The Effect of Illumination on Positive Fusional Vergence.

Background: Positive fusional vergence (PFV) is vital in maintaining fusion in critical and continuous near tasks such as reading or performing digital screen tasks. This study investigated how PFV changed under various lighting conditions. Methods: This cross-sectional study recruited 34 participants aged between 21 and 25 years, with best corrected visual acuity (BCVA) 0.0 logMAR and insignificant refractive error. Three different illuminations-low illumination (50 lux), medium lighting (100 lux), and high illumination (150 lux)-were used to examine the ocular parameters PFV (blur, break, and recovery points), contrast sensitivity and pupil diameter. Results: Pupil diameter changed significantly in different room illuminations (p = 0.00). There was no significant difference in contrast sensitivity across the three levels of room illumination (p = 0.368). Mean PFV (SD) (blur) was 14.5 (2.5) in 50 lux, 10.2 (2.2) in 100 lux, and 8.2 (2.1) in 150 lux. Under 50, 100 and 150 lux, respectively, the mean PFV (SD) (break) values were 16.7 (2.4), 13.4 (1.8), and 10.8 (2.2), and the mean PFV (SD) (recovery) values were 13.3 (2.1), 10.7 (2.1), and 7.5 (2.7). With increased illumination levels, PFV blur, break, and recovery values were significantly lower (p < 0.001). Conclusions: PFV values were significantly higher in lower illumination. Clinicians should be aware that room illumination affected the PFV values measured.

Structure specific neuro-toxicity of α-synuclein oligomer.

Parkinson's disease (PD) is linked to α-synuclein (aS) aggregation and deposition of amyloid in the substantia nigra region of the brain tissues. In the current investigation we produced two distinct classes of aS oligomer of differed protein conformation, stability and compared their toxic nature to cultured neuronal cells. Lyophilized oligomer (LO) was produced in storage of aS at-20 °C for 7 days and it was enriched with loosely hold molten globule like structure with residues having preferences for α-helical conformational space. The size of the oligomer was 4-5.5 nm under AFM. This kind of oligomer exhibited potential toxicity towards neuronal cell lines and did not transform into compact ß-sheet rich amyloid fiber even after incubation at 37 °C for several days. Formation of another type of oligomer was often observed in the lag phase of aS fibrillation that often occurred at an elevated temperature (37 °C). This kind of heat induced oligomer (IO) was more hydrophobic and relatively less toxic to neuronal cells compared to lyophilized oligomer (LO). Importantly, initiation of hydrophobic zipping of aS caused the transformation of IO into thermodynamically stable ß-sheet rich amyloid fibril. On the other hand, the presence of molten globule like conformation in LO, rendered greater toxicity to cultured neuronal cells.

Single point mutations at the S129 residue of α-synuclein and their effect on structure, aggregation, and neurotoxicity.

Parkinson's disease is an age-related neurological disorder, and the pathology of the disease is linked to different types of aggregates of α-synuclein or alpha-synuclein (aS), which is an intrinsically disordered protein. The C-terminal domain (residues 96-140) of the protein is highly fluctuating and possesses random/disordered coil conformation. Thus, the region plays a significant role in the protein's solubility and stability by an interaction with other parts of the protein. In the current investigation, we examined the structure and aggregation behavior of two artificial single point mutations at a C-terminal residue at position 129 that represent a serine residue in the wild-type human aS (wt aS). Circular Dichroism (CD) and Raman spectroscopy were performed to analyse the secondary structure of the mutated proteins and compare it to the wt aS. Thioflavin T assay and atomic force microscopy imaging helped in understanding the aggregation kinetics and type of aggregates formed. Finally, the cytotoxicity assay gave an idea about the toxicity of the aggregates formed at different stages of incubation due to mutations. Compared to wt aS, the mutants S129A and S129W imparted structural stability and showed enhanced propensity toward the α-helical secondary structure. CD analysis showed proclivity of the mutant proteins toward α-helical conformation. The enhancement of α-helical propensity lengthened the lag phase of fibril formation. The growth rate of ß-sheet-rich fibrillation was also reduced. Cytotoxicity tests on SH-SY5Y neuronal cell lines established that the S129A and S129W mutants and their aggregates were potentially less toxic than wt aS. The average survivability rate was ∼40% for cells treated with oligomers (presumably formed after 24 h of incubation of the freshly prepared monomeric protein solution) produced from wt aS and ∼80% for cells treated with oligomers obtained from mutant proteins. The relative structural stability with α-helical propensity of the mutants could be a plausible reason for their slow rate of oligomerization and fibrillation, and this was also the possible reason for reduced toxicity to neuronal cells.

