Gamma knife capsulotomy for intractable OCD: Neuroimage analysis of lesion size, location, and clinical response.

Obsessive-compulsive disorder (OCD) affects 2-3% of the population. One-third of patients are poorly responsive to conventional therapies, and for a subgroup, gamma knife capsulotomy (GKC) is an option. We examined lesion characteristics in patients previously treated with GKC through well-established programs in Providence, RI (Butler Hospital/Rhode Island Hospital/Alpert Medical School of Brown University) and São Paulo, Brazil (University of São Paolo). Lesions were traced on T1 images from 26 patients who had received GKC targeting the ventral half of the anterior limb of the internal capsule (ALIC), and the masks were transformed into MNI space. Voxel-wise lesion-symptom mapping was performed to assess the influence of lesion location on Y-BOCS ratings. General linear models were built to compare the relationship between lesion size/location along different axes of the ALIC and above or below-average change in Y-BOCS ratings. Sixty-nine percent of this sample were full responders (≥35% improvement in OCD). Lesion occurrence anywhere within the targeted region was associated with clinical improvement, but modeling results demonstrated that lesions occurring posteriorly (closer to the anterior commissure) and dorsally (closer to the mid-ALIC) were associated with the greatest Y-BOCS reduction. No association was found between Y-BOCS reduction and overall lesion volume. GKC remains an effective treatment for refractory OCD. Our data suggest that continuing to target the bottom half of the ALIC in the coronal plane is likely to provide the dorsal-ventral height required to achieve optimal outcomes, as it will cover the white matter pathways relevant to change. Further analysis of individual variability will be essential for improving targeting and clinical outcomes, and potentially further reducing the lesion size necessary for beneficial outcomes.

Deep Transfer Learning Based Classification Model for COVID-19 Disease.

The COVID-19 infection is increasing at a rapid rate, with the availability of limited number of testing kits. Therefore, the development of COVID-19 testing kits is still an open area of research. Recently, many studies have shown that chest Computed Tomography (CT) images can be used for COVID-19 testing, as chest CT images show a bilateral change in COVID-19 infected patients. However, the classification of COVID-19 patients from chest CT images is not an easy task as predicting the bilateral change is defined as an ill-posed problem. Therefore, in this paper, a deep transfer learning technique is used to classify COVID-19 infected patients. Additionally, a top-2 smooth loss function with cost-sensitive attributes is also utilized to handle noisy and imbalanced COVID-19 dataset kind of problems. Experimental results reveal that the proposed deep transfer learning-based COVID-19 classification model provides efficient results as compared to the other supervised learning models.

Covered conduction of individual C(60) nanowhiskers.

We investigate the electronic properties of individual C(60) nanowhiskers by exploiting conductive atomic force microscopy at room temperature in ambient atmosphere. The pristine individual C(60) nanowhiskers exhibit conducting behavior. The outer C(60) oxide covering, confirmed by Auger electron spectroscopy, shelters the conductive properties of the C(60) nanowhiskers. It is proposed that the insulating outer C(60) oxide covering might be used as the dielectric layer in potential single C(60) nanowhisker-based field-effect transistors for nanoelectronics.

Aluminum polymeric implants: in vitro-in vivo evaluations.

The purpose of this investigation is to study the effect of long-term subcutaneous aluminum polymeric implants on aluminum release and accumulation in various tissues in rats. The implants were formulated using silicone rubber and polyurethane polymers and three different aluminum salts. The polymeric matrices were evaluated for in vitro release studies. These matrices released aluminum in vitro up to the period of four months. The aluminum matrices were implanted in rats and animals were sacrificed at various time intervals. Various tissues such as brain, kidney, liver, intestine, and heart were isolated. Aluminum in dried tissues was analyzed by Neutron Activation Analysis. Results from this investigation suggest that polymeric aluminum implants raise the aluminum concentration in the brain and liver. However, these implants did not increase aluminum levels in intestine, heart, and kidney. The polymeric aluminum implants could be used to establish an animal model for the neuropathology of dementia.

Polyethylene-starch extrudates as erodible carriers for bioactive materials: I. Erodibility and in vitro dye release studies.

