Numerical analysis of an enhanced cooling rate cryopreservation process in a biological tissue.

Cryopreservation is the method of preservation of biological tissues for future references without causing significant damages to their physical and functional properties. This can be done by exposing them to very low cryogenic temperature that involves a greater heat removal rate. A two dimensional numerical model is developed to study the temperature distribution, cooling rate attained and movement of the freezing front during the cryopreservation process. The Pennes Bio-heat model is used for current study. The Finite Volume Method is employed for discretization of the governing differential equations while the Tri-Diagonal Matrix Algorithm is used to solve the discretized algebraic equations to find temperature distribution inside the domain. The Enthalpy-Porosity method is used to track the solid-liquid interfaces during the freezing process. The current model is first validated with the result of the existing literature. In the present work, freezing of tissue is done from one and two sides in two separate cases and the resulting temperature distribution inside the tissue and cooling rate in the two cases are compared. It is found that the freezing rate of tissue is enhanced about two times when it is freezed from two sides as compared to freezing from single side. Further, it is observed that a lower value of blood perfusion rate causes a lower value of the final temperature of the tissue after freezing. Thus, it can be concluded that the tissue with high blood perfusion rate is to be freezed in a lower cooling medium temperature. In the present condition, metabolic heat generation plays no significant role in the temperature distribution inside the healthy tissue.

Pathway-based analysis of primary biliary cirrhosis genome-wide association studies.

Genome-wide association studies (GWAS) have successfully identified several loci associated with primary biliary cirrhosis (PBC) risk. Pathway analysis complements conventional GWAS analysis. We applied the recently developed linear combination test for pathways to datasets drawn from independent PBC GWAS in Italian and Canadian subjects. Of the Kyoto Encyclopedia of Genes and Genomes and BioCarta pathways tested, 25 pathways in the Italian dataset (449 cases, 940 controls) and 26 pathways in the Canadian dataset (530 cases, 398 controls) were associated with PBC susceptibility (P<0.05). After correcting for multiple comparisons, only the eight most significant pathways in the Italian dataset had FDR <0.25 with tumor necrosis factor/stress-related signaling emerging as the top pathway (P=7.38 × 10⁻4, FDR=0.18). Two pathways, phosphatidylinositol signaling and hedgehog signaling, were replicated in both datasets (P<0.05), and subjected to two additional complementary pathway tests. Both pathway signals remained significant in the Italian dataset on modified gene set enrichment analysis (P<0.05). In both GWAS, variants nominally associated with PBC were significantly overrepresented in the phosphatidylinositol pathway (Fisher exact P<0.05). These results point to established and novel pathway-level associations with inherited predisposition to PBC that, on further independent replication and functional validation, may provide fresh insights into PBC etiology.

Total bladder replacement by detubularised sigmoid colon segment.

A preliminary report of 3 cases of carcinoma bladder is presented in whom, after radical cystoprostatectomy, a low pressure neobladder is created from detubularised pelvic colon, with subsequent colo-urethral anastomosis. In selected cases, this is a feasible procedure with good patient acceptance as the normal body image is maintained. Also the low pressure neobladder ensures protection to the upper urinary tract from backpressure damage.