A Prospective Observational Study on Clinical Profile and Visual Outcomes in Neovascular Age-Related Macular Degeneration.

Background and objectives Over the years, several treatment options have been developed for neovascular age-related macular degeneration (AMD), the most notable being intravitreal injections of anti-vascular endothelial growth factor drugs. The rationale for treating neovascular AMD is to preserve and improve central vision, enhance the quality of life for affected individuals, stabilize or improve vision, and prevent further structural damage to the macula. The objective of the present study was to evaluate the clinical course of different disease types of neovascular age-related macular degeneration and their treatment response to anti-vascular endothelial growth factor (anti-VEGF) injections. Methods This prospective observational study was conducted at a tertiary care referral hospital in Eastern India during October 2019 and September 2021. Patients diagnosed with neovascular AMD attending our Outpatient department and retina clinic were recruited for the study. An experienced ophthalmologist examined all patients, meeting the inclusion criteria. The clinical profile, including initial best corrected visual acuity (BCVA), ophthalmoscopic, fluorescein angiographic, and optical coherence tomography (OCT) findings of different patterns of neovascular AMD, were collected and analyzed. Patients were subjected to intravitreal Ranibizumab every month for three months and then on a when-required basis. Visual outcomes were recorded at each follow-up, and a comparison was done between initial and final visual acuity. Descriptive statistics were used for analysis, with p< 0.05 taken as statistically significant. Results A total of 72 patients were included in the study. Fundus fluorescein angiography revealed that 52.78% were classic, 15.28% were minimally classic, and 31.94% were of occult variety. 41.66% of lesions were subfoveal in location, 47.22% were juxtafoveal, and 11.11% lesions were extrafoveal in location. The mean BCVA was Log MAR (Logarithm of the Minimum Angle of Resolution) 1.061±0.25. The average number of intravitreal Ranibizumab injections given to each eye was five. BCVA of patients after the third injection was log MAR 0.818±0.296. There was a significant improvement in mean BCVA from baseline 1.061±0.254 to 0.787±0.317 after the study (p-valve: p<0.05). After the first injection, 49 patients (68.05%) experienced an initial improvement of at least one line, 20 patients (27.77%) did not exhibit any improvement, and 3 patients (4.16%) had a decline of one line in Snellen's visual acuity chart. Over the follow-up period,10 showed improvement in 1 line in the Snellen chart after subsequent injection. At the end of the study, six patients showed no change, and four patients showed deterioration after the completion of injections. No adverse events were noted during the study period. Conclusions Intravitreal Ranibizumab is effective in improving visual outcomes in treatment-naïve individuals with neovascular age-related macular degeneration. The decision for repeat intravitreal anti-VEGF injection should be based on OCT findings of subretinal fluid, pigment epithelial detachment, and cystoid macular edema as an indicator of disease activity. This can also lessen the number of intravitreal injections and morbidity in these patients.

Stocking density affects immune and stress-related gene expression of Butter catfish (Ompok bimaculatus) fry in biofloc landscapes.

Scientific research into fish wellness is critical, and the concerns about crowding-related stress due to increased stocking density are inevitable. Taking this into consideration, the study defines the physiological signature of Ompok bimaculatus (Butter catfish) in a biofloc system when subjected to varying levels of stocking density. Fish (mean weight = 1.21 g ± 0.08, n = 600) were randomly stocked in 40-L glass aquaria at stocking densities of 0.5 g/L (T1), 1 g/L (T2), 1.5 g/L (T3), and 2 g/L (T4) and fed a 35% protein diet. After the 90-day trial, the physio-biochemical, molecular, and tissue-level changes were assessed. An integrated biomarker response (IBR) analysis for the key stress indicators aided us in better understanding them. There was a significant difference in blood count between T1 and T4 (total erythrocyte count, hemoglobin, and packed cell volume). T1 had higher levels of globulin and total plasma protein, but T2 had higher levels of albumin. Only in T1 did the respiratory burst and lysozyme activity appear to be higher (p < 0.05). Increased stocking densities had a significant impact on the liver function enzymes, GOT and GPT (p < 0.05). In comparison to lower densities (T1 & T2), higher stocking density (T3 & T4) was found to raise glucose and cortisol levels (p < 0.05). Antioxidant enzymes such as catalase, glutathione-S-transferase, and malondialdehyde were found to be more pronounced in lower density tissues (T1). Furthermore, the IBR plots show that lower densities have better health than higher densities. At higher stocking densities, mRNA expression of HSP70, IL-1, and IL-20 increased (p < 0.05) in kidney and liver tissues. The Nrf-2 and Tlr-9 genes were also upregulated. Also, when stocking density was increased, tissue-level histo-architectural changes were more pronounced than when stocking density was kept low. The findings of this study show that the welfare of Butter catfish cultured at high density in biofloc systems suffers from severe stress, and therefore draw more attention to the development of a species-specific standard rearing methodology in the pursuit of a profitable aqua-farming enterprise.