The objective of the present investigation is to develop and evaluate polyethylene-starch based carriers for sustaining the release of bioactive materials. Polyethylene-starch carriers were prepared by incorporating various amounts of corn starch 0, 40, 80, and 100% in polyethylene beads with and without dye. Acid orange dye was incorporated (1%) to study release patterns and the effect of starch (%) on release. The granulated mixtures were extruded to form uniform dispersions of starch and polyethylene throughout the extrudate. The extrudates obtained were studied for SEM surface characterization before, during, and after release studies to study the erosion process. In the case of 100% starch, 80% of the matrix was eroded in 5 weeks, while with 40% and 80% starch, erosion was less than 20%. The dye release studies showed that release could be sustained well over 12 weeks, depending on the starch (%) incorporated. The erosion process was studied using scanning electron microscopic techniques, which showed gradual erosion of starch particles, leaving a polyethylene skeleton. These materials show promising potential for use as carriers for bioactive materials.

Synergistic inhibition of the calcification of glutaraldehyde pretreated bovine pericardium in a rat subdermal model by FeCl3 and ethanehydroxydiphosphonate: preincubation and polymeric controlled release studies.

Calcification is a frequent cause of the clinical failure of bioprosthetic heart valves fabricated from glutaraldehyde-pretreated porcine aortic valves or glutaraldehyde-pretreated bovine pericardium (GPBP). We investigated the hypothesis that ferric chloride (FeCl3) and sodium-ethanehydroxydiphosphonate (EHDP) may act synergistically to prevent bioprosthetic tissue calcification. Pre-incubations and controlled release systems were studied individually. FeCl3-EHDP polymeric controlled release matrices were formulated using silicone rubber and evaluated for in vitro release kinetics at pH 7.4 and 37 degrees C. The effects of Fe-EHDP synergism on GPBP calcification were investigated with 21 d subdermal implants in 3 wk-old male rats. Results demonstrated that levels of Fe3+ and EHDP uptake, measured in GPBP tissues pre-incubated first in an FeCl3 solution (10(-5) M) followed by an EHDP solution (0.1 M), were higher than in the reverse order of incubation. In the first series of rat implants, GPBP was pre-incubated in either FeCl3 or Na2EHDP solutions, or sequential pre-incubations of first FeCl3 and then Na2EHDP solutions, or the reverse. The inhibition of calcification was greatest when FeCl3 (first pre-incubation, 10(-5) M) was combined with Na2EHDP (second pre-incubation, 0.1 M) (1.78 +/- 0.2 micrograms of Ca2+/mg of dried tissue) compared with the other pre-incubation groups: EHDP (first pre-incubation) combined with FeCl3 (second pre-incubation) (21.7 +/- 6.4), FeCl3 solution alone at 10(-5) M (27.9 +/- 10.7), Na2EHDP solution alone at 0.1 M (52.3 +/- 11.9) and the control group (72.3 +/- 10.2). In a second series of implants, GPBP specimens were co-implanted with individual controlled release systems containing one of the following formulations (weight percentage in silicone rubber): 1% FeCl3, 20% CaEHDP, 20% protamine sulphate, 1% FeCl3-20% CaEHDP, and 1% FeCl3-20% protamine sulphate. The 1% FeCl3-20% CaEHDP silicone-rubber matrices were the most effective for inhibiting GPBP mineralization (13.7 +/- 3.0 micrograms Ca2+/mg of dried tissue) compared with non-drug silicone co-implant controls (74.7 +/- 5.58 micrograms Ca2+/mg of dried tissue) and other polymeric treatment groups (32.3 +/- 2.3-80.0 +/- 19.7). No adverse effects on bone or overall growth of any treatment protocols were noted. Thus, combinations of FeCl3 and EHDP, using either pre-incubations or polymeric controlled release, were synergistic for inhibiting GPBP calcification.

In vitro release and intestinal absorption of physostigmine salicylate from submicron emulsions.

The in vitro release of physostigmine salicylate (PS) from a submicron emulsion and an aqueous solution was studied using the dialysis bag method. These formulations were then perfused to various locations along the rat small intestine (proximal, mid, and distal jejunum), and two lengths (10 and 55 cm). The disappearance of PS from the luminal compartment and its appearance in the blood compartment was monitored. In the in vitro drug release from emulsion experiments, a biphasic appearance of PS in the sink solution was observed, suggesting a possible sustained release from the emulsion. However, absorption data from perfusion studies did not correlate with this in vitro observation. No significant difference was found in absorption from emulsion versus solution in the mid jejunum where PS absorption was maximal. The difference between the two liquid formulations was observed only in those intestinal segments where the absorption was relatively low [absorption rate values of 4.6 +/- 0.86 and 9.98 +/- 2.04 (log%/min) x 10(-3) in the proximal and distal parts of the small intestine, respectively, as compared with 14.0 +/- 1.2-14.8 +/- 1.1 (log%/min) x 10(-3) in the mid jejunum]. In the distal part of the rat small intestine, PS was absorbed significantly better from solution than from the submicron emulsion. Cholinesterase activity in blood samples collected after intestinal perfusion with emulsion or solution revealed lower enzyme activity following emulsion administration.

