunteers recruited for the clinical trial.Trial registration: The trial is registered at the current controlled trials ISRCTN registry #ISRCTN15534557.

Parasitic Eye Diseases: Nuances in Rapid Identification and Advanced Microscopy.

AIM: To study parasitic eye diseases in a tertiary institute of North-east India by live examination of parasites, rapid staining, and scanning electron microscopy (SEM). METHODS: A 12-year retrospective analysis was performed and all patients diagnosed with ocular parasitic diseases were identified. Examination under a compound microscope, fluorescein staining, and scanning electron microscopy were done. RESULTS: A total of 160 ocular parasitosis cases were identified. The cases for which rapid staining and SEM studies were done included Cysticercosis (n = 18, 11.25%), Hydatidosis (n = 5, 3.13%), Dirofilariasis (n = 5, 3.13%), Thelaziasis (n = 3, 1.87%), and Gnathostomiasis (n = 2, 1.25%). Live examination was performed in 11 cases (6.63%) and 8 cases (4.82%) underwent scanning electron microscopy. . CONCLUSION: Fluorescein staining for identification of parasites and SEM study helped in detailing microscopic and ultrastructural findings.

Histopathology of pigment dispersion syndrome and glaucoma: A Case Report.

Pigment dispersion syndrome (PDS) can have varied manifestations. Anterior and posterior segment involvement by dispersed pigments was documented in gross pathology and by staining under microscopy. Pigmentary changes in the sclera, cornea, anterior chamber, iris, trabecular meshwork, lens, and retinal pigment epithelium and optic nerve findings were consistent with PDS. External scleral and vitreous pigmentation has never been reported before in the scientific literature. Retinal pigment degeneration and granule dispersion were seen throughout the retina which could be a contributing factor in the etiology of PDS.

Nanotherapeutic potential of antibacterial folic acid-functionalized nanoceria for wound-healing applications.

Aim: The functionalization and characterization of antibacterial nanoceria with folic acid (FA) and elucidation of their in vivo wound-healing application. Materials & methods: Functionalization of nanoceria were done with FA using a chemical method and their antibacterial activity, cellular biocompatibility and in vivo wound-healing application were evaluated. Results: The functionalization of nanoceria with FA was done with 10-20 nm size and -20.1 mV zeta potential. The nanoformulation showed a bacteriostatic effect along with biocompatibility to different cell lines; 0.1% w/v spray of FA-nanoceria demonstrated excellent wound-healing capacity within 14 days in a Wister rat model. Conclusion: The antioxidant and reactive oxygen species scavenging activity of the FA-nanoceria make it a promising therapeutic agent as a unique spray formulation in wound-healing applications.

The emergence of chronic wounds is a main reason for mortality in patients with diabetes and other severe pathological complications. Advances in the use of nanotechnology have resulted in beneficial technology for tailoring of pharmacokinetic properties of different drug-delivery vehicles for different biomedical applications. In this study, folic acid (FA) functionalized nanoceria (FA-nanoceria) were formulated and their potential efficacy in the wound-healing process was explored. The nanoformulation showed a remarkable bacteriostatic effect on both Gram-negative and Gram-positive bacteria. In vitro cell line studies showed satisfactory biocompatibility in three different types of cell lines. In addition, a 0.1% w/v spray of FA-nanoceria was applied to full-thickness wounds in an in vivo mice model where it demonstrated excellent wound-healing capacity within 14 days. The combined antioxidant and reactive oxygen species scavenging activity of both the FA and nanoceria makes FA-nanoceria a promising therapeutic agent as a unique spray formulation in wound-healing applications.

Intraocular and neuro-cysticercosis with diffuse stromal choroiditis.

Intraocular cysticercosis with central nervous system involvement is not that rare. We report a male child with a right-sided painful blind eye who had intraocular cysticercosis and granuloma in the left frontal lobe of the brain. There was an incidental finding of chronic inflammation in the choroid of that eye supported by histopathology. Immunohistochemistry for T-cells marker and B-cells marker was variable. The patient was treated with antiparasitic, anti-epileptic medications, and oral steroids subsequently.

Studies on spray dried topical ophthalmic emulsions containing cyclosporin A (0.05% w/w): systematic optimization, in vitro preclinical toxicity and in vivo assessments.

Cyclosporin A (CsA, 0.05% w/w)-loaded positively charged emulsions were prepared based on castor oil, chitosan, poloxamer 188, glycerin and double-distilled water. To augment the shelf/storage-stability of original emulsions, the solid-dry powder for reconstitution was made by spray drying technique. The screening (Taguchi OA) and optimization (face-centered central composite) designs produced the optimized conditions for spray drying: 40 Nm3/h aspirator flow rate, 15 ml/min feed rate, 115 °C inlet temperature, 10% mannitol and 1.25% trehalose. The % drug entrapment efficiency values of original and reconstituted emulsions ranged from 73.20 ± 0.13 to 71.55 ± 1.25%. At 20 min post-dissolution, two times higher CsA release was seen from reconstituted emulsions than the original emulsions (85.78 ± 1.14 vs. 42.25 ± 1.84%) in simulated tear fluid. Using MTT assay, the reconstituted emulsions with or without CsA produced 94.512 ± 2.12 to 99.941 ± 1.89% cell viability values in HCE-2 cells. No appreciable change in capillary integrity was visualized in HET CAM following reconstituted emulsions treatment. At equivalent 15 µg drug, the in vitro protein denaturation assay showed augmented inhibition value (~ 85%) for tested CsA emulsions compared to diclofenac reference (68.30 ± 2.05) indicating enhanced anti-inflammatory activity. The CsA concentrations in multiple ocular matrices of rabbit eyes determined by the UPLC-MS/MS method attained the therapeutic drug level of 50-300 ng/ml even at 90 min post-topical instillation of both emulsions. Overall, the CsA emulsion eyedrops can be supplied as a spray dried storable intermediate product for reconstitution.