Naringenin-Functionalized Gold Nanoparticles and Their Role in α-Synuclein Stabilization.

Misfolding and self-assembly of several intrinsically disordered proteins into ordered ß-sheet-rich amyloid aggregates emerged as hallmarks of several neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Here we show how the naringenin-embedded nanostructure effectively retards aggregation and fibril formation of α-synuclein, which is strongly associated with the pathology of Parkinson's-like diseases. Naringenin is a polyphenolic compound from a plant source, and in our current investigation, we reported the one-pot synthesis of naringenin-coated spherical and monophasic gold nanoparticles (NAR-AuNPs) under optimized conditions. The average hydrodynamic diameter of the produced nanoparticle was ∼24 nm and showed a distinct absorption band at 533 nm. The zeta potential of the nanocomposite was ∼-22 mV and indicated the presence of naringenin on the surface of nanoparticles. Core-level XPS spectrum analysis showed prominent peaks at 84.02 and 87.68 eV, suggesting the zero oxidation state of metal in the nanostructure. Additionally, the peaks at 86.14 and 89.76 eV were due to the Au-O bond, induced by the hydroxyl groups of the naringenin molecule. The FT-IR analysis further confirmed strong interactions of the molecule with the gold nanosurface via the phenolic oxygen group. The composite surface was found to interact with monomeric α-synuclein and caused a red shift in the nanoparticle absorption band by ∼5 nm. The binding affinity of the composite nanostructure toward α-synuclein was in the micromolar range (Ka∼ 5.02 × 106 M-1) and may produce a protein corona over the gold nanosurface. A circular dichroism study showed that the nanocomposite can arrest the conformational fluctuation of the protein and hindered its transformation into a compact cross-ß-sheet conformation, a prerequisite for amyloid fibril formation. Furthermore, it was found that naringenin and its nanocomplex did not perturb the viability of neuronal cells. It thus appeared that engineering of the nanosurface with naringenin could be an alternative strategy in developing treatment approaches for Parkinson's and other diseases linked to protein conformation.

Accommodative spasm and its different treatment approaches: A systematic review.

This article is about the accommodation spasm. The primary rule for near vision is ciliary muscle constriction, synchronised convergence of both eyes, and pupil constriction. Any weaknesses in these components could result in an accommodative spasm. Variable retinoscopic reflex, unstable refractive error, and lead of accommodation in near retinoscopy are common causes of spasm. We conducted a thorough literature search in the PubMed and Google Scholar databases for published journals prior to June 2022, with no data limitations. This review contains twenty-eight case reports, six cohort studies, four book references, four review articles, and two comparative studies after applying the inclusion and exclusion criteria. The majority of studies looked at accommodative spasm, near reflex spasm, and pseudomyopia. The most common causes of accommodative spasm are excessive close work, emotional distress, head injury, and strabismus. Despite side effects or an insufficient regimen, cycloplegic drops are effective in diagnosing accommodation spasm. The modified optical fogging technique is also effective and may be an option for treating accommodative spasm symptoms. Bifocals for near work, manifest refraction, base-in prisms, and vision therapy are some of the other management options. As a result, it requires a comprehensive clinical treatment strategy. This review aims to investigate the various aetiology and treatments responsible for accommodative spasm and proposes widely implementing the modified optical fogging method and vision therapy in clinics as comprehensive management to reduce the future upward trend of accommodative spasm.

Expression analysis of cyclin D, Ki-67, MCM3 and MCM2 in oral squamous cell carcinoma.

