We report the cloning and sequencing of 18 mutant alleles of the benA, beta-tubulin gene of Aspergillus nidulans that confer resistance to the benzimidazole antifungal, antimicrotubule compounds benomyl, carbendazim, nocodazole, and thiabendazole. In 12 cases, amino acid 6 was changed from histidine to tyrosine or leucine. In four cases, amino acid 198 was changed from glutamic acid to aspartic acid, glutamine, or lysine. In two cases, amino acid 200 was altered from phenylalanine to tyrosine. These data, along with previous data indicating that amino acid 165 is involved in the binding of the R2 group of these compounds [Jung and Oakley, 1990: Cell Motil. Cytoskeleton 17:87-94], suggest that regions of beta-tubulin containing amino acids 6, 165, and 198-200 interact to form the binding site of benzimidazole antimicrotubule agents. These results also suggest that the presence of phenylalanine at amino acid 200 contributes to the great sensitivity of many fungi to benzimidazole antimicrotubule agents.
Robotic RYGB is not only safe and feasible, but also a valid option in comparison to laparoscopy. At the cost of a longer operative time, we observed better short-term outcomes with the robotic approach.
A RSSC with a real-time near-infrared fluorescent cholangiography can be performed safely. In addition, for selected patients with a low BMI, ICG could shorten the operative time during RSSC. Larger studies are still required before drawing definitive conclusions.
Background & Aims
Bariatric surgery is associated with improved outcomes in subjects with severe obesity. We investigated the prognostic relevance of non-alcoholic steatohepatitis (NASH) and liver gene expression patterns in patients undergoing bariatric surgery.
Methods
We performed a retrospective analysis of 492 subjects who underwent gastric bypass bariatric surgery at a single center in Switzerland from January 1997 through December 2004; routine peri-operative liver biopsies were collected, analyzed histologically, and RNA was isolated. We collected data on overall survival and clinical and biochemical parameters and compared these with data from propensity score-matched subjects participating in the third National Health and Nutrition Examination Survey (NHANES III). We used liver biopsies to identify bariatric surgery patients with NASH; NHANES III participants with NASH were identified based on a hyperechogenic liver at ultrasound and increased alanine transaminase levels. We analyzed a 32-gene signature associated with NAFLD severity in the liver tissues collected from 47 bariatric surgery patients with NASH, and assessed its prognostic features using nearest template prediction and survival analysis.
Results
At baseline, the median body mass index of patients who underwent bariatric surgery was 43.6 kg/m2; based on histologic findings, 12% had NASH and 16% had fibrosis. During a median follow-up of 10.2 years after the surgery, 4.2% of the subjects died. In multivariable Cox regression, the presence of NASH (hazard ratio [HR], 2.9; P=.02) and arterial hypertension (HR, 3.9; P=.02) were associated with overall mortality. When bariatric surgery patients were matched with NHANES III participants, bariatric surgery reduced the risk of death during the follow-up period (HR, 0.54; P=.04). However, bariatric surgery patients with NASH did not have a reduced risk of death compared to NHANES III participants with NASH (HR, 0.90; P=.85). We identified an expression pattern of 32 genes in liver tissues from patients with NASH that was associated with increased risk of death in multivariable analysis (HR, 7.7; P=.045).
Conclusions
Histologically proven NASH is associated with increased risk of death within a median follow-up of 10.2 years after bariatric surgery, compared to patients who undergo bariatric surgery without NASH. The survival benefit of bariatric surgery in subjects with NASH may be reduced. A 32-gene expression pattern identified NASH patients who underwent bariatric surgery and had shorter survival times.
With similar early postoperative clinical results and a higher rate of re-operations, perioperative and long-term costs are significantly higher with robotic Single-Site cholecystectomy compared with multiport cholecystectomy. Considering the unclear clinical value of robotic single-site cholecystectomy and the significant short- and long-term costs, a call for further research and a debate as to who should bear the costs beyond the ones of the gold-standard treatment appear reasonable.
Coexpression of p21/Ki-67 is a strong negative prognostic factor in HNSCC and could be of particular relevance in tumors treated by primary radiotherapy.
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