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Litter size is a complex and sex limited trait that depends on various biological, managemental and environmental factors. Owing to its low heritability it is inefficaciously selected by traditional methods. However, due to higher heritability of ovulation rate and embryo survival, selection based on component traits of litter size is advocated. QTL analysis and candidate gene approach are among the various supplementary/alternate strategies for selection of litter size. QTL analysis is aimed at identifying genomic regions affecting trait of interest significantly. Candidate gene approach necessitates identification of genes potentially affecting the trait. There are various genes that significantly affect litter size and its component traits viz. ESR, LEP, BF, IGFBP, RBP4, PRLR, CTNNAL1, WNT10B, TCF12, DAZ, and RNF4. These genes affect litter size in a complex interacting manner. Lately, genome wide association study (GWAS) have been utilized to unveil the genetic and biological background of litter traits, and elucidate the genes governing litter size. Favorable SNPs in these genes have been identified and offers a scope for inclusion in selection programs thereby increasing breeding efficiency and profit in pigs.

For increasing milk production in the country, number of efforts has been made to improve technical knowledge of the farmer and ensure supply of inputs and services. The most predominant one is the strengthening of dairy cooperatives in the country under the project Operation Flood. The present study estimated the technical efficiency among farmers of the Sirsa dairy cooperative union in Haryana and determined factor affecting it. The study found that the technical efficiency of dairy farmers in the milkshed was considerably high for all herd size categories (> 80 per cent). It was the highest for medium herd size category (86 per cent) followed by large category (85 per cent). Among households of a herd-size category, technical efficiency was consistent and found to be uniform among the household as revealed by the lower value of standard deviation. The major determinants of technical efficiency were the age of the farmer, period of becoming member of cooperative society, fixed cost and the marketed surplus.

Hypothesis: A large number of contact lens wearers drop out each year due to end of day discomfort, which could possibly be reduced by designing lenses with highly lubricious surfaces. We hypothesize that polymerizing a thin film of dimethyl acrylamide (DMA) on the surface of the lenses will improve lubricity. Experiments: The thin film is polymerized by loading a commercial contact lens (1-DAY ACUVUE® TruEye®) with N,N,N′,N′-Tetramethylethane-1,2-diamine (TEMED) and soaking it in a solution of DMA and ammonium per sulfate (APS). The two components of the redox couple (APS and TEMED) mix near the surface of the lens due to diffusion and react rapidly to form free radicals. The free radicals lead the polymerization of the DMA monomer near the surface resulting in the formation of the thin hydrogel layer that is attached to the lens matrix through activation of unreacted vinyl groups or possibly through formation of entanglements with the lens polymer. Findings: The thickness of the layer is controlled by the polymerization time which is limited to 30 s to create a layer of DMA only at the surface. The presence of the DMA layer is confirmed through measurements of Fourier-transform infrared spectroscopy (FTIR) spectra in total internal reflection mode. The layer is determined to be about 3–5 µm thick with a water content of about 285%. The presence of the layer significantly improves lubricity as is evident through the qualitative rubbing test and quantitative measurement of the friction coefficient. A preliminary one-week safety study in rabbits show that lens wear does not cause any toxicity.

The present study was undertaken to characterize the distinct immune response in indigenous Ghurrah and exotic Landrace pigs by challenging monocyte-derived macrophages (MDMs) with CSF virus under in-vitro conditions and assessing the variations in the transcriptome profile at 48 h post-infection (hpi). RNA-sequencing was carried out in infected and non-infected MDMs of Ghurrah (n = 3) and Landrace (n = 3) piglets prior- as well as post-stimulation. MDMs of Ghurrah showed greater immune regulation in response to CSF infection with 518 significantly differentially expressed genes (DEG) in infected versus non-infected MDMs, as compared to only 31 DEGs in Landrace MDMs. In Landrace, the principal regulators of inflammation (IL1α, IL1β and TNF) were upregulated in infected cells while in Ghurrah, these were downregulated. Overall, macrophages from indigenous Ghurrah showed more immunological dysregulation in response to virulent CSF virus infection as compared to the exotic Landrace pigs.