The expression analysis of cyclin D1, Ki-67, MCM3 and MCM2 in oral squamous cell carcinoma to identify biomarkers is of interest. 45 formalin-fixed paraffin embedded tissue blocks collected from archives of Department of Oral and Maxillofacial Pathology and Oral Microbiology, Government Dental College and Hospital, Jamnagar, India were subjected to a retrospective cross-sectional immuno-histo-chemistry examination. 30 blocks of OSCC with histological diagnosis have 15 tissue blocks of well-differentiated oral carcinoma and 15 tissue blocks of moderately-differentiated oral carcinoma. 15 specimens of normal oral mucosa (NM) were also examined for comparison. In each of the categories, the immuno-histo-chemistry expression of cyclin D1, MCM 3, MCM 2, and ki67 was studied. Data shows that cyclin D1, Ki-67, MCM3 and MCM2 effectively indicate cellular proliferation for consideration as potential biomarkers of oral squamous cell carcinoma.

Comprehensive Assessment of Albumin and Uric Acid Levels in Oral Submucous Fibrosis: A Comparative Case-Control Study Involving Different Risk Groups.

Background Oral submucous fibrosis (OSMF) is a premalignant disorder that impacts the oral cavity and pharynx. Major risk factors for OSMF are attributed to the consumption of betel nuts or tobacco. These substances harbor various carcinogens that trigger the production of free radicals and reactive oxygen species. Antioxidants are pivotal in preserving cellular integrity and impeding the oncogenic transformation of body cells. In this context, albumin and uric acid, being primary antioxidants present in body fluids, bestow a defensive effect against this condition. Thus, the present study is designed to elucidate the differential concentration of albumin and uric acid between patient cases and healthy cohorts. Methodology This case-control study was conducted to evaluate the albumin and uric acid levels in individuals diagnosed with OSMF (cases) and compare them with healthy controls for a period of six months. A cohort of 100 individuals was partitioned into four groups, with each group comprising 25 individuals: Group I was made up of healthy individuals; Group II consisted of individuals who chew tobacco and areca nuts but are not affected by OSMF; Group III included individuals who only use tobacco without areca nuts and are afflicted with OSMF; and Group IV comprised individuals who consume a combination of areca nuts and tobacco and are diagnosed with OSMF. Biochemical evaluation was carried out using the BS-380 chemistry autoanalyzer (Mindray, Shenzhen, China), and the quantification of serum albumin and uric acid was performed by the uricase-peroxidase (POD) method with dihydroxybenzene sulfonic acid (DHBS). Results The study cohort of 100 individuals was made up of 70 males and 30 females, with an average age of 42.51 (11.62) years. The comparison of the mean concentration of serum albumin across all groups revealed that healthy controls exhibited the highest serum albumin concentration of 4.284 (0.618), with a statistically significant p-value (0.001) across all groups. A comparison of the mean value of serum uric acid among all groups showed that healthy controls had the highest value of serum uric acid (5.26±1.161), with a considerable p-value (0.001) between all groups. Conclusion The present study concluded that serum biomarkers assessed were high in healthy individuals and consumption of areca nuts, tobacco, and their products was significantly associated with low levels of albumin and uric acid. Therefore, both albumin and uric acid can be used as important biomarkers for uncovering oral premalignant lesions and conditions ahead of time and can also be used in mass screening.

A quick accelerating microwave-assisted sustainable technique: permutated spiro-casing for imaging experiment.

A quick access tool for the one-pot, chromatography-free synthesis of the diversified dihydrospiro[indeno[1,2-b]pyridine-4,3'-indoline or acenaphthylene-1,4'-indeno[1,2-b]pyridine spiro-analogous via sustainable microwave condition in minimal 1:1 (v/v) aqueous ethanol without any metal catalyst is demonstrated here. This permutated spiro-casing was designed as fluorescence probe at physiological pH for selective detection of Zn2+, even in the presence of other competitive ions and showed a fluorescent enhancement with 1:1 metal/ligand complex. Moreover, this spiro sensor was successfully applied as an effective intracellular Zn2+ imaging agent in the biomedical study of human hepatocellular liver carcinoma cells (HepG2) due to its cell permeability property. A quick access technique for the permutated dihydrospiro-pyridine via chromatography-free sustainable microwave condition and its applications as organic fluorescence probe at physiological pH for selective detection of Zn2+ and effective intracellular Zn2+ imaging in HepG2 cells.

Order, Disorder, and Reorder State of Lysozyme: Aggregation Mechanism by Raman Spectroscopy.

