Gender and Nationality Trends in Manuscripts Published in Prominent Gastroenterology Journals Between 1997 and 2017

Digestive Diseases and Sciences - Gender disparities remain in the field of gastroenterology (GI) despite the decreasing gender gap in the medical field overall. We sought to examine primary and...     

Manual versus rotary instrumentation for primary molar pulpectomies- A 24 months randomized clinical trial

Objective

The study compared manual and rotary canal instrumentation differences in primary molars receiving pulpectomy and their effect on clinical success after two years.

Detection of BCR-ABL kinase mutations in CD34+ cells from chronic myelogenous leukemia patients in complete cytogenetic remission on imatinib mesylate treatment

The BCR-ABL kinase inhibitor imatinib mesylate induces complete cytogenetic response (CCR) in a high proportion of chronic myelogenous leukemia (CML) patients. However, patients in CCR usually demonstrate evidence of residual BCR-ABL-positive progenitors. The mechanisms underlying persistence of small numbers of malignant progenitors in imatinib-sensitive patients are unclear. BCR-ABL kinase domain mutations affecting drug binding can lead to secondary resistance to imatinib. We show here that kinase mutations could be detected in CD34+ cells isolated from CML patients in CCR on imatinib. Most mutations seen have not been reported in previous clinical studies. Interestingly, several of the involved amino acid positions have been implicated in an in vitro mutagenesis screen. These BCR-ABL mutations were associated with varying levels of imatinib resistance. Two of 5 patients in whom mutations were detected on initial evaluation have relapsed. In addition, 4 patients in whom mutations were not initially detected, but with rising BCR-ABL mRNA levels on quantitative polymerase chain reaction (Q-PCR) analysis, had mutations detected on follow-up evaluation. We conclude that BCR-ABL kinase mutations can be detected in CD34+ cells from CML patients in CCR on imatinib, may contribute to persistence of small populations of malignant progenitors, and could be a potential source of relapse.     

Use of imidazole-based eradication regimens for Helicobacter pylori should be abandoned in North India regardless of in vitro antibiotic sensitivity

BACKGROUND AND AIM: The purpose of this study was to compare the efficacy of tinidazole- versus clarithromycin-based triple regimens for eradication of Helicobacter pylori in North Indian patients of peptic ulcer disease, and to correlate the outcome with in vitro antibiotic susceptibility. METHODS: One hundred and forty-six H. pylori-infected patients with active ulcer were included in the prospective, randomized study. A total of 70 patients received lansoprazole 30 mg b.d., amoxycillin 1000 mg b.d. and tinidazole 500 mg b.d. (LAT), and 76 patients received lansoprazole 30 mg b.d., amoxycillin 1000 mg b.d. and clarithromycin 500 mg b.d. (LAC) for 14 days. The H. pylori status was assessed by urea breath test, rapid urease test, and histology and antibiotic sensitivity pattern by Epsilometer test. RESULTS: In per-protocol analysis of 112 patients the H. pylori eradication rate was 42.3% (95% confidence interval (CI): 0.29-0.56) in LAT, and 64.8% (95%CI: 0.52-0.78) in LAC (95%CI of difference of proportions: 0.13-0.33, P = 0.01). Ulcer healed in 69.2% in the LAT group (95%CI: 0.57-0.82) and 81.7% in the LAC group (95%CI: 0.72-0.92; P = 0.02). Antibiotic susceptibility testing was done in 31 patients. Metronidazole resistance was present in 41.9% isolates but was unrelated to the outcome of the LAT regimen. CONCLUSION: Imidazole-based eradication regimens should be abandoned in North India regardless of in vitro susceptibility results.     

Error-free replicative bypass of thymine glycol by the combined action of DNA polymerases κ and ζ in human cells

Thymine glycol (Tg) is the most common DNA lesion of thymine induced by interaction with reactive oxygen species. Because of the addition of hydroxyl groups at C5 and C6 in a Tg lesion, the damaged base loses its aromatic character and becomes nonplanar; consequently, the C5 methyl group protrudes in an axial direction and that prevents the stacking of the 5′ base above the Tg lesion. Because Tg presents a severe block to continued synthesis by replicative DNA polymerases, we determine here how human cells manage to replicate through this lesion. Using a duplex plasmid system where bidirectional replication ensues from an origin of replication, we show that translesion synthesis (TLS) makes a prominent contribution to Tg bypass and that it occurs in a predominantly error-free fashion. Also, we provide evidence that Polκ and Polζ function together in promoting error-free replication through the lesion, and based on structural and biochemical information, we propose a role for Polκ at the insertion step and of Polζ at the extension step of Tg bypass. We discuss the implications of these observations and suggest that human cells have adapted the TLS machinery to function in a much more error-free fashion than could have been predicted from the intrinsic catalytic efficiencies and fidelities of TLS polymerases.     

Evidence for the transmission of neoplastic properties from transformed to normal human stem cells

The in vivo relationship between human tumor cells and interacting normal cells in their local environment is poorly understood. Here, using a uniquely developed in vitro co-culture system for human embryonic stem cells (hESCs), we examined the interactions between transformed and normal human stem cells. Co-culture of transformed-hESCs (t-hESCs) with normal hESCs led to enhanced self-renewal and niche independence in normal hESCs. Global gene expression analysis of normal hESCs after timed exposure to t-hESCs indicated a transition of the molecular network controlling the hESC state, which included epigenetic changes, towards neoplastic features. These included enhanced pluripotent marker expression and a differentiation blockade as major hallmark changes. Functional studies revealed a loss in normal terminal differentiation programs for both hematopoiesis and neural lineages after normal stem cell co-culture with transformed variants. This transmission of neoplastic properties from t-hESCs to normal hESCs was dependent on direct cell-cell contact. Our study indicates that normal human stem cells can co-opt neoplastic cancer stem cell properties, raising the possibility that assimilation of healthy cells towards neoplastic behavior maybe a contributing feature of sustained tumorigenesis in vivo.