Hypothesis Topical and systemic methods are not able to deliver ophthalmic drugs for treatment of retinal diseases. Consequently, invasive monthly intravitreal injections through the eyeball are required to deliver retinal drugs. A reduction in the frequency of the injection through extended release of the drugs could have significant clinical benefits. Experiments Oleogels containing ethyl cellulose as the gelator at 10% (wt%) in soybean oil were loaded with dexamethasone above the solubility limit and expunged from a syringe to create cylindrical rods for extended drug delivery. The devices were imaged to explore particle distribution and drug release was measured under sink conditions in buffer. A model was developed and fitted to data to determine effective drug diffusivity. Findings Dexamethasone is released slowly due to the presence of the drug particles that serve as drug depots. The release increases from 600 to 3000 h as the drug loading is increased from 3% to 28%. The release profiles can be modeled by considering drug dissolution and diffusion, as well as the tortuosity of the matrix due to the presence of the voids formed after the drug particles have dissolved. The proposed approach is promising as the release profiles of the drug are comparable to commercial devices.

The present study investigated production, marketed surplus, consumption and disposal pattern of milk in Andhra Pradesh. The study covered 160 milk producers selected randomly from eight village dairy cooperatives which were post-stratified into small, medium and large herd size category. The study revealed that Overall average milk production was higher for member households (42.15 litres) as compared to non-member households (24.99 litres), respectively. Overall average milk consumption per day per household was lower in the member group (1.51 litres) than non-member group (2.06 litres), respectively. The average quantity of marketed surplus of milk per day per household was higher in the member group (40.64 litres) as compared to the non-member group (22.93 litres), respectively. Out of total quantity of milk disposed off per day by the member households, 96.21 per cent was disposed to dairy cooperatives followed by 2.84 per cent to milk vendors, 1.03 per cent to tea shops and only 0.91 per cent to consumers directly. Similarly, for non-member households, 80.50 per cent was disposed to dairy cooperatives followed by 12.88 per cent to private dairies, 2.49 per cent to milk vendors, 2.11 per cent to tea shops and only 2.03 per cent to consumers directly in the study area.

The permeability through the cornea determines the ability of a drug or any topically applied compound to cross the tissue and reach the intraocular area. Most of the permeability values found in the literature are obtained considering topical drug formulations, and therefore, refer to the drug permeability inward the eye. However, due to the asymmetry of the corneal tissue, outward drug permeability constitutes a more meaningful parameter when dealing with intraocular drug-delivery systems (i.e., drug-loaded intraocular lenses, intraocular implants or injections). Herein, the permeability coefficients of two commonly administered anti-inflammatory drugs (i.e., bromfenac sodium and dexamethasone sodium) were determined ex vivo using Franz diffusion cells and porcine corneas in both inward and outward configurations. A significantly higher drug accumulation in the cornea was detected in the outward direction, which is consistent with the different characteristics of the corneal layers. Coherently, a higher permeability coefficient was obtained for bromfenac sodium in the outward direction, but no differences were detected for dexamethasone sodium in the two directions. Drug accumulation in the cornea can prolong the therapeutic effect of intraocular drug-release system This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement N° 813440 (ORBITAL—Ocular Research by Integrated Training And Learning) and is also supported by the Fundação para a Ciência e Tecnologia (FCT) [UID/QUI/00100/2019, UIDB/00100/2020 and UID/BIM/04585/2020] SI

Cystinosis is a rare genetic disorder order affecting the transport of the amino acid cystine across the lysosomal membrane, leading to crystal formation throughout the body. The formation of these crystals in the cornea leads to photophobia and other ocular complications. The current treatment is to use eye drops of a thiol called cysteamine, delivered at a rate about 8–12 drops per day due to very low bioavailability intrinsic to eye drops. This paper examines an alternative and possibly more effective method of using contact lenses, which are suggested to have a bioavailability of around 50%, to deliver cysteamine to the cornea. This paper focuses on first designing in vitro, ex vivo and in vivo rabbit models of cornea containing cystine crystals and testing for feasibility of crystal dissolution by using contact lenses. In each model, cystine crystals were formed by loading cysteine into the cornea followed by oxidation to form cystine crystals. In some cases, cystine was directly transported into the cornea to form the crystals. The in vitro model—using a cystine-laden hydroxyl ethyl methacrylate hydrogel in the shape of a cornea—demonstrated an effectiveness of roughly 52% of loaded cysteamine reaching the “hydrogel cornea.” The ex vivo model—using rabbit cadaver eyes impregnated with cystine crystals—again showed a near 50% bioavailability—using 27 ± 2 lenses to lead to crystal dissolution when 13 lenses were needed if 100% bioavailability could be reached. The in vivo studies showed that exposing the cornea of a normal animal can lead to crystal formation but the crystals dissolve rapidly likely due to clearance through the aqueous humor. Thus, efficacy of eluting contacts at dissolving crystals could not be tested in vivo. These results suggest that cysteamine loaded contact lens could transport cysteamine into the cornea at higher bioavailability compared to the eye drops and thus be potentially effective at treating cystinosis.