Thermomechanical Properties of Nontoxic Plasticizers for Polyvinyl Chloride Predicted from Molecular Dynamics Simulations.

Environmental and toxicity concerns dictate replacement of di(2-ethylhexyl) phthalate (DEHP) plasticizer used to impart flexibility and thermal stability to polyvinyl chloride (PVC). Potential alternatives to DEHP in PVC include diheptyl succinate (DHS), diethyl adipate (DEA), 1,4-butanediol dibenzoate (1,4-BDB), and dibutyl sebacate (DBS). To examine whether that these bio-based plasticizers can compete with DEHP, we need to compare their tensile, mechanical, and diffusional properties. This work focuses on predicting the effect these plasticizers have on Tg, Young's modulus, shear modulus, fractional free volume, and diffusion for PVC-plasticizer systems. Where data was available, the results from this study are in good agreement with the experiment; we conclude that DBS and DHS are most promising green plasticizers for PVC, since they have properties comparable to DEHP but not the environmental and toxicity concerns.

Carboxymethylcellulose hybrid nanodispersions for edible coatings with potential anti-cancer properties.

Curcumin loaded lipid-polymer hybrid nanoparticles dispersions were fabricated from carboxymethylcellulose, stearic acid, polyethylene glycol and sesame oil using emulsion solvent evaporation method for their possible application as edible coatings for fresh vegetables and fruits. They were characterized by FTIR and TEM analysis. In addition, anti-bacterial, blood compatibility, cytotoxicity and anticancer studies were also carried out. The prepared nanodispersions showed excellent mixed nanostructured morphology with an average size of 94.96 nm. The hybrid nanodispersions showed excellent blood compatibility, non-toxicity and antitumor activity. The synthesized nanoparticle dispersion was employed as an edible coating solution for fresh apples and tomatoes. The hybrid system coated vegetables and fruits shows minimal weight loss after 15 days of storage. Hence, the formulated hybrid nanostructures of CMC are promising as edible coating solution, in addition to possessing the properties to fight cancer.

Novel core-shell dextran hybrid nanosystem for anti-viral drug delivery.

Zidovudine (AZT) is an antiviral drug extensively used for combating the global pandemic- HIV/AIDS. However, its uses are overshadowed by its short half -life, poor aqueous solubility and inability to cross physiological barriers. This study highlights a nanosystem consisting of dextran and stearic acid for AZT delivery. This hybrid nanoparticle was prepared by double emulsion solvent evaporation method. The morphological analysis of the prepared nanoparticles was carried out by transmission electron microscopy (TEM) and structural analysis through FTIR spectroscopy. Haemolysis, blood cell aggregation and cytotoxicity evaluations were also performed. These biological evaluations indicated that the nanoparticles were compatible and fluorescence microscopy studies demonstrated increased cellular internalization of drug loaded hybrid nanoparticles when compared with free drug molecules. The experimental outcomes indicate that the prepared nanoparticles are highly biocompatible haemocompatible and effective in getting internalized into cells of neural origin. These results highlight the feasibility and efficacy of the hybrid nanoparticles for effective delivery of zidovudine.

Biofabricated silver nanoparticles incorporated polymethyl methacrylate as a dental adhesive material with antibacterial and antibiofilm activity against Streptococcus mutans.