Lysozyme, like many other well-folded globular proteins, under stressful conditions produces nanoscale oligomer assembly and amyloid-like fibrillar aggregates. With engaging Raman microscopy, we made a critical structural analysis of oligomer and other assembly structures of lysozyme obtained from hen egg white and provided a quantitative estimation of a protein secondary structure in different states of its fibrillation. A strong amide I Raman band at 1660 cm-1 and a N-Cα-C stretching band at ∼930 cm-1 clearly indicated the presence of a substantial amount of α-helical folds of the protein in its oligomeric assembly state. In addition, analysis of the amide III region and Raman difference spectra suggested an ample presence of a PPII-like secondary structure in these oligomers without causing major loss of α-helical folds, which is found in the case of monomeric samples. Circular dichroism study also revealed the presence of typical α-helical folds in the oligomeric state. Nonetheless, most of the Raman bands associated with aromatic residues and disulfide (-S-S-) linkages broadened in the oligomeric state and indicated a collapse in the tertiary structure. In the fibrillar state of assembly, the amide I band became much sharper and enriched with the ß-sheet secondary structure. Also, the disulfide bond vibration in matured fibrils became much weaker compared to monomer and oligomers and thus confirmed certain loss/cleavage of this bond during fibrillation. The Raman band of tryptophan and tyrosine residues indicated that some of these residues experienced a greater hydrophobic microenvironment in the fibrillar state than the protein in the oligomeric state of the assembly structure.

Pseudo five component reaction towards densely functionalized spiro[indole-3,2'-pyrrole] by picric acid, an efficient syn-diastereoselective catalyst: insight into the diastereoselection on C(sp3)-C(sp3) axial conformation.

A new series of highly-functionalized spiro compounds of pyrrole were synthesized by a one pot, step-economic condensation of isatin, arylamine and ß-keto ester catalyzed by wet picric acid. Initially, the reaction was proposed with an expectation of the formation of a multi-spiro heterocyclic framework of highly-substituted piperidine. However, the isomeric compound was characterized to be a five-membered pyrrole derivative with a diverse scope of variations having different types of substituents in the three components respectively. The possibility of formation of various diastereomers around the hindered single bond and the spiro carbon was limited, as only syn products syn-60 and syn-60' were isolated in all the reactions performed under the standard conditions. Probably the reactions were mediated by the si-facial formation of the bonds in a picric acid stabilized charge transfer complex transition state. Also, the manner a molecule achieves the most stabilized energy minimized arrangement with all its substituents in space was studied by DFT calculations where syn-60 was more stable than syn-60'. The studies on the formation of syn-60 and syn-60' were carried out by variation of electronic and steric factors in each of the components of the reactions.

Dihydroindeno[1,2-b]pyrroles: new Al3+ selective off-on chemosensors for bio-imaging in living HepG2 cells.

In this study, a new molecular organic probe has been designed and synthesized by using recyclable, inexpensive and non-toxic polyethylene glycol (PEG-400) as a promoting reaction medium in water under environmentally benevolent conditions. The probe has been explored as a potential chemosensor to detect Al3+ ions using a HEPES buffer (pH = 7.4) solution. Investigations of the fluorescence behaviour of this sensor in DMSO/H2O (2 : 8, v/v) solution displayed a dramatic switch-on response only in the presence of Al3+, while other metal ions, like Li+, Na+, K+, Ag+, Ca2+, Mg2+, Mn2+, Ba2+, Cu2+, Ni2+, Co2+, Fe2+, Zn2+, Cd2+, Hg2+, Pb2+, Sr2+, Fe3+ or Cr3+, have almost no influence on the fluorescence behaviour. Various common anions, such as ClO4-, Cl-, or NO3- in the form of Al3+ salts [e.g. Al(ClO4)3, AlCl3 or Al(NO3)3], had no influence on the fluorescence behaviour of the sensors. The detection limit for Al3+ is in the order of 10-6 M in DMSO/H2O (2 : 8, v/v) HEPES buffer (pH = 7.4) solution. Notably, this is the first report of a dihydroindeno[1,2-b]pyrrole moiety acting as a sensor for the selective detection of Al3+ ions through an off-on fluorescence response. The potential of the probe was also confirmed by employing it for fluorescence bio-imaging with Al3+ on HepG2 cells.