The aim of this study was to identify the single-nucleotide polymorphisms (SNPs) in bovine candidate genes

Ophthalmic drug delivery via eye drops is inefficient because only about 1-5% of the drug permeates the cornea during the short residence time of a few minutes. Contact lenses are receiving considerable attention for delivering ophthalmic drugs because of higher bioavailability and the possibility of sustained release from hour to days, and possibly longer. The drug release durations from contact lenses are typically measured in vitro and it is challenging to relate the in vitro release to in vivo release, particularly for hydrophobic drugs which may not exhibit sink release in vitro and in vivo. The in vitro release can be fitted to diffusion equation to determine the partition coefficient and diffusivity, which can then be utilized to model in vivo release. The Higuchi equation is frequently used to model the short time release from a contact lens to determine diffusivity with the implicit assumption that the release is under sink conditions and the starting concentration in the lens was uniform. Both conditions may be violated when measuring release of hydrophobic drugs from contact lenses because the diffusivity and partition coefficient, and also the time needed for equilibrium are not known a priori. Here we develop a method to use the data for both loading and release of cyclosporine, which is a common hydrophobic ophthalmic drug, to determine the partition coefficient and diffusivity. The proposed approach does not require sink conditions and also does not require the lens to be fully equilibrated during loading, which may take almost a month for lenses considered here. The model is based on solving the diffusion equation in the gel along with a mass balance in the fluid. The model equations are solved numerically by finite difference. When the value of partition coefficient is high, such as it is for cyclosporine, the dynamic data is only sensitive to a ratio of partition coefficient and diffusivity, and this ratio had to first be determined from the loading data. Then the two unknown parameters were obtained by minimizing the error between the model prediction and experimental data. The method was used to determine D and K for several silicone hydrogel formulations with varying ratio of hydrogel and silicone fractions.

The aim of this study was to identify the single-nucleotide polymorphisms (SNPs) in bovine candidate genes CLEC7A, CD209 and TLR4, and explore the association between these SNPs with the occurrence of bovine paratuberculosis (PTB) disease. For this purpose, 549 animals were screened by a panel of four diagnostic tests, namely Johnin PPD test, ELISA test, faecal microscopy and IS900 blood PCR against Mycobacterium avium ssp. paratuberculosis (MAP) to develop case–control populations. SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism method. Genotypic–phenotypic associations were assessed by the PROC-LOGISTIC procedure of SAS 9.3. Of the seven SNPs; rs110353594 in CLEC7A gene and rs8193046 in TLR4 gene were found to be associated with PTB. For SNP rs110353594, odds of CC and CT genotypes vs TT genotype was 1.543 (0.420–5.667; 95% CI) and 0.284 (0.104–0.774; 95% CI), respectively which means that CT genotype was more resistant than TT and CC genotypes against bovine PTB. For SNP rs8193046, odds of AA and AG genotypes versus GG genotype was 0.947 (0.296–3.034; 95% CI) and 3.947 (1.555–10.022; 95% CI), respectively, i.e. probability for getting an infection in animals with AG genotype was 3.94 times more as compared to GG genotype. Hence, a selection programme favouring CT genotype for rs110353594 and against AG genotype for rs8193046 may be beneficial for conferring resistance against bovine PTB.

In vitro screening and testing of drugs and devices is necessary, but in vitro conditions differ greatly from those found in vivo. These differences can lead to false promises of efficacy, or can hide problems of tissue compatibility. Models with ex vivo tissues can be highly valuable bridges which provide relevant matrices for testing [1], [2], [3], [4], [5], [6], [7], [8], [9]. Ex vivo tissue models which are closer both biochemically and biophysically can provide useful feedback in a more time- and cost-efficient manner. Herein we describe an ex vivo corneal model for use in drug delivery testing and corneal infection modeling [10]. The protocol covers the tissue harvesting, sterilization, inoculation, and bacterial load quantification. We envision that the model can be used to study bacterial physiology on metabolizable matrices and to study the direct effects of microbial colonization on the cornea's integrity and clarity.•Devitalized cornea.•Non-submersed conditions.•Contact lens compatible., Graphical abstract Image, graphical abstract