In this study, polymethyl methacrylate (PMMA) thin films incorporated with biofabricated silver nanoparticles were used to evaluate the in vitro antimicrobial and antibiofilm activity against the cariogenic bacterium Streptococcus mutans. For this, silver nanoparticles (AgNPs) were generated using Bacillus amyloliquefaciens SJ14 culture (MAgNPs) and extract from Curcuma aromatica rhizome (CAgNPs). The AgNPs were further characterized by UV-Vis spectroscopy and high-resolution transmission electron microscopy. The minimum inhibitory concentration, minimum bactericidal concentration and antibiofilm activity of AgNPs against S. mutans were also assessed. Here, MAgNPs were found to have superior antimicrobial activity when compared to CAgNPs. The MAgNPs and CAgNPs also demonstrated 99% and 94% inhibition of biofilm formation of S. mutans at concentrations of 3 µg/mL and 50 µg/mL, respectively. The AgNPs were further incorporated into PMMA thin films using solvent casting method. The thin films were also characterized by scanning electron microscopy and UV-Vis spectroscopy. Subsequently, both PMMA/MAgNPs and PMMA/CAgNPs nanocomposite thin films were subjected to antimicrobial and antibiofilm analysis. The microbicidal activity was found to be higher for the PMMA/MAgNPs thin film, which highlights the potency of microbially synthesized AgNPs as excellent agents to inhibit cariogenic bacteria from colonising dental restorative material.

Kinetic study of gold nanoparticle mediated photocatalytic degradation of Victoria blue.

In the study, biogenic gold nanoparticles (AuNPs) were used for the photocatalytic degradation of triphenylmethane dyes Victoria blue B (VBB) and R (VBR). The process was found to result in an approximate degradation of 65 and 52%, respectively, for VBB and VBR within a period of 8 h. The relative rate of photocatalytic degradation of VBB and VBR was identified to be 0.0195 ± 0.0031/min and 0.0295 ± 0.0025/min, respectively, by using the Langmuir-Hinshelwood model. By using the Vigna unguiculata model system, the degradation products were demonstrated to have non-toxic effect. Moreover, the less toxic nature of AuNPs used for dye removal highlights its feasibility for large-scale application. Hence, the AuNPs-based photocatalytic dye degradation as described in the study is cost-effective, rapid and environment-friendly.

Encapsulation of zidovudine in PF-68 coated alginate conjugate nanoparticles for anti-HIV drug delivery.

Retroviral drug delivery faces many challenges due to its low bioavailability, short half life and hydrophobicity. In this study, the anti viral drug zidovudine (AZT) was encapsulated inside the amide functionalised alginate nanoparticles (AZT-GAAD NPs) using emulsion solvent evaporation method. The amide derivative of alginate was prepared by coupling reaction with d,l glutamic acid using carbodiimide activation chemistry. The stabilizer, PF-68 was integrated during the preparation of nanoparticles. The alginate nanoparticles were prepared via chemical cross linking. The novelty of this work imparts the absence of chemical cross-linking for the preparation of nanoparticles.The resulting nanoparticles had spherical shape with an average size of 432±11.9nm as confirmed by TEM images. The nanoparticles had a loading efficacy of 29.5±3.2% obtained by dialysis method. The release of AZT in PBS(pH-7.4) was studied and a slow and sustained release of AZT was observed. The nanoparticles were found to be biocompatible and in vitro cellular internalization studies indicated significantly higher internalization efficiency. All these results suggested that (AZT-GAAD NPs) can function as a promising delivery vectors for efficient antiviral drug delivery.

Poly (vinyl pyrrolidone)-lipid based hybrid nanoparticles for anti viral drug delivery.

Zidovudine (AZT) is an antiviral drug with moderate solubility in water. It has limited application due to its short half life in vivo and consequent requirement for frequent administrations. To solve this problem, zidovudine loaded polyvinylpyrrolidone (PVP)/stearic acid (SA)-polyethylene glycol (PEG) nanoparticles (PSNPs) were developed.The hybrid nanoparticles were prepared by emulsification-solvent evaporation method. The physico chemical characterizations of the PSNPs was done by dynamic light scattering (DLS), transmission electron microscopy (TEM), and fourier transform infra-red spectroscopy (FT-IR). The in vitro release behavior and haemocompatibility studies were also performed. The in vitro cytotoxicity and cell uptake studies of the PSNPs were assessed in murine neuro-2a and HeLa cells. Our results revealed that the core shell PSNPs prepared from lipid and polymer led to significant improvement in cellular internalization. Therefore, it is envisaged that nanoparticles composed of lipid and polymer moieties may constitute a preferred embodiment for anti-viral drug delivery for use in HIV/AIDS therapy.

Zinc oxide-curcumin nanocomposite loaded collagen membrane as an effective material against methicillin-resistant coagulase-negative Staphylococci.

