Fundoplication for gastroesophageal reflux disease: regional variability and factors predicting operative approach

We have recently shown that the majority of patients undergoing fundoplication in the United States are women. Based on these findings, we hypothesized that nonbiological factors contribute to the decisions on surgical reflux therapy. Using State Inpatient Databases of the Agency for Healthcare Research and Quality, we extracted annual fundoplication rates, sex distribution, age cohorts, racial background, and insurance coverage. To account for potential differences in state populations, the results were normalized and correlated with Census data, adult obesity rates, median income, poverty rates, and physician workforce within the state. Fundoplication rates varied fivefold between states, ranging from 4.1 ± 0.1 per 100 000 in New Jersey to 21.8 ± 0.4 per 100 000 in Oregon. Higher poverty rates and a higher fraction of Caucasians within a state independently predicted higher fundoplication rates. While the majority of operations were performed laparoscopically, surgical approaches also differed between states with rates of laparoscopic ranging from 52.3 ± 1.8% in Oklahoma to 87.4 ± 1.7% in Hawaii. A lower number of pediatric and Medicaid‐insured patient and a higher fraction of privately insured patients best predicted higher rates of laparoscopic surgery. Our study shows significant regional variation in surgical reflux management, which cannot be explained by differences in disease mechanisms. Insurance coverage and racial background influenced the likelihood of surgery, suggesting a role of financial incentives.     

Laparoscopic-assisted one-stage resection of rectal cancer with synchronous liver metastasis utilizing a pfannenstiel incision

Laparoscopic approaches have been increasingly used in selected patients with either colorectal or liver cancer. However, simultaneous resection of colorectal carcinoma with synchronous liver metastases is still a subject of debate. The present case describes combined laparoscopic rectal and liver resections for a patient with primary rectal cancer and a synchronous liver metastasis utilizing a Pfannenstiel incision for specimen extraction. The operative time was 370 min and estimated blood loss was 400 mL. Postoperatively, the patient required parenteral analgesia for 48 h, resumed normal diet on day 3 and was discharged on day 7 after the operation. A laparoscopic approach utilizing a Pfannenstiel extraction incision may present an advantageous and attractive option for simultaneous laparoscopic rectal and liver resection in selected patients with the aim of improving short-term outcomes.     

Modulation of JNK-1/ β-catenin signaling by Lactobacillus casei,inulin and their combination in 1,2-dimethylhydrazine-induced colon cancer in mice

Colon cancer is a complex disease that involves numerous genetic alterations that change the normal colonic mucosa into invasive adenocarcinoma. In the current study, the protective effects of inulin (prebiotic), Lactobacillus casei (L. casei, probiotic) and their combination (synbiotic) on 1,2-dimethylhydrazine (DMH)-induced colon cancer in male Swiss mice were evaluated. Animals were divided into: Control group, DMH-treated group, DMH plus inulin, DMH plus L. casei and DMH plus inulin plus L. casei-treated groups. Fecal microbiome analysis, biochemical measurements, histopathological examination of the colon tissues, immunostaining and Western blotting analysis of β-catenin, GSK3β and JNK-1 were performed. The prebiotic-, probiotic- and synbiotic-treated groups showed decreased levels of carcinoembryonic antigen and a lower number of aberrant crypt foci compared to the DMH-treated group with the synbiotic group exhibiting a superior effect. Furthermore, all treatments showed a body weight-reducing effect. Administration of inulin, L. casei or their combination increased the expression level of phospho-JNK-1 while they decreased the expression level of β-catenin and phospho-GSK3β. Remarkably, L. casei treatment resulted in enrichment of certain beneficial bacterial genera i.e. Akkermansia and Turicibacter. Therefore, administration of L. casei and inulin as a synbiotic combination protects against colon cancer in mice.

The lactobacillus casei and inulin modulate the expression of JNK-1, GSK3β and β-catenin proteins and enrich the beneficial bacteria to protect from colon cancer in mice.     

Serotonin transporter polyadenylation polymorphism modulates the retention of fear extinction memory

Growing evidence suggests serotonin's role in anxiety and depression is mediated by its effects on learned fear associations. Pharmacological and genetic manipulations of serotonin signaling in mice alter the retention of fear extinction learning, which is inversely associated with anxious temperament in mice and humans. Here, we test whether genetic variation in serotonin signaling in the form of a common human serotonin transporter polyadenylation polymorphism (STPP/rs3813034) is associated with spontaneous fear recovery after extinction. We show that the risk allele of this polymorphism is associated with impaired retention of fear extinction memory and heightened anxiety and depressive symptoms. These STPP associations in humans mirror the phenotypic effects of serotonin transporter knockout in mice, highlighting the STPP as a potential genetic locus underlying interindividual differences in serotonin transporter function in humans. Furthermore, we show that the serotonin transporter polyadenylation profile associated with the STPP risk allele is altered through the chronic administration of fluoxetine, a treatment that also facilitates retention of extinction learning. The propensity to form persistent fear associations due to poor extinction recall may be an intermediate phenotype mediating the effects of genetic variation in serotonergic function on anxiety and depression. The consistency and specificity of these data across species provide robust support for this hypothesis and suggest that the little-studied STPP may be an important risk factor for mood and anxiety disorders in humans.     

Multiple self-splicing introns in the 16S rRNA genes of giant sulfur bacteria

The gene encoding the small subunit rRNA serves as a prominent tool for the phylogenetic analysis and classification of Bacteria and Archaea owing to its high degree of conservation and its fundamental function in living organisms. Here we show that the 16S rRNA genes of not-yet-cultivated large sulfur bacteria, among them the largest known bacterium Thiomargarita namibiensis, regularly contain numerous self-splicing introns of variable length. The 16S rRNA genes can thus be enlarged to up to 3.5 kb. Remarkably, introns have never been identified in bacterial 16S rRNA genes before, although they are the most frequently sequenced genes today. This may be caused in part by a bias during the PCR amplification step that discriminates against longer homologs, as we show experimentally. Such length heterogeneity of 16S rRNA genes has so far never been considered when constructing 16S rRNA-based clone libraries, even though an elongation of rRNA genes due to intervening sequences has been reported previously. The detection of elongated 16S rRNA genes has profound implications for common methods in molecular ecology and may cause systematic biases in several techniques. In this study, catalyzed reporter deposition-fluorescence in situ hybridization on both ribosomes and rRNA precursor molecules as well as in vitro splicing experiments were performed and confirmed self-splicing of the introns. Accordingly, the introns do not inhibit the formation of functional ribosomes.