Mastitis is a complex disease responsible for huge economic losses to the dairy sector. The causal organisms include a wide variety of micro-organisms including several species of bacteria. Escherichia coli has been identified as one of the most common gram-negative bacteria causing clinical mastitis in cattle. The immune system, of different species and/or breeds, tries to combat these pathogens in an inconsistent manner with differential mode and intensity of immune response, eventually producing contradicting outcomes of this disease. Several reports suggest the existence of variability among different animal breeds/species, resulting in a dissimilar outcome of this disease among them. In order to evaluate the variation among different breeds/species, the present study was undertaken to examine the stimulant effect of E. coli lipopolysaccharide (LPS) on peripheral blood mononuclear cells (PBMCs). The PBMCs were harvested from blood samples of crossbred cattle, Tharparkar cattle and Murrah buffaloes. After 6 h of in vitro stimulation, qRT-PCR was employed to measure the relative mRNA expression levels of CCL5, IL-1β, IL-12β, IFN-γ and IL-10 genes in stimulated and unstimulated PBMCs. The selected genes revealed significant differences in the pattern of innate immune response among crossbred cattle, Tharparkar cattle and Murrah buffaloes. The results clearly indicate the presence of variation in the outcome of immune response even when the immunocytes were stimulated with the same dose of the antigen.

Purpose Delivering ophthalmic drugs to the target tissues in eye is challenging due to transport barriers. Rapid tear clearance of the drug instilled as eye drops to treat anterior segment diseases results in a low ocular permeability of 1-5%. The blood-retina barrier and clearance mechanisms which eliminate drug from tears and ocular tissue make systemic or topical delivery techniques ineffective in delivering drugs to the back of the eye. Intravitreal injections into the eye are the only viable option even though repeated monthly injections increase risk for infections and retinal detachment. Controlled and sustained drug delivery could reduce the frequency of injections and lower the associated risk of side effects. Methods Oleogels comprising of 10% (w/w) ethyl cellulose as the gelator in soybean oil are loaded with metformin HCl and timolol maleate above the solubility limit resulting in a dispersion of the drug particles in the gelled oil. In an alternative approach, hydrophilic drugs are dissolved in the water phase of water-in-oil emulsions, followed by gelling the oil phase. Each formulation was expunged from one mL syringes with attached 22-gauge needles (0.4 mm inner diameter) into buffer to form a cylindrical rod that maintained its shape due to the high viscosity of the oleogel. Dynamic drug concentration was measured in the release medium to determine drug release profiles. Also, the devices were imaged to show the dispersal of drug particles as well as the degradation of the device over time. Effective drug diffusivity for both particle-based and emulsion-based approaches was determined by fitting data to dynamic drug concentration models. The effect of particle size and drug loading are explored. Results The release durations for metformin HCl are 120 hours for the particulate formulation and almost 1400 hours for the gelled emulsion formulation. For particulate timolol maleate formulation, the release duration increases from about 400 to over 1000 hours as the drug loading is increased from 1% to 25%, while the gelled emulsion formulation releases drug for 2200 hours. Drug release from oleogels can be modeled by considering formulation properties such as diffusion and solubility, however, tortuosity within the gel due to void formation and binding of drug to gelator molecules must also be taken into account to accurately model particle-based systems. Conclusions Oleogel rods are useful devices for extended delivery of ophthalmic drugs. The release duration can be controlled by drug loading and partition coefficient. Release of the drugs from the oleogels results in voids that increase the tortuosity resulting in an increase in release duration. Binding of drugs to the gelator decreases the effective diffusivity further increasing the release duration.

The stabilization of oil-in-water emulsions is critical for a wide variety of fields. Here, we explore the reaction dynamics of and emulsion stabilization by in situ surfactant generation through the saponification of esters that are commonly used in cosmetics and drug delivery. We combine measurements of dynamic interfacial tension and surface elasticity with emulsion stability to determine the dynamics of the interfacial reaction and its effect on interfacial properties. The rate of surfactant production through the in situ reaction depends on the surface area and thus the dynamics measured in a pendant drop may not reflect the dynamics in emulsification. To test this, we also measure the dynamics of surfactant production after emulsification. Further, we explore the effect of surfactant chain length and solution pH on the interfacial tension dynamics and the emulsion stability. The results show that the interfacial tension transients in a pendant drop correlate with the in situ reaction dynamics but that there are others factors to consider. The steady state interfacial tension represents a pseudo-steady state between rate of surfactant produced and that desorbing into the aqueous phase. The interfacial tension dynamics and emulsion stability also depend strongly on the charge. The emulsions retain stability after aqueous pH neutralization, suggesting that a portion of the adsorbed surfactant molecules remain ionized at neutral pH. Emulsion stability increases with increasing surfactant chain length, which is the expected trend because a longer chain length reduces aqueous solubility thereby increasing the surfactant surface coverage. Therefore, the approach of emulsion stabilization by in situ surfactant production is more useful for surfactants with very low aqueous solubility. Finally, the transients of surfactant concentration in the emulsions show a reduction in the rate of the in situ reaction with increasing coverage of the surface by the adsorbed anionic surfactant most likely due to the buildup of surface charge that reduces the concentration of the hydroxyl ions at the surface.