Zinc oxide nanoparticles and curcumin are excellent antimicrobial agents. They have the potential to be used as alternative to antibiotics in wound infection management. In this study, ZnO-curcumin nanocomposite was synthesized and characterized. Physical adsorption of the nanocomposite onto collagen skin wound dressing was conducted and structural investigation was carried out by SEM. Antimicrobial assay, minimum inhibitory concentration (MIC), and viability assays of different concentrations of nanocomposite loaded collagen membrane were conducted against clinically isolated methicillin-resistant coagulase-negative Staphylococci (MRCoNS), such as S. epidermidis, S. hemolyticus, and S. saprophyticus. The nanocomposite showed excellent anti-CoNS activity on time kill assay with the MIC value of 195 µg/mL against S. epidermidis, S. hemolyticus and 390 µg/mL against S. saprophyticus. The nanocomposite loaded collagen membrane also showed excellent in vitro antistaphylococcal activity. This study may lead to the development of antibiotic alternate strategies to control and limit the MRCoNS in wound-related infections.

Sleep quality in temporomandibular disorder cases.

OBJECTIVE: The aim of this study was to characterize self-reported sleep quality (SQ) in cases with temporomandibular disorder (TMD) and to compare their results with those of healthy controls. METHODS: The Pittsburgh Sleep Quality Index (PSQI) was used to measure SQ in a convenience sample of 609 TMD cases and 88 controls. The Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) Axis I diagnostic nomenclature was used, but Axis I diagnoses were based on the consensus of two reliable criterion examiners and not the RDC/TMD algorithms. The PSQI scores for TMD cases were calculated also for the RDC/TMD Axis II measures assessing chronic pain and disability, depression, and nonspecific physical symptoms. PSQI scores of the TMD cases were compared with those from controls. RESULTS: TMD cases with one to five TMD diagnoses (n = 609) had a mean PSQI score of 7.0 [95% confidence interval (CI) = 6.7-7.4]. In comparison, the mean score was 5.2 (95% CI = 4.6-5.9) for control subjects. For the subset of TMD cases with pain-free diagnoses (n = 113), the PSQI score was similar to controls with 5.1 (95% CI = 4.5-5.6), whereas it was significantly different for cases with pain-related diagnoses 7.5 (95% CI = 6.6-8.3; n = 87). Although the number of TMD diagnoses and participant age had some influence on SQ, psychosocial status, and pain-related impairment assessed with RDC/TMD Axis II measures had the strongest association with SQ, in particular, dysfunctional chronic pain. CONCLUSION: SQ is impaired in TMD patients with pain-related diagnoses, and even more in those with dysfunctional pain. This relationship between sleep and pain suggests that SQ should be assessed in TMD pain patients, especially in those with significant Axis II involvement.

Effects of diet and behavioral enrichment on free fatty acids in the aged canine brain.

Despite several recent studies suggesting that dysregulation of brain lipid metabolism might contribute to the mechanisms of aging and Alzheimer's disease (AD), lipid metabolism has not been evaluated extensively in the aging brain. Here, we use a lipidomic approach to demonstrate that antioxidants plus mitochondrial cofactors treatment, either alone or in combination with behavioral enrichment, attenuates lipid abnormalities in the frontal cortices of aged canine in a manner correlated with cognitive scores. Our analyses revealed that the levels of free palmitoleic acid and nervonic acid were decreased in frontal cortices of aged dogs (n=5-6/group) treated with antioxidant compared with the control group. The monounsaturated/saturated fatty acid ratio, also known as "desaturation index"-an ex-vivo indicator of stearoyl-CoA desaturase activity, was also reduced in the frontal cortex of dogs treated with antioxidants compared with control groups. Increased palmitoleic acid levels and desaturation index were positively correlated with increased reversal learning errors and decreased cognitive performance. In conclusion, our study indicates that the addition of antioxidants and mitochondrial cofactors to the regular diet alters the composition of free fatty acids in the aged brain. Together with data showing increased palmitoleic acid levels in AD patients, our data suggest that reducing palmitoleic acid levels and desaturation index in the brain may be associated with improved cognitive performance.

Attenuation of phencyclidine-induced object recognition deficits by the combination of atypical antipsychotic drugs and pimavanserin (ACP 103), a 5-hydroxytryptamine(2A) receptor inverse agonist.

