Developmental Potential of embryos does not Impact Pregnancy Outcomes, but it Affects Live Birth Rates in Frozen Blastocyst Transfer Cycles.

OBJECTIVE: This study aimed to determine whether or not developmental potential impacts clinical outcomes, when good grade blastocysts from Days 5 and 6 were transferred in frozen embryo transfer (FET) cycles. METHODS: 654 women, including 460 (70.33%) on Day 5 and 194 (29.66%) on Day 6 were analyzed, in which 905 Day-5 and 274 Day-6 blastocysts were transferred. Only grade AA, AB, BA, BB quality and expansion grade between 3-6 (Gardner grading system) blastocysts survived and were included. RESULTS: The implantation rate was higher, 41.9% (379/905) in normal Day-5 compared to delayed Day-6 blastocyst transfers - 36.5% (100/274), but not significant (p=0.1). The clinical pregnancy rate was similar and not significant (p=0.4) in normal Day-5 (32.4%), compared to delayed Day-6 (35%). Miscarriage rates were higher in normal Day-5 (13.3%) compared to delayed Day-6 (6.3%) blastocyst transfers but were not significant (p=0.06). On the other hand, the biochemical pregnancy rate was significantly higher (p=0.001) in the delayed Day-6 blastocysts (16.7%) transfer group compared to patients with normal Day-5 (2.4%) blastocyst transfers. Two patients had ectopic pregnancies from the delayed Day-6 blastocyst transfer group. Live-Birth rates were significantly higher in Day-5 blastocysts compared to Day-6 (p=0.03). CONCLUSIONS: The developmental potential of embryos should not be considered a negative influence on pregnancy outcomes, especially good grade blastocysts vitrified on Days 5 and 6. Fully expanded blastocysts on Day-5 are considered similar in terms of outcomes to delayed Day-6 blastocysts; however, live-birth rates are significantly higher in Day-5 blastocysts.

Patterns of Tobacco Use and its Relation to Oral Precancers and Cancers among Individuals Visiting a Tertiary Hospital in South India.

AIM: The aim of this study was to evaluate the use of tobacco and its association with oral precancers and cancers. MATERIALS AND METHODS: Medical records of 1,007 individuals were assessed for the patterns of tobacco abuse and the presence of tobacco-related oral mucosal alterations. RESULTS: This study comprised 1,007 individuals (M:F: 95.4%:4.6%). In the cohort, 60.1% had smoking habit and 56.1% had smokeless habit. Of the bidi smokers, 18.2% developed carcinoma, 14.3% developed leukoplakia, which is statistically significant (p < 0.001). A logistic regression analysis of the development of oral submucous fibrosis (OSMF) shows that habit of smokeless forms of tobacco has an odds ratio (OR) of 18+ when compared with smoking. Combination of bidi and gutkha had 12.3 times higher risk of developing oral cancer and 4.4 times risk of developing leukoplakia. A total of 33.3% betel quid and gutkha chewers presented with tobacco pouch keratosis, which is statistically significant. CONCLUSION: Smoked and smokeless forms of tobacco were equally popular among the study population. The packeted form of smokeless tobacco (gutkha) was more prevalent. Oral submucous fibrosis was more common than leukoplakia, and oral cancer developed more frequently in elderly men smoking bidis. CLINICAL SIGNIFICANCE: This study throws light on the fact that the use of both smoke and smokeless forms of tobacco is still prevalent, and the use of gutkha was most prevalent. These findings will help tobacco cessation and counseling centers to focus their effort in motivating people to stop gutkha chewing habit. This also brings to the forefront the need to create better treatment strategies to manage OSMF.

NPM-ALK up-regulates iNOS expression through a STAT3/microRNA-26a-dependent mechanism.

NPM-ALK chimeric oncogene is aberrantly expressed in an aggressive subset of T-cell lymphomas that frequently occurs in children and young adults. The mechanisms underlying the oncogenic effects of NPM-ALK are not completely elucidated. Inducible nitric oxide synthase (iNOS) promotes the survival and maintains the malignant phenotype of cancer cells by generating NO, a highly active free radical. We tested the hypothesis that iNOS is deregulated in NPM-ALK(+) T-cell lymphoma and promotes the survival of this lymphoma. In line with this possibility, an iNOS inhibitor and NO scavenger decreased the viability, adhesion, and migration of NPM-ALK(+) T-cell lymphoma cells, and an NO donor reversed these effects. Moreover, the NO donor salvaged the viability of lymphoma cells treated with ALK inhibitors. In further support of an important role of iNOS, we found iNOS protein to be highly expressed in NPM-ALK(+) T-cell lymphoma cell lines and in 79% of primary tumours but not in human T lymphocytes. Although expression of iNOS mRNA was identified in NPM-ALK(+) T-cell lymphoma cell lines and tumours, iNOS mRNA was remarkably elevated in T lymphocytes, suggesting post-transcriptional regulation. Consistently, we found that miR-26a contains potential binding sites and interacts with the 3'-UTR of iNOS. In addition, miR-26a was significantly decreased in NPM-ALK(+) T-cell lymphoma cell lines and tumours compared with T lymphocytes and reactive lymph nodes. Restoration of miR-26a in lymphoma cells abrogated iNOS protein expression and decreased NO production and cell viability, adhesion, and migration. Importantly, the effects of miR-26a were substantially attenuated when the NO donor was simultaneously used to treat lymphoma cells. Our investigation of the mechanisms underlying the decrease in miR-26a in this lymphoma revealed novel evidence that STAT3, a major downstream substrate of NPM-ALK tyrosine kinase activity, suppresses MIR26A1 gene expression.