During the Deep Water Horizon oil spill in 2010, approximately 4200 m 3 of Corexit 9500 were introduced to the Gulf of Mexico to disperse the 4.9 million barrels of crude oil that were released. This was the first time that dispersants were applied below the ocean surface. For such subsurface applications, rates of adsorption could provide critical insight about a dispersant’s ability to interact with a gushing oil plume. Most of the published literature, however, focuses on swirling flask and wave tank tests to quantify dispersant effectiveness and is more applicable to surface applications. To obtain a more comprehensive understanding of the interface and insight about adsorption rates, we measure dynamic interfacial tension and dilational rheology, which have not been previously reported for the Corexit 9500 system. Measurements show that increasing the aqueous salinity to approximately that of sea water drastically increases Corexit 9500s adsorption rates and lowers interfacial tensions. Specifically, the interfacial tension decreases from a pure interface value of 22.4 mN/m to approximately 2 mN/m at 10 wt% Corexit 9500 and 0.01 wt% Corexit 9500 for the fresh and salt water systems, respectively. The time for achieving equilibrium is inversely proportional to the concentration. Dynamic and equilibrium interfacial tensions for both systems are well described by a simplified predictive model for several orders of magnitude in concentration. Finally, moderately high dilational moduli values which are frequency independent and primarily elastic in nature were measured. The time scales for adsorption reported here could be useful in designing the process for spraying the dispersant in deep-sea applications. The model parameters, although not physically correct due to the assumption of a single component system, could be useful in predicting the adsorption of the sprayed dispersant to the rising oil plume.

Purpose Contact lens induced discomfort (CLD) has been recognized as the most common cause of contact lens wearer drop-out over the past four decades. Many studies show correlation between comfort and lubricity, which can be increased by incorporation of lubricating polymers in lenses to serve as comfort agents. The objective of this study is to measure the effect of two different comfort-agent incorporation on lubricity, and also to determine the changes in lubricity with release of the agents from the lenses. Materials and methods The two comfort agents in this study, polyvinyl alcohol (PVA) and carboxymethylcellulose (CMC), were loaded into 1-DAY ACUVUE® TruEye® and ACUVUE® MOIST contact lenses (made of narafilcon A and etafilcon A respectively) in a 1 week soaking process. These lenses were then placed into phosphate buffered saline (PBS) solutions and analyzed periodically using UV–vis spectrophotometry to determine the rate of lubricant release from the lenses. A lab-made contact lens lubricity testing device (CLLTD) was subsequently used to determine their respective lubricities. Results During trial testing, most of the PVA and CMC was released in both the narafilcon A and etafilcon lenses within the first one to three hours. After an initial increase in lubricity relative to baseline values, these release profiles were accompanied by corresponding decreases in lubricity levels for each ocular lubricant and lens material combination. Conclusions These results indicate that the lubricity of a contact lens can decrease with wear time due to release of the comfort agents, which could potentially lead to the commonly observed end of day discomfort. Thus, increasing the duration of release by increasing molecular weight or incorporating controlled-release strategies could be very valuable in addressing the issue of end-of-day discomfort.