I2 catalyzed access of spiro[indoline-3,4'-pyridine] appended amine dyad: new ON-OFF chemosensors for Cu2+ and imaging in living cells.

An easy access to an amine-appended spiro[indoline-3,4'-pyridine] ON-OFF chemosensor by a one-pot four-component reaction using commercially available and an environmentally benign catalytic amount of molecular I2 (10 mol%) in aqueous ethanol at ambient temperature is described. The generated system could be utilized for the selective detection of Cu2+ as it demonstrated a colorimetric naked eye change along with an ON-OFF fluorescence response towards Cu2+ at physiological pH. The sensors exhibited high selectivity for Cu2+ over other common cations with detection limit in the range of 10-7 (M). Notably, this is the first report of a spiro[indoline-3,4'-pyridine] moiety acting as a sensor for Cu2+via a on-off fluorescence response. In addition, the probe system was successfully applied for imaging Cu2+ in human hepatocellular liver carcinoma cells (HepG2), demonstrating a new avenue for molecular imaging and biomedical applications.

Mesoporous silica nanoparticle based enzyme responsive system for colon specific drug delivery through guar gum capping.

In the global context of increasing colonic diseases, colon specific oral drug delivery systems have shown promise as an effective therapeutic modality. Herein, we developed a mesoporous silica nanoparticle (MSN) based enzyme responsive materials for colon specific drug delivery. We have utilized guar gum, a natural carbohydrate polymer as a capping layer to contain a model drug, such as 5-flurouracil (5FU) within the mesoporous channels of MSN. Analytical characterization including electron microscopy, PXRD, nitrogen sorption, thermogravimetric analysis and FTIR, confirmed that the synthesized MSN with size less than 100nm is of MCM-41type. The studies further showed that the MSN maintained their discrete nanoparticle identity after guar gum capping through non-covalent interaction. The release of 5FU from guar gum capped MSN (GG-MSN) was specifically triggered via enzymatic biodegradation of guar gum by colonic enzymes in the simulated colonic microenvironment. Subsequently, the released drug manifested anticancer activity in colon cancer cell lines in vitro confirmed by flow cytometry and biochemical assay. The drug loaded GG-MSN system also demonstrated near perfect 'zero release' property in absence of enzymes in different simulated conditions of the gastrointestinal tract. Our study provides an important intermediate step to apply such GG-MSN based engineered nanomaterials for further detailed in vivo investigation.

Evaluation of genetic diversity in some promising varieties of lentil using karyological characters and protein profiling.

Somatic chromosome study from root tip cells using the squash technique of the cytological method and seed protein profile of 5 varieties of Lens culinaris (Lentil) through SDS-PAGE were investigated. Karyotype analysis showed gross uniformity in morphology. Somatic chromosome number 2n = 14 is constant for all the varieties. Chromosomes are mostly long to medium in length with secondary constrictions in one pair of chromosome. Primary constrictions in chromosome ranged from nearly median to nearly submedian in most of the cases. Notwithstanding the gross homogeneity, karyotype analysis revealed minute differences in details. Each lentil variety is thus characterized by its own karyotype, serving as one of the identifying criteria. The seed protein profile revealed that varieties are very close to each other with respect to similarity index that ranged from 0.594 to 0.690. With regard to seed protein banding patterns, slight polymorphism (14.285%) indicating low genetic diversity has been identified among the 5 varieties. A dendrogram indicates one variety is plesiomorphic and rest varieties are apomorphic. All the experimental varieties of lentil studied here show low genetic diversity due to their similar genetic base, indigenous genetic resources and conservative nature of the seed protein.

FeCl3-Catalyzed Combinatorial Synthesis of Functionalized Spiro[Indolo-3,10'-indeno [1,2-b]quinolin]-trione Derivatives.

An efficient, inexpensive, environmentally friendly and high yield one-pot route to new spiro[indolo-3,10'-indeno [1,2-b]quinolin]-trione derivatives has been developed, involving three-component reaction of enaminones, N-substituted isatins and Indane-1,3-dione catalyzed by FeCl3. The approach to this spiro-heterocycle is noteworthy because it results in the formation of three new σ (two C-C and one C-N) bonds in a single operation, leading to the construction of novel spiro skeleton. This method works on a large scale in excellent yields.