Microparticle formation and its mechanism in single and double emulsion solvent evaporation.

The emulsification is the first step of the emulsification solvent evaporation method and has been extensively investigated. On the contrary the second step, the solvent transport out from the emulsion droplets that determine the particle morphology and with great influence on the microparticles encapsulation and release behavior has been scarcely studied. This study investigates the mechanism of the solvent elimination from the emulsion droplets and its influence on the particle morphology, encapsulation and release behavior. Usually, the solvent is highly volatile that makes the solvent elimination process very fast thus difficult to observe. In order to observe in detail the microparticle formation, the initial emulsion was monitored by optical microscope under controlled solvent evaporation conditions. The results from the optical microscopic observations corroborated with laser diffractometry analysis showed that in single emulsion formulations, spherical microparticles are formed by accelerated solvent elimination due to the combined effects of high solvent volatility and polymer precipitation. The solvent expulsion accompanied by important shrinkage generates on the microparticle surface a thin layer of nanoparticles attested by scanning electron microscopy and laser diffractometry. During the intense solvent elimination, the encapsulated substance is drained, affecting the loading efficiency. Furthermore, it will concentrate towards the microparticle surface contributing to the initial burst release. In double emulsion formulations, microparticles with different morphologies are generated due to the presence of the aqueous-phase microdroplets inside the emulsion droplet. During the solvent elimination, these microdroplets generally coalesce under the pressure of the precipitating polymer. Depending mainly on the polymer concentration and emulsification energies, the final microparticles will be a mixture of honeycomb, capsule or plain structure. During the shrinkage due to the incompressibility of the inner microdroplets, the precipitating polymer wall around them may break forming holes through which the encapsulated substance is partly expulsed. Through these holes, the encapsulated substance is further partitioning with the external aqueous phase during solvent evaporation and contributes to the initial burst release during the application.     

Prevalence of urinary incontinence in middle-aged women

An anonymous questionnaire was used to interview 946 premenopausal women (age 29-52 years), previously either hysterectomized or laparoscopically sterilized, concerning disorders of the urinary tract. Of the 750 (79.3%) women that responded, 307 (40.9%) admitted to some degree of urinary disorder. The prevalence of urinary disorders was 170/415 (40.9%) for the women with a previous supravaginal or total hysterectomy and 137/335 (40.8%) for the women in the sterilization group. Of the responding women 85 (11.3%) experienced a urinary loss sufficient to necessitate the wearing of a sanitary napkin or change of underclothing several times a day.     

Numerical Modeling of Blood Flow in the Ventricular Cavity of the Artificial Heart

Summary: The flow of blood as a viscous, Newtonian, incompressible liquid in an expanding spherical cavity with a ball-type inlet valve was examined. This type of flow can serve as a model of the phase of ventricular diastole in a sac-type artificial heart. The critical values of Reynolds numbers at which flow interruption behind the valve occurs were found. The optimum geometric ratios of the dimensions of the ventricular cavity and valve that permit a decrease in the input resistance of the cavity, the size of the valve, and the surface tensions in the bloodstream were determined.     

Sling operation for urinary incontinence

105 women with urinary stress incontinence were treated over an 8-year period. The operations carried out were: 44 Zoedler slings using mersilene and 61 slings using lyodura. Follow-up lasting from 3 to 11 years showed complete failure in 17 patients (16%). The plastic slings of the Zoedler type led to an increased risk of complications such as retropubic infections, rejection of the mersilene, and chronic urinary retention. The lyodura sling was considered good prosthetic material. Our experience shows that a sling operation, as a primary method, may be selected for patients with stress urinary incontinence and a large degree of descent of the anterior vaginal wall and/or uterus.     

Predicting the transactivation activity of p53 missense mutants using a four-body potential score derived from Delaunay tessellations

We describe a novel statistical scoring method based on a computational geometry approach to predict the functional impact (transactivation activity) of missense mutations in the DNA-binding domain (DBD) of the tumor suppressor TP53, which is the most frequently mutated gene in human cancer. Residual scores (RS) for each residue were calculated to reflect differences in the compositional preferences of four nearest-neighbor residues between mutant and wild-type proteins. The RS were then combined into a residual score profile (RSP) representing the RS values for all 194 residues in the DBD. Mutants were grouped into functional categories based on their transactivation activities experimentally measured in yeast functional assays using p53-response elements from eight different promoters. While these functional categories showed significant differences in average RS, the latter lacked resolution power to predict the transactivation activities of individual mutants. In contrast, using decision tree models, we found that the RSP predicted transactivation with an accuracy varying between 64.2% and 78.5% depending on the promoter. Lastly, we used the best model to predict the functional outcome of all missense mutants in the DBD of p53 and compared the predictions with their frequency of occurrence in human cancers. We found that mutants predicted as functional (F) accounted for approximately 14% of all missense mutants found in cancers, while mutants predicted as nonfunctional (NF) represented approximately 86% of the mutants. These results show that this computational approach provides a fast and reliable method for predicting the functional impact of p53 mutants associated with cancer.