Purpose Currently, invasive monthly intravitreal injections through the eyeball are required to deliver retinal drugs. Injections of oleogels into the vitreous have the potential for extended release of both hydrophobic and hydrophilic drugs for extended durations which could decrease the frequency of injections. The type of gelator used is critical because it may impact drug release and also the biocompatibility of the device. Methods Oleogels containing soybean oil as the liquid component and beeswax, a combination of β-sitosterol and lecithin, sorbitan monostearate, sunflower wax, ethyl cellulose, or a combination of γ-oryzanol with β-sitosterol as the gelator were loaded with the drugs dexamethasone, cyclosporine, triamcinolone, vancomycin above the solubility limit and expunged from a syringe to create cylindrical rods for extended drug delivery. Images of the devices were taken to observe the dispersal of drug particles. In vitro drug release in buffer solutions was measured and effective drug diffusivity was determined from a fitted model. Effect of molecular weight and drug binding to the gelator on diffusivity was explored. Results At loading above the solubility limit, the oleogel formulation contains drug particles that act as distributed depots resulting in extended release. The oleogels prepared with different gelators presented a wide range of drug release profiles. The release durations for 10% loading dexamethasone are 35 days for the β-sitosterol/lecithin gel and 135 days for the sorbitan monostearate gel. The γ-oryzanol/β-sitosterol gels released 81% after 135 days and the beeswax and sunflower wax gels released about 78% and 79% of the loaded dexamethasone after 30 days, respectively. In ethyl cellulose gels, the release duration of 28% cyclosporine was 13 days, 28% loaded dexamethasone released 66% after 125 days, 28% triamcinolone released 46% after 108 days, and vancomycin released 80% after 21 days. The solubility limit of the drug in the oleogel was increased in presence of gelator suggesting significant drug binding to the gelator. The effective diffusivity decreased with drug binding likely because the bound drug does not diffuse. The model based on accounting for drug particle depots fit the release data. Dissolution of the particles results in void formation that increases tortosity impacting effective diffusivity. Conclusions Oleogel based rods can provide extended release of many hydrophobic drugs. Solubility of drugs in the gels are affected by gelator type, which suggests some interaction between the drug and the gelling agent. Drug dissolution, diffusion, binding as well as tortuosity due to the formation of voids must be considered to model drug release. Hypothesis Currently, invasive monthly intravitreal injections through the eyeball are required to deliver retinal drugs. Consequently, oleogels have been explored as an extended release ocular implant for delivery of drug to the retina. The gelator component in these gels is ethyl cellulose, a polysaccharide that is not readily degradable in the eye. Comparing various biocompatible gelator molecules’ ability to form drug incorporated oleogel formulations and their effect on drug release profiles could provide significant insight into development of oleogel devices. Experiments Oleogels containing soybean oil as the liquid component and beeswax, a combination of β-sitosterol and lecithin, sorbitan monostearate, sunflower wax, ethyl cellulose, or a combination of γ-oryzanol with β-sitosterol as the gelator were loaded with the drugs dexamethasone, cyclosporine, triamcinolone, vancomycin above the solubility limit and expunged from a syringe to create cylindrical rods for extended drug delivery. Images of the devices were taken to observe the dispersal of drug particles. In vitro drug release in buffer solutions was measured and effective drug diffusivity was determined from a fitted model. Findings At sufficient loading concentrations, drug particles are suspended in the gel and slowly release. The oleogels prepared with different gelators presented a wide range of drug release profiles. The release durations for 10% loading dexamethasone are 35 days for the β-sitosterol/lecithin gel and 135 days for the sorbitan monostearate gel. The γ-oryzanol/β-sitosterol gels released 81% after 135 days and the beeswax and sunflower wax gels released about 78% and 79% of the loaded dexamethasone after 30 days, respectively. In ethyl cellulose gels, the release duration of 28% cyclosporine was 13 days, 28% loaded dexamethasone released 66% after 125 days, 28% triamcinolone released 46% after 108 days, and vancomycin released 80% after 21 days. Solubility of drugs in the gels are affected by gelator type, which suggests some interaction between the drug and the gelling agent. Drug dissolution, diffusion, as well as tortuosity due to the formation of voids must be considered to model drug release.

Glaucoma is effectively treated by prostaglandin analogs. Low corneal bioavailability (5%) of daily-instilled prostaglandin drops complemented by frequent application results in low patient compliance (50%). One alternative route is ocular delivery via commercial hydrogel contact lens. Commercial lenses, however, release prostaglandins rapidly in a few hours owing to their small molecular size, resulting in toxic side-effects. Here, the feasibility of sustained prostaglandin, namely bimatoprost and latanoprost delivery by vitamin-E integrated polymeric hydrogels is explored. Inclusion of these barriers is expected to augment transport resistance and influence delivery rates.Lens immersion in vitamin-E concentrated ethanol is done to enable formation of nano-barrier depots.Pilot in vitro studies indicate that ACUVUE® OASYS® and ACUVUE® TruEye™ lenses loaded with ∼0.2 g of vitamin-E/g of hydrogel effectively prolong bimatoprost dynamics by 10-40-fold, delivering therapeutic dosages for10 days. Incorporation of vitamin-E into the lenses retains visible light transmission and other properties. Further, vitamin-E integration does not influence latanoprost transport. An in vivo model involving coupled mass transport in the lens and post-lens tear film (POLTF) domains predicts50% corneal bioavailability of bimatoprost delivered via modified lenses.