Predicting serum hormone concentration by estimation of urinary hormones through a home-use device.

STUDY QUESTION: Can a home-use device be used to predict serum hormone levels? SUMMARY ANSWER: A home-use device can predict urinary hormone values which are well-correlated to serum concentrations of respective hormones and hence can be used as a proxy for serum measurements. WHAT IS KNOWN ALREADY: Home-use devices that predict ovulation are calibrated against the actual day of ovulation. However, the correlation of any quantitative system to serum hormone concentrations has not been established. STUDY DESIGN SIZE DURATION: A total of 73 data points obtained from 20 participants across different phases of the menstrual cycle, i.e. bleeding days, follicular phase and luteal phase were used to establish the correlation between serum hormones and urinary metabolite values. Single data points from 20 random users were used to assess the correlation established. PARTICIPANTS/MATERIALS SETTING METHODS: Participants were women in the fertile age groups and only current users of the home-use device. Selection was done based on inclusion and exclusion criteria. Blood hormones were tested using chemiluminescent immunoassays and urinary measurements were taken on the home-use device at home. MAIN RESULTS AND THE ROLE OF CHANCE: Serum estradiol (E2), progesterone (P4) and LH were correlated with urinary estrone-3-glucuronide (E3G), pregnanediol glucuronide (PdG) and LH with an R 2 of 0.96, 0.95 and 0.98, respectively. Repredicted serum concentration obtained by using the correlation equation had a correlation of 0.92, 0.94 and 0.93 in unknown samples. LIMITATIONS REASONS FOR CAUTION: The study was designed to include women who have normal cycle lengths regularly; therefore, the values obtained were in the normal range. Certain infertility conditions may cause the values to be higher and correlation in such cases needs to be established. WIDER IMPLICATIONS OF THE FINDINGS: The results of this study imply a new tool that can be used by fertility specialists as a proxy for blood tests whenever required. Extended study on this system can enable its use in assisted reproductive techniques as well. STUDY FUNDING/COMPETING INTERESTS: No funding was received for this study. S.P. and D.D. are employees of the research and development division of Samplytics Technologies Pvt. Ltd. which is a forwarder for Inito Inc., USA. A.R. and V.A.V. are co-founders of Inito Inc., USA. TRIAL REGISTRATION NUMBER: The trial was registered at the International Standard Randomised Controlled Trial Number (ISRCTN) registry (Identifier: ISRCTN15534557).

Bare Eye Detection of Bacterial Enzymes of Pseudomonas aeruginosa with Polymer Modified Nanoporous Silicon Rugate Filters.

The fabrication, characterization and application of a nanoporous Silicon Rugate Filter (pSiRF) loaded with an enzymatically degradable polymer is reported as a bare eye detection optical sensor for enzymes of pathogenic bacteria, which is devoid of any dyes. The nanopores of pSiRF were filled with poly(lactic acid) (PLA), which, upon enzymatic degradation, resulted in a change in the effective refractive index of the pSiRF film, leading to a readily discernible color change of the sensor. The shifts in the characteristic fringe patterns before and after the enzymatic reaction were analyzed quantitatively by Reflectometric Interference Spectroscopy (RIfS) to estimate the apparent kinetics and its dependence on enzyme concentration. A clear color change from green to blue was observed by the bare eye after PLA degradation by proteinase K. Moreover, the color change was further confirmed in measurements in bacterial suspensions of the pathogen Pseudomonas aeruginosa (PAO1) as well as in situ in the corresponding bacterial supernatants. This study highlights the potential of the approach in point of care bacteria detection.

Forecasting adversities of COVID-19 waves in India using intelligent computing.

The second wave of the COVID-19 pandemic outburst triggered enormously all over India. This ill-fated and fatal brawl affected millions of Indian citizens, with many active and infected Indians struggling to recover from this deadly disease to date, leading to a grief situation. The present situation warrants developing a robust and sound forecasting model to evaluate the adversities of the epidemic with reasonable accuracy to assist officials in curbing this hazard. Consequently, we employed Auto-ARIMA, Auto-ETS, Auto-MLP, Auto-ELM, AM, MLP and proposed ELM methods for assessing accumulative infected COVID-19 individuals by the end of July 2021. We made 90 days of advanced forecasting, i.e., up to 24 July 2021, for the number of cumulative infected COVID-19 cases of India using all seven methods in 15 days' intervals. We fine-tuned the hyper-parameters to enhance the prediction performance of these models and observed that the proposed ELM model offers satisfactory accuracy with MAPE of 5.01, and it rendered better accuracy than the other six models. To comprehend the dataset's nature, five features are extracted. The resulting feature values encouraged further investigation of the models for an updated dataset, where the proposed model provides encouraging results.