Prevention of calcification of glutaraldehyde pretreated bovine pericardium through controlled release polymeric implants: studies of Fe3+, Al3+, protamine sulphate and levamisole.

Calcification is the principal cause of the clinical failure of bioprosthetic heart valves fabricated from glutaraldehyde pretreated porcine aortic valves or bovine pericardium. The present study investigated controlled-release implants for prevention of the calcification of glutaraldehyde pretreated bovine pericardium in a rat subdermal model. Either Al3+ and Fe3+ (inhibitors of the growth and dissolution rate of hydroxyapatite crystals), levamisole (alkaline phosphatase inhibitor) or protamine sulphate (charge modifier) were individually incorporated into various polymeric carriers (either silicone rubber, polyurethane or silicone rubber-polyurethane copolymer). Polymeric implants were evaluated for in vitro release kinetics, which revealed that sustained drug release was obtained from 21 d to more than 90 d from various drug matrices. In vivo efficacy was studied by co-implanting the polymeric delivery systems with glutaraldehyde pretreated bovine pericardium for 21 d using a subdermal rat model; glutaraldehyde pretreated bovine pericardium calcium levels were quantitated by atomic absorption spectroscopy in the explanted tissues. Fe3+ and Al3+ polymeric implants were the most effective for inhibiting deposition of calcium mineral. Al3+ demonstrated 82% inhibition of calcification compared to controls and Fe3+ resulted in 80% inhibition of calcification. Specific histologic staining methods showed that Fe3+ and Al3+ were localized within the devitalized cells of the explanted glutaraldehyde pretreated bovine pericardium. No adverse effects on somatic growth or recipient bone morphology were noted following controlled-release drug administration. Controlled release of protamine sulphate or levamisole did not significantly inhibit glutaraldehyde pretreated bovine pericardium calcification. It is concluded that regional controlled release of Fe3+ or Al3+ inhibits glutaraldehyde pretreated bovine pericardium calcification in the rat subdermal model without adverse effects.

Rosin and rosin derivatives as hydrophobic matrix materials for controlled release of drugs.

The evaluation of rosin, a rosin hard paraffin adduct, and four rosin esters as hydrophobic matrix materials for the controlled release of drugs is reported, using aspirin as a drug model. Aspirin matrix tablets were prepared using a wet granulation (nonaqueous) method, and were evaluated for various pharmaceutical parameters. Dissolution studies in pH 7.2 phosphate buffer showed that all formulations had hardness greater than 6 kg/cm2 and disintegration time greater than 150 min. Release of aspirin from the formulations obeyed a diffusion controlled first order kinetic and linear to the square root of time function. Two of the resin ester formulations had a T80% of more than 4 hr. The results suggest that these esters may find application in the development of sustained release formulations for the local treatment of dental diseases, or--as tablet matrices suitably coated with acid resistant material--in the development of oral sustained release drug delivery systems.

Release kinetic study of RHPC coated aspirin microcapsules.

The present communication deals with the study of the effect of pH on the drug release characteristics and the drug release kinetic from the RHPC (Rosin Hard Paraffin Combination) coated aspirin microcapsules. For the purpose of the present study the aspirin microcapsules were prepared by pan coating method imparting 15 coats using 10 per cent RHPC solution in acetone. A standard coating procedure was used to coat the aspirin granules. Dissolution studies were carried out in media with different pH. To get a clear picture drug release studies were conducted in each media for 3 h. The results showed that the RHPC films were resistant to acidic pH releasing less than 5 per cent and 15 per cent drug in 3 h in pH 1.2 and 3.0 respectively. The T 50% in pH 5.0 media was 163 min. The drug was released very quickly in pH 7.2 and 8.0. The release kinetic study showed that the release followed the classical first order pattern though the coated microcapsules used to be intact during the dissolution process, in case of the acidic pH media. The release kinetic was changed when the pH of the dissolution media was 7.2 and above. It was found that during the dissolution process the granules undergo erosion and the release mechanism does not follow a single process.

Evaluation of methyl cellulose as controlled release matrix material.