Subchronic administration of the N-methyl-d-aspartate receptor antagonist, phencyclidine (PCP), in rodents has been shown to produce impairment in novel object recognition (NOR), a model of visual learning and memory. We tested the hypothesis that the selective 5-HT(2A) inverse agonists, pimavanserin and (R)-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl]-4-piperidinemethanol (M100907), would potentiate subeffective doses of atypical antipsychotic drugs (APDs) to reverse the NOR deficits. Female rats received vehicle or PCP (2 mg/kg b.i.d.) for 7 days, followed by a 7-day washout. Pimavanserin (3 mg/kg) or M100907 (1 mg/kg) alone, or four atypicial APDs, risperidone (0.05-0.1 mg/kg), melperone (1-3 mg/kg), olanzapine (1-2 mg/kg), or N-desmethylclozapine (1-2 mg/kg), and the typical APD, haloperidol (0.05-0.1 mg/kg), were administered alone, or in combination with pimavanserin or M100907, before NOR testing. The exploration times of objects during 3-min acquisition and retention trials, separated by a 1-min interval, were compared by analysis of variance. Vehicle-, but not PCP-treated, animals, explored the novel object significantly more than the familiar in the retention trial (p < 0.05-0.01). Pretreatment with the higher doses of the atypical APDs, but not pimavanserin, M100907, or haloperidol alone, reversed the effects of PCP. The effect of risperidone was blocked by haloperidol pretreatment. Coadministration of pimavanserin or M100907, with ineffective doses of the atypical APDs, but not haloperidol, also reversed the PCP-induced deficit in NOR. These results support the importance of 5-hydroxytryptamine(2A) receptor blockade relative to D(2) receptor blockade in the ability of atypicals to ameliorate the effect of subchronic PCP, a putative measure of cognitive dysfunction in schizophrenia.

Ziprasidone and aripiprazole attenuate olanzapine-induced hyperphagia in rats.

Weight gain induced by some second-generation anti-psychotics such as olanzapine has emerged as a most debilitating side-effect. This study investigates whether co-administration with either ziprasidone or aripiprazole, which have little propensity to induce weight gain, can attenuate the hyperphagic effect of olanzapine. Female hooded-Lister rats (n=8 per group) were treated acutely with either vehicle, olanzapine (1 mg/kg), ziprasidone (1 mg/kg), aripiprazole (2 mg/kg) or olanzapine in combination with ziprasidone or aripiprazole and placed in automated locomotor activity (LMA) boxes with preweighed palatable mash. Food intake and LMA were measured for 60 min postdrug treatment. All olanzapine-treated groups demonstrated significant increases in food intake (P<0.001). This effect was attenuated following co-administration of olanzapine with either ziprasidone or aripiprazole (P<0.001), neither of which affected food intake alone. The lack of hyperphagia induced by aripiprazole and ziprasidone may reflect an inherent pharmacological mechanism preventing weight gain.

Treatment of complex sleep apnea syndrome: a retrospective comparative review.

BACKGROUND AND PURPOSE: Some patients with obstructive sleep apnea syndrome (OSAS) develop problematic central apneas or Cheyne-Stokes pattern with acute application of continuous positive airway pressure (CPAP), herein called complex sleep apnea syndrome (CompSAS). This response makes it difficult to be certain that CPAP will be a successful treatment strategy. We sought to compare treatments between patients with CompSAS vs. OSAS and hypothesized that CompSAS patients would find CPAP less effective and have more problems with adherence than patients with OSAS. PATIENTS AND METHODS: We performed a retrospective review of patients studied in our sleep disorders center over 1 month. RESULTS: There were 133 patients with OSAS (mean age=57.6+/-12.2 years; males=63.9%) and 34 with CompSAS (mean age=54.4+/-16 years; males=82.35%). CPAP was prescribed in 93.7 and 87.9% of OSAS and CompSAS patients, respectively (P=0.284), with no significant difference in required CPAP pressures (P=0.112). There was no difference in prescription frequency of alternative therapies. Mean time to the first follow-up was shorter in CompSAS patients (46.2+/-47.3 vs. 53.8+/-36.8 days; P=0.022). CPAP compliance in OSAS and CompSAS patients (5.1+/-1.6 vs. 6.1+/-1.5h, P=0.156) and improvement in Epworth Sleepiness Scale (ESS) (-4.6+/-4.8 vs. -5.9+/-6.9, P=0.483) was similar. However, interface problems were more common in CompSAS patients, especially air hunger/dyspnea (0.8 vs. 8.8%) and inadvertent mask removal (2.6 vs. 17.7%) (all P<0.050). CONCLUSION: CompSAS patients have more CPAP interface problems and require more follow-up than OSAS patients but with intervention may have similar treatment results compared to patients with OSAS.