In the present study, polymorphisms at two single nucleotide polymorphisms (SNPs) and one microsatellite locus of SLC11A1 gene were investigated for finding their association with susceptibility to bovine tuberculosis trait (tuberculin reaction) in Indian cattle. A total of 245 animals were tested with single intradermal tuberculin test for screening positive animals for tuberculin reaction. At rs109915208 locus very low polymorphism information content of 0.0454 was observed, whereas it was moderate (0.352) at rs109453173 locus of SLC11A1. At rs109915208 locus the genotypic as well as allelic frequencies were differing significantly (p-value

This paper focuses on exploring the effect of the side walls on dispersion in oscillatory Poiseuille flows in rectangular channels. The method of multiple time scales with regular expansions is utilized to obtain analytical expressions for the effective dispersivity D3D⁎. The dispersion coefficient is of the form D3D⁎/Pe2=f(Ω≡ωh2/D,Sc≡D/ν,χ≡w/h) where Pe≡ h/DPe≡ h/D, is the root mean square of the cross-section averaged velocity, ω is the angular velocity, 2w and 2h are, respectively, the width and the height of the cross-section, D is the solute diffusivity, and ν is the fluid kinematic viscosity. The analytical results are compared with full numerical simulations and asymptotic expressions. Also effect of various parameters on dispersion coefficient is explored. For small oscillation frequency ΩΩ the dispersion coefficient approaches the time averaged dispersion of the Poiseuille flow and for large ΩΩ, D3D⁎ scales as Pe2/Ω2 where Pe= h/D. Due to its relative simplicity, the 2D model is frequently utilized for calculating dispersion in channels. However at small dimensionless frequencies the 2D model can significantly underestimate the dispersion, particularly for channels with large χ . At large ΩΩ the dispersion coefficient predicted from the 2D model becomes reasonably accurate, particularly for channels with large χ. For a square channel, the 2D prediction is reasonably accurate for all frequencies. The results of this study will enhance our understanding of transport in microscale systems that are subjected to oscillating flows, and potentially aid technological advances in diverse areas relevant to microfluidic devices.

In the original article the typesetter made several errors. Figures 7 and 9 are incorrect. Following are the correct figures.

Dryness and discomfort are considered to be the biggest causes of dropouts in contact lens wearers. We propose a new method to improve lubricity by polymerizing a thin film of a hydrophilic polymer poly-dimethylacrylamide (DMA) on the contact lens. The proposed approach involving soaking the lens in a solution of azobisisobutyronitrile (AIBN) in methanol to load the hydrophobic thermal initiator into the lens. The AIBN-loaded lens is then placed in an N, N-dimethylacrylamide (DMA) solution at elevated temperature to initiate the thermal polymerization of the monomer to polymerize a film on the surface of the lens. Though AIBN is hydrophobic, it is released into the solution at high temperatures due to the high solubility of the free radicals generated by decomposition of the initiator, which results in polymerization of the bulk solution as well. The processing parameters must be optimized to achieve a surface DMA film of desired thickness without causing the bulk solution to gel and without significant changes to the lens shape. ACUVUE® ADVANCE® lenses were successfully modified using 3.4% AIBN solution to load the initiator and then placing that in a 4% DMA solution at 70 °C for 12 h. The FTIR spectra confirm a surface DMA film and the results are further substantiated by measuring the weight of the surface-film as well as wettability (contact angle) and lubricity (coefficient of friction). The optimized poly-DMA film has a hydrated weight of about 10 mg with a water content of about 400%. The film reduces contact angle from 105.9 ± 0.1° to 45.3 ± 0.12° for ACUVUE® ADVANCE® lens, and reduces the coefficient of friction in contact with excised cornea significantly from 0.0385 ± 0.010 to 0.0063 ± 0.0017. This method is effective only in lenses in which the release duration of the AIBN is sufficiently long to initiate the DMA film within the release duration. The release duration is about 30 min in ACUVUE® ADVANCE® and AIR OPTIX® contact lenses. For other lens types, a modified approach can be developed by first loading vitamin E, which is an effective diffusion barrier into the lens to slow the AIBN release from the lens. This method can be successfully used with other lenses, such as ACUVUE® OASYS®.