The formulation for the controlled release of NaF from matrix tablets using Methyl cellulose to prepare chewable NaF tablets for the prevention of dental caries is developed. Various micromeritic studies of granules and tablets containing different concentrations of matrix were studied. Dissolution studies were also carried out in distilled water at 37 +/- 1 degrees C. Significant variations in granule and tablet characteristics were observed depending upon the concentration of the Methyl cellulose used observed. The in vitro drug release reveals that, T 80% values for 30% concentration of matrix is greatest, which seems to be ideal concentration. The drug dissolution is diffusion controlled and follows the Higuchi equation. The fraction of the drug release is proportional to time 1/2 Clinical study is in progress and is encouraging.

Evaluation of compressibility of pentaestergum coated aspirin microcapsules.

We have earlier reported the usefulness of the pentaerythritol rosin ester (pentaestergum) as a coating material, its dissolution kinetics and in vivo release studies in dogs. The present communication deals with the compressibility of the pentaestergum-coated aspirin microcapsules. The microcapsules were prepared by the pan-coating method described earlier. These were compressed into the tablets using a single punch machine. The tablets were evaluated for hardness, friability loss, disintegration time and dissolution studies. The results showed that there were significant differences in the release characteristics from the microcapsules and the compressed tablets. The effect of 5 per cent starch as a disintegrating agent in the tablet formulation was also studied. The results showed that the tablets can be a suitable dosage form for pentaestergum-coated microcapsules to give a delayed drug release.

Micronized emulsion for controlled release of physostigmine after oral administration. Part I. Formulation design.

Our aim was to incorporate physostigmine in a fine micronized emulsion delivery system which would prolong drug release following oral administration. Investigation of various types of equipment and experimental conditions led to a fine micronized emulsion of mean droplet size around 1 micron, which was stable at pH 5.5. The effect of physostigmine concentration and salt formation on the interfacial tension and zeta potential of the emulsion was studied. Physostigmine base markedly decreased the interfacial tension as compared to physostigmine hemisulfate and salicylate. Zeta potential was highest in the case of the salicylate. After storage at 4 37 degrees C for four months, the emulsion did not undergo any significant change.

Micronized emulsion for controlled release of physostigmine after oral administration. Part II. Release characteristics and pharmacological evaluation.

In vitro release of physostigmine from an emulsion was more prolonged than from a tablet. This prolongation was attributed to the retention capacity of the dispersed oil droplets. Increase of the oily phase volume ratio from 20 to 50% did not substantially decrease the rate of release, and decrease of the mean oil droplet size did not affect the release profile, indicating that the drug was mainly localized in the external phase of the emulsion. The profiles agreed with those predicted from our earlier mathematical equation based on a three compartment model system. In rabbits there were no significant differences in the Tmax and AUC values obtained by use of a tablet and the emulsion form, but the emulsion form elicited less enzyme inhibition. T20 (the therapeutic occupancy time) was markedly extended following use of the emulsion form.

Effect of pH on the release characteristics of pentaestergum microcapsules and a study of dissolution kinetics.

Rosin and rosin esters have excellent film-forming properties. Pentaerythritol-rosin ester (penta-ester gum) is found to be useful as moisture-protecting material with delayed release of drug. This communication relates the effect of pH on the release characteristics of a drug from penta-ester gum coated microcapsules. Salicylic acid granules were encapsulated using a 10 per cent solution of penta-ester gum in acetone. The microcapsules were evaluated for their drug release characteristics. Various pH media (pH 1.2, 3.0, 5.0, 7.2 and 8.0) were used. The results showed that penta-ester gum exhibits excellent resistance to higher pH levels and can be used for the sustained release of the drug. Dissolution rate constants were calculated and they agree with the assumption of Hixson and Crowell's cube-root equation.

Study of rosin-glycerol esters as microencapsulating materials. II. Quantitative correlation between physico-chemical properties and release characteristics.

Rosin-glycerol esters have been used as microencapsulating materials. A quantitative correlation has been observed between the physico-chemical properties, i.e. acid value and moisture affinity, and the release characteristics from the encapsulated drug.

Study of rosin glycerol esters as microencapsulating materials.

Rosin esters were prepared by heating rosin with glycerol and intermediate reaction products with different acid values were withdrawn. Salicylic acid granules were encapsulated using a 10 per cent solution of rosin esters in acetone. The coated microcapsules were evaluated for moisture absorption, flow properties and dissolution studies. The results showed that rosin and rosin-glycerol intermediates with acid values of 122, 105 and 55 had excellent moisture protection properties. Dissolution studies showed that these could be used for delayed release of drug.