Objectives Liposome (LIP)-like lipid dispersions have emerged as useful detoxification vehicles in vitro. The authors compare resuscitation with tailored LIPs, 20% intravenous lipid emulsion (ILE), and sodium bicarbonate (BIC), in a rabbit model of clomipramine toxicity. Methods Sedated, instrumented New Zealand white rabbits underwent clomipramine infusion at 3.2 mg/kg/min to 50% baseline mean arterial pressure (MAP) and then at 1.6 mg/kg/min for 30 minutes. BIC (3 mL/kg 8.4%), ILE (3 mL/kg 20%), or LIP (24 mg/kg) were infused as rescue treatments at toxicity and were repeated at 10 minutes (n = 5 in each group). Results Thirty-minute MAP was greatest in ILE-treated animals: 61 mm Hg ILE (interquartile range [IQR] = 49 to 64 mm Hg), 43 mm Hg LIP (IQR = 36.5 to 49 mm Hg), and 10 mm Hg BIC (IQR = 10 to 44 mm Hg; all p = 0.02). Two of the five BIC-treated animals survived to 30 minutes, compared with all five of the ILE-treated animals and all five of the LIP-treated animals (p = 0.044). Conclusions Both ILE and LIPs improved hemodynamic recovery compared with bicarbonate in clomipramine-induced cardiotoxicity in rabbits. Greater 30-minute MAP was observed in the ILE group. Resumen Comparacion de la Emulsion Lipidica Intravenosa, el Bicarbonato y los Liposomas Adaptados en el Tratamiento de la Toxicidad de la Clomipramina en el Conejo Objetivos Las dispersiones lipidicas semejantes a los liposomas han emergido como vehiculos utiles para eliminar la toxicidad in vitro. Los autores comparan la resucitacion con liposomas adaptados (L), emulsion lipidica intravenosa al 20% (ELI) y bicarbonato sodico (B), en la intoxicacion por clomipramina en un modelo experimental con conejos. Metodologia En conejos blancos de Nueva Zelanda sedados e instrumentalizados, se llevo a cabo una perfusion de clomipramina (3,2 mg/kg/min) hasta el 50% de la presion arterial media (PAM) basal, y despues a 1,6 mg/kg/min durante 30 minutos. Se perfundio B (3 ml/kg 8,4%), ELI (3 ml/kg 20%) o L (24 mg/kg) como tratamientos de rescate del toxico, y se repitieron a los 10 minutos (n =5 en cada grupo). Resultados La PAM a los 30 minutos fue mayor en los animales tratados con ELI: 61 mm Hg para la ELI (RIC 49 a 64 mm Hg) 43 mm Hg para los L (RIC 36,5 a 49 mm Hg), y 10 mm Hg para el B (RIC 10 a 44 mm Hg); p = 0,02. Dos de los cincos animales tratados con B sobrevivieron a los 30 minutos, en comparacion con los cinco de los tratados con ELI y los cinco animales tratados con L (p= 0,044). Conclusiones Tanto la ELI como los L mejoran la recuperacion hemodinamica en compracion con el B en la cardiotoxicidad inducida por clomipramina en los conejos. Se observaron mayores PAM a los 30 minutos en el grupo tratado con la ELI.

Dilution of protein-surfactant complexes is an integrated step in microfluidic protein sizing, where the contribution of free micelles to the overall fluorescence is reduced by dilution. This process can be further improved by establishing an optimum surfactant concentration and quantifying the amount of protein based on the fluorescence intensity. To this end, we study the interaction of proteins with anionic sodium dodecyl sulfate (SDS) and cationic hexadecyl trimethyl ammonium bromide (CTAB) using a hydrophobic fluorescent dye (sypro orange). We analyze these interactions fluourometrically with bovine serum albumin, carbonic anhydrase, and beta-galactosidase as model proteins. The fluorescent signature of protein-surfactant complexes at various dilution points shows three distinct regions, surfactant dominant, breakdown, and protein dominant region. Based on the dilution behavior of protein-surfactant complexes, we propose a fluorescence model to explain the contribution of free and bound micelles to the overall fluorescence. Our results show that protein peak is observed at 3 mM SDS as the optimum dilution concentration. Furthermore, we study the effect of protein concentration on fluorescence intensity. In a single protein model with a constant dye quantum yield, the peak height increases with protein concentration. Finally, addition of CTAB to the protein-SDS complex at mole fractions above 0.1 shifts the protein peak from 3 mM to 4 mM SDS. The knowledge of protein-surfactant interactions obtained from these studies provides significant insights for novel detection and quantification techniques in microfluidics.